Do you even need supplements for stress?

First, I want to discuss what “stress” feels like and why.  You’d be amazed at how many people find themselves stress-eating while standing in front of an open refrigerator. They don’t even necessarily know they’re feeling anxious. It’s not yet time to dive into a discussion about any supplements or “cool stuff” like probiotics for anxiety, often called psychobiotics, because first, we need to clarify what’s going on.

If you’ve ever experienced stress-eating, this article will help you break free from this ‘mindless eating’ cycle. By understanding the hormones that cause stress and anxiety, you can regain control over your reactions and responses. I’ll cover the following.

• Understanding stress
• GABA’s Role in Anxiety
• Healthy habits and practices to raise GABA
• GABA enhancing supplements
• Psychobiotics
• Functional meds: Selank and LDN

Adrenaline

Adrenaline, or epinephrine, is the hormone that kicks in during the fight-or-flight response. It’s produced by the adrenal glands when the brain signals a stressful situation. Understanding this hormone can empower you to manage your stress levels better.

Adrenaline, the fight-or-flight hormone, is the star of our immediate stress reactions. Imagine this: you’re driving, attempting to change lanes when a car zooms past you from your blind spot at a staggering 100 miles per hour. You swerve back into your original lane, your heart pounding, muscles tense, breath quickened, and sweat forming on your brow. That’s the power of adrenaline, your body’s natural stress response.

Along with the increase in heart rate, adrenaline causes a surge in energy. This comes from the need for the fright to make you take flight, and there’s the energy to do it. Adrenaline directs blood flow to our arms and legs. Heart rate and respiration quicken, and we may start sweating. Adrenaline is released from the adrenal glands after the brain warns of imminent danger.

Nor-epinephrine

This hormone is similar to adrenaline, released from the adrenal glands and also somewhat from the brain. It makes you very alert, more responsive, and invigorated.

It also diverts blood from the skin, the digestive tract, and other non-essential areas and shifts it towards the muscles. This can further aid in any fighting or fleeing you may need to do.

Nor-epinephrine might seem a bit “redundant,” considering adrenaline mirrors its effects. However, this is not the case. It works as both a backup and a complement to adrenaline. If your adrenal glands are not working well, you can still get a solid shot of nor-epinephrine from your brain.

Note that although nor-epinephrine “accompanies” epinephrine in times of stress, it is needed to stay happy and balanced. It does not produce the “jitter” effect that elevated epinephrine levels will cause.

Cortisol

This steroid hormone, produced by the adrenal glands, is commonly known as the stress hormone. It takes a little more time (minutes rather than seconds) to feel the effects of cortisol in the face of stress because releasing this hormone involves two additional minor hormones.

First, the amygdala, a part of the brain that identifies a threat, sends a message to the hypothalamus, which releases corticotropin-releasing hormone (CRH).

CRH then tells the pituitary gland to release adrenocorticotropic hormone (ACTH), which tells the adrenal glands to produce cortisol.

When you dwell on a perceived negative situation, the body continuously releases cortisol, and chronically elevated levels can lead to health issues as serious as cancer.

Too much cortisol can suppress immune function, increase blood pressure and blood sugar, decrease libido, produce acne, contribute to weight gain, depressed mood, and much more. We recently have seen a strong connection between chronic cortisol elevations and leaky gut, inflammatory bowel disease, and even a decrease in cognitive function due to its (literally) ability to kill brain cells. The best supplements for stress will bring down elevated cortisol levels as well.

As an aside, if you feel tired for “no reason, ” you may have had chronically elevated cortisol levels, which impair mitochondrial biogenesis and cause mitochondrially-based fatigue. This is all correctable—you need to know what you’re dealing with.

The “minor players” in the stress cascade

Endorphins are released in times of stress to act as natural painkillers. Many people report not feeling any pain from injuries until after the threat to life or limb has passed. I’m sure you know some of these stories. “Woman lifts car off of children” and so on, right?

Fibrinogen is a protein that aids in blood clotting and provides some protection against excessive bleeding. Cortisol increases the secretion of fibrinogen, which is why high levels of long-term stress cause the body to form plaque in the arteries.

Vasopressin is also known as anti-diuretic hormone (ADH). This hormone causes the kidneys to reabsorb water, making urine darker and more concentrated. This is why we are less likely to think about bathroom breaks in highly stressful situations.

Sex Hormones

Lastly, we have the female and male “main hormones,” estrogen, progesterone, and testosterone, which also affect how we react to stress. In addition, brain chemicals, dopamine and serotonin play a role. If we are deficient in any of these, we will respond more negatively to stress. Therefore, it’s about balancing the mind, the chemicals of the mind, the body, the hormones of the body, and being aware of our feelings so we can “manage them.” Now let’s turn for a moment to anxiety you might feel “for no reason.”

What exactly is Anxiety?

Common anxiety symptoms include excessive worrying, generalized feelings of “gloom and doom,” as well as inner turmoil, again for no particular reason. The reason some people develop anxiety disorders is theorized to be a flawed processing of perceived threats.

While it is necessary to experience fear and increased vigilance in response to an actual threat, someone with anxiety will over-interpret non-threatening signals. This over-interpretation will cause them to maintain an unnecessarily high state of arousal, worry, and perceived sense of stress.

Anxiety disorders are commonly associated with dysregulation in brain structures that control threat response and fear generation. Here’s a breakdown of the involved brain structures and their functions:

Amygdala: The amygdala plays a crucial role in processing emotions, including fear. It is responsible for activating the fight-or-flight response in threatening situations. In individuals with anxiety disorders, the amygdala is often overactive, leading to an exaggerated fear response.

Prefrontal cortex: The prefrontal cortex involves higher-order cognitive processes, including inhibitory control. It helps modulate the fear response generated by the amygdala. In individuals with anxiety disorders, the prefrontal cortex may be underactive, resulting in a reduced ability to regulate fear and anxiety.

Hippocampus: The hippocampus is essential for storing and retrieving information related to emotional experiences. It also plays a role in contextualizing fear responses. Impairments in hippocampal function have been reported in individuals with anxiety disorders, potentially contributing to the persistence and generalization of fear.

Striatum: The striatum is involved in reward processing and forming habitual behaviors. Dysfunction in this brain region may contribute to the excessive avoidance and repetitive behaviors often observed in anxiety disorders.

Anterior cingulate cortex (ACC): The ACC is associated with conflict monitoring, error detection, and regulating emotional responses. It may be implicated in anxiety disorders as it helps modulate the emotional response to aversive stimuli.

Insula: The insula plays a role in interoception, which involves perceiving and experiencing bodily sensations. It is also involved in processing emotional states. Dysregulation in the insula can contribute to the heightened awareness of physical sensations and discomfort often seen in anxiety disorders.

Overall, anxiety disorders involve dysfunction across various brain structures involved in threat response, fear generation, emotional regulation, and information processing. Understanding these neurobiological underpinnings can help inform the development of practical treatment approaches for anxiety.

Despite the roles of serotonin and other neurotransmitters (as well as neurotrophic factors) in the perception of anxiety, the “big player” is GABA or gamma-hydroxybutyric acid. This article will focus on supplements for stress, probiotics for anxiety, music, aromatherapy—you name it—all of which are targeted at raising GABA and lowering cortisol. So, what exactly is GABA?

GABA and Anxiety

The GABA-deficit hypothesis proposes that low levels of GABA (gamma-aminobutyric acid) in the brain can lead to overactivation of the HPA (hypothalamic-pituitary-adrenal) axis, which is our body’s central stress response system.

According to this hypothesis, chronic stress can reduce GABA levels in the brain, resulting in an overactive emotional response through the HPA axis. This, in turn, can lead to the release of stress hormones such as CRH (corticotropin-releasing hormone) and ACTH (adrenocorticotropic hormone), creating a feedback loop that further lowers GABA levels and contributes to anxiety.

Supporters of this theory argue that GABA functions as a natural anxiety reliever and can help calm the HPA axis, comparing its effects to that of a “natural Valium.” GABA is an inhibitory neurotransmitter crucial in regulating brain activity and promoting relaxation. However, it is essential to note that while the GABA-deficit hypothesis offers a potential explanation for the relationship between GABA, the HPA axis, and anxiety, it is still a theoretical framework. To explain this concept further, let’s use the autonomic nervous system’s sympathetic (flight/fright) arm.

Let’s talk about stress

GABA (gamma-aminobutyric acid) can help manage stress and its associated effects. As mentioned earlier, chronic stress can lead to a decrease in GABA levels in the brain. GABA is an inhibitory neurotransmitter that helps regulate brain activity and promote relaxation.

Increasing GABA levels through medications or natural approaches may counterbalance excessive sympathetic activity and promote a shift toward parasympathetic control associated with relaxation.

GABA’s ability to inhibit brain activity and calm the nervous system can help alleviate symptoms of stress, such as anxiety, by reducing the overactivity of the sympathetic nervous system. It may help induce a sense of calmness, reduce racing thoughts, promote better sleep quality, and improve mood.

However, it’s important to note that GABA supplements or medications may not be sufficient on their own to manage chronic stress or address its underlying causes.

Adopting a holistic approach to stress management is crucial. This may include lifestyle modifications, stress-reducing techniques (such as relaxation exercises, meditation, or mindfulness practices—which I’ll discuss), seeking social support, and addressing any underlying issues or conditions contributing to chronic stress. So, how exactly does GABA help with all of this?

How GABA Works

The balance between GABA, the inhibitory neurotransmitter, and glutamate, the excitatory neurotransmitter, is essential for maintaining brain activity within a healthy range. Too much glutamate can lead to hyperexcitation, while an overly stimulated GABA system can cause excessive sedation.

In situations where the mind is constantly activated, under stress, or anxious, glutamate levels may increase, while GABA levels may drop. This imbalance can disrupt stress resilience and contribute to symptoms such as anxiety, headaches, muscle tension, chronic pain, and even certain neurological conditions.

While GABA is primarily known for its calming and relaxing effects, its direct impact on cognition remains unclear. However, we do know that individuals may struggle with focus and cognition when experiencing stress and anxiety. Mental health disorders, such as schizophrenia and anxiety, often present with cognitive impairments.

Ongoing research explores the potential links between GABA activity and emotional intelligence, socialization, and empathy. While some studies suggest positive associations, more research is needed to establish definitive conclusions regarding these relationships.

It is vital to balance GABA’s calming effects and glutamate’s excitatory effects to maintain optimal brain and mental health. The specific receptors in the brain where GABA binds also play a role in this balance.

It’s important to note that the interplay between GABA, glutamate, and other neurotransmitters is complex, and even the receptors in the brain for GABA play a role.

GABA Receptors

As with all neurotransmitters, GABA needs to bind to receptors in the brain to exert its effect. It can act on two receptors in the brain called GABA-A and GABA-B.

GABA-A

Studies show that GABA-A receptors respond rapidly to GABA. The excited neurons are quickly blocked, leading to the following possible effects.

• Reduced anxiety
• Relaxed, slowed, deeper breathing
• Feelings of relaxation and calmness
• Sleepiness or even sleep itself
• Sedation or unconsciousness in excess
• Euphoria from stimulation of the reward system
• Memory impairment; if via certain pharmaceuticals

Substances that activate GABA-A include benzodiazepines (e.g., Xanax), general anesthetics, and the herb kava, as well as the oft-used social lubricant- alcohol.

GABA-B

GABA-B receptors are more complex and act more slowly.

Based on the available research, GABA-B activity may play an essential role in the following:

• Increasing sociability and even empathy
• Reducing social anxiety
• Reducing anxiety in general
• Boosting cognitive ability
• Improving depression
• Relaxing muscles
• Reducing pain

The muscle relaxant baclofen is the only legal way to activate GABA-B receptors.

Recent research has led to the discovery of GABA-C receptors, which differ from the well-known GABA-A and GABA-B receptors. Some studies suggest that GABA-C receptors may play a role in regulating slow-wave sleep during the non-REM stage of sleep. Slow-wave sleep has been linked to restorative functions in the brain, such as memory consolidation and synaptic plasticity.

Restoration/Increasing GABA Receptors

Research is ongoing regarding increasing the density of GABA receptors, with restorative sleep, a healthy diet, exercise, and, per recent data, vagal nerve stimulation as ways to accomplish this. One thing we do know is that long-term use of medications such as benzodiazepines (e.g., Xanax, Valium, Clonazepam) will decrease the density of GABA receptors, as will several other psychotropic medications.

The use of pharmaceutical nootropics is being explored as another avenue to enhance the efficacy of GABA. Still, I’m not a fan of using pharmaceuticals, as those of you who are regular readers already know! Now, let’s talk about healthy ways to raise GABA levels.

Behavioral-cognitive therapy

Cognitive behavioral therapy (CBT) is a practical and structured form of psychotherapy that aims to understand and manage the cognitive, behavioral, and physiological components of anxiety.

Therapy begins with thoroughly assessing the patient’s needs, characteristics, and anxiety level. This assessment helps develop an individualized treatment plan and set goals for therapy. Psychoeducation is an essential component, where the therapist provides the patient with information about anxiety and helps them develop a better understanding of their condition.

CBT utilizes various techniques, such as relaxation strategies, cognitive restructuring, and exposure, to help patients learn new skills and manage their anxiety symptoms effectively. The therapist continuously evaluates the patient’s progress and adjusts the therapy to meet their needs.

CBT interventions can be offered individually or in group settings. Group therapy has advantages, such as allowing therapists to work with more people at once and providing social exposure opportunities for individuals with social fears. However, group therapy may not be suitable for everyone, as participants must be willing to share personal experiences and be comfortable expressing themselves freely.

Therapists must consider participants’ characteristics and maintain an interactive and lively group atmosphere rather than a classroom-like setting. Group therapy can be offered as either preventive or treatment interventions.

If individuals have concerns about group therapy, it is recommended that they schedule a session to discuss their specific needs and problems with a qualified therapist.

Overall, CBT, whether provided individually or in a group, has proven to be effective in addressing anxiety disorders and improving daily functioning for individuals impacted by anxiety.

Since these interventions are being discussed “in no particular order,” let’s next turn to something we all should be doing for optimal physical and mental health– exercise.

Exercise

Exercise is a superb way to relieve all types of stress, as well as being an excellent boost for your overall health and well-being. Here’s how it directly impacts stress:

It pumps up your endorphins. When you move your body, your brain’s feel-good neurotransmitters, endorphins, are increased. Although this function is often referred to as a runner’s high, a rousing game of tennis or a nature hike can also contribute to this feeling.

It’s meditation in motion. After a fast-paced game of racquetball or several laps in the pool, you’ll often find that you’ve forgotten the day’s irritations and can concentrate solely on your body’s movements. With a regular exercise regimen, you may find that movement and physical activity can offer a great way to give you a positive outlook and make you relax.

Improved mood. Regular exercise can increase relaxation, self-confidence, and overall mood. It can improve sleep and associated mood issues.

These benefits from exercise can provide lower stress levels and an overall sense of self-determination and control over your life, which, if you reflect, leads to less stress.

A successful exercise program begins with a few simple steps. Weight training is a must, and this article on weight loss and strength gains provides all the how-to’s.

Consult with your doctor. Before beginning any exercise regimen, obtaining medical clearance from your doctor is essential.

Walk before you run. When starting your fitness regimen, it is essential to work your way up to avoid overexertion and even injury. Find an aerobic activity, such as walking, that you can start with by doing it two to three days per week. Within time, you can increase your activity by walking faster, combining it with HIIT intervals, and doing it daily. Ideally, you’ll add strength-strengthening and flexibility exercises for a complete program.

Do what you love. Find what makes you happy, relieves stress, and helps you reach your fitness goals. You can choose from an abundance of activities, but it is important to choose one you enjoy.

Pencil it in. Creating a plan is essential. Start by adding it in before work, during lunch, after work, or in the evening. Work around your schedule, or make time!

Anyone can start an exercise program, but sticking with it is hard. However, after 6-8 weeks, you will have created good habits in life. Here are some tips:

Find a Workout Buddy. When you have someone willing to exercise with you, you can become motivated and more committed. Remember that your dog can be your buddy!

Change up your routine. Change up your routine regularly, from walking to yoga to weight lifting. You don’t have to stick with one regimen. Choose activities you will enjoy, stick with, and notice are lowering your stress levels. If you “feel it,” your cortisol levels are dropping, and your GABA levels are increasing; more about these things to come.

Set SMART goals. Write down SMART goals—specific, measurable, attainable, relevant, and time-limited goals. If your primary goal is to reduce stress and recharge your batteries, your specific goals might include walking during lunch at least thrice weekly or attending a cycling class.

Exercise in increments. The time you spend working out “doesn’t count” if there is no effort. If you put in the effort, you only need half the time. Interval training, which entails brief (typically 60 to 90 seconds) bursts of intense activity at almost complete intensity, is a safe, effective, and efficient way of gaining many benefits of longer-duration exercise. What’s most important is making regular physical activity part of your lifestyle.

No matter what you choose as your new exercise regimen, remember to enjoy it. This can vary from walking your dog daily to taking a hike you always wanted to explore. Whatever it is, any form of physical activity can help you unwind and become an essential part of your approach to easing stress.

Mindful Walking

Walking can help you clear your mind and relieve daily stressors. When practicing mindful walking, you meditate while in motion. You focus on breathing and your body’s natural response to the movement.

Try this simple stress reliever before an important meeting, after a workday, or whenever you need to re-capture a calmer, more centered state of mind.

Choose a relaxing area, such as around the lake, rather than a busy mall. Don’t rush. Your goal here is to unwind, take your time, and relax. Keep your pace comfortable (as if you don’t need to get anywhere fast) and your stride short.

Start to focus on areas where you feel tense. Take deep breaths with each exhalation, imagining stress release. Spend several breaths on each area, gradually inviting every part of your body to relax. Walk for at least 15 minutes or longer if you have time. Focus on tension hot spots throughout your body; this will help you open up and unwind. Do you need a furry companion to make this more fun? I do! Here’s why you need pets, if you didn’t already know.

Pets and Stress

Pets have been shown to provide various health benefits, with lower stress levels being one of them. While human friends provide excellent social support and have some fabulous benefits, this section is dedicated to the benefits of furry friends: cats and dogs! (And yes- horses, rabbits, ferrets, guinea pigs, and all creatures who give you love, of course, “count!”)  Research has shown that pets can provide excellent social support, stress relief, and other benefits if someone can care for and love them properly. The following are more health benefits of pets.

Pets Encourage You to Get Out and Exercise: Dog owners have been shown to take more steps throughout the day than those who do not have pets, especially in urban settings. You can take long or short walks. They are equally beneficial for all types of stress.

Pets Can Improve Your Mood: Animal lovers find it difficult to be upset with an animal as they are always forgiving and loving creatures. Research has shown how moods can be enhanced because of pets, with a recent study finding that men with AIDS were less likely to suffer from depression if they owned a pet.

Pets Control Blood Pressure Better Than Drugs: Pharmaceuticals are often used to reduce blood pressure, but they are not helpful for BP spikes due to stress. However, in a study on pets and blood pressure, groups of hypertensive New York stockbrokers who got dogs or cats had lower blood pressure and heart rates than those who didn’t. When they heard of the results, most of those in the non-pet group got pets!

Pets Can Help with Social Support: We become more approachable when out with our animals, such as walking or at a dog park. This gives people a reason to meet and greet us. It is also an opportunity to increase our network of friends and acquaintances, which has excellent stress management benefits.

Pets Decrease Loneliness and Provide Unconditional Love: When you are sad, lonely, or “need an ear,” pets provide silent, unconditional love. They give the best hugs while listening to your sorrows with no judgment. They may well be the best antidote to loneliness. One study found that nursing home residents reported less loneliness when visited by dogs alone than when they spent time with dogs and other people! These benefits can reduce the stress those lacking social support or experiencing social isolation feel.

Pets Can Reduce Stress—Sometimes More Than People: Having your pet around can be a more significant benefit than being with a friend. One study showed that, when conducting a stressful task, people experienced less stress when their pets were with them than when a supportive friend or spouse was present. (This may be partially true because pets are great listeners with no judgment.)

It’s important to realize that owning a pet isn’t for everyone. Pets come with additional work and responsibility, which can bring stress. However, for most people, the benefits of having a pet outweigh the drawbacks. Having a furry best friend can reduce all types of stress in your life and bring you support when times get tough.

I couldn’t live without my four rescue collies hanging out with me all day. Next, let’s turn to some breathing techniques. Remember, every little bit helps, so as you’re reading these suggestions, remember stress management is often “one from column A, one from column B, and perhaps two from column C.”

I want to remind you that proper breathing techniques can make us less stressed. Let’s review them all now. First, let’s review something you have undoubtedly heard of- relaxation breathing. And before I get into this technique, CALM is excellent for those who love apps for things! Now, let’s talk about breathing techniques.

The Relaxation Breath

Relaxation breathing can be practiced while sitting or lying down anywhere, but it is most effective with relaxation positions described later.
To practice this technique, close your eyes (unless you use a visual app).

1. Inhale normally through your nose, using a full diaphragmatic breath.
   2. Exhale normally through your nose.
   3. Pause without breathing and count to yourself, “One thousand one, one thousand two.” During this pause, allow your exhalation to come to a natural, unforced conclusion.
   4. Repeat steps 1, 2, and 3. Continue breathing like this for several minutes.

As you breathe, try to keep your eyes closed and look down as if you were looking at your lower eyelids. Resist the tendency to look up each time you inhale. If you are wearing contact lenses and this is uncomfortable, look straight ahead.
Remember your diaphragmatic breathing techniques as you are breathing comfortably through your nose.

If you are congested and cannot breathe through your nose, go ahead and breathe through your mouth, letting your stomach and chest expand fully with each breath.

Most people do not complete exhalations. More notably, when we become anxious, the exhalations become shorter, and breathing becomes more rapid. This escalates the sensation of anxiety, causing blood pressure and pulse to increase. In extreme instances, we can hyperventilate and even bring on a panic attack, so learning proper breathing techniques can come in quite handy for everyone. If simply managing breathing isn’t enough to abort an attack, try doing what I describe in the next section.

How to do “The Relaxation Response”

The relaxation response is the physiologic opposite of the stress response. Your heart rate slows down, and your muscles relax. By utilizing this stress-busting technique, you may even reduce your blood pressure and pain levels. Here’s how to do it.

Find a quiet place where you won’t be disturbed for 10 – 20 minutes. Sit on the floor or in a chair, whichever is more comfortable. Slowly close your eyes.

Start to relax your muscles, beginning with your feet. Hold both legs straight out and point your toes away from your face. Then relax. Now point your toes toward your head, then relax.

Next, relax your torso. Pull your shoulders back and arch your spine. Relax and repeat. Tighten your stomach muscles so that they feel stiff, then relax. Take a deep breath slowly to fill your lungs. Hold it for five seconds, then exhale slowly.

Now, relax your hands and arms. Hold both arms straight out and stretch, then relax. Bend back. Straighten and relax.

Relax your facial muscles. Press your lips tightly together, then relax. Bring your tongue upward to the roof of your mouth, press it there, then relax. Clench your teeth and relax. Wrinkle your forehead, raise your eyebrows, then relax. Squeeze your eyes closed, then relax them.

When you are feeling relaxed, focus on your relaxation breathing. Remember: “one one thousand, two one thousand….” as per the breathing techniques described above.

If you just read that section and thought, “I don’t have 10-20 minutes in my day for stress relief”, then get the app and see if using that plus a vagal nerve stimulation device “does the trick,” as it does for me. The VNS device I like, recommend, and use only takes two minutes per session, and you indeed can find two minutes, right? The data on VNS comes from heart rate variability data correlated with increased vagal tone. And yes, increased vagal (parasympathetic nervous system) tone means lower cortisol and higher GABA, along with feeling less stressed. Here’s the science behind it.

HRV and Sympathetic Overdrive

Research has shown that stressful situations influence heart rate variability (HRV). Specifically, low parasympathetic activity and decreased vagus nerve activity contribute to changes in HRV variables. Neuroimaging studies also suggest a connection between HRV and brain regions involved in evaluating and appraising stressful situations, such as the ventromedial prefrontal cortex.

The current neurobiological evidence supports using HRV as an objective measure to assess psychological health and stress levels. HRV can be measured using smartphone apps, providing insights into the relationship between vagal nerve tone and heart rhythm. In general, high levels of HRV are associated with good health, while low levels are associated with poorer health.

Some people refer to these symptoms as “vagus nerve symptoms,” even though they are due to reduced vagal activity. Now let’s explore some areas where high vagal tone and HRV are beneficial:

1. Metabolic Syndrome: Epidemiological evidence suggests inverse associations between vagal nerve activity, HRV, and metabolic syndrome.
2. Mortality Risk: High HRV has been associated with a reduced risk of overall mortality and a lower risk of death from cancer.
3. Diabetes: HRV is inversely related to insulin resistance and levels of HbA1C, which indicates the severity of diabetes and potential complications.

Let’s focus on the gut-brain axis, a relevant topic where research has demonstrated the advantages of increased vagal tone.

Gut-brain-microbiome communication via the vagus nerve

The vagus nerve, mixed with afferent and efferent fibers, plays a vital role in conveying information between the brain and various organs. In the context of the microbiota-gut-brain axis, the vagus nerve is involved in interoceptive awareness, allowing it to sense microbiota metabolites through its afferent fibers and convey this information to the central nervous system for integration into the autonomic network.

Furthermore, a cholinergic anti-inflammatory pathway has been identified through vagal fibers. This pathway can help mitigate peripheral inflammation and reduce intestinal permeability, potentially influencing the composition of the microbiota and aiding in the healing of “leaky gut.”

Conversely, stress and elevated cortisol levels can inhibit the function of the vagus nerve, potentially leading to adverse effects on the gastrointestinal tract and the microbiota. Stress has been implicated in the pathophysiology of conditions such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), both of which are characterized by dysbiosis and increased gut permeability.

Given the vagus nerve’s importance in mediating these interactions, it’s interesting to see how it protects my favorite organ: the brain.

The Vagus-Gut-Brain Connection

The vagus nerve plays a critical role in regulating communication between the brain and the gut microbiome, and its interaction with gut flora can significantly affect immune-inflammatory activity.

Studies have demonstrated that the balance of gut flora and the presence of probiotics can influence the brain-gut axis. A healthy gut microbiome has been shown to positively impact mood and cognitive functions through the vagus nerve’s cholinergic anti-inflammatory pathway. Conversely, an imbalanced gut flora can lead to increased stress on vagal activity, potentially contributing to negative mood and cognitive challenges and even exhibiting symptoms resembling ADHD.

It’s intriguing to see the impact of the gut microbiome on psychological health and cognitive function, an area of growing interest in psychobiotics. We’ll discuss this topic when we discuss probiotics for anxiety.

Now, let’s get back to some simple things you can do to manage stress. Speaking of apps, do you have Spotify? This app has relaxing music, but that’s not the point; it’s about music in general. Here are some interesting facts.

Music and stress

Another method of reducing anxiety is music therapy. 432 Hz is the closest frequency to the natural human frequency. Music at this frequency is melodic, slow, and relaxing. These features make the music ‘neutral’ and able to avoid triggering negative feelings or physiological responses.  An example of a popular song at this frequency (you can google a list of them) is this Phil Collins song.

Music therapy (at this frequency) has been found to reduce blood pressure, normalize arrhythmias, and induce relaxation. Other studies show that music can decrease pain and anxiety. Music has reduced cancer patients’ stress associated with chemotherapy and radiation therapy.

Studies behind music therapy are relatively new, but some researchers believe the brain’s response to music can help ease pain, stress, and depression. It might even enhance creativity and tolerance to pain. Listening to slower musical beats can also alter brainwave speed. The brainwave activity is similar to when we’re in a more meditative or hypnotic state.

Music and the Brain

Music can do so much more for your body than simple auditory processing. It triggers activity in the nucleus accumbens, a section of your brain that releases the feel-good chemical dopamine and forms expectations. At the same time, the amygdala, which is involved in processing emotion, and the prefrontal cortex, which makes abstract decision-making possible, are also activated. Researchers can even see in an MRI how music can affect brain activity in certain regions. Other sounds that can induce relaxation include, most notably, listening to binaural beats.

Binaural beats

Binaural beats are an auditory phenomenon created by presenting two sine waves with slightly different frequencies to each ear, resulting in a unified percept as a ‘beat.’ This process, known as binaural integration, is crucial in sound localization and can lead to various psychophysiological effects.

The carrier frequency, beat rate, volume of carrier tones, and the presence of additional tones all play a role in determining the perceived salience of the binaural beat. The beat rate refers explicitly to the unified binaural beat percept frequency, influenced by the degree of frequency difference between the tones. The beat rate appears to be a significant factor in the effect elicited by binaural beats.

Research suggests that the synchronization of neural oscillations with the frequency of the auditory beat can lead to changes in the relative power of different EEG frequency ranges, a phenomenon referred to as brainwave entrainment. This entrainment effect could be responsible for the reported benefits of binaural beats, such as enhanced memory and attention or reduced anxiety and stress.

Binaural beat audio tracts are easy to find and use, so don’t be shy about looking for them, even though you may not have heard of using this technique to beat stress. Something you have heard of, massage is still a go-to for when you have the time and funds for it.

Massage

Each massage therapy technique manipulates the body’s muscles and soft tissues to relieve pain or decrease stress. Different strategies range from deep tissue (often called Swedish) massage to trigger point therapy, where the therapist applies pressure to a specific point on the body to relieve pain.

Massage can help with a wide range of ailments. One recent study found that massage therapy can decrease pain, promote muscle relaxation, and improve mood and sleep quality. Yes, it’s great for stress relief, but it does so much more than that. Here’s more proof of how it works for stress.

A large clinical study found that after subjects had been massaged, the cortisol levels in their saliva decreased. GABA wasn’t measured, but it tracks cortisol levels. And how about Yoga?

Yoga

Yoga is a mind-body practice that combines physical poses, controlled breathing, and meditation or relaxation. It may help reduce stress, blood pressure, and heart rate. Notably, almost anyone can do it.

Yoga brings together physical and mental disciplines that may help you achieve peacefulness of body and mind. It promotes relaxation, which in return can relieve stress and anxiety. It comes in various forms and intensities. Hatha yoga, in particular, may be a good choice for stress management. Hatha is one of the most common styles of yoga, and beginners may like its slower pace and easier movements. Here are the main components of Yoga in general and Hatha Yoga in particular.

Poses. Yoga poses are a series of movements designed to promote strength and flexibility. These poses can range from lying on the floor while completely relaxed to challenging postures that may have you stretching your physical limits.

Breathing. Controlling your breathing is an integral part of the yoga experience. It helps you maintain your body and quiet your mind.

Meditation or relaxation. You can incorporate meditation or relaxation in yoga as it can promote mindfulness and awareness.

The combination of all of the above is a trifecta for stress relief. Many studies have shown yoga’s impact in reducing stress and anxiety. It can also enhance your mood and overall sense of well-being. It is widely believed that practicing a religion can help manage stress.

 Religion, Spirituality, and Stress Relief

Studies have demonstrated that if religion (or spirituality alone) is an integral part of someone’s life, they can experience lower levels of anxiety. When surveyed about why people were members of a particular large church, anxiety relief was mentioned over 75% of the time. Next up, something we all can appreciate: aromatherapy and essential oils in particular.

Aromatherapy

Aromas profoundly impact our daily lives, and research suggests that they possess various pharmacological properties, including anxiolytic, anti-stress, relaxing, and sedative effects. Both animal and human studies have demonstrated the potential of aromas and their constituents in reducing anxiety-related symptoms and behaviors.

While the exact mechanism of action by which these aromas exert their anxiolytic effects is not fully understood, the GABAergic system is believed to play a significant role. The fragrance emitted by particular plant essential oils has shown promise in recent studies for modulating GABAergic neurotransmission, with GABA-A receptors implicated as the primary therapeutic target.

GABA (gamma-aminobutyric acid) is an inhibitory neurotransmitter in the brain that helps regulate neuronal excitability. Enhancing GABAergic neurotransmission can promote a calming and relaxing effect, potentially contributing to the anxiolytic properties of aromas.

While further research is needed to elucidate the specific mechanisms involved and to explore the efficacy and safety of aromatherapy in different populations, the existing evidence highlights the potential of aromas and essential oils in promoting relaxation and reducing anxiety-related symptoms. Meanwhile, research on the relaxing effect of familiar “smells” like coffee is ongoing. I won’t delve into all that since there is so much data regarding aromatherapy with essential oils.

Essential oils have been proven to lower cortisol or bring on noticeable feelings of relaxation to relieve stress or anxiety. I’ll discuss the concept of essential oils, a “blend” versus “monotherapy,” and how to use essential oils. You can then decide if this form of de-stressing is for you.

In my opinion, Aromatherapy is a beautiful addition to all techniques and supplements for stress.  Aromatherapy with pure essential oils is a safe and natural way to treat stress symptoms, so it’s well worth trying if you find the proper formulation. The definition of aromatherapy is the use of essential oils to support physical health and well-being. However, does that mean the essential oils need to be pure? Of course, it does. Let me explain.

What are Essential Oils?

Essential oils carry biologically active volatile compounds of flowers and plants in a very concentrated form. They are the plant’s essence and provide therapeutic benefits in tiny amounts. The particles in essential oils, which come from flowers, twigs, leaves, or bark, can be inhaled, initiating many beneficial effects. There are many uses for aromatherapy, but one of the most active areas of research is for stress and anxiety. There is a remarkable quantity of research that shows essential oils help relieve anxiety without the side effects of drugs.

Further, pure, therapeutic-grade essential oils from plants, not synthetic fragrances or perfumes, are “real” essential oils. However, the quality of essential oils can vary, depending on things like growing conditions and manufacturing and storage methods. There are international standards for essential oils.

One of the most important considerations is to look for a statement of purity. To clarify, you need to look for 100% essential oil (mixed with nothing else). Price can be a great tip-off. So, if it’s cheap, it’s also likely poor quality. Essential oils work synergistically, and using a combination of oils usually creates a much more powerful effect than any individual oil.

How does Aromatherapy work?

Our sense of smell triggers robust emotional responses. We sort through quite a bit of information through our sense of smell. This occurs in the brain next to the area where we process emotions, called the limbic region. When we inhale the scent of an essential oil, molecules enter the nasal cavities and stimulate limbic system “firings.”

The scents of the essential oils we’ll discuss can regulate stress responses, such as breathing patterns, brain chemical production, adrenal gland chemicals and hormones, heart rate, and blood pressure.

Following are the results of my review of over 15 clinical trials examining the anxiety-inhibiting effects of aromatherapy. I have not included studies or mentions of herbs where I found no definitive anxiety-reducing effects. Markedly, no adverse effects were noted in all of these studies. 

Bergamot (Citrus bergamia): Bergamot essential oil is calming and used to treat depression, stress, and anxiety. It can help those with sleep initiation issues fall asleep. It’s been proven to reduce the spike in cortisol as a stress response. It also increases the level of the brain chemical serotonin, which then induces feelings of relaxation and sedation.

A study that used a blend of this oil plus lavender essential oil showed a synergistic effect between the two oils. People exposed to bergamot essential oil aromatherapy with lavender oil before surgery had a more significant reduction in pre-operative anxiety than those in control groups receiving only bergamot oil. In addition, compared with the placebo, the dual blended essential oil participants in another pre-op study group rated themselves as “calmer” and “more relaxed” than the control group.

Bergamot is safe but photo-sensitizing, meaning it can increase the risk of sunburn. Therefore, avoiding using it within 12 hours of sun exposure is best.

Frankincense (Boswellia carteri or Boswellia sacra): Frankincense provides a calming and tranquil energy and is frequently used in meditation for its ” mind-quieting” effect. According to many users, Frankincense oil is very effective as a sedative because it induces a feeling of mental peace, relaxation, satisfaction, and spirituality. Frankincense essential oil promotes deep breathing and relaxation when used in a diffuser. Reports reveal that it is also a mechanism to lower blood pressure.

This essential oil was mixed with lavender and bergamot oils in a well-done study. This blend (when inhaled via diffusion) reduced stress symptoms, pain, and depression in hospice patients. Furthermore, in a 2014 study, 60 hospice patients had this same blend massaged on their hands. All of the patients who received the aromatherapy hand massage reported less pain, anxiety, and depression.

Sweet orange oil: This essential oil has anxiety-inhibiting effects in humans. In one recent study, diffused scents of sweet orange and lavender blended essential oils reduced anxiety and improved mood in patients waiting for dental treatments. Compared to the controls, those inhaling the “piped-in” oils reported a more incredible feeling of calmness.

Clove oil: Clove oil is an excellent stress reliever. It has a nontoxic stimulating effect on the brain and helps to relieve mental exhaustion and “brain fatigue.” Studies based on questionnaires reveal that many study participants found it to be a way to regain mental energy after “brain drain.” Additional studies have found that clove oil also helps induce sleep and is another essential oil that helps insomnia.

Ylang-ylang essential oil: Due to its pleasing and delicate fragrance, ylang-ylang essential oil is widely used in perfumes and aromatherapy treatments and is also used for various science-based medicinal purposes.

A significant health benefit of ylang-ylang is its ability to relieve stress and anxiety, which clinical studies repeatedly demonstrate.

Other well studied Essential Oils for Stress Relief

Lavender, cited in studies above, smells yummy. It has been validated in many multiple-blend studies. Notably, it has been approved for use in Alzheimer’s patients for everything from anxiety to agitation with excellent results. Clinical studies also support using lemon, Rose Absolute, Jasmine Sambac, and Roman chamomile essential oils. All these blends have been demonstrated to help manage stress and lower cortisol levels, so what you find pleasant to inhale is a matter of personal taste. Please note that you need to check with your Veterinarian regarding what is safe to apply or allow to be inhaled by your pets.

How to Use Essential Oils

Essential oils can be administered in three ways: inhalation, ingestion, or topical. Aromatherapy is used in a bath, as a direct inhalation, or, best yet, via aromatherapy diffusers.

Oral Application: Many essential oils can be ingested by mouth; however, ensuring they are safe and pure is super important. I don’t personally recommend this route.

Topical Application: Topical application is placing an essential oil on the skin, hair, mouth, nails, or mucous membranes of the body. When the oils touch the skin, they penetrate rapidly. Since they are so potent, diluting and blending with a carrier oil, such as sweet almond or coconut, is crucial.

If you are getting a massage for stress relief, have your therapist add a good aromatherapy oil to a massage balm for a double-stress-buster. Another fantastic topical use is adding drops of a particular blend to a relaxing bath.

Inhalation: Essential oil can be sprinkled on a pillow, a sachet pinned to your collar, or simply intermittently “sniffed.” However, using a diffuser is the easiest way to give yourself a continuous relaxing “dose” of essential oils. As a side note, I mix up my cleaning solution (vinegar and water) and add the essential oils I like so that the house smells great each time it’s dusted or mopped. Next, I’d like to touch on GABA-infused “functional foods.”

Functional GABA-infused Foods and Beverages

Since GABA is the major inhibitory neurotransmitter in the brain and plays a vital role in brain metabolism, it makes sense that it is being extensively studied as a dietary supplement.

GABA (gamma-aminobutyric acid) is found in potatoes, other plants, and bacteria. Procedures have been developed to increase the GABA content in certain food supplements.

These GABA-enhanced food supplements can include a range of products such as barley, chocolate, honey, Lactobacillus bacteria, rice, soybean products, yeast, and different types of tea. Such products aim to provide an additional source of GABA for potential health benefits.

More research is needed on the effectiveness of oral ingestion in crossing the blood-brain barrier. The blood-brain barrier protects the brain from potentially harmful substances in the bloodstream and can restrict the passage of specific molecules, including GABA, into the brain. The extent to which orally ingested GABA can effectively cross the blood-brain barrier and reach the brain is still not fully understood.

Research on the bioavailability and efficacy of GABA supplementation through oral ingestion is ongoing. I’ll discuss this when I discuss supplements for stress. But first, I’d like to give a big shout-out to the largest area of GABA-infusion products-teas. Who knew?

GABA infused Teas

It’s interesting to learn about the potential benefits of GABA-enriched teas on blood pressure, stress, and anxiety and the complex interplay of active constituents in these teas. The anaerobic production methods for GABA-enriched teas, which can increase GABA levels by 10–20 times, also significantly alter the levels of other compounds, such as epigallocatechin gallate, caffeine, and theanine. These compounds may interact with the actions of GABA, making the understanding of the effects of GABA-enriched teas quite complex.

The interactions of these active constituents highlight the need for more data to comprehensively establish where and how GABA acts after consuming GABA-enriched teas. While evidence suggests that GABA could act on GABA receptors in the periphery, less evidence indicates direct action in the brain.

This complexity underscores that the effects of GABA-enriched teas are not solely attributable to GABA itself. Instead, the combined actions of GABA and other compounds in these teas likely contribute to their overall effects on the central and peripheral nervous systems.

Further research in this area is crucial to fully understand the mechanisms and effects of GABA-enriched teas, their potential interactions with other compounds, and their impact on physiological and psychological outcomes.

There is insufficient data regarding these GABA teas, but it’s an exciting space to watch.” Now, let’s get to the so-called supplements for stress.

Supplements for Stress

Vitamin D and stress

Research indicates that individuals with low Vitamin D levels are at higher risk of stress and depression.

Sunlight is rarely enough of a “fix.” To get enough usable vitamin D, the amount of exposure would cause skin damage.

Here are some ways to increase your vitamin D levels naturally:

1. Sunlight exposure: Vitamin D is often called the “sunshine vitamin” because our skin produces it when exposed to sunlight. Spending time outdoors, especially during midday, can help your body produce vitamin D. Aim for about 15-30 minutes of sun exposure on your face, arms, and legs a few times a week. However, it’s essential to balance sun exposure with skin protection to prevent sunburn and reduce the risk of skin cancer.
2. Fatty fish: Fatty fish like salmon, mackerel, and sardines are excellent sources of vitamin D. Including these fishes in your diet can help increase your vitamin D levels. Aim to consume fatty fish at least twice a week.
3. Liver: Some types of liver, such as beef liver, are rich in vitamin D. In moderation, Adding liver to your diet can be a source of this essential vitamin.
4. Egg yolks: Vitamin D is naturally present in egg yolks. Including eggs in your diet can contribute to your vitamin D intake. It’s important to note that vitamin D is mainly found in the yolk, while the whites primarily contain protein.
5. Dairy products: Some dairy products, such as milk, yogurt, and cheese, are often fortified with vitamin D. Check the labels to ensure they contain added vitamin D.
6. Fortified foods: Many foods, such as breakfast cereals, orange juice, and plant-based milk alternatives, are fortified with vitamin D. These products can be a good option, especially for individuals with dietary restrictions.

In a small trial involving individuals with generalized anxiety disorder, it was observed that those who received supplementary vitamin D in addition to conventional medication experienced a more significant anxiety reduction. This suggests a potential benefit of vitamin D supplementation as an add-on therapy for managing symptoms of anxiety disorders. Vitamin D is liked with better general health parameters and should be optimized anyway.

Magnesium and stress

Magnesium plays a critical role in biochemical reactions all over the body, yet up to 80% of us may be deficient. Over 300 different chemical reactions in our body are needed to maintain energy. It aids in relaxation. Also, it’s vital to sustain the health of your heart and blood vessels.

Magnesium is an anti-stress mineral. The nervous system uses it to prevent nerve cells from becoming excitable and overreactive.

The lack of sufficient magnesium in the body can cause anxiety. When emotional, mental, or physical stress becomes a constant in our lives, the results of a continual state of hyper-vigilance are worsened by a magnesium deficit.

Chronic stress often produces excessive cortisol, eventually damaging the brain’s and immune system’s hippocampus (memory center).

Magnesium will lessen the increase in cortisol and, more importantly, help protect the brain from its toxic effects.

Magnesium l-threonate is the only form of magnesium that crosses the blood-brain barrier to increase the brain’s magnesium levels. This helps prevent the entrance of stress hormones to the brain. Clinical studies show that this one form of magnesium improves short—and long-term memory and concentration. It also helps reduce anxiety via its down-regulation of glutamate.

 B6 to raise GABA

A large study by Smith et al. highlights the potential role of vitamin B6 in synthesizing the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) from glutamate. The conversion of glutamate to GABA is a well-established mechanism for regulating neural excitation and promoting relaxation.

Additionally, the researchers discussed that while vitamin B6 may play a crucial role in GABA synthesis, the observed effects could also be due to the supplement’s high levels of vitamin B12 and other B vitamins. These vitamins have their potential mechanisms of action, as do the presence of glutamate and tryptophan (a serotonin precursor).

Furthermore, the study aimed to test the hypothesis directly that high-dose vitamin B6 supplementation can influence behavioral outcomes related to neural inhibition and overall excitation levels. The researchers proposed multiple pathways through which vitamin B6 could potentially reduce neural excitation, including its role as a coenzyme for producing neurotransmitters such as serotonin, dopamine, and noradrenaline.

They also highlighted its involvement in reducing the amount of quinolinic acid (an agonist to the excitatory NMDA receptor) and its role in lowering homocysteine levels and providing cysteine to the glutathione cycle, which can help reduce levels of the excitatory neurotransmitter glutamate.

In conclusion, the study demonstrated that supplementation with a high dose of a single vitamin (B6) could influence behavioral outcomes such as self-reported anxiety. This focused approach proved more effective than typical multivitamin studies in identifying potential mechanisms. The increase in surround suppression of visual contrast detection suggests an underlying inhibitory GABA-related mechanism.

It’s important to note that while these findings are promising, further research is necessary to understand better the specific mechanisms through which vitamin B6 and other components in the supplement may affect anxiety and neural excitation. Additionally, individual responses to supplementation may vary, and the findings should be interpreted in the context of the unique complexities of each individual’s biochemistry and physiology. The bottom line is that it won’t hurt and may help! Now, onto something you’ve likely heard of: medicinal plants.

Medicinal plants

Although the supplements for anxiety “movement” (if you will) started with plant or herbal names you have likely heard, such as Valerian root and Kava, they are less effective than other modalities when used alone. However, they all deserve an honorable mention and are effective for some people.

Valeriana officinalis, Citrus aurantium, Commelina benghalensis, Achyranthes aspera, Mimosa pudica, Achillea millefolium, Nymphaea alba, Leonurus cardiac, Camellia sinensis, Turnera aphrodisiaca, Crataegus oxyacantha and Piper methysticum have all showed promising effects on anxiety in animal models.

In clinical studies, passion flower, kava, valerian, St John’s wort, and ashwagandha showed the most positive results. More studies are needed to explore the anti-anxiety properties of medicinal plants. Of all of these, CBD earns a special shout-out.

CBD (cannabidiol) has shown promise in reducing anxiety in various studies:

1. Performance anxiety: CBD has been found to reduce stress related to public speaking and stressful situations in healthy individuals. Several trials have shown that CBD can help alleviate anxiety and improve performance during tasks such as public speaking or undergoing medical procedures.
2. Anxiety disorders: While research is still limited, preliminary evidence suggests that CBD may have potential benefits for individuals with anxiety disorders. Studies have indicated that CBD may help reduce anxiety symptoms in conditions such as generalized anxiety disorder (GAD), social anxiety disorder (SAD), post-traumatic stress disorder (PTSD), and panic disorder.
3. Autism-related anxiety: Some studies have explored the use of CBD in managing anxiety associated with autism spectrum disorders. Although limited in scope, initial findings have shown potential for CBD in reducing stress in individuals with autism.
4. Substance use disorders: Research suggests that CBD may have a role in reducing anxiety related to drug use and withdrawal symptoms. Studies have shown that CBD might help alleviate stress and cravings associated with drug addiction, particularly opioids and cannabis use disorders.

While CBD shows promise as a potential treatment for anxiety-related conditions, it’s important to note that more research is needed to fully understand its effects, optimal dosages, and long-term safety. It’s advisable to consult with a healthcare professional before incorporating CBD into your wellness routine, especially if you have any underlying medical conditions or are taking other medications.

GABA Supplements

Despite the hype, there are limited studies on any forms of GABA supplementation besides the oral route. And those studies are inconclusive, meaning we don’t know how much oral GABA gets in there to do its job. It appears that GABA doesn’t pass the blood-brain barrier much, if at all. Therefore, when using GABA supplements, I suggest a liposomal or topical preparation rather than oral. Liposomal preparations have been shown to enter the bloodstream directly, as have some topical preparations, thus making them a candidate to enter the brain.

Perhaps the most exciting avenue for increasing GABA is through its production in the GI tract. Let’s review just how this is accomplished.

GABA and the Microbiome

Although the human microbiome houses various types of microorganisms, certain bacterial species have been identified that play a vital role in controlling immune function and inflammation. Maintaining a healthy balance of bacteria in the microbiome is critical for overall health and well-being. Microbiome dysbiosis has already been identified as a risk factor for many illnesses.

These imbalances in the microbiome have been associated with various health conditions, including obesity, autoimmune disorders, cognitive decline, and inflammation.

Obesity: Studies have found that individuals with an unhealthy microbiome, characterized by a reduced diversity of bacterial species, tend to have a higher risk of obesity. Certain bacteria in the gut can influence energy regulation, fat storage, and metabolism, and an imbalance in their populations may contribute to weight gain and obesity.

Autoimmune Disorders: The gut microbiome is crucial in regulating immune function. When the balance between beneficial and harmful bacteria is disrupted, it can lead to an overactive immune response, contributing to autoimmune disorders such as rheumatoid arthritis, Crohn’s disease, and multiple sclerosis.

Cognitive Decline: Recent research suggests that the microbiome’s composition may impact brain health and cognitive function. Imbalances in gut bacteria have been associated with neurodegenerative diseases like Alzheimer’s and Parkinson’s. The gut-brain axis, which involves bidirectional communication between the gut and the brain, may influence brain health and cognition.

Inflammation: An unhealthy microbiome can contribute to chronic low-grade inflammation linked to numerous conditions, including cardiovascular disease, type 2 diabetes, and certain cancers. Imbalances in the microbiome can lead to increased gut permeability, allowing bacteria and toxins to enter the bloodstream and trigger an inflammatory response.

Knowledge is now accumulating on the importance of a healthy microbiome in a healthy mood, including managing stress and anxiety. We are only at the cusp of our knowledge regarding manipulating the microbiome to achieve improved clinical goals. One area involves mental health and the use of what are called psychobiotics.

Psychobiotics (Probiotics for Anxiety and Depression)

The term “psychobiotic” refers to live bacterial strains, such as lactobacilli and bifidobacteria, that can influence the function of the central nervous system (CNS). These beneficial bacteria produce various compounds, including proteins, peptides, and cell wall components, which mediate the communication between the bacteria and their hosts.

One significant way psychobiotics impact CNS function is through the production of neurotransmitters like gamma-aminobutyric acid (GABA). Certain bacteria in the human gut microbiota, including lactobacilli and bifidobacteria, have been found to produce GABA through the action of genes like gad, which encode glutamate decarboxylase.

Studies have shown that an increased level of GABA in the gut can result from the ability of the intestinal microbiota or ingested probiotics, such as bifidobacteria and lactobacilli, to metabolize dietary monosodium glutamate (MSG). Among bifidobacterial species, only a few, such as Bifidobacterium dentium and Bifidobacterium longum subsp. infantis and Bifidobacterium adolescentis have been identified to have GABA production capabilities based on in vitro studies.

The utilization of probiotics containing these specific GABA-producing strains, such as Bifidobacterium dentium and Bifidobacterium longum subsp. infantis, and Bifidobacterium adolescentis, may offer potential benefits in supporting CNS function and mental health. These psychobiotics can influence neurotransmitter production, creating connections between the gut microbiota and brain function. Here is an excellent GABA-producing probiotic.

Although the term “psychobiotic” was introduced for beneficial live bacteria (probiotics), it is also commonly used for other compounds (prebiotics, synbiotics) that may influence gut neurotransmitters.

Studies have shown that psychobiotics can influence mood, decrease anxiety, and improve mental health. The interaction between psychobiotics and the gut microbiota can affect the production of neurotransmitters, such as GABA and serotonin, which play a crucial role in mood regulation. By promoting the production of GABA and other neuroactive molecules, psychobiotics may contribute to the improvement of mental disorders.

I did not explore the use of psychobiotics for the production of other neurotransmitters associated with depression, such as serotonin, dopamine, and norepinephrine, as that is not within the scope of this article.

Two classes of prebiotics have been shown to enhance the proliferation of GABA-producing “gut bugs.”

GABA Assisting Prebiotics (B-GOS and F-GOS)

GOS are oligosaccharides of linked galactose moieties with galactose or glucose at the reducing end. They occur naturally in the milk of certain mammals, with marsupial milk being exceptionally high in GOS1. However, GOS can also be commercially produced and are commonly used as prebiotics in supplements and infant formulas. GOS serve as food for beneficial bacteria like bifidobacterium strains in the gut, which produce GABA.

On the other hand, fructo-oligosaccharides (FOS) are oligosaccharides that naturally occur in various plants, including onion, chicory, garlic, asparagus, and banana, among others. FOS are linear chains of fructose units linked by beta (2-1) bonds. Like GOS, FOS are considered prebiotics, and they can also support the growth of GABA-producing strains of bacteria, including both Bifidobacterium and Lactobacillus.

GOS and FOS are examples of prebiotics, which are non-digestible carbohydrates that promote the growth and activity of beneficial bacteria in the gut. By providing a food source for these bacteria, prebiotics like GOS and FOS contribute to maintaining a healthy gut microbiota, which has downstream effects on various aspects of health, including mental well-being.

Since some oligosaccharides are “high FODMAP” foods, caution should be used if you have IBS or inflammatory bowel disease.  I would be remiss if I didn’t mention synthetic drugs that raise GABA.

Synthetic GABA-raising or mimicking drugs

Phenibut is made by modifying GABA with a phenyl group to produce (beta-phenyl-GABA. Sold as a drug in other countries, in the US, it’s classified as a supplement. I would advise against purchasing it, as it is associated with withdrawal symptoms, the same as with “benzos,” and is technically “a drug.”

It will not fix your GABA issues or serve as a healthy supplement for stress management and will only worsen anxiety issues in the long run. The following two products are made by chemically modifying GABA to cross the blood-brain barrier.

Picamilon is made of GABA and vitamin B3 (niacin). It’s sold as an unapproved supplement in the U.S.; again, I don’t recommend using it.

Gamma-hydroxybutyrate is an illegal drug that is abused as a date-rape drug but can be purchased on “black market” sites. I do not recommend this product.

The anti-seizure drugs sodium valproate and vigabatrin also increase GABA but should not be used solely for this purpose.

Benzodiazepines such as Xanax, Valium, and Clonazepam cause drug dependency, kill brain cells and reduce GABA receptor density. Recent studies link long-term use with cognitive loss. You know how I feel about them, right?

Gabapentin is a synthetic GABA pharmaceutical used for pain. It is commonly accepted that anxiety heightens the perception of pain, hence the use of gabapentin for this purpose. I’m also not a fan of this drug, either. However, there are Functional medications that are useful for pain and anxiety.

Low Dose Naltrexone

Naltrexone was initially approved in 1984 to help people with a substance use disorder wean off heroin. It works by blocking the opioid receptors in the brain, which reduces the effects of opioid drugs and prevents cravings for opioids. However, researchers have since studied smaller doses of naltrexone (1-5 mg) and discovered other potential benefits.

At these lower doses, naltrexone can produce something called the opioid rebound effect, which increases the production of beta-endorphins and met-enkephalins. When opioid receptors are blocked, the body increases its production of these endogenous opioids to compensate for the lack of opioid agonists. This increase in endogenous opioids can relieve pain by reducing inflammation and thereby promote healing.

In addition to the opioid rebound effect, naltrexone at low doses can also upregulate something called opioid growth factor (OGF). OGF is believed to have various effects on the body, including reducing inflammation and promoting cell growth and repair.  By upregulating OGF via the temporary blockade of opioid receptors, naltrexone may provide additional benefits beyond pain relief.

This up-regulation of OGF via the temporary blockade of opioid receptors causes an increase in circulating endorphins and enkephalins via the reduced inflammatory response.

Similarly, LDN blocks GABA receptors to increase circulating GABA. This calms anxiety, which, in turn, adds to pain relief.

Selank

Heptapeptide Selank: (Thr-Lys-Pro-Arg-Pro-Gly-Pro)

Numerous clinical studies have shown that Selank has strong anti-anxiety effects similar to those of benzodiazepines. One proposed mechanism of action for Selank is enhancing the activity of the calming neurotransmitter GABA on its receptors, which is also how benzodiazepines work.

Furthermore, there is evidence to suggest that Selank’s anti-anxiety and pain-reducing effects may be due to its ability to inhibit the hydrolysis of enkephalins. Enkephalins are endogenous opioids that reduce pain and produce a sense of well-being. Studies have found that individuals with anxiety disorders have reduced enkephalin levels and shortened enkephalin half-life, which may contribute to the perception of pain and anxiety.

Selank, as a potent enkephalinase inhibitor, can block the enzyme that destroys enkephalins and increase their levels in the body. This increase in enkephalins may contribute to Selank’s ability to reduce anxiety and perception of pain.

Conclusion

We are (hopefully!) moving away from the treatment of stress, raised cortisol, and anxiety with pharmaceuticals such as Xanax and Valium. We don’t use these drugs in Functional Medicine because we know they are harmful. One medication I didn’t mention above was the class of blood pressure medications called beta blockers. Beta-blocker medication (e.g., metoprolol) increases GABA binding in the brain and may also increase the density of GABA receptors. I will sometimes prescribe this medication to someone with elevated blood pressure and uncontrolled anxiety. As an aside, anxiety is the #1 symptom reported to me by 18-30-year-olds with mold and mycotoxin illness, and metoprolol works well in this group of patients.

We now have functional medicine tools to help us raise GABA levels. We can check levels (if needed) with 24-hour urine testing. But the most exciting research comes from gut microbiome analysis, where we can see exactly what is in our microbiome, measure how much GABA it produces, and do something about it! The best and only “actionable” microbiome test kit is found in your app store: the Injoy app; worth it and feel free to use my discount code: DRKIM10.

It will be exciting to see how this area of research evolves, as I predict it will be our future go-to therapy for treating a host of medical conditions, including anxiety. If you were to ask me to name the best supplement for anxiety, I’d end up wanting to look at your microbiome, as it is the most physiologic way to correct this problem. But meanwhile, yes, I’d prescribe some Selank.

Introduction

If you follow medical news, you know the gut microbiome is largely responsible for your overall health. Amazing, isn’t it? Hippocrates was right! After reviewing the ins and outs of the gut microbiome, I’ll get into gut health supplements and recommend the best gut microbiome test. Here’s what I’ll cover.

• What is the gut microbiome?.
• Gut microbiome components
• How the gut microbiome works
• Functions of a healthy gut microbiome
• Normal versus abnormal gut microbiome
• Prebiotics
• Benefits and specifics of Prebiotics
• Prebiotic Fibers
• Prebiotic Oligosaccharides
• Galacto-oligosaccharides
• Resistant Starch
• Polyphenols
• Flavonoid Polyphenols
• Other Flavonoid Polyphenols
• Hydroxycinnamic Acids
• Probiotics
• Synbiotics
• Postbiotics=Paraprobiotics=Ghostbiotics
• Beneficial gut microbiome byproducts
• Short-chain Fatty Acids
• SCFA production in commensal(host) and probiotic strains of bacteria
• Butyrate and gut health
• Butyrate and the gut-brain barrier
• Butyrate and Aging
• Propionic acid (Propionate)
• Acetate
• Acetate from Dietary Sources
• What Shapes the Adult Microbiome?
• Healthiest Microbiome Diet
• Foods that promote inflammation= avoid
• Anti-inflammatory foods
• Best gut microbiome supplements
• Best microbiome test=microbiome labs (Yes, there’s an app for it!)

What is the Gut Microbiome?

The gut microbiome is a complex ecosystem comprising trillions of microorganisms, including bacteria, fungi, and viruses (specifically bacteriophages). These microorganisms and their genes collectively make up the gut microbiome.

Bacteriophages, or the “virome,” are viruses that specifically infect and replicate within bacteria. Interestingly, they outnumber gut bacteria and help shape the composition of the gut bacterial communities.

On the other hand, Fungi make up a smaller portion of the gut microbiome, known as the “mycobiome.” Candida is a prevalent genus of fungi in this microbiome.

Understanding the composition and dynamics of the gut microbiome, including these various components, is an active area of research as it has implications for our overall health and well-being.

The gut microbiome’s organisms are categorized into various taxonomic levels, including phyla, classes, orders, families, genera, and species. These taxonomic classifications help researchers understand the diversity and structure of microbial communities in the gut.

The gut microbiota can vary among individuals, and differences in the abundance of specific phyla can significantly impact health. The four dominant phyla commonly found in the gut microbiome are Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. Firmicutes and Bacteroidetes comprise around 90% of the gut microbiota.

Within the Firmicutes phylum, the Clostridium genus is particularly abundant, representing a large percentage of this group. Other genera within Firmicutes, such as Lactobacillus, Bacillus, Enterococcus, and Ruminicoccus, also play essential roles in the gut microbiome.

Understanding the distribution and abundance of these different taxonomic groups within the gut microbiome is crucial for studying their functions and potential impacts on human health.

While the focus has often been on bacteria in the gut microbiome, research has shown that both the mycobiome and virome can also play important roles in gut health.

The mycobiome, or fungal community in the gut, can be influenced by various factors, including diet and environmental factors. Dysbiosis or imbalances in the mycobiome have been associated with some immunodeficiency states and inflammatory disorders, such as Inflammatory Bowel Disease (IBD).

For example, specific fungal cell wall epitopes, such as anti-Saccharomyces cerevisiae antibodies (ASCA), have been found to be a biomarker for Crohn’s disease and are cross-reactive with the fungus Candida albicans.

Antibiotic use can also affect the balance of the mycobiome and lead to the overgrowth of certain fungi in the gut. We’ll discuss this later on in this article.

Overall, the mycobiome is an essential component of the gut microbiome, and its contribution to gut health is an active area of research.

The virome, composed chiefly of bacteriophages, is a highly diverse biological system within the gut. Bacteriophages are viruses that specifically infect bacterial cells, and their presence and activity can directly impact the immune system.

Bacteriophages can influence the immune system by stimulating the production of specific immune molecules, such as interleukin-1b and tumor necrosis factor-alpha, by macrophages. These molecules are involved in immune responses and inflammation.

Additionally, the gut virome is responsive to changes in diet. Different dietary compositions can influence the abundance and activity of specific bacteriophages within the gut.

In the next section, we’ll discuss the “gut bugs” populations found in each section of the gastrointestinal (GI) tract.

Understanding the population dynamics and functions of gut bacteria in different sections of the GI tract is crucial for comprehending their roles in digestion, nutrient metabolism, immune function, and overall gut health.

Gut Microbiome Components

The microbiota composition varies along the length of the gastrointestinal tract, from the mouth to the colon.

The colon, specifically the large intestine, harbors the highest density and diversity of bacteria in the gut. This is primarily due to increased nutrient availability (such as undigested dietary fibers) and slower material transit time through the colon. The colon’s lower pH also favors certain bacterial species’ growth.

In contrast, the small intestine generally has a lower abundance and diversity of microbiota than the colon. Several reasons contribute to this difference. Firstly, the transit time in the small intestine is relatively faster, allowing less time for the bacteria to colonize and establish. Additionally, the small intestine is exposed to the influx of digestive enzymes and bile from the liver, which can impact the growth and survival of certain bacterial species. Lastly, food substrates are delivered intermittently to the small intestine, further limiting the availability of nutrients for bacterial growth.

It’s important to note that even though the small intestine has a lower bacterial population, it still plays a crucial role in the digestion and absorption of nutrients.

Understanding these regional differences in the composition and function of the gut microbiota is essential for unraveling their contributions to overall gastrointestinal health and metabolic processes.

The human oral cavity harbors a diverse and abundant microbial community known as the oral microbiome. This microbiome typically exists in the form of a biofilm, commonly called dental plaque.

The oral microbiome includes various bacteria, such as Streptococcus mutans, Porphyromonas gingivalis, Staphylococcus, and Lactobacillus. Streptococcus mutans is a prominent component of the oral microbiota and is strongly associated with the formation of dental plaque and tooth decay (caries). It can metabolize sugars, produce acid, and contribute to the demineralization of tooth enamel.

Lactobacillus is another bacterium in the oral microbiome that can ferment sugar and produce lactic acid. This acid can also contribute to the development of dental caries.

Beyond oral diseases like caries and periodontitis, the oral microbiome has been linked to several systemic diseases. Research has found associations between oral microbiota and conditions such as esophageal, colorectal, and pancreatic cancers, diabetes, Alzheimer’s disease, cardiovascular disease, cystic fibrosis, and rheumatoid arthritis.

However, it’s important to note that these associations do not necessarily imply causation, and further research is needed to fully understand the complex relationship between the oral microbiome and systemic diseases.

Interestingly, the oral microbiome can also be targeted for disease treatment. Probiotics, such as a particular strain of Streptococcus called Streptococcus A12, have been investigated for their ability to buffer the acidic pH within biofilms. This buffering effect may help prevent dental caries caused by acid-producing bacteria in the oral microbiome.

Understanding the composition, dynamics, and interactions within the oral microbiome is crucial for maintaining oral health, preventing oral diseases, and potentially influencing systemic health.

While the esophagus has its distinct microbiome, that is beyond the scope of this discussion. Moving on to the stomach, let’s discuss the basics.

The human stomach harbors a diverse array of microbes, with five major phyla dominating the microbial population: Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria, and Proteobacteria. At the genera level, certain microbial genera are particularly prevalent in the stomach microbiome. These include Prevotella, Streptococcus, Veillonella, Rothia, and Haemophilus, among the most common genera in the gastric environment.

Observing the intricate composition of the human stomach microbiome and the key players contributing to its microbial diversity is fascinating. Understanding the role of these significant phyla and genera in the stomach microbiota is crucial for unraveling the complexities of digestive health and disease susceptibility.

Several factors influence the composition and diversity of the gastric microbiota, including diet, medication usage, inflammation, and Helicobacter pylori infection.

Diet: Dietary patterns and nutrient composition can affect the microbial composition of the stomach. Studies have shown that diets high in fruits, vegetables, and fiber are associated with a more diverse and stable gastric microbiome. In contrast, diets high in fat and sugar can disrupt the microbial balance in the stomach and promote the growth of potentially harmful bacteria.

Medication Usage: Medications such as proton pump inhibitors (PPIs) and antibiotics can significantly affect the gastric microbiota. PPIs work by reducing stomach acid production, which can alter the stomach’s environment and affect the growth of certain bacteria. Antibiotics, conversely, can cause extensive changes in the gastric microbiota by eliminating harmful and beneficial bacteria and allowing opportunistic pathogens to colonize.

Inflammation and Gastric Mucosa: Inflammation of the gastric mucosa and atrophic gastritis can also impact the composition of the gastric microbiota. Chronic inflammation can decrease microbial diversity, promote the growth of pathogenic bacteria, and cause imbalances in the stomach microbial community.

Helicobacter pylori Infection: Helicobacter pylori infection is one of the most significant factors affecting the gastric microbiota. H. pylori is a Gram-negative bacterium that colonizes the stomach mucosa, and its presence can cause a range of gastric conditions, including gastritis, peptic ulcers, and gastric cancer. H. pylori has been shown to alter the gastric microbiota by reducing microbial diversity and increasing the numbers of certain bacterial species.

Understanding the factors influencing the gastric microbiota is essential for developing strategies to promote a healthy microbial community and prevent or treat gastric diseases.

The small intestine is the most extended section of the gastrointestinal (GI) tract and has its own microbiome. Its microbial composition differs from that of the stomach and colon. Some bacterial genera commonly found in the small intestine include Lactobacillus, Clostridium, Staphylococcus, Streptococcus, and Bacteroides.

The population of bacteria in the small intestine increases as you move from the duodenum (the first part of the small intestine) to the distal ileum (the last part before the large intestine). The bacterial counts in the duodenum range from around 104-105 colony-forming units (CFU) per milliliter, while in the distal ileum, where transit slows down, the counts increase to 107-108 CFU/mL.

The composition of the small intestinal microbiota also changes gradually along the length of the small intestine. There is an increase in the proportion of gram-positive bacteria compared to gram-negative bacteria, as well as a shift from facultative anaerobic (oxygen-tolerant) to strict anaerobic species.

Small Intestinal Bacterial Overgrowth (SIBO) is a condition characterized by excessive bacteria within the small intestine. This overgrowth can disrupt the normal digestion and absorption processes, causing abnormal fermentation of nutrients and leading to symptoms such as excessive gas, bloating, diarrhea, and malabsorption.

SIBO has been linked to various conditions, with up to 78% of irritable bowel syndrome (IBS) cases being associated with SIBO.

It’s interesting to note that hormonal deficiencies can contribute to the development of SIBO. Hormones play a crucial role in regulating gut motility and maintaining the balance of gut bacteria. Any disruption in hormonal levels can affect food movement through the GI tract and promote the growth of bacteria in the small intestine.

Indeed, the various aspects of our health, including gut health and hormonal balance, are interconnected, and disruptions in one area can impact others. Understanding the role of the small intestine microbiome and conditions like SIBO can help develop effective treatments and maintain overall health. Now, let’s talk about the section of the G.I. tract where much of the “action” is: the colon.

The colon, also known as the large intestine, houses the most diverse and abundant microbiome in the human gastrointestinal tract. This microbiome is composed mainly of obligate anaerobes, which thrive in the colon’s low-oxygen environment.

Among the most abundant bacteria in the colon are members of the genus Bacteroides and anaerobic gram-positive cocci like Peptostreptococcus, Eubacterium, Lactobacillus, and Clostridium.

The colonic microflora plays a vital role in various host digestive processes. One of its primary functions is the fermentation of non-digestible carbohydrates, including dietary fibers that escape digestion in the upper gastrointestinal tract.

The colonic bacteria break down these fibers through fermentation, producing several beneficial byproducts, such as short-chain fatty acids (SCFAs). SCFAs, mainly acetate, propionate, and butyrate, are important energy sources for the colonic epithelial cells and contribute to overall colon health.

The gut microbiome is also involved in other essential functions, including:

1. Nutrient metabolism: The colonic bacteria metabolize certain compounds that the host cannot digest, such as complex polysaccharides, proteins, and bile acids. The microbiome can influence nutrient availability and absorption in the host through these metabolic processes.
2. Vitamin synthesis: Some colon bacteria can produce vitamins, such as vitamin K and specific B vitamins. These microbial-synthesized vitamins can contribute to the host’s vitamin status and play essential roles in various physiological processes.
3. Immune modulation: The gut microbiome interacts with the host immune system, helping to educate and shape its development. The microbial community in the colon can regulate immune responses, promote immune tolerance, and protect against potential pathogens.

Many studies on the gut microbiome rely on analyzing fecal samples to study the luminal “fecal” colonic microbiome. Fecal samples provide valuable insights into the overall composition and functions of the colonic microbiota.

However, it’s worth noting that there are also colonic-adherent microbiota that interact more directly with the host immune system. These adherent microbes require sampling through intestinal biopsies during procedures like colonoscopy to study their specific interactions with the host.

Understanding the functioning of the gut microbiome is a complex and evolving field of research. Ongoing studies uncover the intricate roles of the colonic microbiota in human health and disease.

How the gut microbiome works

Yes, it is true that approximately ten times as many microbial organisms inhabit our bodies as there are human cells. These microbes colonize various body parts, including the gut, digestive tract, genitals, mouth, and nose.

The health of someone’s microbiome is determined by the balance between “bad bacteria” and “good bacteria.” A healthy microbiome requires a higher ratio of beneficial to harmful bacteria to maintain resilience and stay symptom-free.

Unfortunately, factors such as a poor diet, high levels of stress, and exposure to environmental toxins can disrupt this balance, leading to an overabundance of potentially dangerous bacteria, fungi, yeast, and pathogens.

Although the human microbiome is home to various types of microorganisms, bacteria have been found to play a vital role in controlling immune function and inflammation. Researchers have identified over 10,000 different species of microbes in the human body, each with unique DNA and specific functions.

Maintaining a healthy balance of bacteria in the microbiome is crucial for overall health and well-being. Promoting diversity and abundance of beneficial bacteria through a balanced diet, reducing stress levels, and minimizing exposure to toxins can help support a healthy microbiome and its associated functions.

Indeed, researchers are still uncovering the many ways that different strains of bacteria affect various aspects of human health. Even so, some general characteristics of a healthy versus unhealthy microbiome have emerged in existing research.

A healthy microbiome is typically characterized by a high diversity of bacterial species, with a balance between “good” and “bad” bacteria. Additionally, it generally is more stable and resilient, able to resist changes in response to various factors such as diet, stress, and environmental toxins.

Conversely, an unhealthy microbiome is often characterized by a lower diversity of bacterial species and an overgrowth of pathogenic or “bad” bacteria. These imbalances in the microbiome have been associated with various health conditions, including obesity, autoimmune disorders, cognitive decline, and inflammation.

In summary, a healthy microbiome is diverse, balanced, and stable, while an unhealthy microbiome lacks these qualities. Ongoing research will likely uncover additional factors contributing to microbiome health and disease. Here are the basic functions of the microbiome.

Functions of a Healthy Gut Microbiome

As you know, the gut microbiome profoundly impacts our overall health and plays a vital role in various physiological processes. Here are some additional points to consider:

1. Mucosal homeostasis and immune cell modulation: The gut microbiome helps maintain the balance and function of immune cells in the gut mucosa. It promotes immune cell development, regulates immune responses, and supports the integrity of the gut lining.
2. Vitamin synthesis: Some beneficial bacteria in the gut can synthesize specific vitamins, such as vitamin K and many B vitamins. These vitamins are essential for various physiological processes in the body.
3. Influence on gastrointestinal hormones: The gut microbiome can impact the production and response to gastrointestinal hormones, such as ghrelin and leptin, which are involved in appetite regulation and metabolism.
4. Maintenance of intestinal homeostasis: The gut microbiome helps maintain a healthy environment in the intestines by regulating factors such as pH levels, bile acid metabolism, and nutrient absorption. This contributes to the overall balance and proper functioning of the digestive system.
5. Regulation of epithelial cell proliferation and differentiation: The gut microbiome influences the growth, proliferation, and differentiation of epithelial cells that line the intestinal wall. This is crucial for maintaining a healthy gut barrier and proper nutrient absorption.
6. Prevention of pathogenic colonization: Beneficial bacteria in the gut compete with and prevent the colonization of pathogenic microorganisms. They help maintain a balanced microbial community and reduce the risk of infections or overgrowth by harmful bacteria.

So, what is “normal?”

Normal Versus Abnormal Gut Microbiome

A healthy microbiome begins to form from birth and develops during early childhood. By age 3, a person’s microbiome closely resembles an adult’s. However, the microbiome continues to evolve throughout life, adapting to changes in diet, lifestyle, and other factors.

While the relative abundances of different microbial species can fluctuate, the overall community and function of the microbiome remain relatively stable and healthy. This stability allows the microbiome to perform important functions, such as synthesizing specific vitamins, aiding digestion, and supporting immune function.

On the other hand, an unhealthy microbiome can also be stable, leading to chronic disease. The concept of resilience is crucial in understanding the impact of disturbances on the microbiome. A resilient microbiome can withstand temporary disruptions, such as a single course of antibiotics, and return to its original state.

However, persistent interferences, like long-term changes in diet, recurrent antibiotic use, or disruptions during vulnerable periods (such as infancy or the peripartum period), can create a new, disease-promoting state in the microbiome.

It’s important to note that the relationship between the microbiome and specific diseases is still an active area of research, and more studies are needed to fully understand the complex interactions. However, maintaining a diverse and resilient microbiome through a balanced diet, healthy lifestyle choices and judicious (sparing) use of medications may support overall gut health.

There are specifically known indicators of a healthy gut microbiome. For example, gut microbiome alpha diversity (diversity in one sample) has been linked to positive human health, while lower levels of diversity are associated with several acute and chronic diseases. Another well-known marker is the Firmicutes to Bacteroidetes (F/B) ratio.

In addition, several particular bacterial species have been recognized for their benefits, such as Faecalibacterium prausnitzii. F. prausnitzii has been consistently reported as one of the primary butyrate producers in the gut, with the ability to reduce gut mucosal inflammation and protect against both colorectal cancer and inflammatory bowel disease. We’ll get “heavily” into the importance of butyrate and other vital fatty acids.

Another important bacterium is Akkermansia muciniphila. A. muciniphilia has been shown to contribute to the maintenance of a healthy gut barrier, regulate immunity, and modulate inflammation. Notably, a lower abundance of this organism has been associated with multiple diseases.

If you are reading this article, chances are you’ve read other articles about the gut microbiome. And perhaps you’ve been as confused as everyone else over the gut microbiome terminology. Let me clarify all of this terminology for you so you know what’s what moving forward. Let’s first discuss the terminology of the gut microbiome and gut health supplements.

Prebiotics

Prebiotics are defined as “selectively fermented ingredients that result in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health.”

The original definition of prebiotics, established in 1995, described these compounds as non-digestible food ingredients that play a crucial role in influencing the growth and activity of specific bacteria in the colon. By selectively stimulating the proliferation of one or a limited number of beneficial bacterial species, prebiotics were believed to enhance host health through their interactions with the gut microbiota.

The updated definition of prebiotics in 2004 introduced three critical criteria to refine the classification further. According to this revised definition, prebiotics should meet the following requirements:

Resistant to Gastric Acidity and Hydrolysis: Prebiotics must demonstrate resistance to gastric acidity, enzymatic hydrolysis by mammalian enzymes, and absorption in the gastrointestinal tract to reach the colon.

Fermented by Intestinal Microbiota: Prebiotics should be fermentable by the intestinal microbiota, indicating their ability to undergo microbial metabolism in the gut environment.

Selective Stimulation of Beneficial Bacteria: Prebiotics must selectively stimulate intestinal bacteria’s growth and/or activity associated with health and well-being, emphasizing their role in promoting the proliferation of beneficial microbial species in the gut.

Now for the benefits and more specifics.

Benefits and specifics of Prebiotics

Prebiotics can modify the gastrointestinal microbiota through dietary strategies for potential health benefits. Studies have shown that increased intake of dietary fiber, particularly fermentable fiber, can promote the growth and diversity of beneficial gut bacteria, leading to improved gut health and reduced risk of chronic diseases.

Low fiber intake, prevalent in Western societies, has been linked to impaired gut microbiota with reduced diversity and an overgrowth of potentially harmful bacterial species. This may contribute to the development of chronic non-communicable diseases, including obesity, cardiovascular disease, type 2 diabetes, and colon cancer.

Intervention studies in humans have also demonstrated that increasing dietary fiber and whole grains intake can increase gut bacterial diversity, highlighting the importance of a high-fiber diet for maintaining a healthy gut microbiome.

Therefore, prebiotic-rich foods such as whole grains, fruits, vegetables, and legumes can be an effective dietary strategy to promote gut health and potentially prevent chronic diseases.

Prebiotic Fibers

According to the definition provided by the Codex Alimentarius Commission in 2009, dietary fibers are described as “carbohydrate polymers with ten or more monomeric units, which are neither digested nor absorbed in the human small intestine,” and they fall into three categories:

1. Edible carbohydrate polymers naturally occurring in foods as consumed.
2. Edible carbohydrate polymers obtained from food raw materials through physical, enzymatic, or chemical means have a beneficial physiological effect supported by generally accepted scientific evidence.
3. Generally accepted scientific evidence supports Edible synthetic carbohydrate polymers with a demonstrated beneficial physiological effect.

This definition recognizes the diverse range of dietary fibers in natural foods and those obtained through various processing methods. It emphasizes that these carbohydrates should resist digestion and absorption in the small intestine and have scientifically demonstrated health benefits.

Indeed, plant-based fibers can be classified into various categories based on their origin, such as cereals and grains, fruits, vegetables, nuts, and legumes. It is important to note that different types of plants contain different fibers with distinct chemical compositions and physicochemical properties.

For example, bananas contain resistant starch and inulin-type fructans, which are prebiotic fibers that can promote the growth of beneficial gut bacteria. On the other hand, apples are a good source of pectin, another dietary fiber with health benefits.

Diets rich in various plant-based foods can provide a wide range of dietary fibers, thus supporting the diversification of the gut microbiota. The different types of fibers in these foods can selectively stimulate the growth of beneficial bacteria in the gastrointestinal tract, leading to a more diverse and balanced microbiota composition.

Therefore, consuming diverse plant-based foods can contribute to a healthier gut microbiome and overall gut health.

The microbial conversion of complex polysaccharides into monosaccharides involves a variety of biochemical pathways, which are facilitated by the enzymatic activities of bacteria in the gut.

When complex carbohydrates, such as dietary fibers, reach the colon, gut bacteria ferment them. The end products of this fermentation process include short-chain fatty acids (SCFAs) and gases such as hydrogen (H2) and carbon dioxide (CO2).

SCFAs, namely acetate, propionate, and butyrate, are the primary products of bacterial fermentation in the colon. These SCFAs are crucial in maintaining gut health and have several beneficial effects on the host.

SCFAs serve as an energy source for colonocytes, promote sodium and water absorption, and help regulate the colon’s pH. They also have immunomodulatory properties and can influence various body processes, including inflammation and metabolism.

The proportions of SCFAs produced during fermentation can vary based on the types of carbohydrates ingested and the gut microbiota composition. Different bacteria have different metabolic capabilities, which can result in variations in the production and ratios of SCFAs among individuals.

Therefore, measuring SCFAs in the colon can provide valuable information about bacterial fermentation and the health status of the gut microbiota.

Prebiotic Oligosaccharides

A regular diet typically contains various prebiotic oligosaccharide carbohydrates, including inulin-type fructans. Inulin-type fructans naturally occur in foods such as chicory root, Jerusalem artichoke, garlic, and certain cereals like wheat.

It is important to note that inulin-type fructans in foods can contribute to their prebiotic effects. Prebiotics are non-digestible dietary fibers that promote the growth and activity of beneficial bacteria in the gut, thus supporting gut health.

Inulin-type fructans, specifically, have been shown to selectively stimulate the growth of Bifidobacteria and Lactobacilli, which are considered beneficial bacteria in the gut microbiota. Remember that wheat grown in the U.S. may be problematic for many people, so watch out for GMOs and gluten.

Galacto-oligosaccharides

These diary-derived prebiotics have potential immune-modulating effects. Beta-galacto-oligosaccharides are prebiotic dietary fiber that can benefit the gut microbiota and immune system.

In a well-done study conducted on elderly subjects, supplementation with β-GOS was shown to have several positive effects on immune function. Some key findings from the study include:

Increased levels of the immuno-regulatory cytokine interleukin-10 (IL-10) regulate the immune response and reduce inflammation.

Significant reduction in the expression of IL-1β, a pro-inflammatory cytokine associated with the inflammatory response.

Increased interleukin-8 (IL-8) blood levels are involved in immune cell recruitment and activation.

Improvement in Natural Killer (NK) cell activity is vital for the body’s defense against viruses and cancer cells. Next, let’s move on to something you probably have heard about called resistant starch.

Resistant Starch

Resistant starch (RS) is naturally present in cereal grains and other starch-containing foods. It refers to a type of starch that resists digestion in the small intestine and reaches the large intestine intact. The resistance to digestion can be influenced by factors such as granule morphology, amylose-amylopectin ratio, and interactions with other food components.

RS is classified into four classes based on its digestibility. These classes help categorize the different types of RS based on their resistance to digestion and their impact on gut health.

One interesting study demonstrated that RS has a bifidogenic effect, meaning it increases the concentration of beneficial bacteria such as Bifidobacteria.

It also increased the levels of other beneficial bacteria, including Bacteroidetes, Akkermansia, and Allobaculum species. These bacteria are essential in maintaining gut health and promoting a balanced gut microbiota.

Furthermore, studies conducted in vitro and on mice have shown that resistant starch increases the production of short-chain fatty acids (SCFAs).

SCFAs are beneficial compounds gut bacteria produce during dietary fiber fermentation, including RS. SCFAs have several health benefits, such as providing energy for colonocytes, promoting gut health, and influencing various physiological processes.

While there are limited studies on humans, some evidence suggests that high amylose maize starch (HAMS) administration, a type of resistant starch, may have prebiotic effects in adults.

Other examples of resistant starch include cooked and cooled pasta and rice, oats, green bananas, certain legumes, and raw potato starch. For my extensive practice of autoimmune patients eating strict AIP, the best choice is green bananas.

Polyphenols

The primary sources of polyphenols are fruits such as berries, grapes, citrus fruits, apricots, apples, plums, cherries, peaches, and tropical fruits. Additionally, polyphenols can be found in popular beverages such as green and black tea, fruit juices, coffee, red wine, cocoa, and beer, as well as in various seeds, grains, and nuts.

Vegetables are also a good source of polyphenols, with onions, spinach, broccoli, cauliflower, artichoke, tomato, beans, soybeans, carrots, capers, and olives being some of the most common sources. Even spices and herbs such as clove bud, turmeric, celery, parsley, mint, rosemary, thyme, sage, dill, curry, and ginger contain high levels of polyphenols.

Polyphenols are a diverse group of compounds, and their concentration and type can vary widely depending on the food source. However, a diet rich in fruits, vegetables, nuts, and whole grains is generally associated with a high intake of polyphenols and other beneficial phytochemicals.

Polyphenols have numerous health benefits, including antioxidant and anti-inflammatory effects. Some studies have suggested they may protect against chronic diseases such as cardiovascular disease, type 2 diabetes, and certain cancers.

Flavonoid Polyphenols

Flavonoids are a major class of dietary polyphenols, constituting up to 60% of polyphenol intake. Due to their widespread presence in various foods and impressive biological functions and activities, flavonoids are continuously being studied for their potential as drugs or food supplements.

Some of the most common flavonoids include:

1. Quercetin: This flavanol is abundant in foods such as onions, broccoli, tea, and apples. Quercetin is known for its antioxidant and anti-inflammatory properties.
2. Catechin: A flavanol found in tea (mainly green tea) and various fruits, catechin is recognized for its potential health benefits, such as cardiovascular protection and anticancer properties.
3. Naringenin: A flavanone present in citrus fruits like oranges, grapefruits, and lemons, naringenin has been studied for its antioxidant and anti-inflammatory effects.
4. Cyanidin and Anthocyanin: These flavonoids give fruits and berries such as blackcurrants, raspberries, strawberries, blueberries, and grapes their vibrant red, purple, or blue color. Anthocyanins have various health benefits, including cardiovascular health and improved cognitive function.
5. Daidzein and Genistein: These are the main isoflavones found in soybeans and soy products. Isoflavones have been studied for their potential role in hormonal balance and reducing the risk of certain chronic diseases.

Other Flavonoid Polyphenols

Isoflavones:

• Naturally occurring phytochemicals of the flavonoid class.
• Referred to as “phytoestrogens” due to their estrogen-like effects.
• Predominant sources are legumes, particularly soy products.
• Commonly found in fermented soy foods like soy paste and unfermented soy products like tofu and soy flour.

Phenolic acids:

• Found in leguminous plants, vegetables (spinach, broccoli, kale), berry fruits, apples, coffee, tea, citrus juices, wine, beer, cereal brans, and olive oil.
• Provide substantial antioxidative and anticancer activities.

Hydroxybenzoic acids:

• Simple aromatic acids with substantial antioxidative and anticancer activities.
• Main representatives are gallic and ellagic acid, abundant in fruits and nuts.

Anthocyanidins:

• Naturally occur as glycosides named anthocyanins.
• Responsible for the red, purple, and blue hues of various fruits, vegetables, cereal grains, and flowers.
• Main sources include teas, honey, wines, fruits (apples, berries), vegetables (beets, onions), nuts, olive oil, cocoa, and certain cereals.

Chalcones:

• Another important class of naturally occurring flavonoids.
• Metabolic precursors of certain flavonoids and isoflavonoids.
• Abundant in hops and, therefore, in beer, as well as citruses, apples, certain vegetables (shallots, tomatoes, potatoes, bean sprouts), and various plants and spices (licorice, cardamom).

Ellagic acid:

• Dimeric derivative of gallic acid.
• Richest sources include blackberries, raspberries, strawberries, cranberries, pomegranates, walnuts, and pecans.
• Possesses anti-carcinogenic, antioxidant, anti-inflammatory, anti-bacterial, anti-atherosclerosis, anti-hyperglycemic, anti-hypertensive, anti-fibrosis, and cardioprotective effects.

Hydroxycinnamic Acids 

Cinnamic acid:

• Acts as the precursor of hydroxycinnamic acids, a diverse group of phenolic substances present in almost every plant.
• Common hydroxycinnamic acids include caffeic acid and ferulic acid.

Caffeic acid:

• Found in many fruits such as apples, plums, tomatoes, and grapes.

Ferulic acid:

• Found in tomatoes and beer in an accessible form, making it efficiently absorbed.
• Also found in an esterified form in grain cell walls (in cereals).

Chlorogenic acid:

• Another essential phenolic acid with varying intake levels.
• Coffee drinkers can consume up to 800 mg per day of chlorogenic acid.

Honorable mentions include rosmarinic acids, curcuminoids, and stilbenes, which will be discussed below in the “supplements” section. Now, let’s switch our focus from prebiotics to probiotics.

Probiotics

Probiotics are live microorganisms that provide health benefits when consumed or applied to the body. They can be found in several sources, such as yogurt and other fermented foods, dietary supplements, and beauty products. Probiotics often contain bacteria from groups like Lactobacillus and Bifidobacterium, which are commonly used. In addition to bacteria, some probiotics may also include yeasts like Saccharomyces boulardii.

Different types of probiotics may have other effects. For example, suppose a specific kind of Lactobacillus helps prevent an illness. That doesn’t necessarily mean another type of Lactobacillus or Bifidobacterium probiotics would do the same thing.

Probiotics work through various mechanisms to exert their beneficial effects on the host. Here are the three primary mechanisms:

1. Synergistic Effects with Indigenous Microbiota: Probiotics interact with the existing beneficial bacteria in the gut. This interaction helps promote a healthy balance of the gut microbiota. Probiotics can influence the production of short-chain fatty acids (SCFAs), which are essential for gut health. SCFAs provide energy for the colon cells, support maintaining the intestinal barrier function, and have anti-inflammatory properties. I’ll go into this in much greater depth shortly.
2. Enhancement of Epithelial Barrier Integrity: Probiotics can strengthen the integrity of the epithelial barrier, which is the gut’s protective lining. By enhancing the barrier function, probiotics help prevent the passage of harmful substances from the gut into the bloodstream, reducing the risk of inflammation and other adverse health outcomes.
3. Modulation of the Host’s Immune System: Probiotics can influence the immune system in the gut. They can help regulate immune responses, promoting a balanced and appropriate immune reaction. This modulation of the immune system can be beneficial in preventing and managing certain inflammatory conditions in the gut.

Additionally, probiotics have been found to affect electrolyte absorption, gut motility, and even the perception of painful sensations. These actions can further contribute to their overall beneficial impact on digestive health.

It’s important to note that the specific mechanisms of action may vary depending on the strain and probiotic used and the individual’s unique microbiome and health condition.

Now, let’s clarify what synbiotics, paraprobiotics, ghostbiotics, and postbiotics are. Whew, right? Let’s start with simple synbiotics.

Synbiotics

Synbiotics are mixtures that consist of live microorganisms (probiotics) and substrates selectively utilized by host microorganisms (prebiotics) that provide a health benefit to the host. A symbiotic blend, which is what is commonly found for sale, typically contains a proven probiotic and a proven prebiotic.

There are two types of synbiotics: complementary and synergistic. A complementary synbiotic contains a live microorganism (which may or may not be a proven probiotic) and a substrate (which may or may not be a proven prebiotic). These components work together to provide a health benefit.

On the other hand, a synergistic synbiotic consists of a live microbe (not necessarily a proven probiotic) and a substrate (not necessarily a proven prebiotic) that the microbe can utilize for its growth. The combination of these components has a synergistic effect in promoting health.

In practical terms, a product labeled as a symbiotic blend typically contains a well-researched and proven probiotic strain combined with a proven prebiotic ingredient. The prebiotic substrate is often a fiber or polyphenol blend, which can selectively support the growth and activity of the probiotic microorganisms in the gut.

Postbiotics=Paraprobiotics=Ghostbiotics

The scientific community has proposed various terms for inanimate microorganisms and their components that can provide health benefits. Some commonly used terms for these substances include non-viable probiotics, paraprobiotics, ghostbiotics, heat-inactivated probiotics, and postbiotics.

In 2021, the International Scientific Association for Probiotics and Prebiotics (ISAPP) defined postbiotics as “a preparation of inanimate microorganisms and/or their components that confer a health benefit on the host.” This definition encompasses various substances derived from microorganisms that can positively affect human health.

Postbiotics can include various components such as cell components, cell fragments, and metabolic products of microorganisms. These substances can be derived from microbial sources, including bacteria, yeast, and fungi.

The health benefits of postbiotics are thought to arise from their interactions with the host’s body, including interactions with the immune system, promoting a healthy gut environment, and influencing various physiological processes.

It’s worth noting that the term postbiotics has gained significant recognition within the scientific community. However, it is important to continue researching and understanding the specific mechanisms of action and health benefits associated with these inanimate microorganisms and their components. Next, let’s identify the by-products we want produced by a healthy gut microbiome.

Beneficial gut microbiome byproducts

Intestinal microorganisms play a crucial role in various metabolic processes, including producing short-chain fatty acids (SCFAs). SCFAs, also known as volatile fatty acids, are an essential carbon flow from the diet to the host microbiome. They have several beneficial effects on the host’s health.

Maintaining a balanced intestinal microbiome promotes overall health and prevents diseases. Probiotic microorganisms have been found to positively impact the balance of the intestinal microbiome and the production of metabolites, including SCFAs.

Only a few of the approximately 60 known phyla of bacteria are commonly found in the human intestines. These include Firmicutes, Bacteroides, Actinobacteria, Fusobacteria, Proteobacteria, Verrucomicrobia, Cyanobacteria, and Spirochaetes. However, the two dominant bacterial phyla in the human gut are Gram-positive Firmicutes (such as Lactobacillus spp., Bacillus spp., and Clostridium spp.) and Gram-negative Bacteroidetes.

These phyla contain various bacterial species that contribute to the diversity and functionality of the gut microbiota. Imbalances in the relative abundance of these phyla have been associated with certain health conditions.

The gut microbiome has a remarkable ability to biotransform various chemical compounds. One of its essential roles is converting complex nutrients into simpler forms that the host can easily absorb and utilize.

Intestinal microorganisms break down complex nutrients, including plant cell wall components such as cellulose, pectin, hemicellulose, and lignin. These components are typically indigestible by the host’s enzymes alone. However, the gut microbiota contains specialized microorganisms with the necessary enzymes to degrade these complex carbohydrates. And when the fermentation starts- magic!

Short-chain Fatty Acids

Gut bacteria microbially ferment complex nutrients, producing short-chain fatty acids (SCFAs) as metabolic byproducts. The most common SCFAs produced in the gut are acetate, propionate, and butyrate, which constitute 95%, while formic, valerian, caproic, and lactic acids comprise approximately 5% and play lesser roles.

SCFAs have several vital functions in the body. They serve as an energy source for the cells lining the colon and are also absorbed into the bloodstream, where they can have systemic effects. For example, butyrate is a primary energy source for colonocytes and helps maintain the integrity and health of the intestinal barrier.

SCFAs also have anti-inflammatory properties, help regulate immune responses, and contribute to overall health and proper gut functioning. They have been associated with various health benefits, including promoting gut motility, improving nutrient absorption, and influencing metabolic processes.

SCFA production in commensal(host) and probiotic strains of bacteria

Commensal (host microbiome) species of bacteria noted to produce beneficial SCFA’s:

Bifidobacterium spp., Blautia hydrogentrophica, Prevotella spp., and Streptococcus spp. have been shown to produce acetic acid. Akkermansia muciniphilia and Bacteroides spp. have both been shown to produce acetic and propionic acid. Dalister succinatiphilus, Eubacterium spp. (e.g., E. halli), Megasphaera elsdenii, Phascolarctobacterium succinatutens, Roseburia spp., Salmonella spp., and Veillonella spp. have all been demonstrated to produce propionic acid.

Coprococcus spp. (e.g., Coprococcus catus), Roseburia inulinivorans produce both propionic and butyric acid. Anaerostipes spp., Coprococcus comes, Coprococcus eutactus, Clostridium symbiosum, Eubacterium rectale, Eubacterium hallii, Faecalibacterium spp. (e.g., Faecalibacterium prausnitzii), Roseburia spp. (e.g., Roseburia intestinalis) are major butyrate producers. Finally, we know that Clostridium spp. and Ruminococcus spp. have been shown to produce acetic, propionic, and butyric acid. I’m sure the database will grow daily and be larger once this article is published!

Let’s take a break here to note that you will find a breakdown of good microbiome labs and testing, which will be discussed at length near the end of this article. Get acquainted with some of the heavy-hitter species you want in your microbiome.  Let me say the same with the upcoming discussion of probiotics, which we are only starting to see being produced for clinical outcomes. Here are the top ones.

Bifidobacterium spp. will produce mainly acetic and lactic acids. Lactobacillus rhamnosus GG (LGG) and Lactobacillus gasseri produce primarily propionic and lactic acids.  Bifidobacterium longum and Bifidobacterium bifidum produce acetic, propionic, and lactic acids. Lactobacillus salivarius spp salcinius and Lactobacillus agilis produce propionic, butyric, and lactic acids. Finally, a well-studied strain, Lactobacillus acidophilus, has been demonstrated to produce acetic, propionic, butyric, and lactic acids.

Now, let’s examine the benefits of the main SCFAs. Butyrate leads the pack for overall health, but acetate and propionate are gaining steam as research progresses. To illustrate the importance of SCFAs, let’s start by discussing the “master SCFA”: butyrate.

Butyrate and gut health

Butyrate is often considered a “master” short-chain fatty acid (SCFA) due to its numerous beneficial effects on the gastrointestinal tract and overall health. Specific gut bacteria primarily produce butyrate through the fermentation of dietary fibers, such as resistant starches and other complex carbohydrates.

Butyrate plays a crucial role in maintaining gut health and function. Some key functions and benefits of butyrate include:

1. Energy Source: Butyrate is the primary energy source for the cells lining the colon, known as colonocytes. These cells rely on butyrate to fuel their metabolic processes and maintain structural integrity.
2. Gut Barrier Integrity: Butyrate helps to strengthen the gut barrier by promoting the production of mucin, which forms a protective barrier in the intestinal lining. This barrier helps prevent the entry of harmful substances into the bloodstream.
3. Anti-Inflammatory Effects: Butyrate has anti-inflammatory properties and can help modulate the immune response in the gut. It can reduce inflammation and promote the balance of immune cells in the gut, which is beneficial for conditions characterized by inflammation, such as inflammatory bowel diseases (IBD).
4. Regulation of Gene Expression: Butyrate can influence gene expression in colon cells, leading to changes in cellular processes related to inflammation, cell proliferation, and apoptosis (cell death). This regulatory function contributes to the maintenance of a healthy gut environment.
5. Metabolic Benefits: Butyrate has been shown to influence metabolic processes related to glucose and lipid homeostasis. It can help regulate blood sugar levels, improve insulin sensitivity, and help maintain a healthy metabolism.

In conditions where there is an imbalance in the gut microbiome, leading to a decrease in the number of butyrate-producing bacteria and a reduction in SCFA levels, such as in inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), type 2 diabetes (T2D), obesity, autoimmune disorders, and cancer, the beneficial effects of butyrate may be disrupted.

This imbalance can contribute to gut barrier dysfunction, low-grade inflammation, and metabolic dysregulation in these conditions.

Therefore, promoting butyrate production and maintaining a healthy balance of SCFAs in the gut through dietary interventions, probiotics, and prebiotics can support gut health, reduce inflammation, and improve metabolic outcomes in these conditions.

Butyrate and the gut-brain barrier

The bidirectional communication between the gut microbiome and the central nervous system, known as the gut-brain axis, is an area of growing research interest. Short-chain fatty acids (SCFAs) influence, particularly butyrate, on neural processes, and neuroinflammation, is critical to this interaction.

While systemic absorption of SCFAs from the intestine into the bloodstream is minimal, with butyrate exhibiting lower concentrations than propionate and acetate, it’s important to note that the concentration of SCFAs in the brain itself is negligible. This means that direct activation of neuronal receptors by SCFAs in the brain is unlikely.

Instead, the proposed mechanism for SCFAs’ influence on neural processes is through the regulation of neuroinflammation. SCFAs, particularly butyrate, have been shown to have anti-inflammatory effects on the gut and systemic circulation.

These anti-inflammatory properties can indirectly impact the brain by modulating immune responses and reducing inflammation.

Neuroinflammation, characterized by activating immune cells and releasing pro-inflammatory molecules in the brain, has been implicated in various neurological disorders and conditions. By regulating neuroinflammation, SCFAs can influence neuronal function, mood, memory, and recovery after injuries.

Moreover, SCFAs can indirectly affect the gut-brain axis by modulating the release of certain neurotransmitters, such as serotonin and gamma-aminobutyric acid (GABA), which play essential roles in mood and cognition.

The specific mechanisms by which SCFAs modulate neuroinflammation and influence neural processes are still an area of ongoing research. However, the emerging evidence suggests that the gut microbiome and its metabolic byproducts, including SCFAs, have the potential to impact brain function and contribute to the pathophysiology of neurological disorders.

Butyrate and Aging

Gut barrier integrity, enhancement of mitochondrial function, enhancement of immune responses, and even beneficial effects on telomeres all point to butyrate’s role in slowing the aging process. Quickly increase your butyrate levels with the consumption of MCT oil. I use this exclusively for cooking: odorless, tasteless, with a low flash point-perfect!

Propionic acid (Propionate)

The gut microbiome has been implicated in developing and progressing atherosclerotic cardiovascular disease (CVD). Compared to healthy controls, individuals with atherosclerotic CVD have observed changes in gut microbial composition, specifically an increased abundance of certain bacteria and a depletion of butyrate and propionate-producing bacteria.

A metagenome-wide association study found that patients with atherosclerotic CVD had higher levels of Enterobacteriaceae and Streptococcus spp. while experiencing a relative depletion of bacteria that produce butyrate and propionate. This suggests that short-chain fatty acids (SCFAs), including butyrate and propionate, may be functional in promoting cardiovascular health.

Propionate has been shown to have vasodilating effects in the vasculature by activating the G protein-coupled receptor 41 (GPR41) in the vascular endothelium. This activation decreases blood pressure.

Consume omega-3-rich fish like sardines, salmon, or mackerel to increase propionate levels. Omega-3 fatty acids, found in abundance in these types of fish, have been associated with beneficial effects on cardiovascular health. Due to propionate levels? At least partially, yes, indeed. Now, let’s turn to our last SCFA, acetate.

Acetate

Acetate, one of the short-chain fatty acids (SCFAs), plays a role in weight control and metabolic issues, particularly insulin sensitivity. The interplay between the gut microbiota, host metabolism, and metabolic health is an area of growing research interest.

The gut microbiota has been found to regulate various aspects of metabolism and peripheral tissues such as adipose tissue, skeletal muscle, liver, and pancreas through the production of metabolites, including SCFAs. Acetate has been shown to benefit host energy and substrate metabolism.

Animal and human studies have demonstrated that acetate influences metabolism by promoting the secretion of gut hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY).

These hormones affect appetite regulation, leading to a reduction in food intake. Additionally, acetate has been found to reduce whole-body lipolysis, lower systemic levels of pro-inflammatory cytokines, increase energy expenditure, and enhance fat oxidation.

These effects of acetate on host metabolism contribute to improved insulin sensitivity and may have implications for weight control and metabolic health. Because of the recent social media attention regarding vinegar ingestion and the national obsession with weight loss, let me discuss how to increase your acetate levels.

Acetate from Dietary Sources

Because recommending a TBSP of vinegar daily has become so commonplace, I will spend some time discussing why this might be beneficial. It’s not for the reasons touted in “folklore.” Commonly consumed kinds of vinegar contain between 4% and 8% acetic acid, and vinegar ingestion has gained attention in the scientific literature because of its acute effects on glucose and lipid metabolism.

Oral ingestion of vinegar can rapidly increase circulating acetate levels. In healthy participants, serum acetate levels increased from 120 µmol/L during placebo conditions to 350 µmol/L (after 15 min) and 200 µmol/L (after 30 min) following intake of vinegar (100 mL containing 0.75 g acetic acid) and acetic acid capsules (containing 0.75 g of acetic acid), respectively.

Acetic acid, a bioactive component with a dominant flavor in different types of vinegar (including cider, malt, plum, sherry, tomato, and wine vinegar), increases circulating acetate levels. It is important to consider the type of vinegar used, as its phenolic, flavonoid, and acetic acid content composition may differ.

Some kinds of vinegar, such as apple cider vinegar, grape vinegar, sherry vinegar, and balsamic vinegar, may contain other polyphenol residual components like gallic acid and catechins. These compounds have been linked to various health benefits, including improved blood sugar control, reduced inflammation, and reduced risk of chronic diseases.

In terms of microbiome alterations that produce more acetate-producing species, human fasting and caloric restriction interventions have described an increase in microbial diversity and abundance of essential acetate producers, such as Akkermansia muciniphila (A. muciniphila) and Bifidobacteria. Now, let’s switch gears back to the gut microbiome and what exactly shapes its composition. We’ll start with the basics.

What Shapes the Adult Microbiome?

Diet: Indeed, short—and long-term dietary habits significantly impact the gut microbiome. Short-term changes in diet can lead to rapid but reversible shifts in the microbiome, often accompanied by intermittent gastrointestinal symptoms.

Fiber, particularly microbiota-accessible carbohydrates (MACs), is crucial in nurturing the gut microbiome. When gut microbes ferment MACs, they produce short-chain fatty acids (SCFAs), such as acetate, butyrate, and propionate. These SCFAs have numerous health benefits, including improving gastrointestinal transit by influencing serotonergic pathways.

Low-MAC diets, which are low in fiber, can cause negative shifts in the gut microbiome. The lack of MACs essentially starves the gut microbes, leading them to seek food sources from the host epithelium and mucus. This epithelial barrier disruption can increase the risk of gut inflammation and other gastrointestinal issues.

In addition to low-fiber diets, additives like emulsifiers and artificial sweeteners can adversely affect the gut microbiome and increase the risk of metabolic and inflammatory disorders.

Optimizing fiber and MAC intake is recommended to promote a healthy gut microbiome and overall health. Including fiber-rich foods like fruits, vegetables, whole grains, legumes, and nuts can support the growth and diversity of beneficial gut bacteria. Minimizing the consumption of processed and packaged foods that contain additives can also help maintain a healthy gut microbiome.

Stress: It is well known that stress can negatively impact immune function. When your body perceives stress, it diverts energy and resources from the immune system to prioritize immediate survival responses. This shift in energy allocation can make you more susceptible to infections and result in more severe symptoms. Furthermore, chronic stress can lead to higher levels of inflammation, which can contribute to various health issues.

During stress, immune compounds called cytokines can contribute to the inflammatory response that damages healthy cells. This chronic inflammation can disrupt normal bodily functions and increase the risk of chronic diseases.

Exercise is a natural stress reliever and has numerous benefits for immune function. Physical activity can help lower inflammation, balance hormones, and strengthen the immune system. Exercise can increase the production of antibodies and stimulate the release of endorphins, which are natural mood elevators. These positive effects of exercise can help reduce stress and its impact on the immune system. Let’s delve into that a bit more.

Exercise: Exercise has been shown to positively impact the gut microbiome by increasing the abundance of beneficial bacteria and promoting gut diversity. Studies have found that athletes tend to have a more diverse gut microbiome and lower levels of inflammatory markers. Animal studies have also demonstrated that exercise-related changes in the gut microbiome can reduce susceptibility to inflammation and weight gain.

It’s important to note that the changes in the gut microbiota induced by exercise can be similar in magnitude to, but different from, dietary changes. While exercise can contribute to weight management, sustained weight loss also requires nutritional changes. Both training and a healthy diet are complementary in improving overall health, including the gut microbiome.

To achieve significant changes in the gut microbiota through exercise, it is generally recommended to engage in moderate to high-intensity exercise for 30 to 90 minutes at least three times per week or accumulate between 150 and 270 minutes weekly for a minimum of eight weeks. This consistent exercise routine will likely produce noticeable changes in the gut microbiome.

Vagal nerve stimulation: The brain, gut, and microbiota are connected through a bidirectional communication pathway known as the microbiota-gut-brain axis. This communication involves the autonomic nervous system, particularly the vagus nerve (V.N.). The Vagus nerve is a mixed nerve composed of approximately 80% afferent fibers (transmitting information from organs to the brain) and 20% efferent fibers (transmitting information from the brain to organs).

The Vagus nerve plays a crucial role in interoceptive awareness, allowing it to sense microbiota metabolites through its afferent fibers and transfer this information to the central nervous system. This information is then integrated into the autonomic network, influencing various physiological processes.

One important pathway mediated by the Vagus nerve is the cholinergic anti-inflammatory pathway. Through this pathway, vagal fibers release anti-inflammatory neurotransmitters, dampening peripheral inflammation and reducing intestinal permeability. By modulating inflammation and gut permeability, this pathway may play a role in shaping the composition of the gut microbiota and promoting healing of the gastrointestinal tract, including the “leaky gut” phenomenon.

Conversely, stress, accompanied by the release of cortisol, can inhibit the function of the Vagus nerve. This can negatively impact the gastrointestinal tract and the gut microbiota.

Chronic stress is implicated in the pathophysiology of conditions such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), which are characterized by dysbiosis (microbial imbalance) and increased gut permeability. Vagal nerve stimulation with a device like the one found here has been demonstrated to improve gut permeability and microbial balance.

Sleep: Lack of sleep and poor sleep quality can significantly impact the quality of the gut microbiome. Research has shown that even two days of sleep deprivation can cause a noticeable shift in the ratio of Firmicutes to Bacteroides, two major bacterial phyla in the gut. This shift may have implications for metabolic health and weight regulation.

Sleep disturbances can also lead to changes in the composition of the gut microbiota, favoring less metabolically friendly species. Studies in mice have shown that chronic sleep fragmentation can decrease the abundance of beneficial Lactobacillus species in the gut, which have various health-promoting effects.

Ongoing research illuminates the importance of adequate and restful sleep for maintaining a healthy gut microbiome. Sleep is a critical restorative process for the body, and disruptions can have wide-ranging effects on various physiological systems, including the gut microbiota.

Medications: PPIs, antibiotics, laxatives, statin drugs, metformin, statins, benzodiazepines, hormones, antidepressants, antihistamines, and nonsteroidal anti-inflammatory drugs are examples of all the medications that are associated with changes in the composition of the gut microbiota. Never has it been more apparent that the fewer pharmaceuticals we ingest, the better!

Smoking: Studies show that smokers have lower levels of acetic, propionic, and butyric acid and decreased levels of beneficial Bifidobacterium. Overall, smokers show less microbiome diversity.

Pollution: Data is emerging showing that pollution negatively impacts the gut microbiome. Some studies correlate pollution exposure to increased levels of inflammation associated with decreased butyrate production.

We are learning more and more about the effects of “forever chemicals” on the immune system and, in parallel, on the microbiome. It’s not good. Specific data links the ubiquitous forever chemical PCB to a notable decrease in microbiome diversity.

Geography, urban versus rural living unrelated to pollution per se reveal quite a range of different microbiome compositions, and this data continues to emerge. Undoubtedly, we’ll see data linking the excellent health in the “blue zones” to more diverse and healthy microbiomes.

Shout-out to older siblings and furry pets: Children with older siblings and (moreso) the owners of furry pets have more diverse and generally healthier microbiomes. This bolsters my theory that every child needs a pet!

Now that we know what can disturb the microbiome let’s discuss the best diet to support our microbiomes.

Healthiest Microbiome Diet

Diet plays a crucial role in establishing gut health and supporting the growth of beneficial bacteria in the microbiome. Over the years, research has shown a strong connection between a person’s microbiota, digestion, body weight, and metabolism.

Studies have revealed that the microbiome environments can differ significantly depending on the diet of humans and other mammalian species. Different dietary patterns can lead to variations in the composition and diversity of the gut microbiota.

Conversely, the health of your gut can also affect how your body processes nutrients from your diet and stores fat. The gut microbiota has been found to play a significant role in obesity, and changes in the bacterial strains present in the gut can lead to notable changes in health and body weight in just a few days.

For example, experiments with mice have shown that germ-free mice, which lack any gut microbiota, become fatter when they receive a transplant of gut microbiota from conventional or fat mice, even without any increase in food intake. This suggests that the gut bacteria can influence hormone production, such as insulin, and affect nutrient extraction and fat storage.

These findings highlight the intricate relationship between gut microbiota, diet, and metabolic health. It is becoming increasingly clear that maintaining a balanced and healthy gut microbiome through a nutritious diet is crucial for optimizing digestion, body weight management, and overall metabolic well-being.

Now that you can see why it’s critical to lower inflammation and support gut health let’s examine how to do this.

Foods that promote inflammation= avoid

 The items listed below are commonly associated with adverse effects on gut health and overall well-being. Let’s go over each of them.

1. Pasteurized dairy products: These can be common allergens for some individuals. Dairy products also contain lactose, a sugar that can be difficult to digest for people with lactose intolerance. Additionally, specific pasteurization processes may reduce the presence of beneficial bacteria in the dairy products.
2. Trans fats/hydrogenated fats: Trans fats, commonly found in processed and fried foods, can harm gut health. They can disrupt the integrity of the gut lining, promote inflammation, and negatively impact the gut microbiota.
3. Added sugars: Excessive added sugars, often found in processed foods and beverages, have been linked to adverse effects on gut health. High sugar intake can disrupt the balance of the gut microbiota and contribute to inflammation and various health issues.
4. Refined carbohydrates and processed grain products: Foods like refined grains, white bread, and processed cereals are often low in fiber and nutrients and can lead to dysbiosis (imbalanced gut microbiota). These foods can also cause rapid spikes in blood sugar levels, negatively impacting gut and overall metabolic health.
5. Refined vegetable oils: Refined vegetable oils, such as canola, corn, and soybean, are often high in pro-inflammatory omega-6 fatty acids. Imbalanced ratios of omega-6 to omega-3 fatty acids can contribute to systemic inflammation, including in the gut.
6. Conventional meat, poultry, and eggs: Conventionally raised meat, poultry, and eggs can contain higher levels of omega-6 fatty acids due to the animals’ diets mainly consisting of corn and cheap feed. This can disrupt the body’s balance of omega-3 to omega-6 fatty acids, leading to inflammation and imbalances in the gut microbiota.

To support gut health, it is recommended that people focus on a diet rich in whole, unprocessed foods—including many fruits, vegetables, whole grains, legumes, and lean protein sources. Choosing healthy fats, such as avocados, nuts, seeds, and olive oil, is also beneficial.

Additionally, incorporating fermented foods like yogurt, sauerkraut, and kimchi can provide beneficial bacteria for the gut. Let’s take these general recommendations and spell them out more useably so that you know what you can and should eat.

Anti-inflammatory foods

1. Fresh vegetables: These are packed with beneficial phytonutrients linked to various health benefits, including reduced cholesterol, triglycerides, and symptoms of multiple diseases. Aim for different vegetables and try to have at least four to five servings daily. Some highly nutritious options include beets, carrots, cruciferous vegetables (broccoli, cabbage, cauliflower, kale), dark leafy greens (collard greens, kale, spinach), onions, peas, salad greens, sea vegetables, and squashes.
2. Wild-caught fish, cage-free eggs, and grass-fed/pasture-raised meat: These options are higher in omega-3 fatty acids and provide essential nutrients like zinc, selenium, and B vitamins. When including fish, eggs, or meat in your diet, opt for these healthier choices.
3. Herbs, spices, and teas: Herbs and spices like turmeric, ginger, basil, oregano, and thyme have potent antioxidant and anti-inflammatory properties. Green tea and organic coffee in moderation can also be beneficial.
4. Whole pieces of fruit: Eating whole fruits instead of fruit juice is essential to get the maximum benefits of the fruits’ nutrients, including antioxidants like resveratrol and flavonoids. Incorporate three to four servings of fruits per day. Some excellent choices include apples, blackberries, blueberries, cherries, nectarines, oranges, pears, pink grapefruit, plums, pomegranates, red grapefruit, or strawberries.
5. Healthy fats: Grass-fed butter, coconut oil, extra virgin olive oil, nuts, and seeds are all excellent sources of healthy fats that can support gut health and well-being.
6. Probiotics: Probiotic foods contain beneficial bacteria that populate the gut and help fight off harmful strains. Including probiotic foods like yogurt, kombucha, kvass, kefir, or cultured veggies in your daily diet can promote a healthy gut microbiota.
7. Ancient grains and legumes/beans: Sprouted and unrefined/whole ancient grains and legumes/beans are a good source of fiber, nutrients, and plant-based protein. Including two to three servings per day or less is recommended. Examples include Anasazi beans, adzuki beans, black beans, black-eyed peas, chickpeas, lentils, black rice, amaranth, buckwheat, and quinoa.

Treats: Red wine and dark chocolate/cocoa in moderation contain prebiotics! These can be consumed several times per week or a small amount daily. Now, what about supplements?

Best gut microbiome supplements

When discussing supplements for the microbiome, we generally talk about prebiotic supplements. I mentioned a few in the discussions above, but here are the main ones used today. Here are some common flavonoid prebiotic supplements that are frequently “multi-use.”

We often use catechins, including EGCG supplements derived from green tea, which have been shown to be anti-cancer in several studies. We also use quercetin and fisetin, both of which are multi-use supplements.

Continuing in the flavonoid class are the curcuminoid polyphenols curcumin and turmeric. Rounding out this class of supplements are stilbenes: resveratrol and pterostilbene.

In the category of resistant starch, potato flakes have gained popularity lately.

Probiotics are next when it comes to supplementation, with species identified to reinforce the gut lining (Akkermansia M.), improve gut microbiome diversity (sporulating species; mostly Bacillus), as well as Lactobacillus and Bifidobacterium species, which help metabolism and mood, and much more. As an example, pouring through PubMed looking for probiotics to help reduce anxiety by increasing GABA yields the following information.

Some probiotic strains that can increase GABA (gamma-aminobutyric acid) include Lactobacillus brevis, Bifidobacterium dentium, Bifidobacterium adolescentis, and Bifidobacterium infantis. These strains are part of the lactic acid bacteria (LAB) and bifidobacteria groups, which have been shown to produce GABA. Additionally, other Bacteroides species have been found to produce large quantities of GABA.

As a reminder, there are many ways to improve SCFA production, from consuming a TBSP of vinegar daily for higher acetate levels to taking fish oil supplements to increase propionate levels and using MCT oil for cooking to increase butyrate levels.

The advent of synbiotics and parabiotics has not developed to the point where I can recommend anything specific regarding these two categories. However, no matter what you plan to do to improve your gut microbiome, isn’t it a good idea to know its composition and whether you have enough diversity and SCFA production?

After reviewing all microbiome tests on the market, I have found only one test with enough data and recommendations to be considered accurate and “actionable.” It’s this one. If you haven’t received it yet, get it on the app and let me explain next.

Best microbiome test=microbiome labs (Yes, there’s an app for it!)

Most microbiome tests out there are, frankly, useless. The Injoy test is different – it integrates microbiome data with dietary, lifestyle, and symptomatic information through Patient-Reported Outcomes (PROs), painting a complete picture of gut health.

1 – In-Depth Longitudinal Analysis:

• They require three samples, not just a one-off snapshot (which invites uncertainty). This approach allows us to track changes over time, providing diagnostic-grade data even in a wellness test. They have published and patented this.
• Their database isn’t just extensive (35K+ samples); it’s specifically focused on people with validated GI issues (IBD/IBS). Meaning you are comparing yourself with a relevant dataset.

2 – Cutting-Edge AI, Gutchat:

• The app’s health check-ins are based on validated questionnaires used in clinical practice, ensuring their relevance.
• They’ve sifted through 50K+ scientific papers, distilled them, and ensured they’re clinically sound. This allows users to ask their GutChat any gut health question and receive personalized responses from a credible source.

3 – Actionable Recommendations:

• Because they capture more than just the microbiome, the reports can be shared with healthcare providers in a way no other report currently can. This enables patients to take action and practitioners to develop more personalized treatment plans.
• Injoy’s recommendations are accompanied by a ‘confidence score,’ indicating the level of evidence from publicly available research articles that support each recommendation.

Bottom line: We all know the field of microbiome testing is full of overhyped promises. Injoy is not about that. They provide tools that work based on solid science. You can find the Injoy app in your Apple or Google app store. Please use my discount code: DRKIM10. You’re welcome!

Conclusion

Hopefully, you have read this article with more knowledge of testing, evaluating, and improving your gut microbiome. You have learned the terminology of the available products to improve your gut health. You have learned what foods help and what foods “hurt.”

Importantly, you have learned what activities and products to utilize and which ones to avoid. If you feel overwhelmed, start cleaning up your diet from ultra-processed foods and getting an Injoy kit. At some point in the not-too-distant future, good medical practices will be based not just on patient history, physical exams, and bloodwork but also on the results of microbiome testing. As an important addendum, there are studies linking various herbal supplements with the production of SCFA in the gut, but rather than give you a huge laundry list, I feel that you will benefit from getting an Injoy kit and then supplementing scientifically with the help of their AI-powered GutChat.

Part 1: The toxins known as forever chemicals

In this article, we will examine the effects of the forever chemicals that cause immunotoxicity and consider immune system boosters that help deal with the fallout. These immune system boosters can protect against a wide range of health problems, but our focus in this article will be on protection from forever chemicals. First, let’s clarify what immunotoxicity actually is.

What Exactly is Immunotoxicity?

Immunotoxicity occurs when a toxic substance alters your immune system, either suppressing it or triggering an exaggerated response. Certain chemical compounds can sneak into your body and disrupt the way that your immune system is able to communicate and function.

As a reminder, before we get into the discussion of forever chemicals: be aware that many things are immunotoxic. Overly processed foods, heavy metals, chronic infections, and chronic inflammatory conditions are immunotoxic. This then causes detox organs to be overloaded, cognitive issues, hormonal problems, depression, and all sorts of other health problems that I’ll review and discuss in the second half of this article, where we focus on immune system boosting.

Common Immunotoxic “additives”

• Pesticides, herbicides, and fertilizers: These chemicals, and yes, some are indeed forever chemicals, are sprayed on many agricultural crops. Buying “organic only” goes a long way.
• Heavy metals: An accumulation of metals like lead, mercury, and nickel are just a few environmental toxins that can suppress your immune system.
• Pharmaceuticals: Medications like “steroids” (e.g., prednisone or Medrol), and all “biologics” are toxic to our immune systems.
• Cigarette smoke: Cigarette smoke – including secondhand smoke – contains a startling number of toxic chemicals.
• Benzene: This carcinogenic industrial chemical is frequently used in paint, detergents, dyes, and glues.
• Beauty and personal care products: Many conventional beauty and personal care products contain a long list of toxic chemicals. These chemicals can be absorbed through your skin and delivered directly into your bloodstream. I’ll get into how to choose wisely later on in this article.
• Indoor air pollution: When we seal up our windows and doors, polluted outdoor air can get trapped inside. But indoor pollution is compounded by pollutants that come from cleaning products, air fresheners, carpeting, furniture, and even paint on walls in the form of VOC’s.

Luckily, I have “just the thing” for you, along with a $500 discount. This amazing indoor air purifier takes care of VOCs from the products just mentioned and also kills viruses (COVID!), bacteria, and mold. Here’s where to get information and a huge discount on the Space Station’s air purification system technology (tailored to your home), not yet on the market.

• Contaminated water: Water is a great solvent, and it circulates throughout our world, potentially exposing us to a plethora of pollutants ranging from heavy metals to pharmaceuticals.
• Outdoor air pollution: Outdoor air pollution can come from natural sources like wildfires or dust storms as well as man-made sources like emissions from vehicles, chemical plant off-gassing, and industrial manufacturing processes.
• Toxin-laden food: Not only are many of the foods we eat drenched in toxic chemicals like pesticides and herbicides, but modern processing and packaging methods can introduce even more chemicals into our food supply.

Although several industrial chemicals and toxins have been identified as carcinogens and subsequently regulated, many more persist in the environment and continue to be used freely. The following are the biggest offenders and will be discussed in this order:

• BPA
• Phthalates
• Pesticides
• Dioxins and Polychlorinated Biphenyls (PCBs)
• Per- and Polyfluoroalkyl Substances (PFAS)
• Microplastics

Bisphenol A (BPA)

Bisphenol A, or BPA, is an additive used to make clear and hard polycarbonate plastics, as well as epoxy and thermal papers. BPA is one of the highest-volume chemicals produced each year, with roughly 6 billion pounds produced annually. It is traditionally found in many clear plastic bottles as well as in the lining of canned foods.

The estrogenic properties of bisphenol-A (BPA) have been associated with cardiovascular disease, obesity, and male sexual dysfunction. Since 2012, BPA has been banned in sippy cups and baby bottles, but there is some debate as to whether its replacements–bisphenol S (BPS) and bisphenol F (BPF)–are any safer; they appear to have similar hormonal effects as BPA.

BPS and BPF are analogs of BPA, not a solution to solve the harmful effects of BPA. The analogs can be found in daily-use products and are used in several industrial applications but are being phased out. Several well-done studies prove that BPA has a high carcinogenic potential, with known mechanisms to trigger breast, ovarian, prostate, cervical, and lung cancers. Therefore, it is clear that its analogs are also xenoestrogens since they can exert similar effects to BPA and cannot be considered viable alternatives for its replacement.

As with phthalates (coming up next), the majority of BPA ingestion is thought to be food-related. A large clinical study finds that 93% of American urine samples contain BPA.

To reduce your exposure, I recommend that you follow some easy steps. Buy only BPA-free canned food. Minimize your contact with so-called thermal papers such as receipts and tickets, or simply use hand sanitizer after handling.

Try to avoid polycarbonate plastics (identifiable with the recycling code number 7). Store leftovers in glass or stainless steel containers. If plastic must be used, opt for polycarbonate- and polyvinyl chloride–free plastics. Never reheat food (including the microwave) in plastic containers or wrapping.

Phthalates

Phthalates are chemicals used to make plastics soft and durable, as well as to bind fragrances. They are found in many common household items such as vinyl flooring and shower curtains; air fresheners, perfumes, candles, and other products that contain scents; and many personal care products such as moisturizers, nail polishes, and removers, hair sprays, and dry shampoo.

Phthalates are chemicals known to disrupt the hormone system, and they have been associated with abnormal sexual development in children as well as lower levels of testosterone in men. It is thought that most human exposures occur via inhalation, ingestion, and skin contact; however, fasting studies demonstrate that most exposure comes from food packaging materials.

Avoid polyvinyl chloride plastics (not yet FDA-banned!), which are identifiable by the recycling code number 3, as well as air fresheners and fragranced products which are chemically based rather than being scented with essential oils. A good source to check for problems is the Environmental Working Group website.

The EWG’s Skin Deep database is a great resource on phthalate-free personal care products and much more, so do check them out.

Pesticides

The United States uses an estimated 1 billion pounds of pesticides each year, including nearly 300 million pounds of glyphosate. The European Union has identified this chemical as a probable carcinogen, although the U.S. Environmental Protection Agency (EPA) has not yet reached this conclusion. The matter is currently being litigated, despite the fact that the makers of Round-up are repeatedly paying out lawsuits for cancers related to this environmental poison.

It has been found that over 90% of the US population have pesticides in their urine and blood, regardless of where they live. The exposures are (obviously) thought to be food-related.

A large European prospective cohort study found that people who ate organic foods had a lower risk for cancer. In addition, tests on the blood of members of this same group showed that relatively elevated levels of a pesticide known as beta-hexachlorocyclohexane (B-HCH) are associated with higher all-cause mortality.

In addition, exposure to DDE – a metabolite of DDT, a pesticide heavily used in the 1940s-1960s that still persists in the environment today – has been shown to increase the risk for Alzheimer ‘s-type dementia as well as overall cognitive decline.

Because chlorinated pesticides are often fat-soluble, they accumulate in animal products. Therefore, people consuming a vegetarian diet have been found to have lower levels of B-HCH than meat eaters. According to studies, consumers of produce should favor organic over conventional if possible. The EWG provides wonderful consumer resources to check for pesticides in produce.

Dioxins and Polychlorinated Biphenyls (PCBs)

Dioxins are byproducts of industrial practices and result from incineration, trash burning, and fires. PCBs (polychlorinated biphenyls), which are structurally related to dioxins, were previously found in products such as flame retardants and coolants. Dioxins and PCBs are often grouped under the umbrella term “persistent organic pollutants” because they break down slowly and remain in the environment even after emissions have been curbed.

The best-known dioxin, tetrachlorodibenzodioxin, is a known carcinogen. Dioxins have also been associated with a host of health implications in development, immunity, and reproductive systems. PCB exposure has also been linked to an increased risk of mortality from cardiovascular disease.

PCBs can also induce dysbiosis of the gut and dysregulate physiology of the gut and brain. Extensive research has been conducted on the importance of the microbiome in the developing brain and its possible links with autism spectrum disorder (ASD) and Alzheimer’s disease.

Since the 1980s, dioxin emissions have been reduced by 90 percent, and since 1979, the US Environmental Protection Agency (EPA) has banned the use of PCBs in industrial manufacturing. However, environmental dioxins and PCBs still enter the food chain and accumulate in fat.

The levels of dioxins and PCBs found in eggs, meat, dairy, and fish are approximately 5-10 times higher than they are in plant-based foods.

Therefore, you can easily limit your exposure by reducing your consumption of animal products, as well as being sure to remove the skin and fat from meats. Research has shown that farmed salmon is one of the most PCB-contaminated protein sources in the U.S. diet! We also know that farmed fish are sprayed with pesticides to kill lice. (Yuk!) So—obviously, my advice to you regarding fish is to eat “wild-caught.”

Per- and Polyfluoroalkyl Substances (PFAS)

PFAS is an acronym for perfluoroalkyl substances, a group of fluorinated compounds discovered in the 1930s. Their chemical composition includes a durable carbon-fluorine bond, giving them a persistence within the environment that has led to their being referred to as “the most forever” of “forever chemicals.”

Perfluorooctanoic acid (PFOA) was used by 3M to make Scotchgard for carpets and fabrics and by Dupont to make Teflon for nonstick pots and pans. Although PFOA was removed from nonstick cookware in 2013, PFAS — a family of thousands of synthetic compounds — remains common in fast-food packaging, water- and stain-repellent clothing, firefighting foam, and personal care products.

PFAS have been detected in the blood of 98% of Americans and in the rainwater of locations as far away as Antarctica! Even low levels of exposure are associated with an increased risk of cancer, hormonal disruptions, and liver disease. Since this is such a forever chemical that not only seems, but is ubiquitous, I’d like to review for you-the main sources for this toxic group of chemicals.

Cosmetics

Cosmetics and personal care products such as dental floss may contain PFAS even if they do not list them on their labels.

Researchers have found that personal care products such as cosmetics contain perfluoroalkyl substances (PFAS). A recent peer-reviewed study of 231 makeup and personal care samples, including lipstick, eyeliner, mascara and foundation, found that more than half of them contained organic fluorine–an indicator of PFAS. It’s also been found in some types of dental floss designed to glide more easily between teeth.

Some makeup manufacturers add PFAS intentionally to make cosmetics last longer and spread easily. In other cases, PFAS is introduced into cosmetics through cross-contamination, such as machinery used in manufacturing or plastic packaging that contains PFAS. A recent lawsuit alleges that cosmetics maker CoverGirl was selling products labeled as “sustainable” despite the presence of PFAS in them.

Food

It’s not the food, it’s the packaging. Food packaging, such as takeout containers and wrappers, pizza boxes, french fry containers, hamburger wrappers, and microwave popcorn bags can all be sources of PFAS contamination in food.

Although some compostable bowls are marketed as being safe for use with hot foods, they may still contain PFAS. The Food and Drug Administration has not restricted the use of PFAS in food packaging; instead it has left it up to states and the public to protect consumers from exposure to these chemicals.

Drinking water

According to an Environmental Working Group report, up to 200 million Americans may be exposed to PFAS in their drinking water. The EPA announced in March 2021 that they will regulate PFAS in drinking water, but the regulations have not yet been finalized. Currently, it is up to individual states to test for its presence in the water. The EWG has compiled a map of all known PFAS contamination sites.

However, it is important to note that PFAS contamination in the water supply is widespread. According to research conducted by the Environmental Working Group, contamination from PFAS has been found in drinking water systems across all 50 states and two U.S. territories, Guam and Puerto Rico.

Bottled water constitutes another emerging risk of PFAS contamination. In 2021, Johns Hopkins researchers found 39 out of 100 bottled waters tested contained PFAS. The Food and Drug Administration has not set PFAS limits for bottled water; however, it is currently considering regulatory action.

Home goods including clothing

New research suggests that people may absorb PFAS through their skin from stain-resistant carpeting, water-repellent textiles and other products. Environmental testing has found indicators of PFAS in everything from athletic clothing to period underwear to stain-resistant clothing.

Firefighting foams

Firefighting foams used on military bases, airports, and forest fires are a big source of PFAS contamination, as this all makes its way to our aquifers.

Wastewater and landfills

Waste from landfills washes PFAS into waterways and soil.

When products such as carpet, clothing, bedding, and food packaging are discarded in landfills, they can release perfluoroalkyl substances (PFAS) into the environment. Rainwater moves these chemicals into nearby rivers and lakes where they create a toxic waste that infiltrates soil and groundwater sources. Typical landfill waste treatment systems do not remove PFAS. Bottom of Form

What can you do to avoid PFAS?

The majority of U.S. states are considering more than 200 bills that would ban or restrict PFAS, including in clothing, personal care products, and food packaging. The U.S. House and Senate are working on their own bills, as well. Until then, you need to protect yourself.

Europe is moving much faster, as they seem to always do when it comes to environmental and consumer protections. The European Union is considering a ban on thousands of PFAS chemicals, other than “essential uses.” A final agreement should come by 2025.

Recall that non-stick cookware is another way that PFAS enters both our food and air. Non-stick cookware still contains alternatives that may be harmful to our health. Labels claiming PFOA-free don’t necessarily mean that the cookware is safe. Look for a PFAS-free label as your safest choice. Instead, use stainless steel, cast iron, glass, or ceramic cookware instead of non-stick pots and pans.

Here are other important ways to limit your PFAS exposure.

• Limit the use of clothing and other products advertised as “waterproof,” “water-resistant,” or “stain-resistant,” as well as anti-fog eyeglass wipes and sprays.
• It bears repeating: Cook with stainless steel, glass, cast iron, or ceramic cookware instead of non-stick options.
• Buy BPI-certified compostable packaging, and ask restaurant servers about the containers they use.
• Avoid food packaged in greaseproof bags or containers. Instead, use your own glass containers for takeout and leftovers. Encourage restaurant owners to offer takeout packaging made from materials that do not leach PFAS into food. Avoid microwave popcorn from PFAS-treated bags. Pop your corn the old-fashioned way- it’s healthier and tastier!
• Read personal care product labeling carefully and avoid those with “polyfluor-,” “PTFE,” “perfluor-,” or Teflon on the label.
• Avoid water and stain-repellent carpeting, upholstery, curtains, tablecloths, napkins and other household textiles.
• In the wake of recent findings about the health risks associated with PFAS, learn if your water source has been tested for these chemicals. If it contains PFAS or hasn’t been tested, a water filter is a good purchase. However, be aware that not all filters are equally effective; a 2020 Duke University study found that reverse osmosis filters and two-stage filters performed best at eliminating PFAS.
• If you drink bottled water, purchase water labeled “purified” rather than spring water.

Microplastics

“Microplastics” is an informal term used to describe small pieces of plastic that have broken down or microbeads from household or personal care products, measuring less than 5 mm in length

Plastic waste is accumulating at an alarming rate. By 2050, it is estimated that there will be more plastic than fish in the oceans. (I know!) This could lead to hundreds of thousands of tons of microplastics and trillions of these particles in the seas. A recent study demonstrated that microplastics were present in the bloodstream in the majority of 22 otherwise healthy participants.

Since the 1950s, studies have shown that exposure to plastics can promote tumorigenesis in animal models, and in vitro experiments have demonstrated that microplastics are toxic at the cellular level. However, it’s not clear whether the plastic itself is toxic or if it simply serves as a carrier for other environmental toxins that accumulate in the body.

Microplastics have been widely detected in fish and in fact, just about all seafood, as well as other products like bottled water, beer, honey, and tap water. Although there are no formal advisories on fish consumption to avoid exposure to microplastics at the moment, the Environmental Working Group recommends limiting seafood intake due to concerns over contamination with heavy metals and other pollutants.

Despite mounting pressure for a ban on microbeads in personal care products, the industry has not yet agreed to phase out the production of these synthetic particles. Until such bans are put in place, Here are some things you can do to protect yourself.

• Avoid single-use plastics
• Use cloth-based reusable tote bags for grocery shopping rather than plastic bags
• Use loose-leaf tea or paper tea bags rather than mesh-based alternatives.
• Check out the EWG website to find personal care products that are microbead-free.

I personally am committed to helping reduce and eventually eliminate plastics from our oceans. You can join me in supporting a great company leading the way called 4Ocean. And now that you have read about all of this pretty nasty stuff, let me help you boost your immune system to counteract your incidental exposures.

Part 2: Immune health and immunotoxicity counter-measures

(Boost Immune System function to counter Immunotoxicity)

To re-cap what these toxins discussed above can do: oxidative stress, inflammation, microbiome disruption, and even “brain damage.” We can use detox products for some of these things, but it’s always best to avoid them where possible. And remember, we don’t have a mechanism to detox from microplastics yet. Therefore, we need to strengthen our immune systems and help with immunotoxicity, viral exposures, and more. Let’s start with the easiest thing to change-your diet. First, I’ll list the topics I’ll cover.

• Diet
• Reduction of Inflammation
• Reduction of oxidative stress
• Reduction of glycation
• Sleep
• Stress management
• Microbiome health
• Hot/cold therapy
• Supplements (links supplied in text below)

Basic Lifestyle Strategies for Immunotoxicity

Diet: I advise all patients to eat an anti-inflammatory diet to help optimize their health.  A simple way to do this is to eliminate highly processed foods, watch your sugar and starchy carb intake, and be careful with gut-damaging lectins found in grains, beans, nightshade vegetables, and low-fat dairy products.

These foods can lead to leaky gut syndrome, which means that your intestinal lining becomes damaged and lets bacteria into your bloodstream. It also leads to disruption and disorder of your microbiome.

Eventually, if you don’t eat an anti-inflammatory diet and instead eat ultra-processed and junk food, you’ll eventually end up with more than immunotoxicity. You’ll end up with systemic inflammation, one of the root causes of all diseases. I’ll get into a more in-depth discussion of inflammation in the next section.

Garlic, horseradish, and wasabi are immune-boosting foods. Garlic is anti-viral and is sometimes used as a supplement; however, this article will not cover its use as such. It’s also essential to eat to support the health of your microbiome.

Microbiome health translates to much better immune system health. I’ll cover this topic in a separate section further on in this discussion.

Vitamin C, vitamin E, and phytochemicals such as carotenoids and polyphenols are dietary constituents with exceptionally high antioxidant and anti-inflammatory capacity. If you don’t consume enough of these compounds, supplement your diet with vitamins or organic vegetable powders like this. Inflammation is the topic to be discussed next.

Inflammation

Acute inflammation is the body’s response to a physical injury. If you have a splinter in your finger and leave it alone, the area will turn red and get puffy. This is because your immune system is rushing to fight off any viruses or bacteria that might have gotten into the injured area. The signs of acute inflammation are heat, redness, swelling, and pain. All of these will dissipate if you allow the body to work through its natural healing process, unencumbered by further injury or infection.

However, if you keep poking yourself in the same spot, the re-injury will keep levels of inflammation elevated and thus, harmful.

That’s exactly what’s happening with chronic internal inflammation, but you can’t  “feel it.”  The inflammatory response is a normal and essential part of the body’s immune system. However, when inflammation becomes chronic, it can cause problems such as lethargy or pain.

As you’ll see, some of the major causes of chronic inflammation include diet, stress levels, and environmental factors like pollution. The following are the major causes of chronic inflammation.

Unhealthy diets:  I know I’ve said this repeatedly, but it’s worth repeating: Eating a healthy diet is not just important; it’s essential to be healthy. Processed sugar and other foods that cause inflammation include sugary foods and beverages, high-processed carbohydrates, high-industrial fat and seed oils, high-gluten foods, and all overly processed and fast foods.

This is the typical U.S. diet, which is why our population is so inflamed! Further, this poor eating pattern also causes oxidative stress, which worsens inflammation. I’ll move on to that next topic when we’re done reviewing inflammation.”

Chronic stress: Life is stressful, indeed. Everything from work to relationships to finances can add up and become too much for us to handle, which can lead to health problems. When this happens, your body has a physiological inflammatory response that includes raising cortisol levels in your blood. Many people eat as a coping mechanism for stress; this is unhealthy because it leads to weight gain; the next topic.

Your weight:  Obesity and being overweight (along with 75% of Americans!) increase inflammation risk. Obese and overweight men and women have higher levels of inflammatory blood markers than men and women of the same age who are not obese or overweight.

Inflammation drops when people lose weight, according to many clinical studies. Luckily, there are now more weight loss tools in our medical kits to make losing weight easier than ever before.

Excessive omega-6 intake: Omega-6 fats form the precursors for inflammatory eicosanoids, which are also an integral part of the inflammatory response. High omega-6 status (especially when combined with poor omega-3 status) means excessive production of inflammatory eicosanoids and a lopsided inflammatory response to normal stimuli. Cut down on your omega-6 intake by reducing your intake of meat and increasing your intake of omega-3 rich seafood.

Insufficient omega-3 intake: Omega-3 fatty acids are precursors for anti-inflammatory eicosanoids, which are integral to the inflammatory process. A poor omega-3 status indicates inadequate production of anti-inflammatory eicosanoids and an unbalanced inflammatory response to normal stimuli. It’s easy to establish good blood levels: eat fish rich in omega-3s such as salmon or sardines, or take supplements containing these essential fatty acids.

Lack of sleep: We know we need it but we don’t do it! Sleep deprivation leads to an increase in blood inflammatory markers. According to the National Sleep Foundation, we either go to bed too late, wake up too early, or use too many electronics late at night-disrupting the sleep quality we get. I’ll go more in-depth into the topic of sleep further on in this article.

Toxins: Heavy metals, biotoxins such as Blue-green algae, Lyme, and mold mycotoxins can cause chronic inflammation. Biotoxins are notorious for causing immunotoxicity. This is why we Functional docs focus on how to boost the immune systems of our CIRS patients.

Lack of movement: Most of us lead far too sedentary lives, which can cause low-grade systemic inflammation. We don’t usually need to walk to get to our destinations; we take escalators and elevators. We sit for hours on end, then don’t make time for regular exercise. If this describes you, make time to move more. Get up on your feet for two to three minutes each hour you’re sitting; better yet, do some push-ups, burpees, or jumping jacks.

Poor recovery and Overtraining: On the other hand, some people move too much, with too little rest and recovery. Overtraining is a form of chronic inflammation. Not just elite athletes, but even casual 10K runners and others who train frequently can overtrain. This degree of over-exertion can cause inflammation, as well as elevated cortisol levels, and disrupted sleep. Now that we’ve gone through some ways not to exercise, let’s discuss how to exercise properly.

Exercise: A large body of research in humans and animals has demonstrated that exercise has a profoundly beneficial impact on immune system function. There is broad agreement that regular, moderate-intensity physical activity (e.g., brisk walking, vacuuming, dancing, doubles tennis, or shooting hoops) for 30 to 45 minutes per day is beneficial for optimal immune function. This correlation has been demonstrated particularly well in older adults and people with chronic diseases.

Exercise is also known to improve intestinal flora composition, so keep this in mind when reading about the microbiome. Some studies have shown that activity is associated with increased microbiome biodiversity and beneficial metabolic functions. Gut microbiota (and all immune functioning) can influence the pathophysiology of distant organs, including skeletal muscle.

The gut-muscle axis regulates muscle protein deposition, muscle function, and insulin sensitivity. This gut-muscle axis may involve maintaining skeletal muscle with aging, which could contribute to improved blood sugar levels and insulin sensitivity.

You may not know that fasting blood sugars, which are not labeled diabetic or even pre-diabetic, will cause cellular glycation, something you might not have heard of. I’ll cover that after we talk about something almost everyone suffers from without knowing it; called oxidative stress.

Oxidative stress

What is it? Oxidative stress occurs when there is an imbalance between the production of free radicals and your body’s ability to counteract their harmful effects through neutralization by antioxidants. Oxidative stress can also occur when you have too many free radicals in relation to your body’s supply of antioxidants. Just as an apple not coated with lemon juice (an antioxidant) turns brown when exposed to air, our cells can “rust” when we have oxidative stress–caused by unopposed free radicals.

Free radicals are unstable molecules that can damage cells or create abnormal ones. Free radicals steal electrons from cell components such as DNA, proteins or lipids to become stabilized. The process destabilizes the cell component molecules and triggers a large chain of free radical reactions.

A proper diet can reverse this unhealthy but common condition. Eat five to twelve servings of organic fruits and vegetables daily or supplement with a high-antioxidant multi-vitamin such as this one. Functional doctors often measure patient’s levels of oxidative stress with a Raman spectroscopy unit, although other methods are available. If you’re aware of this phenomenon, you can prevent it! Here’s what to watch out for and adjust your intake of antioxidants accordingly:

What Causes Free Radicals? Free radicals are a byproduct of energy consumption in our mitochondria, the factories producing energy in each of our cells; especially in the brain, heart, and muscles. When we exercise, our respiratory and heart rates increase, creating more free radicals that need to be quenched by good levels of antioxidants.

However, the free radicals that deplete our antioxidant supply are environmental (for example, cigarette smoke) and result from our lifestyles (for example, eating junk food). Here are the big offenders:

Consuming a “bad” diet: As referenced in the “diet section,” it’s essential to eat as if your health depends on it (because it does!). Eating too many calories, sugars, refined or starchy carbohydrates, processed and fast foods, and lectins do indeed cause oxidative stress and inflammation. Unhealthy foods force our mitochondria to work harder and release more “exhaust,” creating higher levels of free radicals burning toxic foods for energy. Speaking of diet, let’s look at two other popular lifestyle choices.

Eating charcoal-broiled foods: These foods-not just meats-contain polycyclic aromatic hydrocarbons, which contribute to oxidative stress. And yes, char-broiled meats are indeed carcinogenic. Now, let’s move on to some other lifestyle factors in oxidative stress levels.

Excessive alcohol: Alcohol consumption increases your levels of inflammatory cytokines-inflammatory molecules linked to oxidative stress.

Exposure to tobacco smoke: Imagine this-tobacco smoke contains more than 4,000 toxic chemicals that can cause oxidative stress. One cigarette produces millions and millions of free radicals. How’s that for incentive to stop? We who use Raman Spec scanners have reviewed the data, which shows that smokers score in the lowest range, equivalent to those with active cancer cases!

Exposure to air pollutants: Air pollution, industrial pollution, and even airborne allergens increase oxidative stress.

Lack of sleep: Sleep deprivation increases oxidative stress through a complex series of chemical reactions. Yes, I’ll discuss sleep in more depth, too.

Excessive psychological stress: The stress hormone cortisol increases inflammation, which further increases free radical production. It also causes a leaky gut, an asymptomatic cause of chronic inflammation, and the root cause of autoimmune disease.

Exercising too much: Exercise is crucial for optimal health. However, too much of it can increase oxidative stress in our bodies. As a rule of thumb, more than 60 minutes per day is considered excessive. Therefore, all elite athletes need to supplement adequately.

Chronic infections: Hidden (asymptomatic) infections will contribute to oxidative stress. One example is a biofilm-secreting sinus organism called MARCoNS, found in people with mold and mycotoxin illness. Dental infections are another excellent example. If you have root canals, you will not feel apical abscesses-so get a panoramic X-ray annually.

Exposure to fungal toxins: Environmental molds (like those in basements and bathrooms) and internal fungi (such as those colonizing your gut in excess) can produce mycotoxins that increase oxidative stress.

Ionizing radiation and EMFs: Exposure to X-rays, excessive sun, radon, cellphones, hairdryers, airplanes, electric blankets, and heating pads can all contribute to oxidative stress.

Inadequate GI-tract detoxification: I saved this one for last because it is especially Germain to this topic of immunotoxicity due to all of the forever chemicals discussed earlier.

When the liver is overwhelmed by toxins from food (e.g. fructose) or the environment (e.g. forever chemicals), it becomes inflamed and produces more free radicals.

Now that you know what causes this problem, you can combat it by including antioxidant-rich foods, smoothies, and supplements in your diet.

Next, let’s look at the lesser-known phenomenon that is just as harmful to the immune system called “glycation.”

Glycation 

 Cellular glycation (also known as AGEs or advanced glycation end-products) is the stiffening and aging of all cells. It occurs at fasting blood sugar levels somewhere in the range of 75-89 ng/dL. Research continues to lower the bar at which we set the definitions of diabetes, glucose intolerance, and cellular glycation. It is directly related to the amount of body fat an individual carries.

High blood sugar levels are associated with immune system depression, increased risk of dementia and heart disease, cellular aging, and even cancer. Cancer is an immune-mediated disease that is largely preventable through diet and lifestyle modifications.

Studies have shown that certain cancers respond more effectively to treatment when blood sugar levels are lower, which can be achieved through ketosis or medication. Research also suggests that better blood glucose control leads to better sleep. Here’s what you should know about sleep:

Sleep

Studies show that sleep loss can affect different parts of the immune system, leading to the development of a wide variety of disorders. Sleep deprivation can affect the thymus gland, bone marrow, and lymph nodes, as well as increasing susceptibility to infections and diseases. Here are a few interesting studies to consider before giving you my recommendations for adequate, restful sleep.

Researchers restricted the sleep of study group participants to 4 hours for only one night. The average NK cell activity of those who got 4 hours of sleep was 72% lower than that of those who slept for a full night.

Genetic mutations have been identified in some people who naturally sleep six or fewer hours a day and appear healthy and functional. While it is not yet known how common these mutations are, it may explain why some individuals can get by on less sleep than others.

Many people who say they do not need much sleep are just pushing themselves to sleep less. As a consequence, they then struggle to stay awake and tend to function sub-optimally during the daytime. They are putting themselves at risk for obesity and chronic illness.

What’s your ideal length of sleep? The average sleep times across 5 to 7 relaxed days can be used to determine an individual’s ideal sleeping time. Record the length of time you sleep during a 7-10 day vacation, when you are awakening spontaneously and going to bed only when you are tired.

During this time, limit your caffeine intake to no more than two cups of regular coffee a day (about 200 mg of caffeine). A relaxing vacation can be mimicked by doing an activity to reduce your stress levels at least a couple of times per day. Stress management is not simply about feeling better; it’s also a matter of your health. Now, more about proper stress management.

Stress Management

Stress depresses the immune system in several ways. First, sustained high levels of cortisol–a hormone produced in response to stress–causes gut hyper-permeability (i.e., “leaky gut”), which causes inflammation and subsequent disease. Cortisol also interferes with T-cell production and function, making your body more susceptible to pathogens; this is why you get more head colds when you’re under pressure. Finally, cortisol kills brain cells (neurons), further interrupting the gut-brain axis crucial for proper immune function.

The best way to manage your stress is to incorporate movement and exercise into your day. You can take a walk, dance, or sing for a few minutes every couple of hours. Exercise should be something you will do, not something you’d like to envision yourself doing. Deep breathing, meditation and singing are great habits to cultivate. Some people also benefit from liposomal GABA supplements and peptides with anti-anxiety benefits. The latest findings show that everyone needs more GABA and less cortisol so getting a vagal nerve stimulator to use for 2 minutes twice daily is a must.

I have touched on the importance of gut health, but now I’ll go deeper into that topic by discussing the microbiome:

Microbiome Health 

The human microbiome is a collection of between 10 and 100 trillion genetically unique (mostly) bacterial cells that live in our guts. The health of our gut microbiota influences our immune system, which is also (primarily) located in our guts. Unhealthy gut bacteria thrive on the things that create inflammation in our body, including refined carbs, sugar, unhealthy fats and processed foods. Conversely, the healthy foods and activities discussed previously all contribute to a healthy microbiome. To augment all of these healthy habits, we can add prebiotic fiber and probiotics into the mix. First of all, we need to eat good prebiotic foods as “fertilizers” for probiotics.

Prebiotic fiber 

Prebiotic fiber is non-digestible carbohydrates found in fibrous foods that assist in the growth of healthy bacteria in the gut. White and red onions, as well as asparagus, chicory, garlic, unripe bananas, and Jerusalem artichokes, are great “gut bug food” because they help healthy gut bacteria produce substances such as butyrate. Butyrate protects the lining of the gut and has anti-inflammatory properties in the gut. If you want to ingest more good gut bug food, you can supplement with this. And when your gut garden is ready with its prebiotic fertilizer, you can add back some good gut bugs. Here’s how.

Probiotics: High-quality kefir or yogurt (home-made) and fermented foods such as sauerkraut or kimchi can supply a fair amount of good bacteria, but I generally supplement everyone to ensure they get enough probiotics to augment immune function and combat immunotoxicity. We see some good evidence that sporulating probiotics are more immune-supporting and microbiome-diversity-supporting than the strains of probiotics we used to recommend only recently.

I currently have all patients use a microbiome-augmenting app to help optimize their microbiome with foods, activities, and supplements, including Akkermansia, if they have an insufficient amount in their gut or if they have a gastrointestinal issue.

Immune enhancement with hot and cold therapy

Heat shock proteins (HSP’s) are proteins that form in the body when it is subjected to cold temperatures or high heat, such as when you immerse your body in ice-cold water or a tub or sauna at 104 degrees F. These proteins help strengthen the immune system and aid in various positive immune modulation functions.

Cold therapy can lower cortisol levels when practiced repeatedly. As a reminder, reducing your cortisol level will help preserve the integrity of your gut lining and enhance the 70% portion of your immune system that resides there. In addition, studies show that cold therapy improves anti-tumor white blood cell activity as well as NK (natural killer T cell) activity.

HSP’s, which are induced by saunas (conventional and FIR), trigger positive effects in the immune system regarding infections, autoimmune disease, and even cancer therapy. For this article, suffice it to say that hot and cold treatments are great for your immune system health. Now let’s discuss immune booster supplements.

Supplements to help get rid of Immunotoxicity

(Links are to DFH-to receive my group discount, use my practitioner code:KimCrawford)

Vitamin D

You need vitamin D for an optimally functioning immune system. I actually believe most Americans are aware of this fact due to the COVID crisis.

Vitamin D inhibits harmful immune pathways and promotes beneficial ones, positively impacting the composition of the microbiome and enforcing the gut barrier. Clinical studies show low levels of vitamin D are associated with increased risk of coronavirus infection; previous studies indicate that low levels of vitamin D are linked to more “flu” in general.

Vitamin D dosing: You need a level of 75-80 ng/dL, which requires most of us (sun or no sun) to take doses of 5000-10,000 IU per day.

Vitamin C and Zinc 

During infection, the concentration of vitamin C in the blood plasma and white blood cells quickly declines. Likewise, zinc deficiency impairs cellular mediators of innate immunity, such as natural killer cell activity, phagocytosis of infectious organisms, and the generation of an oxidative burst.

Supplementation with vitamin C and zinc has been shown to improve various components of the immune system, including natural killer cell activity, migration of white blood cells (chemotaxis), the appropriate and proper proliferation of specific white cells called lymphocytes, and overall antimicrobial activity.

Vitamin C and zinc contribute to the antioxidant status of cells, protecting them against reactive oxygen species. Quercetin, a flavonoid found in fruits and vegetables that has antioxidant properties similar to those of vitamin C, can also benefit specific components of the immune system when supplemented along with zinc.

Both zinc and vitamin C are essential nutrients that play important roles in immune function and help attenuate the risk of infection when taken as dietary supplements. Research shows they reduce the risk, severity, and duration of many infectious diseases. When taking long-term zinc supplementation, make sure you are ingesting enough dietary or supplemental copper.

Zinc dosing: Ideal dosing is about 25-60 mg per day. I take two of these each evening at bedtime, as it can cause nausea when taken during the day.

Vitamin C dosing: Liposomal preparations can be taken in doses up to 3 grams (usually 1 TBSP) per dose without causing gastrointestinal distress. Multiple clinical studies use 1.5 grams 4 times per day (for a total of 6 grams), but this tends to be too inconvenient for most patients of mine. Therefore, I generally recommend 1 TBSP 2x/day during “flu season,” including during this year’s “tripledemic.”  And yes, for those wondering, quercetin is up next.

Quercetin

Quercetin reportedly exerts potent anti-inflammatory effects by inhibiting the production of cytokines, reducing the expression of cyclooxygenase and lipoxygenase enzymes, and maintaining the stability of mast cells, cells responsible for allergies.

In addition, it can reduce the production of pro-inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6. And there’s more!

Quercetin has been shown to exhibit anti-inflammatory, antioxidant, neuroprotective, and anti-allergic activities. It is often combined with nettles for a more potent “concoction.”

Quercetin dosing: Dosing to suppress inflammatory markers of IL-6 and TNF-alpha are recommended.

A good prophylactic dose of this super immune booster is 500-600 mg per day, which is then doubled for infections.

Multivitamin supplements

Over 10,000 companies sell vitamin supplements. You want to choose GMP-certified and NSF-certified multivitamins that contain antioxidants such as carotenoids (forms of vitamin A), iodine, and selenium. Good MVI supplements also contain polyphenols, which you may recall are needed to “fertilize” your microbiome.

Reishi mushroom extract

Mushrooms contain polysaccharides called beta-glucans, which boost the immune system by enhancing the action of macrophages (a type of white blood cell that kills foreign invaders), activating the “complement” component of the immune system, and boosting natural killer (NK) cell function. The most potent immune-boosting mushroom is Ganoderma lucidum or reishi mushrooms. They are not especially tasty but are used to formulate potent immune-enhancing supplements.

Reishi dosing: Make sure to find a good brand that uses cracked reishi spores to make the powder put in capsules, and take 1000 mg per day.

Melatonin

Melatonin is a potent anti-inflammatory and antioxidant–not simply a sleep aid. The fact that it helps establish our circadian rhythm is a boon to our immune system, as it helps limit tissue damage during an infection. Melatonin does much more than this, but for this article, I’ll state that it’s good for your immune system and will indeed help you sleep more soundly. There’s a good reason that the “expanded” use of melatonin won its scientists the  2017 Nobel Prize in Physiology or Medicine.

Melatonin dosing: Studies have shown that the maximal efficacy (to work up to slowly) occurs at 10-20 mg per night, which would be two to three of these each night.

Nitric Oxide

Nitric oxide (NO) is bactericidal, meaning that it can act directly as an anti-microbial compound that destroys bacteria. Certain families of immune cells called dendritic cells produce NO, contributing to the resolution of both viral and bacterial infections.

The inference in many studies is that increased NO levels contribute to a more rapid and efficient clearing of these pathogens. It’s good for your vasculature and heart – is an immune booster, so it absolutely is on my list.

NO dosing: Find a product like this one with an equal amount of l-arginine and l-citrulline such that you take 1.5 grams of each 2x/day. Alternatively, you can eat a serving of both arugula and beets daily.

DHEA

The hormone DHEA (dehydroepiandrosterone) is known to positively affect adrenal function, lowering cortisol levels. It has verifiable anti-inflammatory properties and likely supports the immune system via several complex hormonal pathways.

DHEA dosing: Important note: Women with PCOS or a history of breast cancer or men with a history of prostate cancer must take the keto form of this hormone, if at all since the keto form has not been proven to be an immune booster. For dosing of regular DHEA, men should take a daily dose of 50 mg; women-25 mg.

The Research Continues

Most of our organ systems function better when we restore both male hormones and female hormones to youthful levels. This includes identifying premenopausal women with a simple but immune-suppressing low progesterone level.

The alpha-thymosin one peptide is so effective at boosting the immune system (increased natural killer cell activity, increased antibody response to viruses, increased T cell function, and more) that the FDA pulled it off the market from compounding pharmacies so that they could give it to “Big Pharma” to turn into a pricey drug. (Yes, I know!) However, research is ongoing with other peptides.

But it’s not all about peptides. A number of other varieties of mushrooms are currently being investigated for their immune-enhancing properties, including lion’s mane mushrooms. Other medications, such as methylene blue look promising. And the most exciting research involves the use of stem cells and exosomes.

Conclusion

I’m aware that this article contains a great deal of information about not just forever chemicals but of ways you can boost your immune system. Obviously, this immune boosting is helpful “no matter what.” Regarding the chemicals, five big steps would be: cookware, water filtration, indoor air purification, avoidance of fast foods for a plethora of reasons, and consultation with the EWG website to check your personal goods, cosmetics, and so on. Until our government steps it up regarding consumer protections, we need to look out for ourselves.

Introduction to the Vagus Nerve

The vagus nerve is a significant component of the parasympathetic nervous system and plays many roles in the body. It is increasingly recognized as an essential driver of gut-brain axis communication, which may be involved in the pathogenesis of several disorders. This article reviews how this ” long and wandering” nerve works and how its activity can affect health. And yes, I’ll get to the discussion about vagus nerve stimulators after I get through the “why.”

I’ll cover everything from vagus nerve symptoms (from insufficient activity) to discussing how to augment vagal tone to going into actual vagus nerve stimulation. Can’t wait? Do you know why you need VNS but don’t know which device works best? It’s this one. And you can get a nice discount using my code (feel free!): DrKim25. And yes, as you’ll learn, this is the best vagus nerve stimulator currently available without surgery and/or a prescription. First, let me cover the following topics.

• Basic anatomy and function of the vagus nerve
• The Autonomic nervous system
• Specific roles of the vagus nerve in our bodies
• Heart rate variability
• Immune and inflammatory mediation
• The gut-brain-microbiome connection via the vagus
• The vagal connection to chronic diseases
• Oxidative stress, inflammation, sympathetic overdrive, and the vagus nerve
• Methods of improving your vagal tone
• What you came for: VNS without the work: using a vagus nerve stimulator

The Basic Anatomy and Function of the Vagus Nerve

The vagus nerve, also known as cranial nerve X (10), is the largest nerve in your body. It runs from your brain stem through your neck, chest, and abdomen. The nerve is nicknamed “the Wanderer” (Latin for vagus) because it wanders so far through different organs.

The vagus is a bundle of nerves connecting the brain to several vital organs, including the heart and stomach. It helps regulate several bodily functions and brings stress under control. When its tone (or activity level) is dampened, it impacts vast activities in your body that lead to a decline in health. Supporting and protecting this great “Wanderer” is vital for optimal health. I’ll get into how to do that later in this article.

The vagus nerve is a nerve that maintains homeostasis of the neuro-endocrine-immune systems and controls the parasympathetic (rest, relax, repair) autonomic nervous system. The following section will cover more specifics of the entire autonomic nervous system.

The vagus nerve originates in your brainstem as a pair of nerves, one traveling down the left side of your neck and the other down the right. It then travels down into the trunk of your body, where it innervates (stimulates) your throat and esophagus (the tube that carries food from your mouth to your stomach).

It then wanders downward to innervate your heart (the organ that pumps blood throughout the body), lungs (organs that extract oxygen from the air), liver (the inner organ that removes toxins from the blood), and spleen (the organ that produces immune cells).

Next, it stimulates your pancreas (the organ that produces insulin), stomach (holding chamber for food), gallbladder (small organ next to the liver that stores bile), urinary bladder (vessel holding urine before disposal) and kidneys (the inner organ that filters excess water from blood).

Its last stop is in your small intestine (the tube connecting the stomach to the large intestine) and the first part of the colon (the large intestinal tube storing waste before disposal).

This master nerve is a two-way communication system that relays information from your brain to your internal organs and back again. This nerve accounts for about 80 percent of the fibers that carry information upward to the brain and 20 percent of those that carry information downward from the brain to your internal organs.

The vagus nerve helps control heartbeat, heart rate, and respiration. It affects blood pressure by modulating vasodilation. It is a vital part of the parasympathetic nervous system (PSNS) and other nerves that support “rest-and-digest” activities such as digestion, sexual arousal, and reproduction. It helps balance against sympathetic (fight, flight, stress) nervous system tone.

Consequently, it buffers against stress-related hormones and inflammatory compounds. Now, I’d like to give you a general idea of the autonomic nervous system.

How Does the Autonomic Nervous System Work?

To understand the workings of the vagus nerve, it is first essential to know how the entire autonomic nervous system works. The ANS is comprised of two sides that usually work in opposition. (We are not including the recently described enteric system in this article).

These two sides are the sympathetic and the parasympathetic arms. The autonomic features of the stress response are mediated by the sympathetic arm, which is sometimes called the fight, flight, or freeze response due to the bodily changes needed to enable you to defend yourself physically, run away from danger, or even freeze in total panic.

The other arm of the ANS, the parasympathetic, is the rest, digest, relax, and restore mode. If that sounds more fun, it is in the sense that it’s what is dominant when relaxing on a couch, meditating in your favorite chair, or socializing with friends.

In this state, your body slows down, heals, and returns to homeostasis. Your organs, including your brain, stick to their maintenance schedules, and everything feels fine.

It is often helpful to think of the sympathetic and parasympathetic nervous systems as gears in a car. The sympathetic gear is responsible for speeding up a car when it is in danger or when the driver wants to overtake, but it also leads to wear and tear over time if used too much. The parasympathetic gear keeps the car running smoothly by slowing down when necessary and stopping other parts from overworking themselves.

In response to danger, the sympathetic arm of the autonomic nervous system activates the body’s inflammatory response–a process that usually causes immune cells to produce cytokines and other chemicals that trigger inflammation. Clinical studies have shown that stress and other stimuli can cause flare-ups in autoimmune diseases, accelerate neurodegenerative disorders, exacerbate atherosclerotic plaque formation, worsen asthma symptoms, and even lead to cancer recurrences.

The many roles of the Vagus Nerve

The vagus nerve stimulates organs throughout the body. Scientific research has focused on its connection to the gut, brain, and immune system–areas where vagus nerve stimulation has been shown to provide benefits. We’ll discuss those three areas in detail, but first, let’s look at some other systems that can be affected by low vagus nerve activity, which produces what some people call vagus nerve symptoms.

Mouth and Ears

The vagus nerve helps control taste and saliva in the tongue, tears in the eyes, and hearing in the ear. Scientists are studying whether ear stimulation can activate the vagus nerve while affecting tinnitus. Thus far, auricular vagal stimulators are considerably less effective than externally applied stimulating devices.

Kidney and Bladder

Some research suggests that the vagus nerve promotes general kidney function by helping to control blood glucose and increasing blood flow, which improves blood filtration. Vagus activation likely also releases dopamine in the kidneys, which helps excrete sodium and, therefore, lower blood pressure. However, the mechanism is not fully clear in humans; more studies are needed.

The vagus nerve innervates the bladder. A potential side effect of its stimulation is urinary retention. On the other hand, less vagus stimulation may make people urinate more frequently.

Although there are no good clinical studies on this topic, some practitioners hypothesize that their patients who complain about frequent urination may have a vagus nerve issue in combination with other factors such as low vasopressin (ADH) and low aldosterone as well as high cortisol.

Spleen

In the spleen, vagal activation can reduce inflammation. It is thought that vagal activation may affect various organs by releasing acetylcholine. However, when it activates in the spleen, its response is believed to be via reduced inflammatory cytokine production.

Liver, Pancreas, and Gallbladder

Glucagon is a pancreatic hormone released via vagal stimulation that acts as a counter-regulatory hormone to insulin. It opposes insulin by stimulating the breakdown of glycogen and triglycerides.

Glucagon also stimulates the release of bile from the gallbladder, which helps break down fat and absorb fat-soluble vitamins.

Female Reproductive Organs

The vagus nerve may affect a woman’s fertility and orgasms by connecting to the cervix, uterus, and vagina. However, since most of what we know about the effects of the vagus nerve on women comes from animal studies, many questions about its impact on male and female reproductive human health remain unanswered.

Heart

In the heart, it controls blood pressure, and something you may have heard about as an app-driven buzzword: heart rate variability. Recent studies reveal that an overactive sympathetic nervous system will lessen heart rate variability (HRV).

HRV and Sympathetic Overdrive

Most studies have found that heart rate variability (HRV) is affected by stressful situations. Low parasympathetic activity, a decrease in the vagus nerve activity, has been reported as a factor related to changes in HRV variables. Neuroimaging studies suggest that HRV may be linked to brain regions that evaluate or appraise stressful situations (e.g., the ventromedial prefrontal cortex).

The current neurobiological evidence suggests that stress impacts heart rate variability and supports its use for objectively assessing psychological health and so-called “stress levels.”

Heart rate variability can be measured using an app. This provides insight into the connection between vagal nerve tone and heart rhythm. The bottom line: high levels of heart rate variability are associated with good health and low levels are linked with poorer health.

Some people call these vagus nerve symptoms, even though the symptoms are due to a reduction in vagal activity. Next, let’s revisit some areas where high vagal tone and high HRV are beneficial.

Epidemiological evidence indicates inverse associations between vagal nerve activity, HRV, and metabolic syndrome.

High HRV is associated with a reduced risk of overall mortality and reduced risk of cancer death.

A meta-analysis of 21 studies found that myocardial infarction patients with low HRV­ had approximately four times the mortality risk compared to those with high HRV.

A 2012 meta-analysis of studies on high heart rate variability (HRV) and survival in cancer patients revealed a statistically significant association between HRV and more prolonged survival, particularly in pancreatic cancer patients. A separate study found that the association was mediated by reduced inflammation.

Low HRV is also associated with complications in COPD.

HRV is inversely related to insulin resistance and HbA1C levels, indicating diabetes severity and potential complications.

Its ease of measurement and independent prognostic role suggest that health policymakers should consider routinely implementing this biomarker to predict and prevent major diseases. More on this is coming, but first, let’s turn to the next important area where the research has borne out the benefits of increased vagal tone.

Immune System Function and Inflammation Management

The vagus nerve directs immune activity, suppressing pro-inflammatory cytokines (chemical messengers) produced by immune cells in the spleen. This helps manage inflammation from the respiratory tract and throughout the body’s immune system. We’ll get deeper into the inflammation part later in this article.

The following section will discuss a different mechanism for reducing inflammation by stimulating the gut. Regular vagal nerve activity dampens pain signals in the brain and spine and reduces pain-related behavior. We will expand on this concept later when we discuss vagus nerve stimulation.

Gut-brain-microbiome communication via the vagus nerve

The brain, gut, and microbiota communicate through the microbiota-gut-brain axis in a bidirectional way that involves the autonomic nervous system. The vagus nerve (V.N.), which transmits information from the brain to many organs, is a mixed nerve composed of 80% afferent and 20% efferent fibers.

The V.N., because of its role in interoceptive awareness, can sense the microbiota metabolites through its afferents and transfer this information to the central nervous system, where it is integrated into the leading autonomic network.

A cholinergic anti-inflammatory pathway has been described through vagal fibers, which can dampen peripheral inflammation and decrease intestinal permeability. This may very well modulate the composition of microbiota and aid in healing “leaky gut.”

In contrast, stress (and its accompanying high cortisol) inhibits the vagus nerve, which can harm the gastrointestinal tract and the microbiota. Stress is involved in the pathophysiology of irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), both characterized by dysbiosis and gut hyperpermeability.

Next up: how the vagus nerve protects my favorite organ: the brain.

The Vagus-Gut-Brain Connection

 The vagal nerve regulates the communication between the brain and the gut microbiome, which is affected by gut flora. The vagus nerve can distinguish between beneficial and potentially pathogenic bacteria in the gut, which modulate immune-inflammatory activity.

Research has shown that the healthy balance of gut flora and probiotics influences the brain-gut axis. A healthy gut microbiome promotes positive mood and cognitive functions via the vagus nerve cholinergic anti-inflammatory pathway. An imbalanced gut flora stresses vagal activity, which enables negative mood stress and cognitive challenges, including symptoms resembling ADHD.

Vagus Nerve Symptoms= Chronic Diseases

Symptoms and disorders listed below have been associated with vagus nerve dysfunction in various and sometimes limited studies. These are the ones worth listing and watching closely.

• IBS and IBD
• Seizures
• Chronic Pain
• Depression
• Sleep disturbances and insomnia
• Chronic fatigue
• Cognitive impairment
• High or low heart rate (and, of course, HRV)
• Gastroparesis, also known as delayed gastric emptying
• Chronic inflammation
• Immune dysfunction
• Obesity and weight gain
• Anxiety
• Chronic degenerative diseases associated with inflammation and oxidative stress are two of the root causes of all chronic diseases. I’ll explain the vagus connection below.

Chronic Disease and the Vagus Nerve

Unlike during the centuries that have preceded us, chronic, degenerative diseases now claim more lives than infectious diseases. Shifting our focus to addressing the root causes of these chronic diseases would save countless lives and alleviate significant suffering. Examples of this include the following:

Major non-communicable causes of death include stroke, cancer, coronary heart disease and its risk factors, and pulmonary conditions. Many risk factors (standard American diets, smoking, lack of exercise, and surprisingly, pollution!) account for many of them. Further, many of these diseases have common underlying biological causes, as shown below. The following discussions include a deep dive into inflammation, oxidative stress, and the role of the autonomic nervous system. Let’s start with oxidative stress.

Oxidative Stress and Chronic Diseases

Oxidation is a chemical reaction in which one or more electrons are added to or removed from an atom. Oxidative stress occurs when the body has more pro-oxidants than antioxidants, leading to DNA damage and diseases.

Oxidative stress is essentially the lack of sufficient antioxidant vitamins (e.g., carotenoids, active forms of vitamin E, vitamin C, and so on). So, you can think of oxidative stress as a lack of sufficient antioxidants, corrected by ingesting enough. Not to be confused with oxidative stress is psychological stress. But, yes, you guessed it, enough psychological stress can deplete antioxidants and cause oxidative stress!

Studies show a correlation between job-related psychological stress and levels of oxidative stress. Furthermore, chronic stress was related to shorter telomeres, which predict disease onset and earlier death. More specifically related to oxidative stress, higher effort-reward imbalance at work–a marker of chronic work stress–was associated with even higher levels of oxidative stress in several clinical studies.

Inflammation and Chronic Diseases

Inflammation is a complex process triggered by various danger signals, including cell damage and infection. Chronic inflammation helps cancer cells escape from apoptosis (programmed cell death) and proliferate, which can lead to metastasis.

Inflammation contributes to the development of atherosclerosis by recruiting macrophages from the bloodstream to form plaques, creating instability in atherosclerotic plaques by stimulating smooth muscle cells to grow within the lesions and promoting plaque rupture with resultant thrombosis.

Inflammation significantly contributes to insulin resistance, one of the main factors underlying diabetes.

Finally, psychosocial stress contributes to elevated pro-inflammatory cytokines and reduced anti-inflammatory cytokines in certain individuals. This imbalance can lead to chronic inflammation, which underlies multiple non-communicable chronic diseases. Now, let’s turn back to the part of the autonomic nervous system we discussed earlier that can cause problems when it’s in the “on position” for too long.

Excessive Sympathetic Nervous System Activity and Chronic Diseases

Excessive activity of the sympathetic nervous system is related to cardiovascular disease by increasing the heart’s oxygen demand, causing vasoconstriction, which can lead to ischemia. High SNS activity also affects the direction in which cancer cells will metastasize.

In addition, studies have found that excessive sympathetic activity is associated with an increased risk of cerebral and cardiovascular events in diabetic patients. Additionally, job stress is associated with higher SNS activity among bus drivers. A study on job stress in bus drivers found that driving in peak traffic was associated with elevated catecholamines–neurohormones secreted by the sympathetic nervous system.

Worth mentioning here is that excessive sympathetic activity worsens sleep, lowers hormone levels such as progesterone, and reduces feelings of well-being and the ability to concentrate, all of which are associated with excess mortality. This sympathetic nervous system over-activity translates to feelings of being stressed. But can “stress” cause all of these problems? Turns out, yes, it can.

Let’s talk about stress.

You know by now that “stress” means overactivity of the sympathetic nervous system. Most of us know how that feels, and it’s not pleasant. Acute stress causes symptoms such as a tight, dry throat and stomach, rapid heartbeat, and shallow breaths. It also induces metabolic changes, immune system reactions, and more.

Stress is not a disease or medical condition in and of itself, but it can exacerbate existing conditions or make predispositions to them worse. Whether you experience stress from constantly having to deal with emergent situations at home or work or (for example)- you’re a doctor who treats patients suffering from the consequences of stress, we have all experienced feelings of stress.

Short periods of stress, like strenuous exercise, doing the NYT crossword puzzle, or taking care of a seriously ill patient, can be good for us. Your brain and body work best when the autonomic nervous system cycles easily and rapidly from sympathetic to parasympathetic control.

However, the problem becomes more serious when chronic stress becomes a constant in your life. When this happens, your body never has a chance to switch back to its normal state of homeostasis entirely. This leads to dysregulation of your organs (primarily caused by innate immune cells), which disrupts all the tasks associated with maintaining proper bodily function.

Instead, these cells remain inflamed for too long and, as a result, lose their ability to return to their original state of homeostasis. This then sets the stage for the short-term (and long-term) effects of “too much sympathetic activity”-or simply too much prolonged stress.

That’s when we initially see insomnia, headaches, anxiety, and depression. Eventually, we see autoimmunity, heart attacks, strokes, dementia, and cancer if our stress becomes chronic. It’s obvious: we need to “manage” our stress and address our oxidative stress and inflammation to escape the ravages of chronic degenerative disease.

A Quick Word about Sleep

Although public health experts have been telling us we need a nightly 7-8 hours of quality sleep, this is achieved by only slightly more than half of the U.S. population. We get into bed and turn on phones, tablets, or (horrors!) television. We revisit the events of the day. We have LED’s in the bedroom. We have pets in the bedroom who can interrupt (or enhance, as in my case) our sleep. We know sleep is essential, but why?

There are plenty of reasons, but I’ll focus on what I believe to be the most essential functions of sleep. It’s when the brain does its repair work, using its unique glymphatic system to clean up damaged (and then inherently inflammatory) brain cells. This is also the optimal time for neurogenesis- when we convert our neural stem cells to neurons and create new neuronal connections.

Sleep is also the time when memories get consolidated in the hippocampus. Deep sleep (check that Oura ring!) boosts the immune system, helps weight loss due to several biochemical pathways, and aids in post-workout muscular recovery.

If you’re not sleeping well, chances are that your sympathetic nervous system is involved (and acting up), which means (obviously) that sleeping pills are not “the answer.” What is? You can now answer that question yourself-it’s stimulation of the parasympathetic nervous system. And yes, we’ll get to that, but first, let’s revisit the concept of taking care of a fair amount of oxidative stress, inflammation, and excess sympathetic activity in one fell swoop.

The Vagus Nerve Inhibits Oxidative Stress, Inflammation, and Sympathetic Activity

Now that we’ve covered the basics of sleep and stress (both worsened by the three things that are associated with all chronic diseases (including insomnia and anxiety), let’s talk about how we can get at least some levels of oxidative stress, inflammation, and excess sympathetic activity under a bit of control.

Research has shown that the vagus nerve inhibits all three major disease-promoting biological factors. For example, a study found that vagus nerve stimulation (VNS) reduces oxidative stress. More recently, scientists found that VNS reduced protein oxidation after myocardial infarction, thus limiting heart damage.

Second, the vagus nerve plays a crucial role in neuroimmune communication. It informs the brain about low-level inflammation through its receptors for interleukin-1 (IL-1), a cytokine involved in inflammatory immune responses.

Notably, the vagus nerve inhibits inflammation by activating the hypothalamic pituitary adrenal axis and the splenic nerve. The first mechanism reduces inflammation by secreting cortisol into the bloodstream, while the second works via cholinergic and noradrenergic signals that trigger specific splenic T-cells.

T-cells secrete acetylcholine, which then binds to the alpha-7 nicotinic acetylcholine receptor on monocytes. This causes an inhibition of inflammatory cytokine synthesis. These two routes constitute the vagal anti-inflammatory reflex.

Third, the vagus nerve plays a significant role in the parasympathetic nervous system, which inhibits sympathetic activity. The vagus nerve specifically increases coronary blood flow by stimulating vasoactive intestinal peptide production, which increases vasodilation.

Anti-hypoxic factors are vital in reducing the risk of cardiovascular disease, stroke, and even cancer since many tumors flourish in hypoxic conditions, and hypoxia is prognostic in cancer.

There is evidence that hypoxia (related to excessive sympathetic vasoconstrictive activity), oxidative stress, and inflammation are causally related to a vicious circle. The vagus nerve inhibits all three promoters of the major chronic diseases mentioned above, and empirical evidence supports this relationship.

All this being said, most highly inflammatory diseases such as mold and mycotoxin illness or CIRS, autoimmune diseases, cancer, and most neurodegenerative diseases require more than VNS to get O.S. and inflammation under control.

Now that you know you should learn how to stimulate your parasympathetic nervous system, specifically your vagus nerve, let’s look at how to do this daily.

Vagus Nerve Stimulation

Meditation

Research suggests that at least three types of meditation may stimulate the vagus nerve indirectly. Loving-kindness meditation, mindfulness meditation, and Om chanting (T.M.) have all been linked to increased heart rate variability (HRV), which is associated with vagal tone, as you now know.

 Cold

According to one study on ten healthy people, when the body adjusts to cold temperatures, your fight-or-flight (sympathetic) system declines, and your rest-and-digest (parasympathetic) system increases, which is mediated by the vagus nerve. In this study, temperatures of 50°F were considered cold.

Other studies have shown the benefits of living in Finland, where ice swimming and cold plunges keep everyone slightly healthier.

Cold water showers, ice baths (brrrrrr!), cold plunges, and even cold water or ice packs to the face activate the vagus nerve. To get started on this practice, which is incidentally great for your mitochondrial health, finish your daily shower with 30-60 seconds of cold water on the back of your neck. Even I can do this!

Positive Thoughts and Social Connections

Research suggests that positive emotions and social connections improve overall physical health.

In a study published in 2014, 65 participants were divided into two groups: one group was instructed to sit quietly and think compassionately about others by silently repeating phrases like “May you feel safe” and “May you feel healthy,” while the other group did not receive any special instruction.

After participating in the mindfulness meditation course, active participants reported overall improvements in positive emotions. These emotional and psychological changes were correlated with a greater sense of connectedness to others and an improvement in vagal function as measured by heart-rate variability.

Laughter

I’ve always bought into the adage that “laughter is the best medicine,” even before knowing the physiology of why that is. That said, studies are not numerous nor conclusive. But somehow, we all know this, right?

Several studies suggest that laughter does indeed stimulate the vagus nerve. One study done in a yoga class where participants were allowed to laugh demonstrated that the “laughter group” experienced increased HRV compared to the control group. I have a powerful urge to tell you a funny joke, but I will resist for now.

Singing or Chanting

Heart rate variability has many beneficial effects, including stress resilience and adaptation, relaxation, and increased parasympathetic activity.

One intriguing study on healthy 18-year-olds shows that singing increases Heart Rate Variability (HRV).

The study’s authors found that humming, hymn singing, mantra chanting, and upbeat, energetic singing all increase heart rate variability slightly differently while still involving the vagus nerve.

Finally, singing in unison, often done in synagogues, mosques, and churches, also increased heart rate variability (HRV) and vagus function in this study.

Deep and Slow Breathing

First, let me define what is meant by deep belly breathing. You can do it immediately when you feel the lump in your throat or the rapid ticking of your heart.

Here’s how: Inhale through your nose for 5 seconds. Hold for 5 seconds. Then exhale for 5 seconds out through your mouth. Do this ten times.

Breathing deeply activates the vagus nerve and parasympathetic nervous system. Shallow breaths through the chest and upper body do not activate these systems.

 Yoga

Studies have found that yoga increases the vagus nerve and parasympathetic system activity.

A 12-week yoga intervention was more strongly associated with improvements in mood and anxiety than walking exercises, which served as the control group. The study found increased thalamic GABA levels in participants who underwent yoga, which is associated with improved mood and decreased anxiety.

Yoga appears to have a positive effect on mental and physical health. However, further research is needed to determine the impact of yoga on vagus nerve tone.

Probiotics

Emerging evidence suggests that the gut microbiota may affect brain function. The gut’s nervous system connects to the brain via the vagus nerve, a pathway known as “the interface of the microbiota-gut-brain axis.”

In a study on mice, supplementation with the probiotic Lactobacillus rhamnosus resulted in positive changes in GABA receptors mediated by the vagus nerve.

Research has shown that the vagus nerve, which (as you recall) connects the brain and the digestive tract, might be stimulated by Lactobacillus rhamnosus (a probiotic). This potential link between L. rhamnosus and enhanced GABA activity adds to emerging evidence about probiotics’ potential health benefits.

  A deeper dive into Probiotics and GABA

GABA is the primary inhibitory neurotransmitter in the central nervous system and regulates many physiological and psychological processes. Yes, it is the “anxiety neurotransmitter” (if its levels get too low), but it’s much more than simply that.

Studies have found that altered GABA receptor expression may play a role in the development of anxiety and depression, which are highly comorbid with both functional and inflammatory bowel disorders such as Ulcerative Colitis.

In one well-done study, scientists demonstrated that treatment with L. rhamnosus induced brain-region-dependent increases in GABA mRNA in the brains of mice compared with control-fed mice.

Notably, the probiotic L. rhamnosus reduced stress-induced levels of cortisol, as well as anxiety- and depression-related behavior in mice. Moreover, these changes were not found in vagotomized mice, identifying the vagus nerve as a significant modulatory communication pathway between gut bacteria and the brain.

The findings suggest that bacteria play an essential role in the bidirectional communication of the gut–brain axis and could prove helpful in treating stress-related disorders such as anxiety and depression.

 Massage

A moderate-to-deep pressure massage may activate the vagus nerve. In one study, infants received regular and full massages. These massages helped infants gain weight by stimulating the gut, attributed mainly to vagus nerve activation.

While the evidence is scant, the anecdotal reports are astounding for good old foot massages. In particular, Reflexology foot massages are also thought to increase heart rate variability (and hence vagal tone) while lowering heart rate and blood pressure. This is according to a tiny study on healthy people and another on patients with heart disease.

Gargling

The vagus nerve activates the muscles in the back of the throat that allow you to gargle. The cranial nerve involved is called the hypoglossal nerve, which runs adjacent to the vagus in the back of the throat.

Gargling contracts these throat muscles, which may activate the vagus nerve.

Sleeping or Lying on Your Right Side

Limited studies suggest that laying on your right side increases heart rate variability and vagus activation more than on your left side. One study found that lying on one’s back led to the lowest vagus activation. If all of this sounds a bit exhausting, you’re in luck! I’m not telling you to avoid healthy foods, activities, stress management, and proper sleep, but I am telling you that you can avoid being fixated on your vagal tone all day. Here’s how.

VNS health benefits

If you don’t have time to do deep breathing, meditation, or any of the things listed above to deal with your vagus nerve symptoms, read on; I’ve got “just the thing” for you coming up soon. Yes, I’ll pre-empt myself: it’s the best vagus nerve stimulator that “has everything” going for it. It works, it’s inexpensive, and it’s a quick usage session. First, let’s see how this device even came to be.

Vagus nerve stimulation (VNS) was developed in the 19th century. Although it did not work well initially, it led to many VNS-related animal studies for seizure control.

Since the 1990s, several early clinical trials have proven the effectiveness of vagus nerve stimulation (VNS) in treating refractory epilepsy and depression. Implantable devices are designed to automate seizure control and for use in heart failure.

Noninvasive transcutaneous vagus nerve stimulators, which stimulate a branch of the auricular vagus nerve, or externally applied devices that work by holding them near the carotid artery-vagus intersection are also undergoing clinical trials for the treatment of epilepsy, pain, inflammation, headache, and much more. These noninvasive VNS devices exhibit greater safety profiles than their invasive counterparts. Speaking of inflammation and brains, let’s take a closer look.

Vagus nerve stimulation for Inflammation and Brain Health

Vagus nerve stimulation (VNS), a stimulating electrode placed on the vagus nerve (in the neck) to deliver low-frequency, intermittent electrical pulses, is approved for refractory depression by the FDA.

VNS affects many brain regions, including those involved in depressive pathology and neurotransmitters such as serotonin and norepinephrine. Research shows that VNS may affect signal transduction mechanisms, including brain-derived neurotrophic factor (BDNF). The exact mechanism of action is unclear at this time.

VNS reduces inflammation by activating the parasympathetic anti-inflammatory pathway, which occurs peripherally (cytokine alterations) and centrally (reduced microglial activation). Stress increases sympathetic excitation, stimulates catecholamine release, and increases brain and peripheral cytokine expression.

The parasympathetic nervous system and acetylcholine release have been shown to have anti-inflammatory effects, which may be responsible for the approximately 50% two-year remission rate for refractory depression with continual, daily use of a vagus nerve stimulator.

Many studies have found that noninvasive vagus nerve stimulation is as effective as direct electrical stimulation for treating refractory epilepsy, pain, Alzheimer’s disease, pain, depression, anxiety, and more.

Autoimmune Disease Potential

Because this is the main focus of my clinical practice, I’d like to give a shout-out to treating autoimmune disorders.

The autonomic nervous system is commonly out of balance in many chronic autoimmune diseases, including rheumatoid arthritis (R.A.), a prototypical immune-mediated inflammatory disease.

Scientists have recently discovered that autonomic dysfunction precedes and predicts the development of symptomatic and seropositive rheumatoid arthritis (R.A.) in people at risk for developing R.A. In addition, R.A. patients with relatively high vagus nerve tone (measured by heart rate variability) respond better to antirheumatic therapies.

These data suggest that a vagus nerve stimulator may help control human inflammation. Experimental studies in animal models of R.A. support this notion by showing that stimulation of the cholinergic anti-inflammatory pathway by efferent electrical vagus nerve stimulation improves clinical signs and symptoms of arthritis, reduces cytokine production, and protects against progressive joint destruction.

The results of these studies, along with previous research in animal models of inflammation, provided the rationale for experimental clinical trials in patients with rheumatoid arthritis. A vagus nerve stimulator has been demonstrated to inhibit human peripheral blood cytokine production.

These studies show that a vagus nerve stimulation device can reduce the production of inflammatory cytokines and improve disease severity in patients with rheumatoid arthritis- even those resistant to other forms of treatment. This work supports further studies using a bioelectronic approach to help treat perhaps all autoimmune disorders.

Takeaway Advice

 Let’s talk about how we all “live” for the most part. We try to eat healthfully, get enough sleep, and exercise, but few of us take the time to lower our stress levels. If you look at national statistics on what foods are consumed, what we collectively weigh, how much we sleep (thank you, Oura rings), and exercise, we’re a bit pathetic. Studies hint that most of us live in a stressed, sympathetic nervous system-driven state most of the time.

Ideally, we’d get all these healthy activities and meditation done daily. We’d also regularly have fun with oxytocin-enhancing friend-and-family bonding. And we’d go back to the list in the middle of this article, choosing vagus-stimulating activities to do daily. Yeah, right, you’re busy enough, you are all thinking. Agreed! So what do we do?

Whatever we all do, you now know we need to ensure that our autonomic nervous system is driven by the parasympathetic, not the sympathetic side.

Twenty years ago, getting VNS required an implantable device=surgery. As little as five years ago, it would have required a prescription. Now, we can purchase a VNS health device because we are informed and want one. The best vagus nerve stimulator is small, easy to use, and it just takes two minutes, twice daily, to get the fantastic results described in this article. And no, it won’t cure cancer, but it sure can make you feel much more “chill.” And, of course, lots more than that.

Emerging research suggests that optimizing the vagus nerve’s functioning can help with various health issues, including digestion, mental health, cognitive health, metabolic health, autoimmune disease, and inflammatory disease. And yes, since fat cells are inflammatory, this does indeed help augment weight loss.

More human research is needed to verify and better understand these connections and how the “wandering” vagus nerve impacts overall health, but make no mistake: your health depends on where you “live” regarding your autonomic nervous system. Not just any vagus nerve stimulator is going to cut it. The auricular devices only capture a tiny branch of the vagus nerve. Only one non-prescription item on the market works externally: this particular vagus nerve stimulation device.

Use my discount code: DrKim25, and then use your chosen (and inexpensive!) vagus nerve stimulation device twice daily, in good health!

Kim Crawford, M.D., is a practicing physician with extensive experience in the fields of internal medicine, anti-aging, and regenerative medicine. The recommendation and materials on this site represent her opinion based on years of practicing medicine. The information and material provided on this site are for educational purposes only and any recommendations are not intended to replace the advice of your physician or health care professional. You are encouraged to seek advice from a competent medical professional regarding the applicability of any recommendations with regard to your specific symptoms or condition. You can also schedule an appointment for an in-office or email/phone consultation.

It is important that you do not reduce, change or discontinue any medication or treatment without consulting your physician first. The personal stories shared on this website are personal to the users and will not be typical of the results you will have if you follow the advice provided on this website. The information and recommendations provided on this website have not been evaluated by the Food and Drug Administration and are provided for educational purposes only.

Introduction to Ulcerative Colitis

The principal causes of Ulcerative colitis are complex, with a weakened epithelial (“gut”) barrier function-AKA “leaky gut” being the hallmark of this and other autoimmune diseases. Other important factors include an altered microbiome, genetic, and often toxic environmental factors such as mold and mycotoxins. Unfortunately, most of the roughly one million American suffering from U.C. receive Ulcerative colitis treatment from G.I. doctors, using toxic “biologics.”

The Two “Sick Patients” with Mold Toxicity

Mold toxicity means you’re sick and your home is sick. Plain and simple. Or is it? Unfortunately not. I always spend a considerable amount of time reviewing the list of symptoms of each one of my patients during our visit. Sometimes, it is evident that someone’s illness results from exposure to mold toxins; sometimes, it’s far from it.

When I have any doubt, I always ask patients to take a quick and simple test available online called a VCS test. False positives occur in up to 5% of cases and false negatives in about 8%, but it is nevertheless beneficial for screening purposes. More details on this later.

However, it is only after reviewing their lab work that I can tell for sure whether or not mold is playing a role in their condition. This rules-out any guesswork and provides the scientific basis that allows me to make a definitive diagnosis.

When I have a diagnosis of mold toxicity, I now find myself dealing with two distinct patients: the 1^st one is a human, and the 2^nd one is a building. In other words, I am now facing a medical issue but also an environmental one.

The importance of this is that no matter how effective my medical treatment is, this patient will never become ultimately better unless their environmental issues are dealt with and remediated properly.

Treating health conditions caused by exposure to mold toxins is undoubtedly not easy. Unfortunately, resolving the environmental issues proves to be even more challenging in many instances. If someone doesn’t know where the problem is, it’s often necessary to obtain a professional inspection to ascertain if there is mold toxicity or not.

Why Perform a Mold Inspection?

A mold inspection is the first step in addressing issues related to a building’s contamination with mold because it provides the assessment of the condition of the building.

Just as physicians need a diagnosis before determining the appropriate medical treatment, the mold inspection will determine the mold remediation plan.

Understandably, there is some psychological trauma resulting from the realization that your home is what is making you sick.

Some patients simply cannot come to grips with the fact that their house, which they built so carefully in some cases, is the culprit.

They, unfortunately, remain in total denial and categorically refuse even to get a proper mold inspection.

When this happens, all I can do is treat their other ailments, but I know that exposure to mold toxins will continue its ravaging effects over the long term.

They usually feel better after a short time due to the treatment of their symptoms, but, ironically, they invariably misinterpret this as evidence that their environment is just fine.

Sadly, feeling better reinforces their conviction, and they become defensive or downright combative when I bring up the mold issue. Luckily, this is not my typical experience with patients. But, let’s circle back a moment regarding mold inspection. Just as many doctors are not “CIRS-literate,” such is the case with many mold inspectors.

Why is it So Important to Find a Good Mold Inspector?

When a patient is diagnosed with CIRS (often called “mold illness”), they need to hire a professional to inspect their dwelling. Still, if they unluckily find someone not adequately qualified, the inspection is usually done improperly and will often fail to identify the full scope of the mold issues.

If an inspector erroneously concludes that nothing is wrong or that a quick clean-up will suffice, CIRS patients get confused since they receive contradictory opinions.

Their physician tells them that their environment is causing their symptoms, but the inspector tells them that this is not possible because their place is just fine.

What we then have is a nightmare scenario for the physician. Why? This patient will be much less likely to take the appropriate steps to get their dwelling more thoroughly decontaminated to the acceptable level.

Why does this happen? Because, in large part, the mold inspection/remediation industry does not yet recognize CIRS as an actual problem.

Until recently, it was impossible to map an individual’s gene sequences quickly and affordably.

But genomic sequencing technology combined with advancements in computer processing power and laboratory equipment has progressed at such an astonishing pace that it is now possible for physicians to order routine tests designed to look for and identify specific genes.

This technology proved to be a potent tool for microbiologists and researchers. It is now well established in the scientific literature that an individual’s specific set of genes often determines the level of mycotoxins that will cause them harm.

In other words, acceptable conditions for some people are not suitable for others.

Several genes have been identified as so-called “mold genes” because they impede the ability of the immune system to detect and eliminate mycotoxins absorbed in an individual’s body during exposure.

Someone can have only one or two “mold genes,” or none. While it is not unheard of for someone without any “mold genes” to develop CIRS, the more “mold genes” one has (meaning two), the higher the likelihood of developing CIRS, and usually, the worse the symptoms are.

Unfortunately, this knowledge has not yet made its way into any state’s mold inspection or remediation training certification programs.

Many mold inspectors and remediators believe that a building is safe for everyone once remediated to current standards. Consequently, these inspectors are skeptical that some individuals require an environment meeting a higher level of decontamination than is taught in their program.

Nothing is perfect, and it is impossible to remove every trace of mold spore dust after remediation of a contaminated building. As a result, the industry has settled on a level of contaminants considered normal (basically “good enough”). The problem is that “normal” is only acceptable for someone who does not have any “mold genes.”

For these reasons, finding a good mold inspector (one who understands that CIRS is a real thing and that everyone is not equal-genetically speaking) is essential.

Without some appropriate extra remediation measures, patients suffering from CIRS will continue having exposure to an unsafe environment. As a physician, treating their conditions is fighting a losing battle. They will get considerably better but will never achieve the results we should expect, which is a full recovery.

Since you can’t necessarily trust mold inspectors or remediators, let me give you a quick course in mycology.

Mold, what is it, and how does it harm us?

Mold is not an animal nor a plant; it is part of the “Fungi Kingdom.” Therefore, it is a living organism that requires food and specific environmental conditions to grow and spread.

While mold is an essential part of the ecosystem and a beneficial one, some species (but not all of them) have developed the nasty ability to produce dangerous toxins called “mycotoxins.”

Mycology is the branch of biology specializing in the systematic study of fungi, including their genetic and biochemical properties. The term “mycotoxins” comes from this branch of biology.

Mold spores are everywhere, outside as well as inside. Therefore, it is customary to find mold spores around your house. However, a “normal fungal ecology,” a term you will find in every mold inspection report, means that the spores captured in your home, despite being alive, have not “set up shop,” representing: established growing colonies.

Spores considered part of a normal fungal ecology should not be producing toxins, the process that certain mold species use to kill other mold species and take over. Instead, it is a fight for food and a matter of survival, one of the pillars of the evolutionary process.

Outside in nature, there is plenty of food for every species. Once inside a building, however, nutrition becomes more limited (we’re talking about organic materials such as drywall, wood, fabric, etc.).

Most toxin-producing species very rarely do so outside in nature. However, they will coincidentally become toxic if they start growing inside a building where they will invariably come in contact with other species.

This phenomenon can be observed under a microscope in a laboratory when growing cultures in a petri dish. Some toxin-producing varieties will not do so if there are no other mold species in the same petri dish. However, the moment you add another species to the mix, you will quickly see mycotoxins appear.

As you might expect, when mold starts growing inside a building, there is always a variety of species. Therefore, it is just a matter of time until some begin producing mycotoxins.

Molds are complex structures, and they come in many different forms. They grow in “colonies,” which we can see on moldy surfaces. On the other hand, spores are too small to see with our eyes, but they are visible under a microscope. Mycotoxins, for their part, are so small that they are invisible under any microscope.

It is essential to understand the distinction between mold, spores, and mycotoxins: mold is a living organism made of cells; a spore is just a component of the mold structure (also made of living cells); a mycotoxin is an organic compound, in other words, a chemical.

As the name implies, mycotoxins are toxic to humans and animals alike. Moreover, they include a particularly dangerous family of toxins called “neurotoxins.”

Neurotoxins are toxins that are destructive to nerve tissue. In other words, they affect and damage the nervous system, including the brain. Other toxins cause symptoms in different tissues such as the liver, the kidneys, and the cells of respiration called mitochondria.

The variety of mycotoxins, in part, explains why symptoms from CIRS can vary wildly from one patient to another. As a result, it is a condition that is not easy to diagnose for the uninitiated physician and is thus so often misdiagnosed.

Speaking of diagnosis, you might be wondering why it seems that more and more buildings are moldy; are they, or are we “spotting it” more? It’s a bit of both, quite frankly.

Mold Contamination: a very old issue, a very modern problem

More and more physicians (particularly in functional medicine) claim that some previously unexplained symptoms could have resulted from toxic mold exposure.

This whole mold toxicity problem might sometimes sound like a new hype. How come we rarely heard about this in the past? Our ancestors were exposed to moldy houses, too (remember those “musty” basements)?

The answer is: yes, indeed, they were. However, a lot of things have changed dramatically since then.

For one, many ailments they were suffering from were not known to be caused by mold toxin exposure. And the field of mycology, along with advancements in mold toxicity, has grown in leaps and bounds.

Maybe this explains, at least in part, why some of the mysterious symptoms our ancestors were experiencing for real were actually “unexplained.”

“Idiopathic” is the medical term used to describe a symptom that has no diagnosis. In other words: unexplained symptoms have no known cause or remedy. How often have you heard someone say: “I was told it’s all in my head”?

As technology (along with new scientific tools) evolve, so does the medical body of knowledge. For example, while it was nearly impossible 30 years ago to map the genetic sequence of some organic tissue, now everyone can quickly get their genetic code identified and analyzed through commercial or medical services.

In this context, it only makes sense that some former “idiopathic” symptoms are just now revealing their long-hidden causes. Therefore, the medical community is just beginning to understand the effects of toxic mold exposure on the human body. This understanding is evolving, and it is slowly making its way into the mainstream medical establishment.

In addition, our homes have changed dramatically.

We use different construction methods and materials when building our modern dwellings. For example, we impregnate them with chemicals and use glue, sealants, paints, coatings, etc.

Depending on your age, you may not realize that air conditioning was very rare until the ’70s and practically nonexistent in residential buildings before the ’60s.

Here are some critical factors that might help explain our “modern mold problem”:

1. Not all mold species are toxic:

Mold spores are plentiful outdoors: the dirt in your backyard garden is full of them, but they are not toxic. The reason some mold spores become toxic in certain conditions is simply a matter of survival and evolution.

Most mold from the “toxic species” begin producing toxins only if “food” is in short supply. These toxins (called “mycotoxins”) are made within the spores but spread to the dense mass bathing the colony (viewed under a microscope; to the naked eye, colonies often look more like a powdery substance).

As the colony grows, anything that comes into contact with it becomes contaminated. So you can picture colonies as tiny blobs of slime that continuously expand to the point where they eventually cover a large area of the material upon which they grow.

Some mold species also expel their spores in the air, which allows them to travel over long distances and seed new colonies wherever they land.

So, what’s the takeaway?

It is essential to understand that mold colonies need three things: Moisture, Heat, and Food (organic matter) to proliferate.

Unless you live in an Igloo, there is enough heat and “food” in your house. However, the amount is limited (compared to a forest). Hopefully, however, there is not enough moisture.

In your garden outdoors, there is plenty of food and moisture (and heat in summertime) for everyone. So there is not a lot of competition. Bring those spores inside your house, though, and that’s a different story altogether.

In a nutshell, mold spores (only certain species) produce toxins to kill other mold species in an attempt to take over. You know, “survival of the fittest.”

The problem for us humans (and animals alike) is that, unfortunately, many of these toxins are “neurotoxins,” meaning they cause damage to our nervous system. The focus on potential neurological issues is why mold growth inside a building is often considered a severe problem. There is simply not the same abundance of organic matter (“food”) indoors as outdoors, and there’s typically not enough moisture.

As a result, if mold is allowed to grow inside a building (due to a water spill or water leakage, for instance), you can be sure that some species of the toxic category will eventually settle in and produce toxins.

Remember that mold spores are plentiful outdoors, and many are airborne. Each time you open a door or a window or go in and out, some of these spores are invariably being brought in with you. However, as long as the conditions for growth are not present in the building, these spores will simply remain dormant and will cause no harm (just like when you are stirring dirt in your garden).

However, this flow of mold spores is also why water leaks or spills, resulting in moist areas in a building quickly becoming a fertile breeding ground for mold even if the house looks otherwise clean. The leak is often limited to a cramped space or semi-enclosed areas, such as behind a bathroom cabinet. This type of space is called a “micro-climate.”

2. Modern houses “cannot breathe”:

How often have you heard that newer houses “cannot breathe” while older homes were very “leaky”?

To reduce energy waste, we build our houses as airtight and insulated as possible to prevent hot or cold air infiltration. While this is a good thing from an energy conservation standpoint, it also means that there is practically no air circulation from the outside and, in turn, less air circulation in-between walls or wall cavities.

Walls in modern construction are never “solid” and contain therefore empty spaces or “cavities.” These enclosed spaces communicate throughout your house, allowing air to migrate from one cavity to another. Still, the volume of air circulation is relatively small and certainly cannot be described as air “flow.” Consequently, the materials will not dry very quickly or easily if a water leak occurs.

Being “leaky,” older constructions allowed some outside air to infiltrate these cavities, promoting air circulation between these enclosed spaces. This air leakage is what some builders or construction workers refer to as “breathing.” One consequence is that water spills were allowed to dry faster than in modern-day construction.

In other words, in a modern “airtight” house, wet materials will take longer to dry unless you control the humidity by dehumidifiers or air conditioning. If a water leak occurs in a modern building and is not quickly addressed, the immediate surrounding area will remain humid, creating a perfect breeding ground for mold. Remember what mold spores need to proliferate: food, heat, and moisture.

So, are older houses better? No, not really. As described in this article, other factors have changed, but an older house is more likely to have experienced water damage at one point or another since it has been around longer. On top of that, unless they have been thoughtfully remodeled, they are typically wasting a lot more energy than newer ones.

3. Mold species are evolving to adapt to their new environment:

As mentioned previously, building materials have also changed significantly. Many modern materials are now impregnated with fungicidals (chemicals that impede fungus growth). Almost every material can be treated this way: paint, drywall, wood, even concrete.

You will be hard-pressed to find any air conditioning duct material in the U.S. not impregnated with one such chemical.

While this seems like a good idea at first glance, scientists now see that many fungi species are becoming more resistant to these fungicidal agents (much like bacteria are becoming more resistant to antibiotics).

This is the paramount principle of evolution.

4. Air conditioning is exacerbating the problem (sometimes causing it):

The advent of residential air conditioning has made our dwellings more comfortable but also more susceptible to mold growth if not designed and installed correctly.

To understand this, let’s first talk about humidity:

“Humidity” is the % of the maximum amount of water molecules held in the ambient air at a given temperature and pressure.

We can ignore the atmospheric pressure variation here for all practical purposes.

It might help to picture air as being just like a glass. 50% humidity simply means that the ambient air is holding ½ of the water it can support at the current temperature (the glass is ½ full.). 100% corresponds to the “saturation point” or “the glass is full” point.

You might remember from your physics class that the higher the air temperature is, the more considerable the amount of water the air can hold (the glass becomes larger as the temperature increases). So keep this thought- this is important because that explains why condensation occurs on cold surfaces.

Picture that glass of iced tea that you bring outside on a hot summer day. All those droplets of water that form on the surface of the glass seem to appear out of thin air because…wait for it- they do.

The air temperature very close to the surface of the glass is cold, much more so than the ambient air. Because of that sudden temperature drop, the air in contact with the glass can no longer hold the water in it, hence the water droplets appearing out of the blue. That’s condensation.

The humidity of the air in contact with the glass has rapidly gone from, let’s say, 60% to above 100%, meaning the glass has overflowed.

What does this have to do with air conditioning? In a nutshell: condensation over cold surfaces.

When your A/C system is running, the air inside the network of ducts is much colder than the ambient air. Therefore, if any outer surface of this ductwork (or any other system component) gets too cold, condensation will occur just as it does on your glass of ice tea in the summer.

All ductwork is insulated for this precise reason. Unfortunately, it is all too easy to compress or damage this insulation during handling and installation unless the installers use a lot of care.

To make matters worse, in a conventional vented attic, it is not possible to avoid having some portions of ducts and register boxes covered by the insulation installed on top of the ceilings.

Since air can migrate through the insulation (no matter whether it is the loose, blown type, or fiberglass batts), the amount of moisture in the air is the same everywhere. However, the temperature is not. The surfaces of the buried duct or boxes are colder than ambient air, a situation worsened by the insulation. The cooler the surface is, the higher the likelihood of condensation.

Therefore, it is critical to look under the insulation by physically displacing it when inspecting the attic to look for condensation and mold. Also, the ducts connected directly to the HVAC air handler cabinet are always the coldest components since the air they carry has just passed the system’s cooling coils. Therefore, you must meticulously inspect these components if you are looking for moisture.

As you can imagine, condensation over any ducts will lead to wet materials (wood, drywall, etc.), perfect organic food for mold.

Since air conditioning was nonexistent in the days of our grandparents, their houses had no or fewer cold surfaces indoors that could cause condensation. But, of course, that also affected their lifestyle as they left windows open in the summertime, and used ceiling fans liberally, all of which promoted more ventilation. We can therefore conclude the following.

What can we conclude about how we build houses?

Mold in houses was not as much of a problem “back in the days” for several reasons:

• We built houses differently, and building materials have changed significantly since then.
• Mold spores that made their way into houses did not necessarily become toxic.
• Some mold species are becoming more resistant to fungicides and becoming more difficult to avoid or eradicate.
• The advent of central air conditioning systems can create conditions favorable to mold growth in modern houses if not installed correctly.

What steps should I take if I suspect that my house is toxic?

1. Don’t ignore it! I have encountered many people who just cannot get past the psychological barrier and are incapable of coming to grips with the idea that their house might be moldy. Somehow, they remain in denial, and their health continues to degrade.
2. If you are a patient of mine, I will ask you to perform an ERMI test as a preliminary confirmation of whether or not our suspicions are confirmed. This also gives me an overall picture of the condition of your house by looking at two things: what species of spores can be found in your home and what kind of concentration levels are present (a lot or just a little). If the ERMI is suspicious for “active mold growth,” I’ll ask you to do #3; below.
3. Hire a professional inspector. They have tools to measure the level of moisture in materials (and even behind them). They also have the instrumentation to detect the presence of mold spores, species, and concentrations. They are trained and know where to look and what to look for. They also follow protocols to perform inspections safely. A good inspector will also guide you and present you with the best plan of action for your situation.

Performing an inspection yourself is unlikely to reveal hidden problems (otherwise, you would already have found them). In addition, this will expose you to dangerous mycotoxins if you were indeed to see mold growth. Finally, realize that stirring up objects or materials contaminated by mold will spread the spores all over and worsen the problem. You don’t want to do this.

4. If the inspection reveals mold contamination, hire a professional mold remediator. Mold growth is a serious matter because your health is at risk. However, there is more to mold remediation than what popular belief would have it. A competent professional remediator will follow strict protocols to do it thoroughly while preventing you and your loved ones from exposure.

References :

History of air-conditioning: https://www.energy.gov/articles/history-air-conditioning

Anti-fungal in building materials: https://pubmed.ncbi.nlm.nih.gov/6045111/

https://www.homeimprovementbase.com/6-mold-resistant-building-materials-to-mold-proof-the-home/

https://www.microban.com/antimicrobial-solutions/applications

https://www.microban.com/antimicrobial-solutions/environments/building-materials

What does it mean when you learn mold is why you feel sick?

Chances are you have been suffering from all sorts of medical issues for a long time, you have seen numerous physicians, have received all kinds of diagnoses, but no treatment turned out to be effective. Unfortunately, this is a story I hear all too often. How do you know mold is making you sick? If you’re not sure after reading this article, please read the one I just linked for you.

Suppose you are coming to me with symptoms that I suspect might result from mold exposure. In that case, I will assess to look for typical symptoms such as gastrointestinal problems, cognitive or mood issues, pain issues, sleep problems, and much more. 

These symptoms result from mold toxicity from exposure to a mold-contaminated environment. People with exposure to live mold or dead mold containing mycotoxins (more on this distinction to come) can develop a condition called CIRS, short for Chronic Inflammatory Response Syndrome.

CIRS, called “Mold Illness” or “Biotoxin Illness,” is a condition caused by other types of biotoxin exposures, such as Lyme bacteria or blue-green algae.

Symptoms are not trivial and can vary substantially from one patient to another. They also often overlap or even mimic symptoms associated with other medical conditions. For example, Lyme Disease, Ehrlichiosis, and even some autoimmune disorders come to mind. As a result, exposure to toxic mold and CIRS are often misdiagnosed or simply not diagnosed.

Since it is one of the easiest and quickest tests for preliminary assessment for CIRS, I will likely ask you to take a Visual Contrast Sensitivity Test or, in short, a VCS test. You will take this test online. Again, it is quick and inexpensive, with results immediately available.

This online test might sound like witchcraft, but it is a genuine scientific assessment. The U.S. Military Medical Services initially developed this test as a visual assessment for jet fighter pilots.

However, this test does not assess visual acuity but rather the ability to distinguish contrast at various levels and shades of black, white, and grey. This capability is part of the brain’s functions using sensory information provided by the optic nerve, which is often affected by mycotoxins. Always try to remember that while live mold produces mycotoxins, there is still a danger from dead mold, as dead mold spores contain active mycotoxins. Mold and mycotoxins are the issue.

Even though VCS is a nonspecific test of neurological function integrity, it provides a high degree of accuracy and sensitivity for biotoxin exposure, such as mycotoxins.

Over 90% of people suffering from CIRS fail a simple VCS test. It is not enough to provide a definitive diagnosis, but it gives an initial indication that CIRS might be a likely diagnosis. Therefore, we need to investigate further to determine the cause (which can potentially be a mold-contaminated environment).

In practice, if you fail the test, you are probably suffering from CIRS. However, if you pass, there is still a possibility that you do have CIRS.

Now What?

If you have failed the VCS test, I will order the appropriate bloodwork panels. I will usually ask you to perform an ERMI test of your environment (home, office, workplace, depending on your specific situation). This easy-to-do swab is another relatively quick and easy test that, once interpreted correctly, allows me to get a very good picture of the following:

1. Were mold spores present at one point or another in this building?
2. What species of mold were present?
3. How bad is the contamination level?

The ERMI test does not tell me whether or not these mold spores are still active (alive). Other tests are required for that (but they are more expensive).

Once I have the results of your lab tests and the ERMI test, I will know a lot more about your situation from a physiological standpoint. In addition, I will learn more about your genetic makeup, and I will also have some suggestions vis-à-vis your environment’s conditions.

At that point, if everything is pointing towards mold contamination, we need to get answers to the following questions:

1. Is mold actively growing in your house (or workplace)?
2. What is the root cause for the presence of mold, and what is the source?
3. What is the best strategy to remove the source, repair the damage, and finally, decontaminate it?

There is only one way to do this right, and it is to hire mold assessment experts.

How do I find Mold Assessment Experts, and How do I check their qualifications?

Great question. I get asked all the time.

The mold assessment & remediation industry is a very crowded space. Therefore, individuals and companies are required to hold State-issued licenses to be considered qualified to perform these services.

Many different combinations of education and experience are accepted, but everyone must pass a written examination to obtain a license (renewable usually every two years). Some states even accept certifications from other states to issue a license (as long as the candidate submits an application and pays the fees).

Despite these legal requirements, unfortunately, quite a few individuals or companies are not following strict protocols or are making unfounded claims, sometimes based on misconceptions, ignorance, or simply “anecdotal evidence.”

Some unscrupulous individuals pretending to be qualified are not even properly licensed. Despite being illegal and subject to fines and penalties, these individuals can be operating for quite some time before any complaints are filed.

As a result, finding a qualified, honest, and thorough mold inspector or remediation company may be challenging. In other words, you need to do your homework.

We have an entire handout dedicated to this topic alone which we give to patients who need us to help them find an inspector, examine a remediation proposal, and so on.

Remember that there are “two patients” when we deal with CIRS, and without environmental clean-up, the human patient will not recover.

Introduction to Leptin and Leptin resistance-NOTE: we now have Semaglutide and Tirzepatide!

Leptin and its receptors are essential regulators of body weight and energy homeostasis. Multiple studies show that decreasing leptin’s tissue (or receptor) sensitivity leads to metabolic disorders, including obesity. Physiologic mechanisms underlying the development of leptin resistance include gene mutations that encode leptin and its receptors, proteins involved in the self-regulation of leptin synthesis, and even factors that alter blood-brain barrier permeability. Leptin resistance is a complex pathophysiological phenomenon with multiple “lines of attack” for potential treatment. Why is this important? Leptin resistance is the leading driver of fat gain in humans so let me break down how I’ll discuss this complex topic.

• What is leptin?
• What are normal leptin levels?
• What is leptin resistance?
• Ways to lower leptin and treat leptin resistance

1. Raise BDNF (this topic is complex)
2. Lower cortisol and stress levels
3. Lower inflammation levels
4. Improve sleep
5. Correct “eating habits”
6. Fix SIRT1 enzyme issues
7. Miscellaneous tips

What is Leptin?

Leptin is a peptide (short-protein) hormone, originally thought to be secreted solely by fat cells; now known also to be secreted by the kidneys, placenta, salivary glands, and stomach. It’s important to note that leptin levels increase exponentially, not linearly, with fat mass. Leptin receptors are found in their highest concentrations in the brain, specifically in the hypothalamus and hippocampus.

In some clinical studies, chronically-elevated leptin levels correlate with overeating, obesity, and, as mentioned above, metabolic diseases, including diabetes, hypertension, heart disease, and metabolic syndrome.

The exact way “leptin works” is unknown, but the leading theory involves leptin release post-meal, penetration of the blood-brain barrier, and satiety signaling in the hypothalamus. The hypothalamus then signals to the rest of the brain (and probably to fat cells and our microbiome) that we have enough fat stored, we no longer need to continue eating. As a result, caloric burning can continue at a regular rate.

What Are Normal Levels?

We can measure leptin levels with a simple blood test. The results are in ng/mL (nanograms per milliliter).

Normal leptin levels are approximately 4.5 – 23.5 ng/ML and vary slightly between labs. They depend on a person’s BMI, age, gender and tend to get higher throughout the day, towards nighttime when they peak. Degrees of severity are loosely given with “mild” as 15-20 ng/ML and “severe” as 50ng/L or more, but this varies from person to person.

It has been called the “weight loss hormone,” the “satiety hormone,” and even the “starvation hormone.” We know that leptin resistance potentiates the extreme hunger experienced by a high ghrelin state. This (leptin-resistant) physiologic state somehow makes fat cells “think” that they must hang onto fat for dear life. This particular metabolic problem makes weight loss quite tricky unless you deal with the leptin resistance head-on.

Leptin Resistance

Leptin resistance occurs when leptin effectively decreases appetite or increases energy expenditure through basal metabolism or lipolysis in fat cells. As a result, tissues become resistant to even high levels of leptin: a similar phenomenon to insulin resistance with (obviously) different hormonal pathways and different treatments involved.

Clinical studies demonstrate that obese people usually have very high levels of leptin that don’t perform their job correctly. One of the reasons for this is that a leading leptin production site: fat cells, make leptin in proportion to their size.

Although leptin suppresses the appetite when slightly raised, it seems to have the opposite effect when it gets too high. That’s why most researchers feel that leptin resistance leads to increased appetite and decreased energy expenditure.

We can measure leptin levels and speculate on why people become leptin resistant. Theories include leptin entering the brain less effectively, decreasing leptin receptors, or an over-activation of negative feedback loops due to chronically high leptin levels. No matter what causes it, we now have some excellent ways to combat this problem and assist with weight loss. As you’ll see, it’s never a one-size-fits-all (no pun intended) when it comes to effective weight loss strategies. Let’s now get into how we address leptin resistance in the functional medicine world.

How to increase BDNF and therefore lower leptin

Regular and especially Intense Exercise

Autophagy is a term that you will be hearing about more and more as a contributor to disease and aging. It’s a process by which cells remove and recycle junk proteins, and some studies link it to leptin resistance. No matter what, we are starting to recommend “meds” to enhance autophagy even now. Next, let’s discuss hormones, many having positive effects on aging, disease, and metabolic issues, including excess fat. In particular, estrogen deficiency is likely to cause leptin insensitivity in the brain based on good animal data.

And believe it or not, there is more research about how what we eat might impact leptin. Some theories suggest that lectins (e.g., gluten, beans, grains, dairy, nightshades)  bind to surface receptors of cells–including leptin receptors–and mimic or block the effects of that receptor. This theory posits that lectins could interfere with the function of leptin, exacerbating leptin resistance. To “cover all bases,” I advise my moderate to severely leptin-resistant patients to avoid lectins.

New data is evolving consistently regarding the use of cold therapy, whether that be cold showers, ice baths, or even cold weather. Of course, cold might play a role in leptin regulation, so stay tuned for more data on this. But, at least we know that cold is excellent for your mitochondria and, therefore, your energy levels, so why not?. One last and critical note- if you are trying to lose weight and have leptin resistance, don’t do a ketogenic diet, or it will worsen the leptin problem; seriously! (Use keto for insulin resistance).

In my clinical practice, I find that adjusting eating and exercise plans, normalizing cortisol, sleep (often using DSIP), and prescribing NMN and dihexa do the trick every time. The “weight loss peptide” AOD-9604 then “kicks in” when leptin is low enough to allow it to accelerate lipolysis. Bon appetit!