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.

The Basics of ADHD in Adults

ADHD is the most common psychiatric disorder of childhood. It is classified as a neurodevelopmental disorder that may persist from childhood into adulthood. In childhood, it is associated with inattention, hyperactivity, and impulsivity. Symptoms often change as a person gets older and are associated with an increased risk of developing depression, anxiety, and substance abuse. However, recent studies have challenged the idea that every adult with ADHD had it as a child. The results of those studies show the following. First of all, ADHD often goes unrecognized throughout childhood. Secondly, families may help children develop good compensation strategies. The conclusions, therefore, remain that, indeed, ADHD in adults is still considered a continuation from childhood.

Attention-Deficit/Hyperactivity Disorder (ADHD) is often a disabling condition in adults. As just noted, a significant portion of patients is not diagnosed during childhood, as diagnosis of the syndrome can be complex, especially when other psychiatric conditions are also associated. As undiagnosed ADHD patients age, they are presenting to memory clinics with attentional and executive disorders. Neuropsychological examinations of these undiagnosed ADHD patients often reveal atypical cognitive profiles that complicate the usual diagnostic procedures for ADHD and increase the risk of misdiagnosis. Therefore, first and foremost, it is recommended that any explorations of cognitive and/or behavioral disorders in adults should systematically screen for ADHD. Let’s now explore adult ADHD symptoms, usual remedies, and then functional alternatives.

• Is it possible for Adults to Develop ADHD out-of-the-blue?
• What are Adult ADHD Symptoms?
• Typical Medical Treatment for ADHD in Adults
• How do the medications work?
• What’s the problem, then?
• Cortisol
• Cortisol part deux
• The gut-brain axis
• Fixing the ravages of high cortisol
• Repairing the gut lining
• Repairing the Microbiome
• Behavioral and supplemental interventions
• The cool stuff: peptides
• Miscellaneous “other”

Can Adults Develop ADHD?

Adults can have ADHD, of course.  About 4% to 5% of U.S. adults have it. But surprisingly, few adults get diagnosed or treated for it. Instead, they often end up being evaluated at memory care centers, as noted above.

Who develops adult ADHD? Every adult who has ADHD has probably had it as a child. Some may have been diagnosed and known it. However, some adults may not have been diagnosed when they were younger and only find out later in life due to having “life issues” crop up, which will be discussed below.

While many children with ADHD do outgrow it, about 60% still have it as adults. Adult ADHD affects men and women equally. Many questions of late-onset ADHD remain incompletely answered, and further research is necessary to understand better and explain the etiology and development of this late-onset disorder. One very important thing we are noticing, and reporting: CIRS patients all have difficulty concentrating and often come to me on Adderall.

What are Adult ADHD Symptoms?

If you have adult ADHD, you might have difficulty with the following:

• Ability to concentrate and focus on tasks
• Task organization
• Following directions
• Remembering information
• Finishing work on time or deadline

If you have ADHD, you may have trouble with one or more of the following:

• Anxiety
• Mood swings
• Procrastination
• Poor organization skills
• Low tolerance for frustration
• Trouble concentrating when reading
• Chronic lateness and forgetfulness
• Impulsiveness
• Depression
• Chronic boredom
• Depression
• Trouble controlling anger
• Low self-esteem
• Substance abuse or addiction
• Low motivation

What is the Typical Medical Treatment for ADHD in Adults?

In a word: Stimulants! Adults with ADHD have usually been prescribed stimulant medications. As a result, studies demonstrate that about two-thirds of adults with ADHD have big improvements in their symptoms, at least at first.

Typical medications used include:

• Amphetamine/dextroamphetamine (Adderall, Adderall XR)
• Lisdexamfetamine (Vyvanse)
• Methylphenidate (Ritalin, Concerta, Metadate, Daytrana, Quillivant XR, and Methylin)
• Dextroamphetamine (Dexedrine)
• Dexmethylphenidate (Focalin)

Studies suggest that these drugs improve (the happy brain chemical)- dopamine transmission by increasing its levels in the striatal region of the brain. Researchers have found that most amphetamines promote dopamine release, while Ritalin blocks the transporters that remove dopamine, keeping levels up. Ritalin also seems to improve norepinephrine transmission as well. This is all well in good, but amphetamines stimulate the adrenal glands to produce more and more cortisol over the long term. So-what’s wrong with that? Plenty.

Let’s Talk about Cortisol

Cortisol modulates many of the changes that occur in the body in response to stress. These include things like blood sugar levels and blood pressure. Cortisol has firm control over proper immune responses. It has anti-inflammatory activity. It also activates our entire nervous system by being coupled with adrenaline (epinephrine) release. As a result, it has a role in sleep, mood, energy, anxiety levels, and more. Short term, it acts in a beneficial way to help us through stressful situations. However, long-term adrenal stimulation by amphetamines causes persistently elevated cortisol levels, which definitely can become a problem. Here’s why.

What happens with long-term high cortisol?

Cortisol helps us deal with stress by shutting down “unnecessary functions,” like reproduction and the immune system, to allow the body to direct its energy towards dealing with the stressor. These functions are supposed to be short-lived to deal with the stress. However, our modern lives are full of stress, and when stress is chronic or caused by amphetamines, this becomes a problem.

Cortisol partially shuts down the immune system when levels are high. It interferes with T-cell (a type of white cell) production and function, making your body more susceptible to pathogens like viruses, bacteria, and fungi. Ever notice how people who are constantly under stress are also always getting sick? This is why.

Cortisol also affects your muscles and bones. Cortisol is “catabolic.” It inhibits the uptake of amino acids into muscle cells, making it impossible to fuel muscle cells. It also inhibits bone formation and decreases intestinal calcium absorption. So when cortisol is high, there’s minimal to no bone growth and little muscle growth going on. And yes, there’s more when you have long-term high cortisol levels.

Adults with ADHD tend to have BDNF levels on the low side of normal for reasons still unknown. BDNF is “brain cell food,” so it’s important to continue neurogenesis throughout our lifetimes. Add high cortisol to the mix, and first, we see gut hyperpermeability. Why? High cortisol can cause the breakdown of your GI lining. It does this by slowing down both GI motility (peristalsis) and the process of digestion. When this happens, some people experience reflux, or “heartburn,” while others have absolutely no symptoms. Blood flow then decreases to all of the digestive organs. This results in a higher concentration of toxic metabolites, which then whittle away at your gut lining.

We then see a breach in the gut-brain barrier, the slow-down of conversion of neural stem cells into neurons, and the further lowering of BDNF needed for that process to happen. Cortisol has even been shown to be a direct neurotoxin!  The result=impaired cognitive performance in terms of memory, executive functioning, speed of thought, and so on. It usually all starts with a little “brain fog.”  More about the gut-brain barrier next.

In addition, we see dampened thyroid function, blood sugar imbalances,  insomnia, osteoporosis, blood pressure elevations, lowered immune function, and universally- increased abdominal fat. 

What happens to the gut-brain axis?

Much recent research shows that changes in gut microbiota could affect the brain’s cognitive, behavioral, and basically- all physiological functions. Although the exact mechanism of the connectivity of the gut-brain axis has not yet been elucidated, the evidence shows that gut microbiota plays an important role by producing immune factors, hormones, and metabolites that influence brain functioning.

Stress, meaning high cortisol, can significantly impact the microbiota-gut-brain axis. Recent studies have implicated the gut microbiota in many brain conditions, including anxiety, autism, Alzheimer’s disease, schizophrenia, and Parkinson’s disease. In addition, ongoing research implicates diseases such as obesity, heart disease, and diabetes.

Fixing the Effects of High Cortisol

When we finally stop someone’s amphetamines, we still have the carnage caused (often) by years of taking them with resultant years of high cortisol levels. We know cortisol is a direct neurotoxin, likely being a risk factor for Alzheimer’s disease. We know all of the things mentioned above. However, when we’re talking about the root cause of Ulcerative colitis, Crohn’s disease, or any autoimmune disease for that matter, we see the direct effect high cortisol has on the gut. As previously mentioned, sustained high cortisol can be the sole reason for having a leaky gut. But for adult ADHD symptoms controlled by the “traditional drugs” discussed previously, it often requires someone to actually experience cognitive changes to bring them to a doctor such as myself. So what do we do?

First, we lower high cortisol levels. Adrenal (herbal) adaptogens, glandulars, liposomal GABA, and certain aromatherapy oils are proven to lower cortisol levels. Stress-reducing techniques such as “vagal breathing,” meditation, and yoga are great practices to maintain overall health as well as lower cortisol levels. Finally, just activating your hypoglossal nerve (the nerve to the tongue and vocal cords) and, therefore, your adjacent vagal nerve to tone down your sympathetic nervous system will help. All you need to do is gargle, sing or do vocal exercises. We also always need to fix the gut lining and the microbiome. Here’s how we do it.

Heal the gut 

The pentadecapeptide BPC-157  (Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val) has been demonstrated to counteract peritonitis, and heal upper intestinal lesions, heal colitis lesions and seal up a hyperpermeable gut lining.

Gastric pentadecapeptide BPC 157, now found to be effective in the upper and lower GI tract, is remarkably free of side effects, as are the other peptides being used in functional medicine. More about peptides to follow.

Re-Balancing your Disturbed Microbiome 

By definition, when you have gut hyperpermeability, you have more “toxic bacteria” than “healthy bacteria” populating your GI tract.  Use prebiotic fiber to feed the good bacteria and (if you are not in a “mold and mycotoxin situation” a little bit of “good yeast” (Saccharomyces boulardii) to begin to re-create a healthy gut microbiome. If you like un-ripe bananas, they make great prebiotic fiber. Other foods include asparagus, Jerusalem artichokes, red onions, and naturally fermented (not pickled) foods such as sauerkraut.

When your gut lining is coming together-usually the 2 to 3-week mark, add probiotics. Historically, we have recommended 50 to 100 billion probiotic CFU’s per day. A mixture (in your main probiotic) of Lactobacillus species and Bifidobacterium species is probably fine. Still, even more evidence supports the use of sporulating probiotics for an even better microbiome. These probiotics are species of Bacillus with b. subtilis and b. coagulans being the most studied. Start as low as 5 billion and increasing to as many as 25 billion CFU’s daily (best done under a doctor’s supervision if you have GI symptoms). But now that you’re weaning from ADHD stimulants, what do you do?

Food, Exercise, Sleep, Therapy, and Supplements 

Studies have associated poor attention and worsened  ADHD symptoms with diets full of the unhealthy things we tell you not to eat, such as refined sugar and fried foods. In addition, artificial food colorings and the preservative-sodium-benzoate may worsen ADHD-hyperactivity in children but otherwise hasn’t been studied for other effects or in adults.

According to some good clinical evidence, regular exercise may reduce adult ADHD symptoms. And I don’t believe I need to tell you that poor sleep quality impairs attention and other cognitive functions, worsening ADHD symptoms.

Cognitive-behavioral therapy has been shown to improve ADHD symptoms in adults. In addition, mindfulness-based therapies improved ADHD symptoms in multiple studies, mostly in adults as well.

Supplements that might be useful: ADHD patients tend to have lower magnesium levels than average, with the caveat that most of us not on MG supplementation are a bit deficient. At any rate, in two clinical trials, magnesium supplementation did indeed improve adult ADHD symptoms. Similarly, there is a higher prevalence of vitamin D deficiency in ADHD patients, and studies suggest that supplementation is helpful. Finally, fish oil supplementation appears to be quite promising, is anti-inflammatory, and is usually a good “health practice” anyway.

L-Tyrosine: This amino acid is being discussed separately because the data supports its use in adults with ADHD. A review of 15 clinical trials concluded that L-tyrosine (a dopamine precursor) boosts attention and cognitive performance in stressful and demanding situations in normal adults. These were not trials done with adult ADHD symptoms, but the extrapolation of that data to patients with ADHD has resulted in numerous clinical reports of the same benefits. There is less data on SAMe (S-adenosyl-L-methionine), but one study indeed suggested that it might be a useful way to increase dopamine and norepinephrine.

Peptides 

Peptides are small chains of amino acids that make up proteins and are available in every part of your body. Because peptides can be found in any part of the body, they each have particular functions. They act as messengers, signaling specific glands and proteins into performing specific tasks. These; essentially bioidentical substances have been isolated and replicated for use by Functional Medicine doctors. Since they are bioidentical, there are no side effects. They are an amazing addition to our arsenal of treatments, and there happen to be three that are quite useful for adult ADHD symptoms.

Heptapeptide Semax: (Met-Glu-His-Phe-Pro-Gly-Pro) 

Semax is considered a brain-enhancing or “nootropic” peptide due to its ability to increase BDNF:brain-derived neurotrophic factor, nick-named “brain fertilizer,” since it is the largest (neurotrophic) stimulator of neurogenesis. In addition, Semax has also been found to be a potent enkephalinase inhibitor. In other words, the enzyme that destroys the natural painkillers and anti-anxiety brain chemicals called enkephalins is blocked by Semax, which has been independently proven to reduce anxiety and, therefore, likely decrease cortisol. In addition, several studies demonstrate its ability to cause the brain to release both serotonin and dopamine, enhancing feelings of well-being and, more-than-likely (due to the dopamine boost) attentiveness.

The heptapeptide Semax is an analog of the N-terminal fragment (4-10) of ACTH (adrenocorticotropic hormone) but is absent any hormonal activity. However, it has been found to stimulate memory and attention in rodents and humans after intranasal application. In addition, evidence from animal studies reveals that Semax augments the effects of psychostimulants on central dopamine release.

As noted above, it stimulates central brain-derived neurotrophic factor (BDNF) synthesis. In addition, Semax is thought to improve selective attention and modulate brain development. Since ADHD is likely to be a neurodevelopmental disorder with disturbance in both dopamine and BDNF function production, it is proposed by many neuroscientists that Semax may have excellent therapeutic potential in ADHD. In Russia, this peptide is used as a common alternative for drug therapy for children with ADHD. In addition, functional doctors in the U.S. prescribe it for mood issues, adult ADHD symptoms, cognitive and pain issues.

Cerebrolysin  

This peptide is widely used in Europe and Russia but not approved in the U.S. However, it has been studied for many years and is a go-to for adult ADHD in other countries. Numerous studies show that this peptide increases cognitive functioning and attention with decreased impulsivity in children and adults with ADHD.

Dihexa    

Dihexa is a peptide derived from angiotensin IV-a metabolite of the potent, naturally occurring vasoconstrictor angiotensin II.  Angiotensin IV  has been shown to enhance acquisition, consolidation, and recall of memory and learning in animal models.  What’s more, the peptide Dihexa has been determined to be seven orders of magnitude more potent than BDNF. Thus, you first read about BDNF as the potent neurogenesis stimulant, but there’s more to it than simply being a cognitive enhancer.

Brain-derived neurotrophic factor is the most dominant neurotrophin in the CNS (central nervous system). It plays a crucial role in physiological brain functions via its two independent receptors: tropomyosin-related kinase B (TrkB) and p75. These two activities are critical during neurodevelopment. In addition, the disrupting of BDNF signaling has been documented in many neuropsychological diseases, including ADHD.

Dihexa is a first-in-class compound that is orally active, penetrates the blood-brain barrier, increases BDNF, improves memory consolidation and retrieval as well as concentration and neural processing speed.

Miscellaneous Functional Medicine tools 

Deserving of more than an honorable mention is functional medication likely to be helpful with adult ADHD symptoms. While definitive research is pending, the logic is compelling for the following.

Oral nicotinamide mononucleotide supplementation increases intracellular NAD+ concentrations, improving mitochondrial biogenesis and ATP (mitochondrial energy) output. It is well known that the brain has an enormous supply of mitochondria, so mitochondrial enhancement should, in theory, benefit all brain functions.

The peptide selank increases BDNF and decreases levels of anxiety by increasing concentrations of GABA in the brain. Due to the importance of BDNF enhancement and, in some cases, lowering anxiety to ameliorate adult ADHD symptoms, it makes sense to utilize this peptide. But, again, data is pending on these two measures.

How to tell if you have a Hormonal Imbalance

A hormonal imbalance is having too much or too little of any of the myriad of hormones I’ll be discussing in this article. Out-of-whack hormone levels can cause just about any symptom imaginable. You can have weight gain or weight loss, hair loss, or excess hair growth. You can become lazy or anxious, sleep too much, or have insomnia! It’s no wonder people scratch their heads trying to self-diagnose. When you receive a diagnosis, you often don’t receive a full explanation, right? Bottom line: If you think you need hormone replacement therapy, seek a physician specializing in hormone replacement. To begin, let’s define “hormones.”

What are Hormones?

Hormones are the body’s “chemical messengers” that transport information from the brain to the “target glands,” The target glands secrete their hormones to affect their target cells.

Next, the cells send their messengers back to the brain to regulate how much message the brain needs to continue or not continue sending. Our bodies contain about 60 trillion cells that must communicate to carry out hormonally based functions. For hormones to be in balance, everything needs to work together, much like a symphony orchestra.

Hormones enter the cells through receptor sites. This can be thought of as akin to a key unlocking a door. Once inside, they flip the switches that control growth, development, and mental and physical functions throughout life.

As we age, the hormones that work to keep us healthy begin to decline. Hormonal balance is lost, causing unwanted symptoms, disorders, and even diseases. In other words, the hormonal symphony plays out of tune and out of cadence.

The A-Z of Where Hormones are Made

• Adrenals: Produces the hormones that control sex drive and the stress hormone cortisol, which controls salt and fluid in the body; aldosterone. DHEA is produced here too.
• Hypothalamus: Responsible for body temperature, hunger, moods, and the release of hormones from other glands. Controls thirst, sleep and is the “master supervisor” endocrine gland.
• Ovaries: Secrete estrogen, testosterone, and progesterone, the female sex hormones.
• Pituitary: The other “master control gland,” which controls other glands and makes the hormones that trigger growth. This is what happens in the anterior pituitary. The posterior pituitary produces ADH, controlling thirst and urination. It also provides pain-relieving endorphins.
• Pancreas: Produces the insulin that helps control blood sugar levels. Glucagon is secreted here too.
• Parathyroid: Controls the amount of calcium in the body.
• Pineal: Produces derivatives of melatonin, which affects sleep and more.
• Testes: Produces the male sex hormone, testosterone, and produces sperm, obviously in males.
• Thyroid: Produces hormones associated with metabolism.
• Thymus: Plays a role in the immune system’s function and the thymus’s maturity and is the primary source for immune “fighter” T-cells early in life.

I’ll cover each of these hormones in alphabetical order, preceded by some basics about hormone replacement therapy and followed by the questions you will be asking yourself about whether or not replacing your diminishing hormones is a good choice for you.

Correct Hormone Replacement Therapy

A little known but important fact about hormone replacement is there are two types of hormones available for hormone replacement therapy: Bioidentical hormones and synthetic hormones. This is extremely important because of the side effects. While some non-functional doctors will “argue” and even publish books touting their opinion that “only FDA approved” hormones-the synthetic ones-are the only ones that should be used, those same doctors are (correctly) touting the effectiveness of the non-FDA-approved mRNA COVID vaccines. It’s a matter of common sense that you, my reader, have or you wouldn’t be reading this article. Here’s why.

Bioidentical hormones are made from natural substances using a compounding process that results in an exact biological replica of the substance produced by our bodies. This is why they do not produce undesirable side effects when administered properly.

In contrast, synthetic hormones are synthesized from a variety of chemicals and, although these molecules resemble those produced by our bodies, they are not biologically identical replicas. As a result, their use can result in severe side effects, as evidenced by the warnings on the labels and research and clinical studies.

Furthermore, in addition to avoiding the risk of side effects and thus being safe, bioidenticals have been shown by most clinical studies to be protective when administered properly. Meanwhile, the latest studies (many of which are listed in the references) refute prior claims that synthetic and bioidentical hormones are “the same.”

I did specify “when administered properly” because hormone replacement therapy is a complex and delicate balancing act that needs to be individually tailored to each patient, often requiring a combination of hormones in conjunction with other mitigating compounded medications. I cannot tell you how often I “clean up the mess” made by unqualified doctors prescribing hormones to patients who “want to save a buck.” Let’s explore whether or not your symptoms sound as if hormone issues cause them.

Do you have Hormone Imbalance Symptoms?

I receive new patient inquiries all of the time, with complaints listed such as decreased energy, sleep disruption, brain fog, and reduced libido. This is usually (at least partially) due to an imbalance (usually too little; not too much) of one or more hormones. However, to determine the problems, I have to “think through” every hormone and organ system—tying everything together like the symphony metaphor I used above. Rather than explain why you can’t self-diagnose your own hormonal imbalance issue or issues, below you’ll find a synopsis of hormone function. This will prepare you to ask the right questions when you see a specialist. As promised, I will go from A to Z, which means we’ll start with aldosterone.

What the heck is Aldosterone?

Calcitonin

Calcitonin is a hormone released by the C-cells in the thyroid gland. It opposes the action of the parathyroid hormone, which you’ll read about further down our list. Both hormones regulate the blood’s calcium and phosphate levels. While it can be used to treat severe osteoporosis, I choose to use the Parathyroid hormone instead. Calcitonin is also used to treat Paget’s disease of the bone.

Cortisol

You have heard about the fight or flight hormones cortisol and adrenaline, right? Cortisol increases under stress which is a good thing for your body in the short term. However, long-term high cortisol levels can lead to increased coronary plaquing, a depressed immune system with associated risks for an increased risk of cancer, and measurably impaired cognitive function, just for starters! In the intermediate term, high cortisol levels can zap your energy by interfering with mitochondrial function. It can make you feel fatigued, and it’s not just because high cortisol levels interfere with regular sleep patterns.

Cortisol causes symptoms I’ll call “annoyances” only because that is how individuals treat them. High cortisol can trigger sugar cravings. It can be the main “driver” of menopausal belly fat. If you are trying to build muscle, it does just the opposite: “catabolic.” It not only can decrease muscle mass, but it also reduces bone mass and can slow down your metabolic rate by interfering with thyroid function too. Lastly and disastrously, it can trigger leaky gut syndrome, a leading cause of systemic inflammation.  This is the only hormone that actually (for the most part) increases as we age.

It is necessary to bring cortisol levels down for people under constant stress and most individuals over 55-65 years of age and older for all of the reasons mentioned above. I usually do this with a combination of adrenal adaptogens (containing ashwagandha, rhodiola, siberian ginseng, and astragalus) as well as an adrenal glandular preparation. Sometimes I use peptides, integratives, or liposomal GABA. There is even a role for some scientifically proven aromatherapy blends. This is the one “hormone arena” where people who read about HPA axis dysfunction (popularly termed adrenal fatigue) can generally self-diagnose much of the time. Please note that you need a medical workup if you self-diagnose and supplement and do not get better within a couple of months.

DHEA (Dehydroepiandrosterone)

I don’t know why this hormone gets a weird “rap”—for instance; it’s linked to anabolic steroids. This wonderful hormone is either not well known or is unfairly demonized, in my opinion. DHEA will amp up your immune system and help calm inflammation. Studies show “older Americans” with good DHEA levels have less depression than those with low levels. Lastly, it’s super important for bone thickness and the prevention of osteoporosis. You wouldn’t detect a DHEA hormone imbalance or deficiency symptomatically, which is why everyone needs key hormones checked as they age. Recent “brain studies” show that DHEA causes brain stem cell stimulation (to produce new neurons), another reason I insist all patients have this hormone normalized.

This hormone is safe to take unless you have a male who has had a “male cancer” or a female who has had “female cancer” or PCOS. DHEA metabolites might be a problem. But, you can safely take the 7-keto form of DHEA, which has the added benefit of being a bit of a metabolic stimulant.

Since when is Vitamin D a hormone?

Vitamin D is a pro-hormone the kidneys produce, which helps control blood calcium concentration and immune system function. The amount of Vitamin D made when sunlight hits the skin and is converted to the active substance called calcitriol by the kidneys is insufficient for most people. Recent studies reveal many cancers are linked to low vitamin D levels.

A low vitamin D level is also related to other issues such as heart disease, autoimmune disease, and even depression. This loosely translates into a minimum of 5000 IU’s per day of vitamin D, which should be consumed with vitamin K for optimal absorption. This is another lab test that should be checked (at least) annually. Recent guidelines recommend levels of 75-80 ng/dl as ideal. If you have an autoimmune disease, the literature strongly suggests higher vitamin D levels as optimal.

Estrogen

Estrogen is responsible for the development of “female pubertal changes.” Most women who contact me are interested in what to do when they have symptoms of estrogen deficiency due to menopause. But please take note that night sweats can be from estrogen deficiency, cortisol excess, mold toxin illness, or infectious diseases, meaning don’t just assume your “hot flashes” are due to estrogen deficiency.

If you have gained “the menopause 25,” it is due to an imbalance of several hormones, including estrogen deficiency. Losing the menopause weight without bioidentical hormone replacement is hard. Poorly done estrogen replacement (and yes, I have seen this) causes weight gain. Estrogen replacement, replacement of other hormones, and balancing cortisol levels make weight loss much easier. Estrogen counters most of the signs and symptoms women find bothersome about menopause.

However, that’s not the only reason to replace your missing estrogen. Estrogen helps your heart, bones, skin, and brain. I don’t know why “length of treatment” remains a controversial topic—likely because dangerous synthetic hormones have clouded the collective thinking on bioidenticals.

I would be remiss if I didn’t touch on two not-uncommon “female illnesses” which are now totally controllable with functional medicine treatment. PCOS (polycystic ovary syndrome) can cause metabolic issues, menstrual abnormalities, symptoms of high testosterone, and generalized inflammation. It can be well controlled, and if hormone replacement therapy is utilized, it is most efficacious if bioidenticals, not synthetics (such as “the pill”), are used for treatment. It is filed here under “estrogen” because often, estrogen levels are low, and cycles are anovulatory.

On the other hand, endometriosis tends to be a disorder associated with high, sometimes super-high estrogen-particularly estradiol levels. The endometrial tissue secretes estradiol, independent of ovarian estrogen secretion, and control of this disorder is also well done in functional medicine therapy, where estrogen levels are brought under control, and new endometrial tissue formation is blocked. Further discussion of these two disorders will be done elsewhere. Now, let’s move on to the pancreas.

Glucagon

This hormone is secreted by the pancreas and directly impacts the liver to control blood sugar levels. Glucagon prevents blood glucose levels from dropping to dangerously low levels. It does this first by stimulating the conversion of stored glycogen to glucose in the liver. It also keeps the liver from consuming glucose. This allows more glucose to enter the bloodstream when needed. Lastly, glucagon is essential for a process called gluconeogenesis: the production of glucose from amino acids.

HGH (Human Growth Hormone)

This is another hormone that gets “maligned”—likely due to its misuse in professional sports. HGH is necessary for many bodily functions. It helps heal injuries. Remember how quickly a sprained ankle healed when you were younger? That’s due to human growth hormone. An M.D-patient of mine had been to several well-known medical centers because he had such fragile skin. He bruised or bled with even a touch from someone else. When he contacted me, he had the lowest HGH markers I have ever seen. Therefore, he had incredibly fragile skin, and that was why he had the problem. Within three months of hormone replacement therapy, his symptoms vanished.

The FDA approves HGH for treating specific problems. The “side effects” are what have made this hormone notorious. It hastens the shedding of body fat and the development of lean muscle mass. It increases bone density and improves immune system function, according to most studies. Overall, it gives people a better sense of well-being. In clinical studies, it increases the dermis thickness—the layer of skin that contains the building blocks of skin called elastin and collagen. In fact, HGH users report they look younger.

Human growth hormone is not to be used in active or recent (within 5 years) cancer cases, as it causes existing tumors or remnant cells to grow. Despite the controversy over whether it does or does not cause cancer, no studies show that it (de novo) causes cancer. But, I need to emphasize this controlled substance should only be used under FDA guidelines. mTOR is one of the pathways stimulated by a marker of HGH called IGF1, and “too much MTor stimulation” might be related to adverse health outcomes. That’s why it’s always a good idea to counteract mTOR stimulation with good health practices such as exercise, intermittent fasting, and correct supplementation. When we stimulate the anterior pituitary to release more HGH by prescribing peptides, we see the same benefits as prescribing HGH for a fraction of the price. Now-back to the pancreas!

Insulin

The pancreas secretes insulin. People with type 1 diabetes have insufficient secretion. It’s an autoimmune disorder, and some cases are completely reversible. People with Type 2 diabetes have inadequate or unresponsive receptors for glucose uptake. Most individuals with Type 2 diabetes are overweight or obese. The entity most doctors call pre-diabetes is as having a fasting blood sugar of 99 ng/dL. What is normal blood sugar? Your fasting blood sugar should be 75-85 ng/dL, or you are “glycating” (stiffening) your body’s cells-all of them.

Insulin is responsible for getting blood sugar into all cells. By doing so, it increases muscle mass and fat storage. However, if insulin levels are too high, there is an increased risk of diabetes, heart disease, Alzheimer’s disease, and cancer. We use insulin as a biomarker for inflammation tied to most if not all disease states and aging in general. This is one hormone you want to keep at a nice, low level—around 2-3 uIU/ml. If applicable, you can get this level down with weight loss, curcumin, omega-3 fatty acids, green tea, and toxin removal. Now, I’d like to discuss a hormone most people think is simply “for sleep.”

Melatonin

Melatonin is one of the most underrated hormones. Most of us need supplementation by the time we’re 30 to have profound, restful, and restorative sleep. You can protect your natural melatonin secretion by maintaining a good circadian rhythm which includes blocking blue lighting as the sun sets. There are apps for tablets and phones you can set to dim your screen at sunset, and I suggest you do so. I recommend slightly higher doses of melatonin than you may be used for patients and families based on research that I find exciting. Here is just a sampling of “what else” melatonin can do for your health.

It reduces oxidative stress (free radical damage), thereby decreasing inflammation. Research shows it also helps block the process, which shortens telomeres, likely affecting genetic aging. It further reduces inflammation by reducing pro-inflammatory cytokines.

It augments immune function by increasing CD4 cells and also increases what is known as natural killer cells. Doing so helps us fight infections and was recently made a part of most good functional medicine COVID protocols.

Melatonin helps preserve brain mitochondria, slows age-related cognitive decline, and inhibits beta-amyloid formation in the brain. In addition, an exciting discovery is that we still have stem cells in our brains, even as adults. And guess what? Melatonin turns on these stem cells. Due to all of the brain-healthy effects, inexpensive but powerful melatonin makes it to my must-have hormones list for everyone.

Oxytocin

In women, oxytocin is responsible for signaling contractions of the womb during labor. The hormone stimulates the uterine muscles to contract, so labor begins. Because of this effect, synthetic oxytocin is sometimes used to induce a woman to start labor if she cannot begin naturally. Once the baby is born, oxytocin promotes lactation by moving the milk into the breast. When the baby sucks at the mother’s breast, oxytocin secretion causes the milk to release so the baby can feed.

At the same time, oxytocin releases into the brain to stimulate further oxytocin production. Once the baby stops feeding, the production of the hormone stops until the next feeding. Oxytocin function is less important for men, but it does appear to affect testosterone production in the testes.

Recent studies show oxytocin is an important hormone that controls some human behavior and social interaction. Oxytocin triggers the bond between a mother and an infant, and it may also play a role in recognition, sexual arousal, trust, and anxiety between partners and friends. It is released when we interact with a loved one, including our dogs; yes, our dogs. A 2017 study proves that you can bond your dog more to you and you- to your dog by staring into your dog’s eyes. And there is leftover oxytocin for you to use with your partner, family, and close friends!

Other fascinating research reveals that oxytocin hormone may affect addiction and stress levels. It also helps people overcome sugar habits with varying success. Recent studies show that it may be useful in pain management regimens as well.

Parathyroid Hormone

In the intestines, parathyroid hormone helps with vitamin D metabolism. This allows the body to absorb more of the calcium it digests from food. The hormone stops calcium release in the kidneys through the urine (stones!) while also increasing vitamin D production. This is one of the hormones where excessive amounts are more common than a deficiency when we are younger, but as with every other gland, the parathyroid glands can fail as we age. Anatomically, these four glands are found on the flip side of the thyroid gland, in the neck.

Pregnenolone

This is another hormone you might not have heard about, but if you’re anxious, you’ll certainly want to see if you’re deficient. It helps repair brain and nerve tissue, decreases anxiety, improves sleep quality, improves general well-being, and is probably brain-protective too. Self-medication with small amounts is generally fine.

Progesterone

Low progesterone complaints are often mistaken for psychological symptoms as all-too-many progesterone-deficient women are handed prescriptions for pharmaceuticals to treat anxiety and depression. Lack of progesterone causes PMDD symptoms, anxiety, irritability, depression, and more. Peri-menopausal sleep issues are generally the result of a dip in progesterone—the first female hormone “to go.”

Adding oral progesterone to the nightly regimen helps with sleep initiation and maintenance. I said “oral” because progesterone creams don’t pass the blood-brain barrier. Please check the referenced article for details on low progesterone symptoms and treatment.

Regarding the role of progesterone replacement in menopause, note that the menopausal weight gain referenced in an earlier section is partially due to the loss of progesterone.

Lastly, if you are on bioidentical estrogens, you must also be on progesterone, whether or not you have had a hysterectomy. You must protect not just your uterus but also your breasts from “unopposed estrogens.”

Testosterone

Testosterone is the most important of all male hormones. We know what happens in puberty, so we’ll skip that part. In adulthood, testosterone is a major energy hormone for men. It increases bone density and is responsible physically for libido and quite a bit of sexual function. The right amount (not too much) is good for cholesterol levels, improving cardiac health.

Bad publicity based on poorly done studies about testosterone supplementation causing heart disease has been completely debunked; testosterone doesn’t cause heart disease. If you take it in massive doses, who knows? But that shouldn’t happen. It also helps prevents prostate enlargement (if aromatization is controlled) and probably helps prevent prostate cancer. It is neuroprotective and decreases the incidence of Alzheimer’s disease in both men and women. Further, it increases muscle mass and bone density in men and women as well. The testosterone that is available on the black market requires self-diagnosis and trust that the substances are safe. Please consult a hormone specialist and don’t treat yourself for “low-T.”

A side note about testosterone is that if you are young, with a low testosterone level, that needs to be investigated, not just replaced. As an example, young men with CIRS will have low testosterone levels due to anterior pituitary involvement. HCG or Clomid is a much more appropriate choice for those patients to augment their testosterone levels while detoxing.

One last thing: if you are a woman who has had estrogen-receptor-positive breast cancer, you should not use testosterone replacement therapy for at least five years after you are done with treatment and considered to be in remission. The reason I’m bringing this up is that I’ve had to repair the damage caused by unqualified doctors who have placed women on testosterone supplementation, not realizing that some of it would be aromatizing to estradiol and then triggering a flare of their breast cancer.

Thyroid hormone

The active form of thyroid hormone (T3) is made from the inactive form (T4), which needs an enzyme (deiodinase)  that requires quite a lot of minerals, so make sure you are on a good multi-vitamin-multi-mineral supplement. I often see labwork where the Free T4 is normal, but Free T3 is low, indicating decreased T4 to T3 conversion the majority of the time. Remember, T3 is the active form of thyroid hormone.

T3 increases energy, fat burning and helps control weight. It increases appetite and heart rate. Too little causes chilliness, a loss of the outer 1/3 of eyebrows, and a decreased morning basal temperature (below 97.3F). If you are looking to self-diagnose before having lab results, you can measure your morning temperature for a week. If it’s lower than 97.3, chances are you’re hypothyroid—no matter what your lab testing shows. Insist on the proper lab testing. Here’s what to ask for: TSH, FREE T3, FREE T4, reverse T3, TPO, and other thyroid auto-antibodies.

Why do Hormones Decline?

However, before jumping into hormone replacement therapy, a good workup is necessary to rule out (or diagnose and treat) weight issues, inflammation, tumors, toxins, food allergies, head trauma, leaky gut, silent autoimmune disease, and excessive stress. A great form of natural hormone replacement is simply repairing the hormonal issue’s underlying cause (s). Once these problems are properly addressed, we can assess what truly needs to be replaced. Here are the basics.

In women, the symptoms of hormonal aging often first appear during early menopause (peri-menopause), when estrogen and progesterone levels begin to wane. Then they continue to decline throughout menopause. The hormone imbalance symptoms can begin as early as age 30.

Men usually experience a more gradual loss of hormones, mainly testosterone, which is called andropause. Unlike the sudden loss of estrogen that women face during menopause, the gradual loss of testosterone happens over time. It is often misdiagnosed or even dismissed as a “male mid-life crisis.” Both men and women usually experience weight gain, loss of energy, sleep disruption, and more during this time of life when (understandably!) most divorces occur.

Is Hormone Replacement Therapy Right for You?