Introduction
If you follow medical news, you know the gut microbiome is largely responsible for your overall health. Amazing, isn’t it? Hippocrates was right! After reviewing the ins and outs of the gut microbiome, I’ll get into gut health supplements and recommend the best gut microbiome test. Here’s what I’ll cover.
What is the Gut Microbiome?
The gut microbiome is a complex ecosystem comprising trillions of microorganisms, including bacteria, fungi, and viruses (specifically bacteriophages). These microorganisms and their genes collectively make up the gut microbiome.
Bacteriophages, or the “virome,” are viruses that specifically infect and replicate within bacteria. Interestingly, they outnumber gut bacteria and help shape the composition of the gut bacterial communities.
On the other hand, Fungi make up a smaller portion of the gut microbiome, known as the “mycobiome.” Candida is a prevalent genus of fungi in this microbiome.
Understanding the composition and dynamics of the gut microbiome, including these various components, is an active area of research as it has implications for our overall health and well-being.
The gut microbiome’s organisms are categorized into various taxonomic levels, including phyla, classes, orders, families, genera, and species. These taxonomic classifications help researchers understand the diversity and structure of microbial communities in the gut.
The gut microbiota can vary among individuals, and differences in the abundance of specific phyla can significantly impact health. The four dominant phyla commonly found in the gut microbiome are Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. Firmicutes and Bacteroidetes comprise around 90% of the gut microbiota.
Within the Firmicutes phylum, the Clostridium genus is particularly abundant, representing a large percentage of this group. Other genera within Firmicutes, such as Lactobacillus, Bacillus, Enterococcus, and Ruminicoccus, also play essential roles in the gut microbiome.
Understanding the distribution and abundance of these different taxonomic groups within the gut microbiome is crucial for studying their functions and potential impacts on human health.
While the focus has often been on bacteria in the gut microbiome, research has shown that both the mycobiome and virome can also play important roles in gut health.
The mycobiome, or fungal community in the gut, can be influenced by various factors, including diet and environmental factors. Dysbiosis or imbalances in the mycobiome have been associated with some immunodeficiency states and inflammatory disorders, such as Inflammatory Bowel Disease (IBD).
For example, specific fungal cell wall epitopes, such as anti-Saccharomyces cerevisiae antibodies (ASCA), have been found to be a biomarker for Crohn’s disease and are cross-reactive with the fungus Candida albicans.
Antibiotic use can also affect the balance of the mycobiome and lead to the overgrowth of certain fungi in the gut. We’ll discuss this later on in this article.
Overall, the mycobiome is an essential component of the gut microbiome, and its contribution to gut health is an active area of research.
The virome, composed chiefly of bacteriophages, is a highly diverse biological system within the gut. Bacteriophages are viruses that specifically infect bacterial cells, and their presence and activity can directly impact the immune system.
Bacteriophages can influence the immune system by stimulating the production of specific immune molecules, such as interleukin-1b and tumor necrosis factor-alpha, by macrophages. These molecules are involved in immune responses and inflammation.
Additionally, the gut virome is responsive to changes in diet. Different dietary compositions can influence the abundance and activity of specific bacteriophages within the gut.
In the next section, we’ll discuss the “gut bugs” populations found in each section of the gastrointestinal (GI) tract.
Understanding the population dynamics and functions of gut bacteria in different sections of the GI tract is crucial for comprehending their roles in digestion, nutrient metabolism, immune function, and overall gut health.
Gut Microbiome Components
The microbiota composition varies along the length of the gastrointestinal tract, from the mouth to the colon.
The colon, specifically the large intestine, harbors the highest density and diversity of bacteria in the gut. This is primarily due to increased nutrient availability (such as undigested dietary fibers) and slower material transit time through the colon. The colon’s lower pH also favors certain bacterial species’ growth.
In contrast, the small intestine generally has a lower abundance and diversity of microbiota than the colon. Several reasons contribute to this difference. Firstly, the transit time in the small intestine is relatively faster, allowing less time for the bacteria to colonize and establish. Additionally, the small intestine is exposed to the influx of digestive enzymes and bile from the liver, which can impact the growth and survival of certain bacterial species. Lastly, food substrates are delivered intermittently to the small intestine, further limiting the availability of nutrients for bacterial growth.
It’s important to note that even though the small intestine has a lower bacterial population, it still plays a crucial role in the digestion and absorption of nutrients.
Understanding these regional differences in the composition and function of the gut microbiota is essential for unraveling their contributions to overall gastrointestinal health and metabolic processes.
The human oral cavity harbors a diverse and abundant microbial community known as the oral microbiome. This microbiome typically exists in the form of a biofilm, commonly called dental plaque.
The oral microbiome includes various bacteria, such as Streptococcus mutans, Porphyromonas gingivalis, Staphylococcus, and Lactobacillus. Streptococcus mutans is a prominent component of the oral microbiota and is strongly associated with the formation of dental plaque and tooth decay (caries). It can metabolize sugars, produce acid, and contribute to the demineralization of tooth enamel.
Lactobacillus is another bacterium in the oral microbiome that can ferment sugar and produce lactic acid. This acid can also contribute to the development of dental caries.
Beyond oral diseases like caries and periodontitis, the oral microbiome has been linked to several systemic diseases. Research has found associations between oral microbiota and conditions such as esophageal, colorectal, and pancreatic cancers, diabetes, Alzheimer’s disease, cardiovascular disease, cystic fibrosis, and rheumatoid arthritis.
However, it’s important to note that these associations do not necessarily imply causation, and further research is needed to fully understand the complex relationship between the oral microbiome and systemic diseases.
Interestingly, the oral microbiome can also be targeted for disease treatment. Probiotics, such as a particular strain of Streptococcus called Streptococcus A12, have been investigated for their ability to buffer the acidic pH within biofilms. This buffering effect may help prevent dental caries caused by acid-producing bacteria in the oral microbiome.
Understanding the composition, dynamics, and interactions within the oral microbiome is crucial for maintaining oral health, preventing oral diseases, and potentially influencing systemic health.
While the esophagus has its distinct microbiome, that is beyond the scope of this discussion. Moving on to the stomach, let’s discuss the basics.
The human stomach harbors a diverse array of microbes, with five major phyla dominating the microbial population: Firmicutes, Bacteroidetes, Actinobacteria, Fusobacteria, and Proteobacteria. At the genera level, certain microbial genera are particularly prevalent in the stomach microbiome. These include Prevotella, Streptococcus, Veillonella, Rothia, and Haemophilus, among the most common genera in the gastric environment.
Observing the intricate composition of the human stomach microbiome and the key players contributing to its microbial diversity is fascinating. Understanding the role of these significant phyla and genera in the stomach microbiota is crucial for unraveling the complexities of digestive health and disease susceptibility.
Several factors influence the composition and diversity of the gastric microbiota, including diet, medication usage, inflammation, and Helicobacter pylori infection.
Diet: Dietary patterns and nutrient composition can affect the microbial composition of the stomach. Studies have shown that diets high in fruits, vegetables, and fiber are associated with a more diverse and stable gastric microbiome. In contrast, diets high in fat and sugar can disrupt the microbial balance in the stomach and promote the growth of potentially harmful bacteria.
Medication Usage: Medications such as proton pump inhibitors (PPIs) and antibiotics can significantly affect the gastric microbiota. PPIs work by reducing stomach acid production, which can alter the stomach’s environment and affect the growth of certain bacteria. Antibiotics, conversely, can cause extensive changes in the gastric microbiota by eliminating harmful and beneficial bacteria and allowing opportunistic pathogens to colonize.
Inflammation and Gastric Mucosa: Inflammation of the gastric mucosa and atrophic gastritis can also impact the composition of the gastric microbiota. Chronic inflammation can decrease microbial diversity, promote the growth of pathogenic bacteria, and cause imbalances in the stomach microbial community.
Helicobacter pylori Infection: Helicobacter pylori infection is one of the most significant factors affecting the gastric microbiota. H. pylori is a Gram-negative bacterium that colonizes the stomach mucosa, and its presence can cause a range of gastric conditions, including gastritis, peptic ulcers, and gastric cancer. H. pylori has been shown to alter the gastric microbiota by reducing microbial diversity and increasing the numbers of certain bacterial species.
Understanding the factors influencing the gastric microbiota is essential for developing strategies to promote a healthy microbial community and prevent or treat gastric diseases.
The small intestine is the most extended section of the gastrointestinal (GI) tract and has its own microbiome. Its microbial composition differs from that of the stomach and colon. Some bacterial genera commonly found in the small intestine include Lactobacillus, Clostridium, Staphylococcus, Streptococcus, and Bacteroides.
The population of bacteria in the small intestine increases as you move from the duodenum (the first part of the small intestine) to the distal ileum (the last part before the large intestine). The bacterial counts in the duodenum range from around 104-105 colony-forming units (CFU) per milliliter, while in the distal ileum, where transit slows down, the counts increase to 107-108 CFU/mL.
The composition of the small intestinal microbiota also changes gradually along the length of the small intestine. There is an increase in the proportion of gram-positive bacteria compared to gram-negative bacteria, as well as a shift from facultative anaerobic (oxygen-tolerant) to strict anaerobic species.
Small Intestinal Bacterial Overgrowth (SIBO) is a condition characterized by excessive bacteria within the small intestine. This overgrowth can disrupt the normal digestion and absorption processes, causing abnormal fermentation of nutrients and leading to symptoms such as excessive gas, bloating, diarrhea, and malabsorption.
SIBO has been linked to various conditions, with up to 78% of irritable bowel syndrome (IBS) cases being associated with SIBO.
It’s interesting to note that hormonal deficiencies can contribute to the development of SIBO. Hormones play a crucial role in regulating gut motility and maintaining the balance of gut bacteria. Any disruption in hormonal levels can affect food movement through the GI tract and promote the growth of bacteria in the small intestine.
Indeed, the various aspects of our health, including gut health and hormonal balance, are interconnected, and disruptions in one area can impact others. Understanding the role of the small intestine microbiome and conditions like SIBO can help develop effective treatments and maintain overall health. Now, let’s talk about the section of the G.I. tract where much of the “action” is: the colon.
The colon, also known as the large intestine, houses the most diverse and abundant microbiome in the human gastrointestinal tract. This microbiome is composed mainly of obligate anaerobes, which thrive in the colon’s low-oxygen environment.
Among the most abundant bacteria in the colon are members of the genus Bacteroides and anaerobic gram-positive cocci like Peptostreptococcus, Eubacterium, Lactobacillus, and Clostridium.
The colonic microflora plays a vital role in various host digestive processes. One of its primary functions is the fermentation of non-digestible carbohydrates, including dietary fibers that escape digestion in the upper gastrointestinal tract.
The colonic bacteria break down these fibers through fermentation, producing several beneficial byproducts, such as short-chain fatty acids (SCFAs). SCFAs, mainly acetate, propionate, and butyrate, are important energy sources for the colonic epithelial cells and contribute to overall colon health.
The gut microbiome is also involved in other essential functions, including:
Many studies on the gut microbiome rely on analyzing fecal samples to study the luminal “fecal” colonic microbiome. Fecal samples provide valuable insights into the overall composition and functions of the colonic microbiota.
However, it’s worth noting that there are also colonic-adherent microbiota that interact more directly with the host immune system. These adherent microbes require sampling through intestinal biopsies during procedures like colonoscopy to study their specific interactions with the host.
Understanding the functioning of the gut microbiome is a complex and evolving field of research. Ongoing studies uncover the intricate roles of the colonic microbiota in human health and disease.
How the gut microbiome works
Yes, it is true that approximately ten times as many microbial organisms inhabit our bodies as there are human cells. These microbes colonize various body parts, including the gut, digestive tract, genitals, mouth, and nose.
The health of someone’s microbiome is determined by the balance between “bad bacteria” and “good bacteria.” A healthy microbiome requires a higher ratio of beneficial to harmful bacteria to maintain resilience and stay symptom-free.
Unfortunately, factors such as a poor diet, high levels of stress, and exposure to environmental toxins can disrupt this balance, leading to an overabundance of potentially dangerous bacteria, fungi, yeast, and pathogens.
Although the human microbiome is home to various types of microorganisms, bacteria have been found to play a vital role in controlling immune function and inflammation. Researchers have identified over 10,000 different species of microbes in the human body, each with unique DNA and specific functions.
Maintaining a healthy balance of bacteria in the microbiome is crucial for overall health and well-being. Promoting diversity and abundance of beneficial bacteria through a balanced diet, reducing stress levels, and minimizing exposure to toxins can help support a healthy microbiome and its associated functions.
Indeed, researchers are still uncovering the many ways that different strains of bacteria affect various aspects of human health. Even so, some general characteristics of a healthy versus unhealthy microbiome have emerged in existing research.
A healthy microbiome is typically characterized by a high diversity of bacterial species, with a balance between “good” and “bad” bacteria. Additionally, it generally is more stable and resilient, able to resist changes in response to various factors such as diet, stress, and environmental toxins.
Conversely, an unhealthy microbiome is often characterized by a lower diversity of bacterial species and an overgrowth of pathogenic or “bad” bacteria. These imbalances in the microbiome have been associated with various health conditions, including obesity, autoimmune disorders, cognitive decline, and inflammation.
In summary, a healthy microbiome is diverse, balanced, and stable, while an unhealthy microbiome lacks these qualities. Ongoing research will likely uncover additional factors contributing to microbiome health and disease. Here are the basic functions of the microbiome.
Functions of a Healthy Gut Microbiome
As you know, the gut microbiome profoundly impacts our overall health and plays a vital role in various physiological processes. Here are some additional points to consider:
So, what is “normal?”
Normal Versus Abnormal Gut Microbiome
A healthy microbiome begins to form from birth and develops during early childhood. By age 3, a person’s microbiome closely resembles an adult’s. However, the microbiome continues to evolve throughout life, adapting to changes in diet, lifestyle, and other factors.
While the relative abundances of different microbial species can fluctuate, the overall community and function of the microbiome remain relatively stable and healthy. This stability allows the microbiome to perform important functions, such as synthesizing specific vitamins, aiding digestion, and supporting immune function.
On the other hand, an unhealthy microbiome can also be stable, leading to chronic disease. The concept of resilience is crucial in understanding the impact of disturbances on the microbiome. A resilient microbiome can withstand temporary disruptions, such as a single course of antibiotics, and return to its original state.
However, persistent interferences, like long-term changes in diet, recurrent antibiotic use, or disruptions during vulnerable periods (such as infancy or the peripartum period), can create a new, disease-promoting state in the microbiome.
It’s important to note that the relationship between the microbiome and specific diseases is still an active area of research, and more studies are needed to fully understand the complex interactions. However, maintaining a diverse and resilient microbiome through a balanced diet, healthy lifestyle choices and judicious (sparing) use of medications may support overall gut health.
There are specifically known indicators of a healthy gut microbiome. For example, gut microbiome alpha diversity (diversity in one sample) has been linked to positive human health, while lower levels of diversity are associated with several acute and chronic diseases. Another well-known marker is the Firmicutes to Bacteroidetes (F/B) ratio.
In addition, several particular bacterial species have been recognized for their benefits, such as Faecalibacterium prausnitzii. F. prausnitzii has been consistently reported as one of the primary butyrate producers in the gut, with the ability to reduce gut mucosal inflammation and protect against both colorectal cancer and inflammatory bowel disease. We’ll get “heavily” into the importance of butyrate and other vital fatty acids.
Another important bacterium is Akkermansia muciniphila. A. muciniphilia has been shown to contribute to the maintenance of a healthy gut barrier, regulate immunity, and modulate inflammation. Notably, a lower abundance of this organism has been associated with multiple diseases.
If you are reading this article, chances are you’ve read other articles about the gut microbiome. And perhaps you’ve been as confused as everyone else over the gut microbiome terminology. Let me clarify all of this terminology for you so you know what’s what moving forward. Let’s first discuss the terminology of the gut microbiome and gut health supplements.
Prebiotics
Prebiotics are defined as “selectively fermented ingredients that result in specific changes in the composition and/or activity of the gastrointestinal microbiota, thus conferring benefit(s) upon host health.”
The original definition of prebiotics, established in 1995, described these compounds as non-digestible food ingredients that play a crucial role in influencing the growth and activity of specific bacteria in the colon. By selectively stimulating the proliferation of one or a limited number of beneficial bacterial species, prebiotics were believed to enhance host health through their interactions with the gut microbiota.
The updated definition of prebiotics in 2004 introduced three critical criteria to refine the classification further. According to this revised definition, prebiotics should meet the following requirements:
Resistant to Gastric Acidity and Hydrolysis: Prebiotics must demonstrate resistance to gastric acidity, enzymatic hydrolysis by mammalian enzymes, and absorption in the gastrointestinal tract to reach the colon.
Fermented by Intestinal Microbiota: Prebiotics should be fermentable by the intestinal microbiota, indicating their ability to undergo microbial metabolism in the gut environment.
Selective Stimulation of Beneficial Bacteria: Prebiotics must selectively stimulate intestinal bacteria’s growth and/or activity associated with health and well-being, emphasizing their role in promoting the proliferation of beneficial microbial species in the gut.
Now for the benefits and more specifics.
Benefits and specifics of Prebiotics
Prebiotics can modify the gastrointestinal microbiota through dietary strategies for potential health benefits. Studies have shown that increased intake of dietary fiber, particularly fermentable fiber, can promote the growth and diversity of beneficial gut bacteria, leading to improved gut health and reduced risk of chronic diseases.
Low fiber intake, prevalent in Western societies, has been linked to impaired gut microbiota with reduced diversity and an overgrowth of potentially harmful bacterial species. This may contribute to the development of chronic non-communicable diseases, including obesity, cardiovascular disease, type 2 diabetes, and colon cancer.
Intervention studies in humans have also demonstrated that increasing dietary fiber and whole grains intake can increase gut bacterial diversity, highlighting the importance of a high-fiber diet for maintaining a healthy gut microbiome.
Therefore, prebiotic-rich foods such as whole grains, fruits, vegetables, and legumes can be an effective dietary strategy to promote gut health and potentially prevent chronic diseases.
Prebiotic Fibers
According to the definition provided by the Codex Alimentarius Commission in 2009, dietary fibers are described as “carbohydrate polymers with ten or more monomeric units, which are neither digested nor absorbed in the human small intestine,” and they fall into three categories:
This definition recognizes the diverse range of dietary fibers in natural foods and those obtained through various processing methods. It emphasizes that these carbohydrates should resist digestion and absorption in the small intestine and have scientifically demonstrated health benefits.
Indeed, plant-based fibers can be classified into various categories based on their origin, such as cereals and grains, fruits, vegetables, nuts, and legumes. It is important to note that different types of plants contain different fibers with distinct chemical compositions and physicochemical properties.
For example, bananas contain resistant starch and inulin-type fructans, which are prebiotic fibers that can promote the growth of beneficial gut bacteria. On the other hand, apples are a good source of pectin, another dietary fiber with health benefits.
Diets rich in various plant-based foods can provide a wide range of dietary fibers, thus supporting the diversification of the gut microbiota. The different types of fibers in these foods can selectively stimulate the growth of beneficial bacteria in the gastrointestinal tract, leading to a more diverse and balanced microbiota composition.
Therefore, consuming diverse plant-based foods can contribute to a healthier gut microbiome and overall gut health.
The microbial conversion of complex polysaccharides into monosaccharides involves a variety of biochemical pathways, which are facilitated by the enzymatic activities of bacteria in the gut.
When complex carbohydrates, such as dietary fibers, reach the colon, gut bacteria ferment them. The end products of this fermentation process include short-chain fatty acids (SCFAs) and gases such as hydrogen (H2) and carbon dioxide (CO2).
SCFAs, namely acetate, propionate, and butyrate, are the primary products of bacterial fermentation in the colon. These SCFAs are crucial in maintaining gut health and have several beneficial effects on the host.
SCFAs serve as an energy source for colonocytes, promote sodium and water absorption, and help regulate the colon’s pH. They also have immunomodulatory properties and can influence various body processes, including inflammation and metabolism.
The proportions of SCFAs produced during fermentation can vary based on the types of carbohydrates ingested and the gut microbiota composition. Different bacteria have different metabolic capabilities, which can result in variations in the production and ratios of SCFAs among individuals.
Therefore, measuring SCFAs in the colon can provide valuable information about bacterial fermentation and the health status of the gut microbiota.
Prebiotic Oligosaccharides
A regular diet typically contains various prebiotic oligosaccharide carbohydrates, including inulin-type fructans. Inulin-type fructans naturally occur in foods such as chicory root, Jerusalem artichoke, garlic, and certain cereals like wheat.
It is important to note that inulin-type fructans in foods can contribute to their prebiotic effects. Prebiotics are non-digestible dietary fibers that promote the growth and activity of beneficial bacteria in the gut, thus supporting gut health.
Inulin-type fructans, specifically, have been shown to selectively stimulate the growth of Bifidobacteria and Lactobacilli, which are considered beneficial bacteria in the gut microbiota. Remember that wheat grown in the U.S. may be problematic for many people, so watch out for GMOs and gluten.
Galacto-oligosaccharides
These diary-derived prebiotics have potential immune-modulating effects. Beta-galacto-oligosaccharides are prebiotic dietary fiber that can benefit the gut microbiota and immune system.
In a well-done study conducted on elderly subjects, supplementation with β-GOS was shown to have several positive effects on immune function. Some key findings from the study include:
Increased levels of the immuno-regulatory cytokine interleukin-10 (IL-10) regulate the immune response and reduce inflammation.
Significant reduction in the expression of IL-1β, a pro-inflammatory cytokine associated with the inflammatory response.
Increased interleukin-8 (IL-8) blood levels are involved in immune cell recruitment and activation.
Improvement in Natural Killer (NK) cell activity is vital for the body’s defense against viruses and cancer cells. Next, let’s move on to something you probably have heard about called resistant starch.
Resistant Starch
Resistant starch (RS) is naturally present in cereal grains and other starch-containing foods. It refers to a type of starch that resists digestion in the small intestine and reaches the large intestine intact. The resistance to digestion can be influenced by factors such as granule morphology, amylose-amylopectin ratio, and interactions with other food components.
RS is classified into four classes based on its digestibility. These classes help categorize the different types of RS based on their resistance to digestion and their impact on gut health.
One interesting study demonstrated that RS has a bifidogenic effect, meaning it increases the concentration of beneficial bacteria such as Bifidobacteria.
It also increased the levels of other beneficial bacteria, including Bacteroidetes, Akkermansia, and Allobaculum species. These bacteria are essential in maintaining gut health and promoting a balanced gut microbiota.
Furthermore, studies conducted in vitro and on mice have shown that resistant starch increases the production of short-chain fatty acids (SCFAs).
SCFAs are beneficial compounds gut bacteria produce during dietary fiber fermentation, including RS. SCFAs have several health benefits, such as providing energy for colonocytes, promoting gut health, and influencing various physiological processes.
While there are limited studies on humans, some evidence suggests that high amylose maize starch (HAMS) administration, a type of resistant starch, may have prebiotic effects in adults.
Other examples of resistant starch include cooked and cooled pasta and rice, oats, green bananas, certain legumes, and raw potato starch. For my extensive practice of autoimmune patients eating strict AIP, the best choice is green bananas.
Polyphenols
The primary sources of polyphenols are fruits such as berries, grapes, citrus fruits, apricots, apples, plums, cherries, peaches, and tropical fruits. Additionally, polyphenols can be found in popular beverages such as green and black tea, fruit juices, coffee, red wine, cocoa, and beer, as well as in various seeds, grains, and nuts.
Vegetables are also a good source of polyphenols, with onions, spinach, broccoli, cauliflower, artichoke, tomato, beans, soybeans, carrots, capers, and olives being some of the most common sources. Even spices and herbs such as clove bud, turmeric, celery, parsley, mint, rosemary, thyme, sage, dill, curry, and ginger contain high levels of polyphenols.
Polyphenols are a diverse group of compounds, and their concentration and type can vary widely depending on the food source. However, a diet rich in fruits, vegetables, nuts, and whole grains is generally associated with a high intake of polyphenols and other beneficial phytochemicals.
Polyphenols have numerous health benefits, including antioxidant and anti-inflammatory effects. Some studies have suggested they may protect against chronic diseases such as cardiovascular disease, type 2 diabetes, and certain cancers.
Flavonoid Polyphenols
Flavonoids are a major class of dietary polyphenols, constituting up to 60% of polyphenol intake. Due to their widespread presence in various foods and impressive biological functions and activities, flavonoids are continuously being studied for their potential as drugs or food supplements.
Some of the most common flavonoids include:
Other Flavonoid Polyphenols
Isoflavones:
Phenolic acids:
Hydroxybenzoic acids:
Anthocyanidins:
Chalcones:
Ellagic acid:
Hydroxycinnamic Acids
Cinnamic acid:
Caffeic acid:
Ferulic acid:
Chlorogenic acid:
Honorable mentions include rosmarinic acids, curcuminoids, and stilbenes, which will be discussed below in the “supplements” section. Now, let’s switch our focus from prebiotics to probiotics.
Probiotics
Probiotics are live microorganisms that provide health benefits when consumed or applied to the body. They can be found in several sources, such as yogurt and other fermented foods, dietary supplements, and beauty products. Probiotics often contain bacteria from groups like Lactobacillus and Bifidobacterium, which are commonly used. In addition to bacteria, some probiotics may also include yeasts like Saccharomyces boulardii.
Different types of probiotics may have other effects. For example, suppose a specific kind of Lactobacillus helps prevent an illness. That doesn’t necessarily mean another type of Lactobacillus or Bifidobacterium probiotics would do the same thing.
Probiotics work through various mechanisms to exert their beneficial effects on the host. Here are the three primary mechanisms:
Additionally, probiotics have been found to affect electrolyte absorption, gut motility, and even the perception of painful sensations. These actions can further contribute to their overall beneficial impact on digestive health.
It’s important to note that the specific mechanisms of action may vary depending on the strain and probiotic used and the individual’s unique microbiome and health condition.
Now, let’s clarify what synbiotics, paraprobiotics, ghostbiotics, and postbiotics are. Whew, right? Let’s start with simple synbiotics.
Synbiotics
Synbiotics are mixtures that consist of live microorganisms (probiotics) and substrates selectively utilized by host microorganisms (prebiotics) that provide a health benefit to the host. A symbiotic blend, which is what is commonly found for sale, typically contains a proven probiotic and a proven prebiotic.
There are two types of synbiotics: complementary and synergistic. A complementary synbiotic contains a live microorganism (which may or may not be a proven probiotic) and a substrate (which may or may not be a proven prebiotic). These components work together to provide a health benefit.
On the other hand, a synergistic synbiotic consists of a live microbe (not necessarily a proven probiotic) and a substrate (not necessarily a proven prebiotic) that the microbe can utilize for its growth. The combination of these components has a synergistic effect in promoting health.
In practical terms, a product labeled as a symbiotic blend typically contains a well-researched and proven probiotic strain combined with a proven prebiotic ingredient. The prebiotic substrate is often a fiber or polyphenol blend, which can selectively support the growth and activity of the probiotic microorganisms in the gut.
Postbiotics=Paraprobiotics=Ghostbiotics
The scientific community has proposed various terms for inanimate microorganisms and their components that can provide health benefits. Some commonly used terms for these substances include non-viable probiotics, paraprobiotics, ghostbiotics, heat-inactivated probiotics, and postbiotics.
In 2021, the International Scientific Association for Probiotics and Prebiotics (ISAPP) defined postbiotics as “a preparation of inanimate microorganisms and/or their components that confer a health benefit on the host.” This definition encompasses various substances derived from microorganisms that can positively affect human health.
Postbiotics can include various components such as cell components, cell fragments, and metabolic products of microorganisms. These substances can be derived from microbial sources, including bacteria, yeast, and fungi.
The health benefits of postbiotics are thought to arise from their interactions with the host’s body, including interactions with the immune system, promoting a healthy gut environment, and influencing various physiological processes.
It’s worth noting that the term postbiotics has gained significant recognition within the scientific community. However, it is important to continue researching and understanding the specific mechanisms of action and health benefits associated with these inanimate microorganisms and their components. Next, let’s identify the by-products we want produced by a healthy gut microbiome.
Beneficial gut microbiome byproducts
Intestinal microorganisms play a crucial role in various metabolic processes, including producing short-chain fatty acids (SCFAs). SCFAs, also known as volatile fatty acids, are an essential carbon flow from the diet to the host microbiome. They have several beneficial effects on the host’s health.
Maintaining a balanced intestinal microbiome promotes overall health and prevents diseases. Probiotic microorganisms have been found to positively impact the balance of the intestinal microbiome and the production of metabolites, including SCFAs.
Only a few of the approximately 60 known phyla of bacteria are commonly found in the human intestines. These include Firmicutes, Bacteroides, Actinobacteria, Fusobacteria, Proteobacteria, Verrucomicrobia, Cyanobacteria, and Spirochaetes. However, the two dominant bacterial phyla in the human gut are Gram-positive Firmicutes (such as Lactobacillus spp., Bacillus spp., and Clostridium spp.) and Gram-negative Bacteroidetes.
These phyla contain various bacterial species that contribute to the diversity and functionality of the gut microbiota. Imbalances in the relative abundance of these phyla have been associated with certain health conditions.
The gut microbiome has a remarkable ability to biotransform various chemical compounds. One of its essential roles is converting complex nutrients into simpler forms that the host can easily absorb and utilize.
Intestinal microorganisms break down complex nutrients, including plant cell wall components such as cellulose, pectin, hemicellulose, and lignin. These components are typically indigestible by the host’s enzymes alone. However, the gut microbiota contains specialized microorganisms with the necessary enzymes to degrade these complex carbohydrates. And when the fermentation starts- magic!
Short-chain Fatty Acids
Gut bacteria microbially ferment complex nutrients, producing short-chain fatty acids (SCFAs) as metabolic byproducts. The most common SCFAs produced in the gut are acetate, propionate, and butyrate, which constitute 95%, while formic, valerian, caproic, and lactic acids comprise approximately 5% and play lesser roles.
SCFAs have several vital functions in the body. They serve as an energy source for the cells lining the colon and are also absorbed into the bloodstream, where they can have systemic effects. For example, butyrate is a primary energy source for colonocytes and helps maintain the integrity and health of the intestinal barrier.
SCFAs also have anti-inflammatory properties, help regulate immune responses, and contribute to overall health and proper gut functioning. They have been associated with various health benefits, including promoting gut motility, improving nutrient absorption, and influencing metabolic processes.
SCFA production in commensal(host) and probiotic strains of bacteria
Commensal (host microbiome) species of bacteria noted to produce beneficial SCFA’s:
Bifidobacterium spp., Blautia hydrogentrophica, Prevotella spp., and Streptococcus spp. have been shown to produce acetic acid. Akkermansia muciniphilia and Bacteroides spp. have both been shown to produce acetic and propionic acid. Dalister succinatiphilus, Eubacterium spp. (e.g., E. halli), Megasphaera elsdenii, Phascolarctobacterium succinatutens, Roseburia spp., Salmonella spp., and Veillonella spp. have all been demonstrated to produce propionic acid.
Coprococcus spp. (e.g., Coprococcus catus), Roseburia inulinivorans produce both propionic and butyric acid. Anaerostipes spp., Coprococcus comes, Coprococcus eutactus, Clostridium symbiosum, Eubacterium rectale, Eubacterium hallii, Faecalibacterium spp. (e.g., Faecalibacterium prausnitzii), Roseburia spp. (e.g., Roseburia intestinalis) are major butyrate producers. Finally, we know that Clostridium spp. and Ruminococcus spp. have been shown to produce acetic, propionic, and butyric acid. I’m sure the database will grow daily and be larger once this article is published!
Let’s take a break here to note that you will find a breakdown of good microbiome labs and testing, which will be discussed at length near the end of this article. Get acquainted with some of the heavy-hitter species you want in your microbiome. Let me say the same with the upcoming discussion of probiotics, which we are only starting to see being produced for clinical outcomes. Here are the top ones.
Bifidobacterium spp. will produce mainly acetic and lactic acids. Lactobacillus rhamnosus GG (LGG) and Lactobacillus gasseri produce primarily propionic and lactic acids. Bifidobacterium longum and Bifidobacterium bifidum produce acetic, propionic, and lactic acids. Lactobacillus salivarius spp salcinius and Lactobacillus agilis produce propionic, butyric, and lactic acids. Finally, a well-studied strain, Lactobacillus acidophilus, has been demonstrated to produce acetic, propionic, butyric, and lactic acids.
Now, let’s examine the benefits of the main SCFAs. Butyrate leads the pack for overall health, but acetate and propionate are gaining steam as research progresses. To illustrate the importance of SCFAs, let’s start by discussing the “master SCFA”: butyrate.
Butyrate and gut health
Butyrate is often considered a “master” short-chain fatty acid (SCFA) due to its numerous beneficial effects on the gastrointestinal tract and overall health. Specific gut bacteria primarily produce butyrate through the fermentation of dietary fibers, such as resistant starches and other complex carbohydrates.
Butyrate plays a crucial role in maintaining gut health and function. Some key functions and benefits of butyrate include:
In conditions where there is an imbalance in the gut microbiome, leading to a decrease in the number of butyrate-producing bacteria and a reduction in SCFA levels, such as in inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), type 2 diabetes (T2D), obesity, autoimmune disorders, and cancer, the beneficial effects of butyrate may be disrupted.
This imbalance can contribute to gut barrier dysfunction, low-grade inflammation, and metabolic dysregulation in these conditions.
Therefore, promoting butyrate production and maintaining a healthy balance of SCFAs in the gut through dietary interventions, probiotics, and prebiotics can support gut health, reduce inflammation, and improve metabolic outcomes in these conditions.
Butyrate and the gut-brain barrier
The bidirectional communication between the gut microbiome and the central nervous system, known as the gut-brain axis, is an area of growing research interest. Short-chain fatty acids (SCFAs) influence, particularly butyrate, on neural processes, and neuroinflammation, is critical to this interaction.
While systemic absorption of SCFAs from the intestine into the bloodstream is minimal, with butyrate exhibiting lower concentrations than propionate and acetate, it’s important to note that the concentration of SCFAs in the brain itself is negligible. This means that direct activation of neuronal receptors by SCFAs in the brain is unlikely.
Instead, the proposed mechanism for SCFAs’ influence on neural processes is through the regulation of neuroinflammation. SCFAs, particularly butyrate, have been shown to have anti-inflammatory effects on the gut and systemic circulation.
These anti-inflammatory properties can indirectly impact the brain by modulating immune responses and reducing inflammation.
Neuroinflammation, characterized by activating immune cells and releasing pro-inflammatory molecules in the brain, has been implicated in various neurological disorders and conditions. By regulating neuroinflammation, SCFAs can influence neuronal function, mood, memory, and recovery after injuries.
Moreover, SCFAs can indirectly affect the gut-brain axis by modulating the release of certain neurotransmitters, such as serotonin and gamma-aminobutyric acid (GABA), which play essential roles in mood and cognition.
The specific mechanisms by which SCFAs modulate neuroinflammation and influence neural processes are still an area of ongoing research. However, the emerging evidence suggests that the gut microbiome and its metabolic byproducts, including SCFAs, have the potential to impact brain function and contribute to the pathophysiology of neurological disorders.
Butyrate and Aging
Gut barrier integrity, enhancement of mitochondrial function, enhancement of immune responses, and even beneficial effects on telomeres all point to butyrate’s role in slowing the aging process. Quickly increase your butyrate levels with the consumption of MCT oil. I use this exclusively for cooking: odorless, tasteless, with a low flash point-perfect!
Propionic acid (Propionate)
The gut microbiome has been implicated in developing and progressing atherosclerotic cardiovascular disease (CVD). Compared to healthy controls, individuals with atherosclerotic CVD have observed changes in gut microbial composition, specifically an increased abundance of certain bacteria and a depletion of butyrate and propionate-producing bacteria.
A metagenome-wide association study found that patients with atherosclerotic CVD had higher levels of Enterobacteriaceae and Streptococcus spp. while experiencing a relative depletion of bacteria that produce butyrate and propionate. This suggests that short-chain fatty acids (SCFAs), including butyrate and propionate, may be functional in promoting cardiovascular health.
Propionate has been shown to have vasodilating effects in the vasculature by activating the G protein-coupled receptor 41 (GPR41) in the vascular endothelium. This activation decreases blood pressure.
Consume omega-3-rich fish like sardines, salmon, or mackerel to increase propionate levels. Omega-3 fatty acids, found in abundance in these types of fish, have been associated with beneficial effects on cardiovascular health. Due to propionate levels? At least partially, yes, indeed. Now, let’s turn to our last SCFA, acetate.
Acetate
Acetate, one of the short-chain fatty acids (SCFAs), plays a role in weight control and metabolic issues, particularly insulin sensitivity. The interplay between the gut microbiota, host metabolism, and metabolic health is an area of growing research interest.
The gut microbiota has been found to regulate various aspects of metabolism and peripheral tissues such as adipose tissue, skeletal muscle, liver, and pancreas through the production of metabolites, including SCFAs. Acetate has been shown to benefit host energy and substrate metabolism.
Animal and human studies have demonstrated that acetate influences metabolism by promoting the secretion of gut hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY).
These hormones affect appetite regulation, leading to a reduction in food intake. Additionally, acetate has been found to reduce whole-body lipolysis, lower systemic levels of pro-inflammatory cytokines, increase energy expenditure, and enhance fat oxidation.
These effects of acetate on host metabolism contribute to improved insulin sensitivity and may have implications for weight control and metabolic health. Because of the recent social media attention regarding vinegar ingestion and the national obsession with weight loss, let me discuss how to increase your acetate levels.
Acetate from Dietary Sources
Because recommending a TBSP of vinegar daily has become so commonplace, I will spend some time discussing why this might be beneficial. It’s not for the reasons touted in “folklore.” Commonly consumed kinds of vinegar contain between 4% and 8% acetic acid, and vinegar ingestion has gained attention in the scientific literature because of its acute effects on glucose and lipid metabolism.
Oral ingestion of vinegar can rapidly increase circulating acetate levels. In healthy participants, serum acetate levels increased from 120 µmol/L during placebo conditions to 350 µmol/L (after 15 min) and 200 µmol/L (after 30 min) following intake of vinegar (100 mL containing 0.75 g acetic acid) and acetic acid capsules (containing 0.75 g of acetic acid), respectively.
Acetic acid, a bioactive component with a dominant flavor in different types of vinegar (including cider, malt, plum, sherry, tomato, and wine vinegar), increases circulating acetate levels. It is important to consider the type of vinegar used, as its phenolic, flavonoid, and acetic acid content composition may differ.
Some kinds of vinegar, such as apple cider vinegar, grape vinegar, sherry vinegar, and balsamic vinegar, may contain other polyphenol residual components like gallic acid and catechins. These compounds have been linked to various health benefits, including improved blood sugar control, reduced inflammation, and reduced risk of chronic diseases.
In terms of microbiome alterations that produce more acetate-producing species, human fasting and caloric restriction interventions have described an increase in microbial diversity and abundance of essential acetate producers, such as Akkermansia muciniphila (A. muciniphila) and Bifidobacteria. Now, let’s switch gears back to the gut microbiome and what exactly shapes its composition. We’ll start with the basics.
What Shapes the Adult Microbiome?
Diet: Indeed, short—and long-term dietary habits significantly impact the gut microbiome. Short-term changes in diet can lead to rapid but reversible shifts in the microbiome, often accompanied by intermittent gastrointestinal symptoms.
Fiber, particularly microbiota-accessible carbohydrates (MACs), is crucial in nurturing the gut microbiome. When gut microbes ferment MACs, they produce short-chain fatty acids (SCFAs), such as acetate, butyrate, and propionate. These SCFAs have numerous health benefits, including improving gastrointestinal transit by influencing serotonergic pathways.
Low-MAC diets, which are low in fiber, can cause negative shifts in the gut microbiome. The lack of MACs essentially starves the gut microbes, leading them to seek food sources from the host epithelium and mucus. This epithelial barrier disruption can increase the risk of gut inflammation and other gastrointestinal issues.
In addition to low-fiber diets, additives like emulsifiers and artificial sweeteners can adversely affect the gut microbiome and increase the risk of metabolic and inflammatory disorders.
Optimizing fiber and MAC intake is recommended to promote a healthy gut microbiome and overall health. Including fiber-rich foods like fruits, vegetables, whole grains, legumes, and nuts can support the growth and diversity of beneficial gut bacteria. Minimizing the consumption of processed and packaged foods that contain additives can also help maintain a healthy gut microbiome.
Stress: It is well known that stress can negatively impact immune function. When your body perceives stress, it diverts energy and resources from the immune system to prioritize immediate survival responses. This shift in energy allocation can make you more susceptible to infections and result in more severe symptoms. Furthermore, chronic stress can lead to higher levels of inflammation, which can contribute to various health issues.
During stress, immune compounds called cytokines can contribute to the inflammatory response that damages healthy cells. This chronic inflammation can disrupt normal bodily functions and increase the risk of chronic diseases.
Exercise is a natural stress reliever and has numerous benefits for immune function. Physical activity can help lower inflammation, balance hormones, and strengthen the immune system. Exercise can increase the production of antibodies and stimulate the release of endorphins, which are natural mood elevators. These positive effects of exercise can help reduce stress and its impact on the immune system. Let’s delve into that a bit more.
Exercise: Exercise has been shown to positively impact the gut microbiome by increasing the abundance of beneficial bacteria and promoting gut diversity. Studies have found that athletes tend to have a more diverse gut microbiome and lower levels of inflammatory markers. Animal studies have also demonstrated that exercise-related changes in the gut microbiome can reduce susceptibility to inflammation and weight gain.
It’s important to note that the changes in the gut microbiota induced by exercise can be similar in magnitude to, but different from, dietary changes. While exercise can contribute to weight management, sustained weight loss also requires nutritional changes. Both training and a healthy diet are complementary in improving overall health, including the gut microbiome.
To achieve significant changes in the gut microbiota through exercise, it is generally recommended to engage in moderate to high-intensity exercise for 30 to 90 minutes at least three times per week or accumulate between 150 and 270 minutes weekly for a minimum of eight weeks. This consistent exercise routine will likely produce noticeable changes in the gut microbiome.
Vagal nerve stimulation: The brain, gut, and microbiota are connected through a bidirectional communication pathway known as the microbiota-gut-brain axis. This communication involves the autonomic nervous system, particularly the vagus nerve (V.N.). The Vagus nerve is a mixed nerve composed of approximately 80% afferent fibers (transmitting information from organs to the brain) and 20% efferent fibers (transmitting information from the brain to organs).
The Vagus nerve plays a crucial role in interoceptive awareness, allowing it to sense microbiota metabolites through its afferent fibers and transfer this information to the central nervous system. This information is then integrated into the autonomic network, influencing various physiological processes.
One important pathway mediated by the Vagus nerve is the cholinergic anti-inflammatory pathway. Through this pathway, vagal fibers release anti-inflammatory neurotransmitters, dampening peripheral inflammation and reducing intestinal permeability. By modulating inflammation and gut permeability, this pathway may play a role in shaping the composition of the gut microbiota and promoting healing of the gastrointestinal tract, including the “leaky gut” phenomenon.
Conversely, stress, accompanied by the release of cortisol, can inhibit the function of the Vagus nerve. This can negatively impact the gastrointestinal tract and the gut microbiota.
Chronic stress is implicated in the pathophysiology of conditions such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD), which are characterized by dysbiosis (microbial imbalance) and increased gut permeability. Vagal nerve stimulation with a device like the one found here has been demonstrated to improve gut permeability and microbial balance.
Sleep: Lack of sleep and poor sleep quality can significantly impact the quality of the gut microbiome. Research has shown that even two days of sleep deprivation can cause a noticeable shift in the ratio of Firmicutes to Bacteroides, two major bacterial phyla in the gut. This shift may have implications for metabolic health and weight regulation.
Sleep disturbances can also lead to changes in the composition of the gut microbiota, favoring less metabolically friendly species. Studies in mice have shown that chronic sleep fragmentation can decrease the abundance of beneficial Lactobacillus species in the gut, which have various health-promoting effects.
Ongoing research illuminates the importance of adequate and restful sleep for maintaining a healthy gut microbiome. Sleep is a critical restorative process for the body, and disruptions can have wide-ranging effects on various physiological systems, including the gut microbiota.
Medications: PPIs, antibiotics, laxatives, statin drugs, metformin, statins, benzodiazepines, hormones, antidepressants, antihistamines, and nonsteroidal anti-inflammatory drugs are examples of all the medications that are associated with changes in the composition of the gut microbiota. Never has it been more apparent that the fewer pharmaceuticals we ingest, the better!
Smoking: Studies show that smokers have lower levels of acetic, propionic, and butyric acid and decreased levels of beneficial Bifidobacterium. Overall, smokers show less microbiome diversity.
Pollution: Data is emerging showing that pollution negatively impacts the gut microbiome. Some studies correlate pollution exposure to increased levels of inflammation associated with decreased butyrate production.
We are learning more and more about the effects of “forever chemicals” on the immune system and, in parallel, on the microbiome. It’s not good. Specific data links the ubiquitous forever chemical PCB to a notable decrease in microbiome diversity.
Geography, urban versus rural living unrelated to pollution per se reveal quite a range of different microbiome compositions, and this data continues to emerge. Undoubtedly, we’ll see data linking the excellent health in the “blue zones” to more diverse and healthy microbiomes.
Shout-out to older siblings and furry pets: Children with older siblings and (moreso) the owners of furry pets have more diverse and generally healthier microbiomes. This bolsters my theory that every child needs a pet!
Now that we know what can disturb the microbiome let’s discuss the best diet to support our microbiomes.
Healthiest Microbiome Diet
Diet plays a crucial role in establishing gut health and supporting the growth of beneficial bacteria in the microbiome. Over the years, research has shown a strong connection between a person’s microbiota, digestion, body weight, and metabolism.
Studies have revealed that the microbiome environments can differ significantly depending on the diet of humans and other mammalian species. Different dietary patterns can lead to variations in the composition and diversity of the gut microbiota.
Conversely, the health of your gut can also affect how your body processes nutrients from your diet and stores fat. The gut microbiota has been found to play a significant role in obesity, and changes in the bacterial strains present in the gut can lead to notable changes in health and body weight in just a few days.
For example, experiments with mice have shown that germ-free mice, which lack any gut microbiota, become fatter when they receive a transplant of gut microbiota from conventional or fat mice, even without any increase in food intake. This suggests that the gut bacteria can influence hormone production, such as insulin, and affect nutrient extraction and fat storage.
These findings highlight the intricate relationship between gut microbiota, diet, and metabolic health. It is becoming increasingly clear that maintaining a balanced and healthy gut microbiome through a nutritious diet is crucial for optimizing digestion, body weight management, and overall metabolic well-being.
Now that you can see why it’s critical to lower inflammation and support gut health let’s examine how to do this.
Foods that promote inflammation= avoid
The items listed below are commonly associated with adverse effects on gut health and overall well-being. Let’s go over each of them.
To support gut health, it is recommended that people focus on a diet rich in whole, unprocessed foods—including many fruits, vegetables, whole grains, legumes, and lean protein sources. Choosing healthy fats, such as avocados, nuts, seeds, and olive oil, is also beneficial.
Additionally, incorporating fermented foods like yogurt, sauerkraut, and kimchi can provide beneficial bacteria for the gut. Let’s take these general recommendations and spell them out more useably so that you know what you can and should eat.
Anti-inflammatory foods
Treats: Red wine and dark chocolate/cocoa in moderation contain prebiotics! These can be consumed several times per week or a small amount daily. Now, what about supplements?
Best gut microbiome supplements
When discussing supplements for the microbiome, we generally talk about prebiotic supplements. I mentioned a few in the discussions above, but here are the main ones used today. Here are some common flavonoid prebiotic supplements that are frequently “multi-use.”
We often use catechins, including EGCG supplements derived from green tea, which have been shown to be anti-cancer in several studies. We also use quercetin and fisetin, both of which are multi-use supplements.
Continuing in the flavonoid class are the curcuminoid polyphenols curcumin and turmeric. Rounding out this class of supplements are stilbenes: resveratrol and pterostilbene.
In the category of resistant starch, potato flakes have gained popularity lately.
Probiotics are next when it comes to supplementation, with species identified to reinforce the gut lining (Akkermansia M.), improve gut microbiome diversity (sporulating species; mostly Bacillus), as well as Lactobacillus and Bifidobacterium species, which help metabolism and mood, and much more. As an example, pouring through PubMed looking for probiotics to help reduce anxiety by increasing GABA yields the following information.
Some probiotic strains that can increase GABA (gamma-aminobutyric acid) include Lactobacillus brevis, Bifidobacterium dentium, Bifidobacterium adolescentis, and Bifidobacterium infantis. These strains are part of the lactic acid bacteria (LAB) and bifidobacteria groups, which have been shown to produce GABA. Additionally, other Bacteroides species have been found to produce large quantities of GABA.
As a reminder, there are many ways to improve SCFA production, from consuming a TBSP of vinegar daily for higher acetate levels to taking fish oil supplements to increase propionate levels and using MCT oil for cooking to increase butyrate levels.
The advent of synbiotics and parabiotics has not developed to the point where I can recommend anything specific regarding these two categories. However, no matter what you plan to do to improve your gut microbiome, isn’t it a good idea to know its composition and whether you have enough diversity and SCFA production?
After reviewing all microbiome tests on the market, I have found only one test with enough data and recommendations to be considered accurate and “actionable.” It’s this one. If you haven’t received it yet, get it on the app and let me explain next.
Best microbiome test=microbiome labs (Yes, there’s an app for it!)
Most microbiome tests out there are, frankly, useless. The Injoy test is different – it integrates microbiome data with dietary, lifestyle, and symptomatic information through Patient-Reported Outcomes (PROs), painting a complete picture of gut health.
1 – In-Depth Longitudinal Analysis:
2 – Cutting-Edge AI, Gutchat:
3 – Actionable Recommendations:
Bottom line: We all know the field of microbiome testing is full of overhyped promises. Injoy is not about that. They provide tools that work based on solid science. You can find the Injoy app in your Apple or Google app store. Please use my discount code: DRKIM10. You’re welcome!
Conclusion
Hopefully, you have read this article with more knowledge of testing, evaluating, and improving your gut microbiome. You have learned the terminology of the available products to improve your gut health. You have learned what foods help and what foods “hurt.”
Importantly, you have learned what activities and products to utilize and which ones to avoid. If you feel overwhelmed, start cleaning up your diet from ultra-processed foods and getting an Injoy kit. At some point in the not-too-distant future, good medical practices will be based not just on patient history, physical exams, and bloodwork but also on the results of microbiome testing. As an important addendum, there are studies linking various herbal supplements with the production of SCFA in the gut, but rather than give you a huge laundry list, I feel that you will benefit from getting an Injoy kit and then supplementing scientifically with the help of their AI-powered GutChat.
Leptin and its receptors are essential regulators of body weight and energy homeostasis. Multiple studies show that decreasing leptin’s tissue (or receptor) sensitivity leads to metabolic disorders, including obesity. Physiologic mechanisms underlying the development of leptin resistance include gene mutations that encode leptin and its receptors, proteins involved in the self-regulation of leptin synthesis, and even factors that alter blood-brain barrier permeability. Leptin resistance is a complex pathophysiological phenomenon with multiple “lines of attack” for potential treatment. Why is this important? Leptin resistance is the leading driver of fat gain in humans so let me break down how I’ll discuss this complex topic.
Leptin is a peptide (short-protein) hormone, originally thought to be secreted solely by fat cells; now known also to be secreted by the kidneys, placenta, salivary glands, and stomach. It’s important to note that leptin levels increase exponentially, not linearly, with fat mass. Leptin receptors are found in their highest concentrations in the brain, specifically in the hypothalamus and hippocampus.
In some clinical studies, chronically-elevated leptin levels correlate with overeating, obesity, and, as mentioned above, metabolic diseases, including diabetes, hypertension, heart disease, and metabolic syndrome.
The exact way “leptin works” is unknown, but the leading theory involves leptin release post-meal, penetration of the blood-brain barrier, and satiety signaling in the hypothalamus. The hypothalamus then signals to the rest of the brain (and probably to fat cells and our microbiome) that we have enough fat stored, we no longer need to continue eating. As a result, caloric burning can continue at a regular rate.
What Are Normal Levels?
We can measure leptin levels with a simple blood test. The results are in ng/mL (nanograms per milliliter).
Normal leptin levels are approximately 4.5 – 23.5 ng/ML and vary slightly between labs. They depend on a person’s BMI, age, gender and tend to get higher throughout the day, towards nighttime when they peak. Degrees of severity are loosely given with “mild” as 15-20 ng/ML and “severe” as 50ng/L or more, but this varies from person to person.
It has been called the “weight loss hormone,” the “satiety hormone,” and even the “starvation hormone.” We know that leptin resistance potentiates the extreme hunger experienced by a high ghrelin state. This (leptin-resistant) physiologic state somehow makes fat cells “think” that they must hang onto fat for dear life. This particular metabolic problem makes weight loss quite tricky unless you deal with the leptin resistance head-on.
Leptin resistance occurs when leptin effectively decreases appetite or increases energy expenditure through basal metabolism or lipolysis in fat cells. As a result, tissues become resistant to even high levels of leptin: a similar phenomenon to insulin resistance with (obviously) different hormonal pathways and different treatments involved.
Clinical studies demonstrate that obese people usually have very high levels of leptin that don’t perform their job correctly. One of the reasons for this is that a leading leptin production site: fat cells, make leptin in proportion to their size.
Although leptin suppresses the appetite when slightly raised, it seems to have the opposite effect when it gets too high. That’s why most researchers feel that leptin resistance leads to increased appetite and decreased energy expenditure.
We can measure leptin levels and speculate on why people become leptin resistant. Theories include leptin entering the brain less effectively, decreasing leptin receptors, or an over-activation of negative feedback loops due to chronically high leptin levels. No matter what causes it, we now have some excellent ways to combat this problem and assist with weight loss. As you’ll see, it’s never a one-size-fits-all (no pun intended) when it comes to effective weight loss strategies. Let’s now get into how we address leptin resistance in the functional medicine world.
A typical American diet, high in refined sugar and “bad” saturated fat, causes negative structural changes in the brain. Those negative changes occur primarily via neurotrophins (“brain cell fertilizers) such as BDNF. What this means in “real life” is that we see a significant decrease in all neurotrophins if you eat an inflammatory diet. Therefore, it is crucial for brain health and overall good health, and as you are learning now: weight loss, you cut out refined sugar and eat only “good” saturated fats. “Good fats” (such as avocado and coconut) help you lose weight and are suitable for your health. In addition, your testable cognitive performance will improve within months when you consume a healthy diet.
Yes, I know this header got a bit of an eye-roll from you. However, I’m just giving you the scientific facts, so know that your body and brain undergo metabolic changes when you are overweight. BDNF will decrease when you are over-fat, with high body weight. When you reduce your weight, you improve your overall health and increase your BDNF levels and help your brain perform its functions better.
Reducing your daily caloric intake or practicing various proven ways to do intermittent fasting can increase levels of BDNF. There is so much data coming in on the brain health benefits of intermittent fasting and the benefits for weight management and overall health that, at a minimum, timed eating intervals should be a part of your life: 5 days per week. Restricting your food intake to 8 hours a day (e.g., 11 AM to 7 PM) is ideal, but difficult for many; and doing a 10-hour window has benefits, as does even a 12-hour window; so do what you are “able” to do and push yourself a day or two per week.
If you are currently a couch potato, you have nowhere to go but up when it comes to BDNF levels. Any exercise at all will boost your BDNF levels. Whether you are walking your dogs, going up stairs, walking from your parked car to the store-anything-will help. However, high-intensity interval training (HIIT) that super-boosts your heart rate will exponentially increase your production of BDNF. Consistency is essential: one intense exercise session once in a while will not make any difference. To reap the full benefits of increasing your BDNF levels through HIIT, you need to train this way a minimum of only once per week.
Of course, doing it three times per week is even better. Studies show that as little as 10 minutes of HIIT will raise BDNF levels. Start by simply jumping rope, running on a treadmill, or doing jumping jacks or burpees for 30 seconds to a minute. Do one of these activities until you feel short of breath, then walk slowly to catch your breath. Perform this sequence three times, working up to 6 times while gradually and comfortably increasing the active intervals.
Of course, I’m going to discuss social connections, not money. Social enrichment (e.g., more meaningful and numerous interactions) for adults increases levels of BDNF. In addition, studies show that children exposed to socially enriched environments experience long-lasting cognitive and behavioral benefits.
A socially enriched environment is also beneficial for animals too. Rodents, for example, have been shown to have a lifelong increase in BDNF levels, as well as positive social behaviors and reduced risk of depression when raised in a stimulating and “rich” social environment.
Some drugs can raise BDNF levels. Short term, they are probably safe, but their long-term use is entirely unclear. I will only discuss one of the classes of drugs here as I do not recommend the use of pharmaceuticals to raise BDNF. Instead, I will explain the mechanism of this one class of medication below only because there is a healthy alternative. And as you will see “in a bit,” there is another bioidentical class of substances that work better than pharmaceuticals.
SSRI Drugs
SSRIs (Selective-serotonin reuptake inhibitors such as Prozac) will increase levels of BDNF when used to treat depression. These drugs do this by elevating levels of the neurotransmitter; serotonin. However, it is unclear how these drugs affect our brains with long-term use. A no-risk way to increase serotonin is to take the building block, 5-OH tryptophan, which is perfectly safe if you are not taking other anti-depressants and not bipolar.
Some supplements will “help the cause” but are nowhere near as strong as the peptides I’ll discuss next in terms of increasing BDNF. However, they are not used only to increase BDNF. Many of these supplements (integratives) are pretty helpful for a myriad of other reasons outside this particular article’s scope. They include green tea extract, curcumin, acetyl-l-carnitine, omega-3 fish oils, resveratrol, and vitamin D, something everyone should be taking. Now for the “seriously good stuff.”
If you’re my patient, you are probably using the intra-nasal peptide Semax or the oral peptide, Dihexa which both far exceed the power of the just-named supplements to increase BDNF. If you are not familiar with peptides as a class of medications (not drugs), here is a description.
Peptides are small sequences of amino acids that make up specific proteins. I’m talking about tiny proteins that have been isolated from human secretions and have many natural target functions. They have been studied and re-purposed for use throughout the body. They act as messengers, signaling specific glands and other proteins into performing or improving particular tasks. These tasks often have no relation to their usual function. These bioidentical substances have been isolated and replicated for use by compounding pharmacies. Since they are bioidentical, there are no side effects. They are a fantastic addition to our arsenal of treatments, and there happen to be two that are quite useful for enhancing BDNF levels. A third peptide called Selank also increases BDNF levels but is more commonly used for anxiety and cortisol issues which I’ll discuss in the next section.
Heptapeptide Semax: (Amino acid sequence: Met-Glu-His-Phe-Pro-Gly-Pro)
Semax is a “nootropic” peptide due to its ability to increase BDNF: the most potent stimulator of neurogenesis. In addition, several studies demonstrate its ability to cause the brain to release both serotonin and dopamine, enhancing feelings of well-being and improving depression.
The heptapeptide Semax is an analog of the N-terminal fragment (4-10) of ACTH (adrenocorticotropic hormone) but lacks any hormonal activity. However, after intranasal application, it stimulates memory and attention in rodents and humans. Therefore, let me just mention that it’s also useful for Adult ADHD.
Dihexa: (Endogenous hexapeptide angiotensin IV)
Dihexa “rules” when it comes to increasing BDNF. It’s a peptide derived from angiotensin IV, a metabolite of the naturally occurring vasoconstrictor angiotensin II. Angiotensin IV enhances memory acquisition, hippocampal consolidation, and recall in animals. In addition, Dihexa is seven times more potent than BDNF itself!
Dihexa is a first-in-class oral compound that penetrates the blood-brain barrier to increase BDNF significantly. As a result, it improves memory consolidation and retrieval and neural processing speed and concentration. The bonus is that it helps drive down leptin levels quite nicely too.
In the hours or even days after the experience of an ongoing stressful event, glucocorticoids (e.g., cortisol and similar substances)increase in the bloodstream. This phenomenon is important when considering what cortisol does to accumulate and store body fat. Glucocorticoids enhance the activity of the enzyme lipoprotein lipase in adipose (fat) tissue, leading to an increase in fat storage. This fat storage occurs even moreso in visceral (deep) fat, where lipoprotein lipase activity is higher. Therefore, chronically elevated cortisol levels contribute to visceral fat accumulation.
High cortisol can trigger sugar cravings for reasons which are not clear. It is one of the principal “drivers” of menopausal belly fat. If you are trying to build muscle, it inhibits that by being catabolic. It not only can decrease muscle mass, but it also reduces bone mass and can slow your metabolic rate by reducing adrenal and, therefore, thyroid functioning. Finally, it can trigger leaky gut syndrome, which causes systemic inflammation, another cause of leptin resistance.
And finally, glucocorticoids influence the function of leptin, whose usual role, as you recall- is to signal satiety and therefore suppress appetite. Although glucocorticoids stimulate leptin release from fatty tissue, they also reduce the brain’s sensitivity to leptin, contributing to leptin resistance.
In functional medicine, we strive to maintain a normal fasting cortisol level in our patients. Therefore, I often re-set the adrenals with adrenal adaptogens and adrenal glandulars. Sometimes I use integratives such as a magnolia bark derivative. Sometimes I will prescribe pure liposomal GABA. Often, I’ll rely on another BDNF-enhancing intra-nasal peptide called Selank.
Heptapeptide Selank: (Thr-Lys-Pro-Arg-Pro-Gly-Pro)
Numerous clinical studies have shown that Selank has strong anti-anxiety and, therefore, cortisol lowering effects. The clinical impact of Selank is similar to those of anti-anxiety medications such as Xanax or Valium-benzodiazepine drugs, which increase the activity of the calming brain chemical: GABA. We see this similarity of effect in several clinical trials, with the advantage of using Selank being its non-addictive properties and its ability to increase BDNF.
Chronic, low-grade inflammation is innately associated with various metabolic disorders, including obesity. Many complex physiologic pathways responsible for this phenomenon are currently under investigation regarding therapeutic, pharmacological intervention. Unfortunately, the discussion of the possibilities is far too premature for this article, which focuses on alleviating leptin resistance. So, let me make sure you know what chronic inflammation is, and then let’s go into how to take care of this particular issue.
What exactly Is inflammation?: Let me clarify the concept of “acute inflammation.” Think about getting a splinter in your finger. If you don’t remove it, the area turns red and gets puffy. That’s acute inflammation- a good thing, as it’s your body responding appropriately to the situation. It’s also your immune system flooding the area to fight off any viruses or bacteria that might have come in with the splinter. If you leave the spot alone with a physical injury, the swelling will go down, and everything will go back to normal. The signs of acute inflammation are swelling, heat, redness, and pain. The symptoms of inflammation will all resolve as healing occurs.
However, if you don’t remove the splinter and instead keep poking at the same spot, you will maintain high levels of inflammation. That’s what happens with chronic internal inflammation, but you can’t feel the splinter or the poking. The inflammatory response is short and precise. When it’s chronic, inflammation can be “silent,” make you feel fatigued or contribute to many other health problems. It can even make you look older! Here are the principal causes of chronic inflammation.
Unhealthy diets: I know I sound like a broken record with this mantra, but it is imperative to eat a healthy diet. Commonly consumed foods considered” inflammatory” are highly-processed carbohydrates, sugary foods, high-industrial fat and seed oils, high-gluten, and quite frankly, all overly processed and fast foods. Unfortunately, this just so happens to be the typical U.S. diet. And a big reason why just about everyone who is not “taking this seriously” is chronically inflamed. Furthermore, this eating pattern causes oxidative stress, which worsens inflammation.
Gut hyperpermeability AKA “leaky gut”: This is another pervasive American problem due to eating habits, consumption of pharmaceuticals (especially antibiotics), high cortisol levels (especially since the COVID pandemic), and the increase of mycotoxin illness. It is easily treated (usually with a gut-specific peptide such as BPC-157). Still, first, you need to recognize that you might have no symptoms or minor symptoms such as gastrointestinal bloating or mild constipation. Since this is the root cause of all autoimmune disease, it’s always a good idea to treat this problem, no matter what.
Your weight: Fat cells are little inflammation-producing factories. The more you have and the bigger they are, the more inflammation they cause for your entire body. The risk of chronic inflammation is a guarantee if you are obese or even just overweight. Obese and overweight women and men have higher levels of inflammatory blood markers than men and women of the same age who are not overweight or obese. According to numerous clinical studies, inflammatory markers decrease when men and women lose weight.
Excessive omega-6 intake: Omega-6 fats form the building blocks for inflammatory eicosanoids, a vital part of the inflammatory response. High omega-6 status (especially when combined with poor omega-3 levels) translates to excessive production of inflammatory eicosanoids and an exaggerated inflammatory response to normal stimuli. Cut down on your omega-6 intake by reducing your intake of meat and dairy products. Lowering omega-6 intake has been demonstrated to lower leptin levels.
Insufficient omega-3 intake: Conversely, omega-3 fats are the precursors for anti-inflammatory eicosanoids. Poor omega-3 status means inadequate anti-inflammatory eicosanoids, which blunts the anti-inflammatory reaction to normal stimuli. It’s easy to get good blood levels: eat omega-3-rich fish such as salmon or sardines and take good omega-3 fish oil supplements. Let me mention that leptin also responds to flipping your Omega 3 to Omega 6 ratio.
Lack of sleep: Poor sleep causes elevated blood inflammatory markers in and of itself. Disordered sleep is a chronic problem in the U.S. We go to bed too late, wake up too early, don’t get enough hours of sleep, or we use too many electronics late at night and disrupt the sleep quality we get. I’ll get more into the topic of sleep in this article, as disordered sleep in many forms will raise leptin levels, and I definitely need to address this issue.
Chronic stress: I know we discussed cortisol earlier as an independent risk factor for elevated leptin levels. But I’d be remiss if I didn’t discuss the relationship to inflammation (independent of causing leaky gut, too!). Your body will have a physiological, inflammatory response to emotional stress, which, as you now know, translates to a high cortisol level.
Toxins: Heavy metals such as mercury and lead, as well as biotoxins such as mycotoxins and Lyme toxins, can cause chronic inflammation.
Lack of movement: A lack of activity causes systemic, low-grade inflammation. We often sit for hours and then don’t make time for regular exercise. We need to get out of the Zoom room and make time to move more. Get up on your feet for two to three minutes each hour you’re sitting. Better yet, do some burpees, jumping jacks, or push-ups. And you may not even have to do “this much” to get positive health benefits. Recent data regarding exercise reveals that “exercise snacks” are great for your health. An exercise snack is as little as 1,2, or 3 minutes of activity. Use your imagination-it can be any sort of movement at all. Doing it just three times a day is demonstrated to be good for your health, even if you aren’t doing anything else that day that “counts” as exercise.
Lack of outdoor time: We all spend too much time cooped up in offices or, more likely “now,” in our home offices, doing those blasted zoom calls. We just don’t spend enough time in nature. Believe it or not, this lack of time out in nature can indeed cause low-grade inflammation.
Poor recovery and Overtraining: Some people move too much- over-exercising, with too little rest and recovery. Overtraining causes chronic inflammation. Obviously, this is a potential issue for elite athletes, but even casual bikers, swimmers, and runners can overtrain. I’m certainly not discouraging regular exercise, but over-exertion to the point of daily fatigue can cause inflammation, as well as elevated cortisol levels and disrupted sleep. Speaking of sleep, I’d like to focus a bit on this near-epidemic problem.
Both “regular” sleep patterns and circadian rhythms modulate daily metabolic shifts. Various sleep deficiencies associated with short sleep duration, insufficient sleep schedules, narcolepsy, sleep apnea, circadian misalignment (including shift work), and even sleep-related eating disorders contribute to metabolic dysregulation. Sleep deficiencies or circadian disruption, which cause or contribute to metabolic dysregulation, will contribute to weight gain and obesity by disrupting energy balance, causing inflammation, impairing glucose tolerance and insulin sensitivity, and raising leptin levels.
Disruption of sleep and circadian rhythms is increasingly evident as a contributing factor to impaired physiological function, especially concerning metabolic dysregulation, overweight and obese conditions. Ongoing research regarding regulating circadian rhythm with melatonin implicates melatonin as a possible way to improve leptin resistance. Once again, what dominates the literature is a “sleep peptide” called DSIP (delta sleep-inducing peptide).
DSIP (Trp‐‐‐Ala‐Gly‐Gly‐Asp‐Ala‐Ser‐‐‐Gly‐Glu)
This highly effective peptide is useful for insomnia of all types; sleep interruptions, re-sleeping issues, and sleep induction problems-all, with enormous success. It is also effective for people with circadian rhythm issues; again, quite successfully. Although there have been no clinical studies looking at the use of DSIP in people trying to shed pounds, I have personally seen quite a correlation in my clinical practice. Of course, this is “anecdotal,” so take that with a grain of salt.
Yes, I know we discussed weight loss, intermittent fasting and have touched on food choices; but now I’d like to get more in-depth about eating habits in general.
Over-eating: Independent of metabolic changes and weight gain, consistently “eating too much” in one sitting appears to raise leptin levels. Based on epidemiologic data, no one should consume much more than 500 calories in a single meal consistently. In addition, hedonically-loaded foods (the seriously fatty-sugary-tasty stuff) interrupt the inhibitory actions of leptin on orexin (satiety) neurons in the brain and interfere with the homeostatic control of feeding.
Specific foods: We discussed the concept of inflammatory foods, but it doesn’t stop there. Unhealthy, fast-food-type diets reportedly induce a different inflammatory response in the hypothalamus in animals. This hypothalamic response subsequently promotes the development of brain leptin resistance and then- obesity.
Protein consumption: In a few small studies, increasing dietary protein intake from 15% to 30% of calories (with a constant carbohydrate intake) produced statistically significant decreases in caloric intake, so those study participants lost weight. The mechanism by which this occurred is unknown, although the theory is that it somehow causes increased brain leptin sensitivity.
Omega-3/6 content in the protein we consume: Whether due to a decrease in inflammation, or other factors, when we increase our Omega 3 fatty acid intake via supplements or fatty fish, and we decrease our Omega 6 fatty acid consumption by substituting plant-based eating for meat and dairy, we see reduced leptin levels.
SIRT1 is a NAD(+)-dependent protein deacetylase enzyme. If you have SIRTT1 dysfunction, you typically have issues with glucose and cholesterol. You also usually have some degree of fatigue caused by decreased NAD(+) levels due to decreased mitochondrial function. In addition, SIRT1 activity improves both leptin sensitivity and insulin sensitivity; conversely, a SIRT1 deficit will impair these pathways. NAD(+) is necessary to transfer energy from cell to cell and help carry out numerous metabolic functions.
Overall, SIRT1 in the hypothalamus improves energy (NAD+ levels), glucose control, and leptin and insulin sensitivity. Both SIRT1 and NAD(+) levels decrease with age in the brain’s temperature regulation center- the hypothalamus. Increased hypothalamic SIRT1 levels prevent age-associated weight gain and improve leptin sensitivity in mice. Therefore, avoiding the age-dependent (as well as disease-dependent and toxin-dependent) loss of SIRT1 and NAD+ function in the hypothalamus could potentially improve leptin sensitivity.
Exciting studies that look quite promising involve improving SIRT1 and, therefore, leptin sensitivity with IV NAD+, intra-nasal NAD+ or oral nicotinamide ribonucleotide (NMN). I use these modalities in my practice currently with (again anecdotally) notable success.
I didn’t mention that high triglyceride levels will contribute to leptin resistance. In this day and age, all primary care doctors know that high triglycerides are an independent cardiac risk factor and, therefore; treated accordingly. So, there’s that. I also didn’t discuss metformin as a viable treatment for leptin resistance, even though doctors routinely use it to treat metabolic issues in women with PCOS (polycystic ovary syndrome).
The reason for that is not due to any inherent danger of metformin use-in fact-it is a pretty safe drug; it just doesn’t work all that well for leptin resistance. Now, let me get into the “mentions” of things that didn’t quite make the cut for having enough data, but they are things that make sense to me (given the data we have), or the emerging data is super-promising. Here they are.
Autophagy is a term that you will be hearing about more and more as a contributor to disease and aging. It’s a process by which cells remove and recycle junk proteins, and some studies link it to leptin resistance. No matter what, we are starting to recommend “meds” to enhance autophagy even now. Next, let’s discuss hormones, many having positive effects on aging, disease, and metabolic issues, including excess fat. In particular, estrogen deficiency is likely to cause leptin insensitivity in the brain based on good animal data.
And believe it or not, there is more research about how what we eat might impact leptin. Some theories suggest that lectins (e.g., gluten, beans, grains, dairy, nightshades) bind to surface receptors of cells–including leptin receptors–and mimic or block the effects of that receptor. This theory posits that lectins could interfere with the function of leptin, exacerbating leptin resistance. To “cover all bases,” I advise my moderate to severely leptin-resistant patients to avoid lectins.
New data is evolving consistently regarding the use of cold therapy, whether that be cold showers, ice baths, or even cold weather. Of course, cold might play a role in leptin regulation, so stay tuned for more data on this. But, at least we know that cold is excellent for your mitochondria and, therefore, your energy levels, so why not?. One last and critical note- if you are trying to lose weight and have leptin resistance, don’t do a ketogenic diet, or it will worsen the leptin problem; seriously! (Use keto for insulin resistance).
In my clinical practice, I find that adjusting eating and exercise plans, normalizing cortisol, sleep (often using DSIP), and prescribing NMN and dihexa do the trick every time. The “weight loss peptide” AOD-9604 then “kicks in” when leptin is low enough to allow it to accelerate lipolysis. Bon appetit!
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.”
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.
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.
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.
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.
Most of you have never heard of this hormone, even though it plays an important role in cardiovascular health. The adrenal glands produce aldosterone. Aldosterone affects the body’s ability to regulate blood pressure. It signals the kidneys to increase or decrease the amount of sodium (salt) the body sends into the bloodstream or the amount of potassium excreted in the urine. Indirectly, aldosterone also helps maintain the blood’s pH and electrolyte levels.
Aldosterone is closely linked to two other hormones: renin and angiotensin—which is basically how your body uses the kidneys to regulate your blood pressure. When these three hormones are “out of whack,” your blood pressure can go up.
In addition, in severe adrenal “fatigue,” aldosterone levels can be reduced, causing worse fatigue as well as postural blood pressure changes, mimicking what is knows as POTS.
The posterior pituitary gland secretes this hormone to work in conjunction with the kidneys, regulating what is called the osmolarity of your blood. Osmolarity is basically how much your blood and urine get concentrated as it passes through the kidneys. People with biotoxin illness (mold and mycotoxin illness and Lyme) often have low ADH issues, as do people with a history of head trauma. The symptoms are excessive thirst and urination—the same symptoms we associate with the onset of diabetes.
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.
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.
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.
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 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.
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.
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!
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 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.
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.
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.
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.
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 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.
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.
Hormonally and physically speaking, your body peaks around the age of 25. We often assume that things like a foggy memory, low libido, menopausal weight gain, hair loss, and wrinkles are simply a part of “getting older.” Worst of all, that’s what most doctors think too! But, we can relieve these symptoms with the use of bioidentical hormones.
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?
In my opinion, most people benefit from melatonin replacement, and it’s “bad medicine” not to replace vitamin D. It’s a good idea to monitor DHEA-S, estrogen, progesterone, thyroid function, insulin, and testosterone levels once you hit age 30-35. If you need treatment, I hope that you’ll “go with” bioidentical hormone replacement therapy. I also hope you will find a well-trained specialist who doesn’t replace your primary care doctor but works with them. Please save this article to refer to in case you develop symptoms in the future.
If you are not currently among almost one-half of U.S. adults with high blood pressure, then the odds are that you might develop high blood pressure at some point in your life without some preventive measures. In this article, I’ll discuss all of the proven natural ways to lower blood pressure.
Some people have high blood pressure caused by an underlying condition. This type of high blood pressure is called secondary (rather than primary) hypertension (HTN), with those underlying conditions spelled out in this article. All types of hypertension increase your risk for serious health problems, such as stroke, heart disease, ocular blood clots, kidney failure, and dementia. So, it’s clear you want to have normal blood pressure. Below you will find a blueprint for achieving your health goals naturally, which will cover the following:
Let’s first review risk factors you can easily control. For example, you can stop smoking, control alcohol consumption and, for those who are “salt-sensitive,” control your salt consumption. In addition, you can increase potassium-containing foods (such as bananas and raisins) and take a good magnesium supplement. Estimates show that 80% of Americans are magnesium deficient, and magnesium relaxes vascular smooth muscle; to directly lower blood pressure. In addition, your weight and the amount of exercise you do affect your blood pressure.
It’s important to have an exercise regimen that will help to lower your insulin levels. Studies have traditionally shown that “cardio” or “aerobic” activities such as jogging and swimming tend to be the most beneficial for lowering blood pressure.
However, more recent studies reveal the good news that you don’t need a 30-60 minute workout to reap the insulin and blood-pressure-lowering benefits. Short, intense workouts such as high-intensity interval training (HIIT) are becoming more popular for both health and efficiency. It’s fairly easy to construct a HIIT regimen to do at home. You don’t need to do exact “timed intervals”; it’s just about getting short of breath, recovering, doing it again, and so on. If you have been exercising regularly, start “low and slow,” and if you haven’t exercised much since your “school years,” get medical clearance. Try doing burpees until you’re short of breath for 3 sets and work up to 6 sets, 2x per week. You can also do sprints on a track or in a pool. You can run in place, jump rope, or do jumping jacks.
Before I get into a more verbose discussion about non-inflammatory eating, I mention two food items we all used to think were healthy foods. Unfortunately, these so-called health foods have become poison for most people with existing high blood pressure, grains, and sugars (including fructose). Since many people still think grains and fruit juices are healthy choices, I want to emphasize they most certainly are not. Now, the science.
Closely linked are the metabolic abnormalities of high blood sugar, high insulin levels, high leptin levels, and, therefore, insulin and leptin resistance at the receptor level.
Hypertension can be caused by cellular glycation (stiffening) from high blood sugar levels, so getting your blood sugar under control is a must. In addition, most people with hypertension have insulin receptors that don’t work efficiently, called insulin resistance. To compensate for this, your body produces more insulin. To lower insulin levels, you need to replace processed foods with real, whole foods. You also need to eliminate or dramatically reduce sugar and processed fructose (fruit) sugar and grains from your diet. Some studies show a closer correlation between fructose consumption and hypertension than even sodium! And then there’s leptin, another hormone that looms upward as you eat poorly and gain weight.
You can easily become leptin-resistant (with the attendant high leptin levels) by eating the same diet full of sugar (particularly fructose and grains once again.) Together, these foods will create the perfect environment for weight-packing bacteria to thrive in your GI tract; or microbiome. You then have your gut telling your metabolism to slow down and your high leptin levels telling you to keep eating and store more fat in your fat cells. It’s not a pretty picture, but it can be easily reversed. Other factors that play into the high leptin scenario include high cortisol levels (to be discussed) and other hormone imbalances. Often this trio shows up as belly fat. Lowering blood sugar, leptin, and insulin are partially achieved by simply losing weight which I’ll discuss next.
I’ve talked about blood sugar, insulin, and leptin. To complete the discussion of the diet plan to normalize your weight for life, you must eat an anti-inflammatory diet. This can be a basic anti-inflammatory diet, a stricter autoimmune,no-lectin diet, or even a ketogenic diet plan. A paleo diet is effective, but you must be sure to compensate for the over-abundance of omega-6 fatty acids in meat. Here’s how you do just that.
Just about everyone needs to normalize their omega 6-to-3 fat ratio. Also, omega-3 fatty acids are vital for healthy blood pressure. Findings from a study of 2,000 healthy men and women between the ages of 25 and 41 showed that those with the highest serum levels of omega-3 also had the lowest blood pressure readings.
Both omega-3 and omega-6 fats are essential for your health, but most Americans consume too many omega-6 fatty acids in their diets and too few omega-3s. This is because we tend to eat more meat and milk and less omega-3 fish. Eating omega-3 fats is a great way to re-sensitize your insulin receptors if you are insulin resistant. It is also essential for normal, healthy blood pressure. Wild-caught salmon and sardines are both low-mercury and high omega-3 containing fish. However, it’s hard to consume enough to compensate for all of the omega-6s we eat, so I always recommend a good omega-3 supplement.
Internal inflammation is associated with all disease states, including hypertension. Because approximately 70% of Americans are overweight, this alone is considered a major cause of reversible inflammation. In addition, eating the standard American diet (S.A.D.) described above will increase inflammation levels. Add in toxins such as heavy metals (mercury) and fluoride in drinking and showering water, and you’ve piled onto our national epidemic of inflammation. On the other hand, if you reduce your weight, clean up your diet, deal with toxins, stress and heal your probable leaky gut, then you will make a big “dent” in your inflammation problem and your blood pressure level, too.
Oxidative stress (defined as an over-abundance of free radicals which are not sufficiently quenched by antioxidants) worsens inflammation. But, this can be easily reversed with enough vegetables, fruits in moderation, and a high-antioxidant supplement.
There is a publicly accepted long-term myth that stress raises your blood pressure. It does short-term, and some so-called “experts” still say it doesn’t raise it or can’t raise it long term. However, sustained high cortisol will routinely cause leaky gut, disturbing the microbiome and potentially elevating blood pressure. So, based on current research, it’s now not a myth anymore! Let me explain the role of the microbiome.
Leaky gut is caused by everything from a poor diet to high “stress levels” to proton pump inhibitor antacid drugs such as Prilosec. It sometimes produces little to no symptoms, but it always causes internal inflammation, which you now know is associated with hypertension. In addition, leaky gut always produces unfavorable alterations in the composition of the GI microbiome. And this is yet another factor in the creation of the hypertensive state.
Doesn’t it seem that lately, you read that all aspects of your health are more and more related to the health of your gut? It turns out that an unhealthy gut microbiome with less “healthy bacteria” (a dysbiotic gut) will cause hypertension; via a different mechanism than through leaky gut and/or inflammation. It also seems that “hypertensive GI tracts” have fewer bacteria that produce (healthy) butyrate and acetate.
There are two easy ways to increase gut butyrate levels that help with weight loss, insulin resistance, leptin resistance, and blood pressure. One way is to take sporulating probiotics. The other is to supplement with MCT (medium-chain triglycerides) oil. I use MCT oil for cooking and suggest that “trick” rather than MCT supplements which often cause diarrhea.
Biotoxins such as mold mycotoxins and Lyme toxins and heavy metals such as lead and mercury can damage the microbiome via other mechanisms, including (most often) the sirtuin pathway, and raise blood pressure. So next, let’s talk about sirtuins.
Sirtuins are enzymes that are produced in decreased amounts in many metabolic disorders such as obesity and metabolic syndrome. SIRT1 (the most well-known and studied sirtuin) causes an increase in leptin sensitivity. It also increases adiponectin production. Both of these actions have both anti-obesity and, therefore, anti-hypertensive effects. The SIRT1 pathway is disordered in toxin-related disorders and many disorders of mitochondrial function. Therefore diseases such as Parkinson’s disease, Hashimoto’s thyroiditis, or Chronic fatigue syndrome are also associated with SIRT1 deficiency, with a built-in risk for metabolic syndrome, including hypertension.
Nitric oxide (NO) protects the lining of blood vessels and vasodilates them as well. When arteries are damaged by inflammation, we see a decrease in nitric oxide near the smooth muscle linings of the blood vessels. In general, nitric oxide levels tend to decrease with age. To some degree, HIIT exercise enhances NO, but to make sure your levels are adequate, try foods or supplements. Below are some foods and supplements which raise NO levels.
Beetroot Juice
This juice is high in NO3, which converts to NO. An 8-ounce glass per day will lower your blood pressure (on average) by 8 mm Hg (systolic) and 4 mm Hg (diastolic), demonstrated in those with existing hypertension. I find this to be much more palatable when mixed with “juiced” carrots and spinach.
Examples of other vegetables high in NO3 include whole beets, arugula (the best!), celery, cabbage, leeks, scallions, radishes, kale, turnip tops, spinach, mustard greens, eggplant, carrots, and string beans.
Vitamin D
It’s a well-known medical fact that vitamin D deficiency is associated with arterial stiffness and subsequent hypertension. Still, a large study involving over 100,000 individuals has now demonstrated that low vitamin D levels can actually cause high blood pressure. To make the correlation even stronger, the highest vitamin D levels were shown to lower hypertension risk the most. High-D foods include the healthiest fish, wild sockeye salmon, and sardines, as well as eggs (only eat “pastured,” please). Most people are clinically deficient unless they take D3+K supplements, with most individuals requiring a minimum of 6000 IU’s per day.
Resveratrol
This multi-use supplement increases endothelial NO production, reduces vascular oxidative stress, and prevents smooth muscle proliferation, vascular remodeling, and arterial stiffness. In addition, resveratrol inhibits immune cell infiltration into the vascular wall and mitigates vascular inflammation. All these mechanisms contribute to the positive effects of resveratrol on vascular function and blood pressure.
L-arginine plus l-citrulline
A good NO-enhancing supplement will contain l-arginine and l-citrulline. Bodybuilders typically use these supplements for the increased “pump,” and some men use them to enhance erectile function. However, if taken often, they too will lower blood pressure by increasing nitric oxide.
The Role of the Oral Microbiome
The critical role of the oral microbiome in both our oral and systemic health is being elucidated more and more with each study that emerges. Elevations in plasma [NO2−] following dietary NO3− ingestion and the associated physiological responses are blunted by the use of antiseptic and antibacterial mouthwashes and even by toothpaste. This blunting is directly related to the diminution of healthy oral bacteria in the oral microbiome. Natural tooth powders are not as pleasant to use as commercial toothpaste products, but natural toothpaste seems to be an improvement from the highly processed supermarket brands. Mouthwash should be used sparingly, if at all.
Natural vitamin E (200 IU’s per day) has been shown to lower blood pressure. Natural vitamin E is always listed as the “d-” form (d-alpha-tocopherol, d-beta-tocopherol). Synthetic vitamin E is listed as “dl-” forms. Don’t take synthetic vitamin E, as it’s ineffective and might even cause harm.
Studies (meaning a review of 29 studies done in 2012) indicate that 500 mg of vitamin C per day might help lower blood pressure. In 2020, another meta-analysis was done, focusing on 8 studies published between 1991 and 2018. Overall, 614 participants were included. The number of participants in the individual studies ranged from 12 to 480. Participants’ mean age ranged from 46 to 78 years. The duration of the intervention varied from 4 to 24 weeks. All participants had essential hypertension. The average SBP and DBP of the participants ranged from 143 to 173 mmHg and from 76 to 97 mmHg, respectively. The supplementary dose of VitC in the treatment group varied between 300 and 1000 mg/dL. The results? There was indeed a correlation between supplemental vitamin C and hypertensive control.
Why? At present, the main theory is that VitC increases intracellular concentrations of tetrahydrobiopterin, an endothelial nitric oxide synthase co-factor that promotes the production of nitric oxide, which is a potent vasodilator. However, there is also evidence that Vitamin C enhances the biological activity of nitric oxide.
This can lower blood pressure by 10%, but only if you take it as a supplement. Although allicin is produced when raw garlic is crushed or chewed, much of it is destroyed during cooking. For about ten years, researchers have been aware the allicin made from alliin in garlic blocks the activity of angiotensin II—a substance that raises blood pressure. In addition, supplemental garlic elevates levels of nitric oxide.
Note, however, the health benefits of garlic supplements are due to ajoene, diithins, and allicin, not just due to allicin. So, shop carefully since ajoene and diithins are considerably more potent than “just allicin.”
Nattokinase enzymes have potent fibrinolytic (blood-clot-busting) activity, anti-atherosclerotic, lipid-lowering, antiplatelet (anti-platelet stickiness), and even neuroprotective effects.
In addition, with regards to the topic of this article, a well done double-blind, placebo-controlled, randomized study showed that supplementing with nattokinase for eight weeks resulted in a significant reduction of both diastolic and systolic blood pressure.
Nattokinase is an enzyme found in the food natto, which is a fermented soy product. Whether consumed as fermented soy or as a supplement, the natto enzyme has been used successfully for 25 years to treat hypertension and various circulatory issues in China and continues to be studied worldwide.
Ongoing research on peptides for weight control and metabolic issues will certainly yield some actionable results soon. Flavonoids such as green tea (EGCG) and pomegranate extract show promise for hypertension as well. Studies looking at herbs such as curcumin, ginger, and hawthorn extract are also quite encouraging. And what about hormones per se?
The idea that menopause or the associated estrogen decrease is associated with blood pressure increase is still under debate. The epidemiological challenge is the coincidence between menopause and aging and the evidence that both rising blood pressure and menopause have common determinants such as diet, body mass index, smoking, and even socio-economic class. In addition, there seems to be no correlation between testosterone levels in men and blood pressure levels. The bottom line, as always, is to eat healthfully, exercise correctly, and supplement smartly. For some, that might include nitric oxide supplementation.
In this article I review some of the basics of pain relief you might have learned in health class, including all the ways to increase your natural painkillers: your endorphins, enkephalins, and endogenous cannabinoids (some of this might be familiar too). I also touch on some integrative, supplement-type methods you can track down on the internet by yourself and will finish by reviewing exciting and new forms of natural pain relief available only through qualified Functional medicine doctors (not on the black market please!).
I will discuss:
But a Word About Diet First
One of the first things I do with new patients is to ask them to alter their diet. Most people aren’t aware how inflammatory, and therefore pain-inducing, some of the foods they typically eat can be. The absolutely most anti-inflammatory diet is my autoimmune protocol diet. Avoiding fast and processed foods, grains (especially gluten), seed oils, dairy, and other lectins such as peppers, eggplants or white potatoes, is totally game-changing. When it comes to natural pain relief, an anti-inflammatory diet is Job #1.
Below are some other basics, which may or may not be helpful, depending where you are on your own “pain journey.” Meaning, hang on. If you are farther along on this road, there are additional and exciting compounded alternatives you have not yet heard of that I will discuss.
Fairly Well-Known Methods of Pain Relief
Many of us know the comfort of a warm bath (‘hot soak’) and a wet, dry, or far-infrared sauna. A simple, long, hot shower helps muscular or non-inflammatory joint pain when we’re stiff and achy. Massage therapy is proven to improve lymph drainage and increase endorphin levels.
Remember that endorphins are your endogenous painkillers, produced (mainly) by the posterior pituitary gland. Although there is speculation about the relative significance of endogenous cannabinoids and enkephalins, endorphins are still considered the #1 endogenous pain reliever.
For most people, the following endorphin boosting methods will bring some temporary pain relief. Unfortunately, these methods don’t work well (if at all) for patients with some pituitary tumors or active mold and mycotoxin illness. But, as someone who treats a lot of mold illness, let me tell you that the posterior pituitary does “bounce back” and these methods will indeed work again.
Massage: Yes, I am repeating myself here, but if you can afford it a massage is not just a feel-good activity. A nice, firm, muscle-kneading massage increases endorphins for several hours, adding yet another layer to pain relief.
Exercise: Most of you know that exercise increases endorphins. But do you know that a “runners high” is now thought to be (at least partially) due to endogenous cannabinoids, not to endorphins? And there is definitely something to be said for group fitness activities. A clinical study found that athletes who rowed together could tolerate two times the pain compared to athletes who rowed alone.
Laughter: Laugh out loud and your body releases endorphins! Read emailed jokes. Watch comedy specials. Laugh every single day as if your health depends on it.
Eat Your Favorite Foods: If you love it on your tastebuds, you will produce endorphins. And Yes, even healthy foods can be delicious, so keep this in mind when you’re looking for an endorphin rush.
Do You Like Dark Chocolate? Dark chocolate contains much more healthy flavonoids – and far less sugar – than milk chocolate, but a couple of squares of either will give your endorphins a boost. Cocoa also contains a mood-boosting substance called phenethylamine. It is the phenethylamine in the cocoa that gives your body an endorphin boost. Interestingly, however, phenylethylamine supplements do not have the same effect.
Eat Hot Peppers: If you have a strong, healed gut and can eat the occasional “nightshade” (a lectin), these really can give you an endorphin rush. Your body senses “heat stress” and responds the same way it responds to pain – by producing endorphins.
Listen to Music: Enjoy the music you love. But did you know that your brain produces even more endorphins when you take part in creating music. If you are not a trained musician…then hum to, or sing along with, or even dance, with abandon, to your favorite tunes.
Have Sex: As you might predict, sex releases a flood of endorphins as well as other feel-good brain chemicals.
Try Acupuncture: The minor amount of pain caused by acupuncture needles sends a message to the brain, which then responds with the release of endorphins. Less data is documented regarding the placement of needles, but logically, of course, there is “something to it.”
Get Some Sunlight: A mere 5 to 10 minutes of direct sunlight will increase mitochondrial ATP as well as endorphins. And if it gets too hot for you, some cold therapy afterwards might just feel great!
Now that I’ve discussed endorphins, let me add another method to my list. Any sort of cold or cryo-therapy will cause your posterior pituitary to release endorphins, but referring back to the “stress” concept, when your body experiences stress or pain, the brain releases endorphins.
There is quite an accumulation of positive data on everything from winter swimming to ice baths regarding pain relief, reduction of inflammation and, Yes, even endorphin production. How to bring on the cold? If you’re up north and it is winter, go outside in shorts and a T-shirt. If not, try an ice vest, or multiple gel cold packs, or a brief ice bath, or even a cryotherapy tank. Cold works, and not just for localized pain due to injuries as most people think.
Several inflammatory cytokines, including TNF-alpha and IL-6 (both of autoimmune disease fame), will increase pain. In clinical studies, levels of TNF-alpha, IL-6, and a host of other inflammatory cytokines have been shown to be epi-genetically down-regulated systemically with the use of cold packs.
Curcumin suppresses inflammation, which is a root causes of all diseases. Curcumin is the most potent of the three curcuminoids found in the spice turmeric. It suppresses pain by decreasing inflammation. It has more mechanisms of action than non-steroidal anti-inflammatory medications such as ibuprofen, and even more than steroids such as cortisone.
Curcumin is a safe inhibitor of the same pathways that the most complex drugs block: COX, COX-2, and LOX. In fact, curcumin inhibits the entire arachidonic acid cascade. In clinical studies, curcumin has worked as well as phenylbutazone and cortisone for osteoarthritis, rheumatoid arthritis, and post-operative inflammation. Studies show that curcumin inhibits the COX pathway better than indomethacin, a very strong mixed COX inhibitor that is still used to treat gouty arthritis.
Notably, curcumin has quite similar anti-inflammatory action as NSAIDs, but without the side effects. NSAIDs can have dangerous side-effects, and the COX-2 inhibitors are even required to include black-box warnings. Long-term NSAID usage causes leaky gut in just about 100% of people. Generally safe, even at doses up to 8,000 mg per day, Curcumin must be taken with meals, and under a doctor’s supervision if at doses exceeding 1-2 grams per day.
Fish Oil: There is a good deal of clinical evidence that fish oils are very anti-inflammatory and therefore pain-inhibiting. As an aside, when my patients have “the occasional headache or backache,” I ask them to take some curcumin and fish oil.
Capsaicin (trans‐8‐methyl‐N‐vanillyl‐6‐nonenamide) is an extract from hot chili peppers. It is a decent topical analgesic for a variety of painful conditions.
Devil’s Claw is a plant native to the African continent. Iridoid glycosides are the active ingredients. Several studies demonstrate relief with topical use for osteoarthritis.
Phytodolor is an herbal formulation containing alcoholic extracts of Populus tremula, Excelsior, and Solidago virgaurea. Studies show that it is often effective in various inflammatory arthritic disorders.
Glucosamine and Chondroitin Sulfate are the principal components of cartilage. There are conflicting studies on the combination of glucosamine and chondroitin, with some demonstrating a beneficial effect on arthritis pain. More recent studies find that chondroitin alone does not reduce joint pain. Therefore, the use of chondroitin has dropped off but there is better news regarding glucosamine.
Glucosamine for Arthritis: There have been 30 or so well-done studies examining the efficacy of glucosamine for joint pain. On review of all data comparing glucosamine to either NSAIDS or placebo, the glucosamine edges out the NSAIDS by a hair. Recent data shows the mechanism of action is via blocking lectins. While there haven’t been any good studies comparing glucosamine to the elimination of lectins in the diet, “it’s a very good thought.”
People rarely realize that CBD is most plentiful in the hemp plant, which contains minimal THC, and that THC is found in the marijuana plant, where the concentration of CBD is more scarce. Both plants are cannabis plants, by the way.
There are many cannabis strains that vary widely in the composition of cannabinoids, terpenes, flavonoids, and other compounds. These components work synergistically to produce wide variations in benefits, side effects, and strain characteristics.
When we discuss the benefits of CBD, we’re talking about “whole hemp CBD” because “extracts” of CBD are relatively useless. Yes, check to see what you have. Medicinal THC, however, can be made in many forms, but the best benefits are found in those plants with more CBD, and the best pain relief is found in those formulations that include the other aforementioned ingredients such as the terpenes.
In a 2018 review article, multiple studies revealed mixed results. It appears that cannabinoids appear to be most effective in controlling neuropathic pain, medication-rebound headache, and chronic noncancer pain, but do not seem to offer any advantage over nonopioid analgesics for acute pain.
Something marijuana enthusiasts don’t mention is that THC-cannabinoid-based analgesia has been linked to memory deficits and cognitive impairment. As with all mood-altering substances, we must be careful of our usage, dosing, and (IMHO) brain health protection, so that we do not experience any negative effects on our most important organ: our brain.
Meanwhile, animal studies demonstrate that whole hemp CBD oil increases endorphins. This has particular implications for patients with chronic pain syndromes such as fibromyalgia, CIRS pain due to EDS (endorphin deficiency syndrome), and neuropathies. An online patient survey by the U.S. National Pain Foundation of 1,300 fibromyalgia patients rated CBD as more effective than Cymbalta, or Lyrica.
If you have fibromyalgia, please read on, as there is much more “out there” for you. Here is the first thing you might want to try.
Naltrexone, was approved in 1984 by the FDA in a 50mg dose to help addicts wean off heroin. Naltrexone’s initial use was an opioid-antagonist drug used in large doses to block opioid receptors, and therefore the effects of opioid drugs.
Naltrexone was since studied in doses of 1-5 mg (hardly even a “drug” at those doses) and was found to perform other functions. It blocks the receptors of the opioid hormones in our brain and adrenal glands. Doing so produces the anti-pain endogenous chemicals called beta-endorphins and met-enkephalins, known as the opioid rebound effect. Blocking opioid receptors also upregulates something called opioid growth factor (OGF).
The mechanism of action of pain relief via OGF is fairly simple. By up-regulation of OGF via the temporary blockade of opioid receptors, you will see an increase in circulating endorphins and enkephalins via reduction of the inflammatory response. LDN is used not only for pain relief, but also to treat many autoimmune diseases; notably Crohn’s disease via different mechanisms of action. In addition, LDN is neuroprotective via the inhibition of microglial activation. But it is in cancer research where the really promising data is being seen, where OGF is identified as an angiogenesis blocker which then suppresses the growth of many types of cancer.
Review of LDN for pain 2020
Eight articles were ultimately selected for evaluation, after hundreds of reports of benefits were identified. Six studies included data on fibromyalgia, two studies included data on chronic regional pain syndrome, and one study included patients with multiple diagnoses, including interstitial cystitis, fibromyalgia, and chronic pelvic pain. The primary outcome of all of the studies was absolute pain intensity reduction. The writers of this review concluded that “Low-dose naltrexone provides an alternative in medical management of chronic pain disorders as a novel anti-inflammatory and immunomodulator.”
Before I move on to the last three new and novel pain therapies, I want to do a quick review of peptides, in case this is your first time hearing about them. Peptides are not “drugs,” because they are recognized by our bodies as “self-produced,” much like bioidentical hormones. Peptides are short segments of amino acids, usually comprised of between two and fifty amino acids.
The peptides we use in functional medicine are derived from human secretions and, being bioidentical, there are no “drug side effects.” There are many excellent peptides that are utilized for various benefits in functional and integrative medicine, but three in particular are used in various forms and combinations for the treatment of pain. They are:
Heptapeptide Selank: (Thr-Lys-Pro-Arg-Pro-Gly-Pro)
Numerous clinical studies have shown that Selank has strong anti-anxiety as well as neuroprotective effects. The clinical effects of Selank are similar to those of anti-anxiety medications such as benzodiazepines, which enhance the activity of the calming neurotransmitter, GABA. This suggests that the molecular mechanism of action of Selank also arises from its ability to enhance GABA’s activity on its receptors. This is supported by the strong positive correlation – in several clinical trials – between the changes in the expression of 45 genes one hour after Selank or GABA is given. Additionally, there is the data that, across-the-board, anxiety increases the perception of pain.
Here is some insight into why this may be true. Examination of patients with various forms of anxiety demonstrates a considerable shortening of enkephalin half-life. Selank dose dependently inhibits enzymatic hydrolysis of plasma enkephalins. Selank has been found to be a potent enkephalinase inhibitor. In other words, the enzyme that destroys the enkephalins is blocked by Selank, which has been proven to reduce anxiety.
Study results suggest that high efficiency of Selank in the therapy of anxiety and phobic disorders is due to its ability to inhibit enkephalin hydrolysis. A very nice side effect of this is that higher enkephalin levels will reduce pain. Ongoing studies suggest that Selank may additionally act via other brain chemical systems such as those that control dopamine and serotonin. Meanwhile, the data regarding these two systems is strong for my next peptide, Semax.
Heptapeptide Semax: (Met-Glu-His-Phe-Pro-Gly-Pro)
Semax is considered a nootropic peptide due to its ability to increase BDNF-brain derived neurotrophic factor. It has the same, and perhaps more pronounced effect, as Selank on enkephalinase, leading to increased levels of enkephalins. In addition, several studies demonstrate its ability to cause the brain to release both serotonin and dopamine, enhancing feelings of well-being, which will also decrease the perception of pain. It is being increasingly recognized as a fairly decent analgesic, despite the paucity of human clinical trials.
DSIP: (Trp‐‐‐Ala‐Gly‐Gly‐Asp‐Ala‐Ser‐‐‐Gly‐Glu)
Delta sleep-inducing peptide (DSIP) has potent analgesic activity in mice. DSIP may play an important role in pain regulation in the central nervous system, but it currently is primarily used for severe insomnia in humans. Research findings in humans are yet sparse, but in a study of seven patients with migraines and vasomotor headaches, this peptide (administered for 5 consecutive days) significantly lowered the perceived pain levels of six of the seven. Additionally, as an “incidental finding,” mood was elevated in all seven subjects.
DSIP does not appear to have binding activity to any subtype of opioid receptors. Animal studies show that DSIP stimulates the release of met-enkephalins. It might also then stimulate a stronger binding effect of those endogenous pain relievers to opioid receptors. More research is obviously needed, but for those with sleep and pain issues it is a great add-on.
Additional Comments
If you are looking to ‘go it alone’ for pain relief, know that there is some data on DL-phenylalanine regarding inhibition of enkephalinase, that you can buy liposomal GABA preparations to decrease anxiety, and that you can purchase 5-HTP supplements to augment serotonin levels – all of this, in addition to the endorphin-enhancing behaviors and the use of ‘cold’ and exercise. Remember that exercise probably not only releases endorphins, but it probably also increases levels of endogenous cannabinoids.
What you do not want to do, however, is increase your use of over-the-counter drugs for pain. Acetaminophen is toxic for your liver (and somewhat so for your gut), and NSAIDs such as Motrin and Aleve are uber-toxic to your kidneys and gut and, in fact, cause many cases of leaky gut, which then leads to all sorts of other issues.
Get some help for pain that does not respond to some of the natural things I have written about here. My last word of advice: Avoid Black Market Sources of Peptides and LDN, as you simply cannot know what you will be getting.
Before we start discussing Hashimoto’s thyroiditis, let’s just touch on the traditional treatment you are probably getting. You are not on a special diet to heal or protect your gut. You have elevated antibodies and are told “don’t worry about them.” You are simply placed on a synthetic version of T4, not a combination of the inactive T4 and the active T3, tailored to your physiology. You are told that your thyroid will “just burn out” if you aren’t yet on thyroid replacement, and that, at that point, you will be treated with synthetic T4. There are many disease processes; notably autoimmune diseases, where the traditional medicine I used to practice really seems dead wrong. One of these instances is Hashimoto’s thyroiditis treatment. You’ll see why after you read this article.
Introduction
Hashimoto Thyroid Disease, AKA Hashimoto’s thyroiditis, is the most common autoimmune disorder in the U.S., affecting between seven and eight percent of the population. While not all people with Hashimoto’s have hypothyroid symptoms, thyroid antibodies are a marker for future thyroid disease. When we talk about hyperthyroidism vs. hypothyroidism, the majority of “Hashi’s” patients are diagnosed after TPO antibodies have destroyed enough of their thyroid gland, so they have low (hypo) thyroid function. Hypothyroidism is characterized by weight gain, loss of the outer 1/3 of the eyebrows, brain fog, dry skin, fatigue, constipation and more. The sad state of medical treatment is such that doctors fail to treat the autoimmune disease and then, simply replace the lost thyroid hormone with synthetic hormones. Standard treatment fails to address many concerns including the underlying cause or the necessary Hashimoto diet. In this article, I’ll discuss Hashimoto Thyroid Disease and treatment including:
Necessary Laboratory Tests
I (personally) find it shocking that the new patients I see who tell me they have “thyroid issues” have never had proper bloodwork done. It’s not hard to order the correct tests, and now I’m going to teach you what to ask your doctor to order. To begin, start with the “usual and customary labwork” including a complete blood count, liver and kidney function tests, a complete chemistry profile, urine analysis and so on. Then for the thyroid specifics, here’s what you want to have done.
Ask your your doctor to order a TSH, a Free T3, Free T4, CRP, r (reverse) T3, TPO antibodies, and anti-thyroglobulin antibodies. Rarely are TSH-stimulation blocking antibody (TSBAb) positive but get those done, too. TPO antibodies are much more apt to be the positive antibodies you find in Hashimoto’s thyroiditis, but why not be thorough? Reverse T3 is a test that has been criticized as being “useless” by Endocrinologists who all tend to ignore an elevated rT3. What is rT3? It’s a metabolite of the inactive form of thyroid hormone- T4. The problem with an elevated rT3 level, is that it means it is clogging up the actual T3 receptor sites. When the receptor sites are clogged, the converted and functional Free T3 cannot bind to the receptors and you are therefore “functionally hypothyroid.” Let’s discuss what that means.
If your lab work shows a high reverse T3 level- you are converting most of your T4 into reverse T3. Reverse T3 is simply an isomer of T3. If you recall-Free T3 is the active form of thyroid hormone and it is converted from T4 as needed by two enzymes called deiodinases. The problem with rT3 is that it binds to T3 receptors but it has no metabolic activity-meaning-high rT3 levels can give you signs of being hypothyroid even though your Free T4 and Free T3 are the “normal range”.
Medical issues that will results in increased rT3 levels are any sort of severe illness, starvation, excessive nutritional deficiencies and high cortisol levels-generally caused by stress. This is why you have likely heard that adrenal and thyroid function are linked. Those with adrenal fatigue or adrenal stress tend to be functionally hypothyroid. It is also more common in hypothyroid patients who have SIBO-more to come on this topic. rT3 obviously will then slow down metabolism and is therefore theorized to aid in survival. A quick fun fact: hibernating bears have high rT3 levels.
We treat high rT3 with T3 for 2 or 3 months. The negative feedback to the pituitary slows down the production of T4- that then slows the production of rT3.
Most physicians don’t analyze why they often see a normal Free T4 and a sub-par Free T3 on a typical patient’s lab work. Here’s the answer: for proper enzymatic (deiodinase) function, these enzymes require quite a few minerals for optimal function. While most people think of iodine and some are aware of selenium as being important for thyroid function, I’ll bet you didn’t know that you also need zinc, molybdenum, boron, copper, chromium, manganese, and the proper balance of calcium and magnesium, did you? Well, neither do your doctors! They also don’t know about the iodine to selenium balance that needs to occur, which we’ll discuss in the next section.
Endocrinologists continue to use the typical thyroid replacement—a synthetic hormone: Levothyroxine (Synthroid). However, if you don’t have a “high enough” Free T3 which is defined as being more than 2.9 pg/ml, you are going to be clinically hypothyroid. And this a totally separate issue from having a high rT3. Now let’s get into the selenium/iodine issue.
Selenium (not iodine!) deficiency is one of the main reasons for clinical hypothyroidism. It’s crucial for the production of thyroxine (T4). It is also needed for the deiodinase to convert T4 to the active T3. But, there’s more: a total of 11 selenium-dependent enzymes have been identified as necessary for thyroid function. If you take iodine without selenium, you can cause selenium deficiency. Conversely; if you take selenium without iodine, you can cause iodine deficiency. Since all regular salt is iodized, you are much more likely to have selenium deficiency if you use iodized salt. Use Himalayan pink salt instead, and it will be less likely to contain plastics, too.
The current recommended dietary intake of selenium in adults is between 55 and 75 mcg daily. Foods rich in selenium are brazil nuts, mushrooms, oysters, most types of meat, and sunflower seeds.
Many people are under the impression that too little iodine is the issue when it comes to any type of thyroid disease. This probably dates back to the days when “goiter” was linked to the lack of iodine; hence the subsequent iodization of our salt supply. However, our national over-consumption of iodized salt now usually causes the opposite problem. Many clinical (epidemiologic) studies demonstrate the presence of more autoimmune hypothyroidism in iodine-replete demographic areas than in iodine-deficient areas.
A number of studies even indicate that mild or moderate iodine excess (meaning a urinary iodine excretion of 220µg per 24 hours) is associated with hypothyroidism. To make matters worse, other studies show that low-dose iodine supplementation may even be associated with increased thyroid autoimmunity. Regardless of the “mechanism”, now will you ditch the iodized salt shaker in exchange for some pink Himalayan salt?
Conventional medicine simply does not have safe, effective treatments for any autoimmune disease. In fact, steroids and even more toxic drugs such as “biologics” are often used to suppress the immune system. If you have Hashimoto’s, it’s even worse, as the autoimmune condition is left to simmer like a boiling pot on a stove. Let me explain.
If you have elevated-let’s say- TPO antibodies, it means your thyroid gland is under attack. Often, the CRP (a biomarker for inflammation) is elevated. If you don’t address (and then lower) these antibodies being made, the thyroid gland will continue to be under attack, and systemic inflammation will continue. Symptoms such as fatigue, sleep disruptions, hair loss, dry skin and more will just continue until the thyroid gland is burned out, at which point you will be deemed “hypothyroid” and placed on thyroid hormone for life. But there’s even more to this story of autoantibodies and inflammation.
All autoimmune disease starts with leaky gut: we’ll cover this topic next. Anyway, since Hashimoto’s thyroiditis also starts with leaky gut, causing systemic inflammation, if you don’t repair the gut, you can’t reduce the antibodies. You’ll also need to change your diet to reduce the antibodies. Here’s why. It is clear that there is thyroid gland tissue and gluten biomimicry—and there are likely also IGG food allergies to things like milk, grains, eggs, and more. Therefore, to get rid of “possible food offenders” and start getting antibody levels and inflammation down, you need to eat an “autoimmune protocol diet” (phase 1-a bit strict) while your gut is healing: the first two months of treatment. A benefit most people love is that they effortlessly drop some unwanted pounds.
Leaky gut (AKA gut hyper-permeability syndrome) is an extremely common condition. It can be caused by antibiotics, anti-inflammatory medications, antibiotics, stress (leading to high cortisol which wrecks your gut and brain), mold and mycotoxins or just “typical American food.” If you have leaky gut, you may or may not have gastrointestinal symptoms. If you are already hypothyroid from your Hashimoto’s thyroiditis you will probably be constipated and possibly have some bloating after meals.
Getting you into remission from any autoimmune disease starts with fixing your leaky gut. Changing your diet to my autoimmune diet is the first step towards healing your gut and reducing your auto-antibody production. Functional doctors use gut-healing peptides and supplements such as collagen powder and l-glutamine. Vitamin D levels need to be normalized, and sporulating probiotics with their “fertilizer”-prebiotics, should be added when the symptoms start to subside. We’ll discuss all of this in upcoming sections.
As you heal your gut over two months, your (probable) food sensitivities and, therefore, your bloating will diminish. If it doesn’t, it often means you have SIBO, which is quite common in those diagnosed with Hashimoto’s thyroiditis.
First, let’s posit that a fair number of those diagnosed with Hashimoto’s thyroiditis have actual or functional hypothyroidism. Since gut motility decreases when someone is hypothyroid, constipation is a common symptom of Hashimoto’s. This constipation, decreased gut motility, as well as the leaky gut, often leads to small intestinal bacterial overgrowth (SIBO.) Small intestinal bacterial overgrowth is an increased number and/or abnormal type of bacteria growing in the small intestine section called the jejunum, a part of the bowel that is supposed to be sterile. It’s estimated in numerous studies that a minimum of half of those with Hashimoto’s have untreated SIBO.
The symptoms of SIBO symptoms are often confused with those of other GI disorders. The most common symptoms are bloating and flatulence and bloating after meals. Other symptoms include abdominal discomfort, constipation; but often- diarrhea, too. This causes many patients to be labelled as having irritable bowel syndrome and never having their symptoms clear up. Multiple food intolerances are also common. If symptoms are mild, they are often “blamed” on the hypothyroid state. Those with SIBO are more likely to have T4 to rT3 conversion issues, causing even more gut issues.
To diagnose this condition, the lactulose hydrogen breath test (LHBT) is often used. However, because breath tests are not very sensitive or specific (up to 60% false negatives), many experienced Functional doctors will treat a patient if they exhibit classic symptoms associated with typical underlying conditions.
Treatment in the non-Functional GI world is typically a long course of Rifaximin-an antibiotic which is not absorbed by the gut. Herbal therapies are at least as effective as rifaximin for curing small intestinal bacterial overgrowth in comparison clinical trials. Some effective herbals include oregano oil, barberry, berberine, olive leaf extract, and wormwood.
The Hashimoto Diet
You can actually get creative with this limited list. As mentioned, you’ll drop the pounds you wanted to lose while you’re at it. You’ll feel great on this diet which is naturally the most anti-inflammatory diet you can eat. To help you: there are many social media groups, pages and websites that contain creative recipes. If you’re my patient, I’ll be communicating with you about your food preferences, and sending you links for food services, alternative bakeries and so on. I’ll help you transition to month 3, 4 and onward, adding as many foods as your Hashi’s can tolerate.
There is firm evidence of a correlation between Vitamin D deficiency and several autoimmune diseases. Notably examples include systemic lupus erythematosus, multiple sclerosis, mixed connective tissue disease, rheumatoid arthritis, type 1 diabetes mellitus, celiac disease, and more.
In general, Vitamin D tends to activate the innate immune response and to regulate the adaptive immune response. This improved adaptive immune response, in the presence of higher levels of vitamin D appears to hold true in autoimmune thyroid disease as well.
Most data on Vitamin D and autoimmune thyroid diseases have come from cross-sectional studies and tend to support the existence of an association. There is additional evidence supporting a relationship between vitamin D and Hashimoto’s thyroiditis in particular. Approximately ten recent studies identify lower 25(OH)D levels in individuals with Hashimoto’s thyroiditis versus control subjects, with a tendency for a higher prevalence of (vitamin D) deficiency in patients with hypothyroidism than those with normal thyroid function tests.
The relationship with antibody titers is characterized by more inconsistent data.
Vitamin D may also affect disease manifestations. There have been several reports of a significant correlation between mild cognitive impairment and 25(OH)D deficiency in adult patients with Hashimoto’s thyroiditis. This complication will be covered in the last section of this article.
Approximately one third of patients with Ulcerative colitis or Crohn’s disease are resistant to all currently available “drug” pharmaceuticals, or they relapse over time. Therefore, when the doctor who first realized that LDN (low dose naltrexone) was helping his patients with multiple sclerosis, he turned the researchers of IBD onto the concept of looking closely at LDN. And, indeed the studies have been remarkable for inflammatory bowel disease and a host of other autoimmune disorders. It works by increasing endorphin levels, secreted by the posterior pituitary gland, and by yet another mechanism which also bolsters the part of the immune system responsible for autoimmunity.
There have been a paucity of controlled, clinical trials using LDN in patients with Hashimoto’s thyroiditis simply because there has been “no will” to do so. If you take a patient with IBD that flares, they have serious gastrointestinal issues such as explosive, non-stop diarrhea, rectal bleeding, awful abdominal cramps and more. If you have a patient with either multiple sclerosis or ALS, the neurological effects can be drastic and are readily observed.
When someone with Hashimoto’s thyroiditis “flares” it may be nothing more than some fatigue, sleeplessness and mild “tummy” upset. Of course, these symptoms are quite bothersome to the patient with Hashi’s, but I strongly believe this is why the research is sorely lacking. Meanwhile, everyone who treats autoimmune disease functionally uses LDN, and patients report that they feel considerably better taking it. I am not one to treat patients based on “anecdotes” but until we get some better research done on Hashimoto’s thyroiditis patients, that’s really what we’re all doing. As an addendum: we all see that it decreases antibody levels and there is one great study showing that pregnant women with Hashi’s who tend to miscarry in the first trimester, not only have significantly less miscarriages when they are taking LDN, but the babies all have better outcomes. That’s a great start, right? Now, let’s talk about something we know is good for everyone’s immune system: having a well balanced microbiome.
In recent years, numerous studies have elucidated the crucial role of gut microbiota on multiple metabolic as well as autoimmune diseases, such as diabetes mellitus, obesity, systemic lupus, Alzheimer’s disease, and inflammatory bowel disease. The active form of thyroid hormone can influence the gastrointestinal structure and function, especially motility of the gut. And on the flip side, a healthy gut microbiota also has quite a beneficial effect on thyroid function.
Numerous studies show that the gut microbiota composition in Hashimoto’s thyroiditis patients are considerably less diverse than in any control group. Interestingly, among the factors that influence the stability and variety of gut microbiota, T3 is thought to be one of the most important.
A healthy gut microbiome is not only beneficial for the function of the immune system, but also for proper thyroid function. It’s not well known, but the prevalence of co-existence of thyroid and intestinal diseases are far larger than mere coincidence. For example, Hashimoto’s thyroiditis is the most common autoimmune thyroid disease and often co-occurs with both Celiac Disease and Non-celiac wheat sensitivity. This can be explained by the damaged intestinal barrier (leaky gut) and the subsequent increase in intestinal permeability, which then allows antigens to pass more easily and activate the immune system or cross-react with extra-intestinal tissues such as the thyroid gland.
Finally, the composition of the gut microbiota influences the availability of essential micronutrients for the thyroid gland we’ve discussed earlier. Iodine and copper are crucial for thyroid hormone synthesis, selenium and zinc are necessary for converting T4 to T3, and vitamin D assists in regulating the immune response. Those micronutrients (and more) are often found to be deficient in Hashi’s patients, resulting in malfunctioning thyroid glands. Supplementation with sporulating probiotics have repeatedly shown beneficial effects on thyroid hormones and thyroid function in general.
Additional Factors Affected by Hashimoto’s Thyroiditis
There are many considerations, when treating someone with Hashimoto’s thyroiditis. Your Endocrinologist will tell you to take your Synthroid, not worry about your antibody levels, not inquire about gut function, and tell you to rest if you’re fatigued. That’s all you’re going to get. You probably won’t even get other important female hormones measured (if you’re a woman).
In functional medicine, we recognize that patients prefer not to have ongoing leaky gut, inflammation, brain inflammation, brain fog, hair loss, skin dryness, sleeping issues and so on. So we treat each and every issue separately and completely. We also take it very very seriously regarding the amount of first term miscarriages that Hashi patients have due to high antibody levels. It’s just not acceptable to us to give someone a T4 synthetic product, and do nothing about the rest of the syndrome. I would hope you would agree.
We can treat the brain issues with designated peptides: Oral or intra-nasal, with two of my favorites being dihexa and semax. We address sleep issues because sleep is when everything repairs, and with inadequate sleep, people feel just awful all day. We address mitochondrial dysfunction; often a product of autoimmune issues, and “fix the energy issues”. We repair the dry skin and the hair loss; even the eyebrow loss. Yes, there are peptides for this, too.
Lastly, since this is yet another disease where we see TNF-alpha elevation, and drugs which lower TNF-alpha are commonly used, It’s certainly worth trying natural supplements which lower TNF-alpha: resveratrol, curcumin and PQQ. They all have a host of other benefits, too! Meanwhile, a whole host of research continues.
The etiology of Inflammatory bowel disease (ulcerative colitis and Crohn’s disease) is complex, with genetic predisposition, an altered microbiome, environmental factors and a weakened epithelial (“gut”) barrier function triggering a chronic immune response in the mucosal layer. These two disorders of chronic intestinal inflammation affect approximately three million people worldwide. U.C. therapy and Crohn’s disease treatment starts with a good understanding of the disease process itself.
Currently, allopathic (versus functional medicine) Crohn’s disease treatment, for example- starts off with with brain and gut damaging corticosteroids and 5-aminosalicylic acid products, adds “immunomodulators” (Azathioprine, 6-mercaptopurine, methotrexate), and eventually, “biological agents” which are “TNF-alpha inhibitors” (infliximab, adalimumab, certolizumab, and golimumab). The story is just about the same for Ulcerative colitis. Just. too. toxic. for. words.
Not one of these drugs are curative, and their long-term use often causes severe side effects including cancer. Around 30% of patients with inflammatory bowel disease (IBD) are refractory to current IBD drugs or relapse over time. As a result, patient surveys show that almost 40% of Crohn’s and U.C. patients use alternative therapies to complement their conventional medical care. The first thing I now do with new patients is to get them using a VNS device to bring down inflammation quickly. Here is the only device that works, is not too pricey, and kicks in immediately. When you purchase yours, feel free to use and share my discount code for $25 off: DrKim25.
Furthermore, because we Functional docs (in conjunction with happy, cooperative patients) obtain such stellar symptomatic control with our IBD patients, many of them will switch entirely to Functional care, stay symptom-free, and experience far less invasive colonoscopies, since a fecal calprotectin level is a great way to monitor all disease activity. U.C. and Crohn’s disease treatment is fairly easy in the “functional world”, and it is helpful to know what it is that you can do to prevent disease occurrence or, at least, lessen your symptoms.
First, I’ll explain the five major factors that you can control regarding what causes inflammatory bowel disease to occur and to flare: the “root cause.”. Then, I’ll review the following list of items that will help you get into and more importantly-remain in remission:
Traditional medicine teaches us that risk factors officially implicated with ulcerative colitis and Crohn’s disease include low fiber-high carbohydrate diets, smoking, altered microbiomes and gut permeability as well as medications such as non-steroidal anti-inflammatory drugs. Each of these things will cause leaky gut, so what you’ll read next will not contradict these conventions. Leaky gut is the root cause of all autoimmune disease, including ulcerative colitis and Crohn’s disease. Here are the reasons you are more likely than not to have some degree of gut hyper-permeability syndrome AKA “leaky gut.”
Direct gastrointestinal toxins we consume or absorb such as the methylmercury in canned tuna fish, the excessive use of plastics for food storage and even the fluoride in unfiltered water- can all damage our gut lining and disturb our microbiome. We even accumulate toxins via skincare products, and from non-filtered showerhead water. We breathe polluted air if we are in or near a city or a factory. We don’t think of “bad air” as a gut issue, but it is. If we’re in a dusty house, even if we don’t have dust mite allergies, dust mites have been demonstrated to cause leaky gut.
Lastly, another problem we don’t generally associate with gut health is mold. The reason I mention this outright is because 25% of us cannot (genetically) clear mold toxins so they not only damage our gut, they are responsible for a host of symptoms and long-term medical problems. If you have or had mold in your home (50% of structures in the U.S. fall into this category), you likely have mycotoxins in your HVAC that you’re breathing in and out of your lungs which may or may not ultimately damage your gut and may or may not cause ulcerative colitis or Crohn’s disease.
Depending on how well your detoxification systems both recognize and clear certain toxins, your toxin loads can build up to damaging levels. Something to keep in mind is the gut-brain barrier. Once the gut barrier is breached, so is the gut-brain barrier which then typically adds brain fog and things like concentration and mood issues to your “gut issue.” Now, let cover the most common way for Americans to wreak havoc on their guts: food.
The food you eat can absolutely cause leaky gut. People who consume the “standard American diet” (SAD) with it’s high-processed and fast foods as well as it’s high-sugar content are putting their guts (and therefore their total health) at risk. As you are likely aware, gut-damaging GMO foods are now dominating the soy, wheat, and corn markets. GMO-gluten used all too ubiquitously in our food supply is increasingly being blamed for non-celiac gluten sensitivity and leaky gut. It’s estimated that 25-75% of Americans have some type of food sensitivity. The most frequent offenders are (in this order) wheat, dairy, eggs, and corn.
Consuming gluten, artificial sweeteners, GMO foods, dyes and additives so non-food-like that they are now dubbed appropriately “franken-foods” as well as the massive amount of sugar (including HFCS and other hidden sugars) in our typical diet results in leaky gut. Add in non-sprouted grains and lectins (found-for example-in beans and nightshade vegetables), fruit juice and excessive caffeine and alcohol, and it’s a wonder we all don’t have leaky guts.
Actually those of you eating a standard inflammatory American diet likely do have a degree of leaky gut. Enough to trigger you to the other side of U.C. or Crohn’s disease? Do you really want to find out the hard way? And if you are someone who has I.B.D. and just “eat what you want” while taking a potentially harmful biologic drug-would you be willing to alter your eating style for improved health and a promise for a better chance for remission? What about your over-the-counter drugs habits? You can certainly alter those, can’t you? Sure you can! You, first, however need to know what is potentially problematic.
Americans pop OTC painkillers as if they’re candy. T.V. commercials feature actors who are pleased with themselves that they take just one non-steroidal anti-inflammatory gut irritant in the morning; and not again, until the end of the day! Your gut lining can be interrupted by everything from Aleve and Ibuprofen to Vioxx or even Tylenol. The majority of people who take OTC pain relievers daily have some degree of leaky gut.
Another category of awful-for-the gut drugs is antibiotics. I hate to bash my own profession, but am always amazed at the amount of antibiotics my new patients tell me they were given for dubious bacterial infections. Antibiotics not only cause leaky gut, they also upset the good to bad ratio of bacteria in the GI microbiome. We now also have proton pump inhibitors sold over the counter; thus sky-rocketing their use. These drugs were never designed for more than short-term use. Many people use these PPI’s (Nexium, Prevacid or Protonix, ) for chronic heartburn and slowly etch away the lining of their GI tract.
Synthetic hormone medications such as birth control pills or cortisone-containing steroids (e.g.: prednisone or a Medrol dose-pack) can propagate the growth of excess candida (yeast), which also often damages the gut lining.
Hormonal imbalances can also cause chronic constipation such as low progesterone levels and low thyroid hormone levels. Indeed, this can readily lead to small intestinal bowel overgrowth (SIBO) as can many types of cancer chemotherapy agents. SIBO disrupts the gastrointestinal balance dysbiosis), often causing gas, bloating and eventually, leaky gut.
If you constantly “feel stressed”, chances are very good that you have a high cortisol level. High cortisol-apart from everything else we’re discussing-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.
Dysbiosis of the gut means that your GI microbiome (gut-bacterial-environment) is out of balance. A properly balanced GI microbiome is absolutely crucial for optimal GI function, immune function, and brain function. Yeast (candida) can invade the lining of the intestinal wall to cause SIFO; small intestinal fungal overgrowth. Toxic E. Coli species are common culprits in SIBO (small intestinal bacterial overgrowth) issues. Other organisms such as giardia (a parasite) and Helicobacter pylori (responsible for ulcers and cases of severe heartburn) can also chip away at the intestinal lining. Deserving of a mention in this section are three things that can lead to lower gut motility and therefore SIBO and SIFO: hypothyroidism, low progesterone levels and low serotonin levels. Lastly, toxins are increasingly found as a cause of leaky gut.
This topic is worth re-visiting. Although the amount of plastics (as an example) we consume is escalating, what is getting a lot of attention as definite gut-busters are mold toxins called mycotoxins. Since 50% of the buildings in the U.S. are estimated to have water damage-a set up to mold growth; with the increasing climate events, we are seeing more and more water damaged buildings and more mold (especially toxic mold) growth.
We know that approximately 25% of the population is genetically unable to recognize and clear mold toxins, leaving them vulnerable to all sorts of medical problems including fatigue, brain fog and leaky gut. Now that we’ve discussed what causes leaky gut which can then lead to ulcerative colitis or Crohn’s disease, let’s talk about how we treat these two conditions with the best Functional Medicine has to offer.
It’s necessary to eliminate foods from your diet that can directly cause leaky gut. Initially, this is typically a huge lifestyle modification that is structured as such so that treatment doesn’t miss any offending foods. Over time leaky gut can precipitate as host of IGG-mediated food sensitivities which can cause a plethora of symptoms. It is much simpler to start with a basic diet and then reintroduce certain foods (e.g.: eggs) when you have your symptoms under control.
If you are eating a standard American diet, you’ll notice that the modifications you need to make will cause you to shed some pounds, have more energy, and in general, you’ll feel better. The first thing to do is to clean out your pantry and make yourself a list of “allowed foods.”
The best diet to follow is an AIP (auto-immune protocol) diet which restricts the “usual gut offenders” such as gluten, dairy, eggs, corn, sugar, processed foods, fast foods, citrus, nightshade vegetables, legumes, grains, as well as alcohol and caffeine. Yes, just like the Paleo diet! It also restricts high FODMAP foods if they cause GI distress, which for most patients, is necessary. You cannot blame your gastrointestinal symptoms on specific foods if you eat this way for the two months it takes to heal a leaky gut. Yes-this diet is restrictive, but it will help to get you well and in two months, you can reintroduce some food items.
What Do You Eliminate?
Follow this eating plan (along with whatever else your Functional M.D. prescribes) until the “explosive diarrhea” wanes. For most people, this occurs within 3-4 weeks. At that time, you can add in a small cup of brewed coffee with a splash of additive free coconut or almond milk. Coconut milk is not included at first because it is a high FODMAP food in more than tiny amounts. Reintroducing food is quite personalized, so I can’t advise you what to add back from this list-if ever-or when.
We’ve reviewed what not to take- so what do you use instead? Instead of NSAIDS for pain, use tylenol. Better still, if your GI tract is healed, use fish oil and curcumin- proven in clinical studies to out-perform even the priciest NSAIDS. For heartburn, try one white Rolaid or TUMS. Better yet: find good digestive enzymes. Herbals can often be substituted for antibiotics and anti-fungals, but you will need guidance for those. Hopefully, this article will make you aware of what you’re taking, and the effect it has on your gut.
Getting you to remission and being asymptomatic from U.C. or Crohn’s disease starts with fixing your leaky gut. Changing your diet is the first step in healing your gut. Use (under medical care) proper gut-healing peptides ( discussed below) and (if needed), supplements for leaky gut such as l-glutamine and collagen powder. Vitamin D levels need to be normalized, and sporulating probiotics should be added when the symptoms start to subside so that they don’t “leak back” into the bloodstream. At this time, you’ll also add prebiotic fibrous carbohydrates (such as a half of an unripe banana) to your diet. More about re-balancing your microbiome (the prebiotics and probiotics) coming up soon. But first, let’s talk about what’s plaguing most of us: stress.
Stress is honestly just terrible for your health. We innately know this- but do you know the physiology of why this is? We know cortisol is a direct neurotoxin; likely being a risk factor for Alzheimer’s disease. We know it adds fat to the belly. When we’re talking about U.C., Crohn’s disease or any autoimmune disease for that matter, we’re looking at 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. As a “not-so-fun-fact”-this is the probable reason so many “hardcore” bodybuilders (who all have high cortisol levels) have leaky gut.
Adrenal (herbal) adaptogens, glandulars, liposomal GABA and certain types of aromatherapy are proven to lower cortisol levels. Stress-busting techniques such as “vagal breathing,” meditation, and yoga are great relaxation practices. Finally, just activating your hypoglossal and therefore your vagal nerve to tone down your sympathetic nervous system will help. Simply sing, or even gargle!
Common toxins that routinely cause leaky gut are the mycotoxins, the dust mites that usually are not numerous enough to be an issue unless there is actively growing mold, (AKA dust mite food) and lastly-heavy metals such as mercury. How do you know if mold is making you sick? If you have gut issues, fatigue and a foggy brain, with a history of mold exposure, there’s your answer. Dust mites? Not nearly as guilty– but in the line-up. Heavy metals? This depends on your environmental history and more. As does “toxicity” in general. Let me explain.
Toxins play more of a critical role if you have “faulty genetics” including glitches in your detoxification pathways. Having a few mercury amalgam fillings isn’t usually “enough” to cause leaky gut. We generally say “having eight or more fillings” is a problem that needs to be addressed after we get the general health of the patient under better control. However, be careful with your diet as a steady diet of canned tuna-fish or tuna sushi is actually enough to cause methylmercury build-up with effects on the gut and other organs.
If you have a history of vaginal yeast infections, you can cross-over infect your gut, especially if you have some sort of gut motility issue as mentioned earlier-things such as thyroid issues, low progesterone or low serotonin. Many cases of small-intestinal-bacterial-overgrowth (SIBO) occurs when colonic bacteria “backwash” into the usually sterile jejunum. The most common yeast (SIFO) and SIBO symptoms are gas, bloating and constipation. Also, be aware of Helicobacter infections, and parasites. When in doubt, breath test, and treat. Sometimes symptoms are just so obvious that we simply treat- especially since Functional doctors tend not to treat SIBO with antibiotics, nor do we treat SIFO with anti-fungals.
Both female hormones and male hormones need to be balanced for optimal gut motility, necessary to prevent “backwash” and infections. The gut “works better,” and the microbiome stays more in balance when your hormones are in balance. A full discussion of this is beyond the scope of this article. Be aware, however that during menopause, the decrease in estrogen causes a rise in cortisol, something we just discussed. Also be aware that adequate progesterone is necessary, as is adequate thyroid hormone for optimal gut motility. Gut motility depends on a healed gut which includes a healed smooth muscle propulsive layer.
As the gut lining becomes destroyed, some segments of the small and large intestine (depending on where the involvement of the disease is) get destroyed and therefore “out of sync.” As the gut heals, we sometimes need to use products to bulk up the stool and therefore improve the transport of “contents” such as modified citrus pectin or a multi-fiber blend. Sometimes we need to also improve GI transit at the smooth muscle level (by utilizing the serotonin precursor 5-HTP for example.) As mentioned, hormones need to be normalized as well. It’s strange to realize that diseases which produce “explosive” diarrhea can actually cause bloating and constipation while healing occurs, but indeed, this can happen. Now, let’s discuss what needs to happen to your microbiome.
By definition, when you have leaky gut, you have more “bad bacteria” than “good bacteria” populating your GI tract. Use prebiotic fiber to feed the good bacteria and (if you are not in a “mold situation”) a little bit of “good yeast” to re-create a healthy gut microbiome. State of the art care is to add a friendly yeast called Saccharomyces boulardii (by prescription: Florastor). Regarding prebiotic fiber, start with asparagus, Jerusalem artichokes, red onions and naturally fermented (not pickled) foods such as sauerkraut. If you like un-ripe bananas, they make great prebiotic fiber.
When your gut lining is coming together-usually the 2 to 3 week mark, add probiotics. Do not purchase or even make your own yogurt; you can’t have dairy yet, remember? 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, but there is increasingly more evidence supporting the use of sporulating probiotics for an even better microbiome. A generic product, VSL3, has yielded some positive remission studies, as have the probiotic strains Lactobacillus casei and Lactobacillus rhamnosus.
The most current research supports the use of sporulating (soil-based) probiotics to create a more diverse and therefore more healthy microbiome. These sporulating probiotics are so potent, you need to be careful not to “overdose”, or you can experience cramping and diarrhea. Start as low as 5 billion and increasing to as many as 25 billion CFU’s daily (best done under a doctor’s supervision). These probiotics are species of Bacillus with b. subtilis and b. coagulans being the most studied. Finally, if you see your diarrhea disappear but still have gas and bloating studies are promising for using 10 billion CFU’s of Lactobacillus plantarum. If that doesn’t work, consider the SIBO/SIFO angle if you haven’t done so already. Next, let’s discuss what has revolutionized the treatment of Crohn’s disease and ulcerative colitis: peptides and LDN. First, let’s discuss peptides.
Peptides are short strings of amino acids, typically composed of 2–50 amino acids. The peptides used in functional medicine are derived from human secretions and therefore bioidentical; meaning no side effects such as what we see with pharmaceuticals. There are many peptides being used for many functions in functional and integrative medicine, but three in particular which are used in various forms, combinations and doses for ulcerative colitis and Crohn’s disease treatment.
The pentadecapeptide Gly-Glu-Pro-Pro-Pro-Gly-Lys-Pro-Ala-Asp-Asp-Ala-Gly-Leu-Val, M.W. 1419, named BPC 157 has been demonstrated to counteract peritonitis and heal intestinal lesions-especially colitis lesions.
Gastric pentadecapeptide BPC 157 (GEPPPGKPADDAGLV, M.W. 1419 as above) is stable in human gastric juice, now found to be effective both in the upper and lower GI tract, and remarkably free of side effects. BPC 157 has been demonstrated to be an efficient therapy of inflammatory bowel disease. It has been shown to interact with the nitric oxide protective system, providing endothelium protection and counteracting severe complications of advanced and poorly controlled inflammatory bowel disease.
The human peptide GHK-Cu (glycyl-l-histidyl-l-lysine) has multiple biological actions, all of which appear to be positive. It stimulates blood vessel and nerve outgrowth, increases collagen, elastin, and glycosaminoglycan synthesis and supports the function of dermal fibroblasts. GHK’s ability to improve tissue repair has been demonstrated for skin, lung connective tissue, bone, liver, and stomach lining. It has been extrapolated to have reparative effects on the lining of the entire gut.
α-Melanocyte-stimulating hormone (α-MSH) is a cleavage product of a melanocortin that has protective and anti-inflammatory effects. Its anti-inflammatory activity has been shown to be mediated by three N-terminal amino acids: lysine-proline-valine (KPV). The KPV peptide alone has been found to exert an even stronger anti-inflammatory effect than the whole α-MSH peptide.
KPV has been demonstrated to attenuate the inflammatory responses of colonic epithelial and immune cells and reduce the incidence of colitis upon oral administration. KPV exerts its anti-inflammatory function inside cells, where it inactivates inflammatory pathways by a decrease in pro-inflammatory cytokine expression. Very importantly, unlike the drugs currently used for U.C. therapy and Crohn’s disease treatment, KPV is a naturally derived tripeptide without any notable side effects. And now to what many of us consider the “game changer” for all autoimmune disorders: low dose naltrexone.
Close to a third of patients with inflammatory bowel disease are resistant to all currently available pharmaceuticals, or they relapse over time. Investigators have turned their eyes to studying the effects of “LDN” on the gut epithelial barrier in treatment resistant patients with ulcerative colitis and Crohn’s disease.
One study utilized low dose naltrexone for 47 patients who were followed prospectively for 12 weeks. Where available, endoscopic data including tissue biopsies were collected. The effect of LDN on wound healing and tissue biopsies from endoscopic procedures were evaluated. The results? Spectacular in my book. Low dose naltrexone resulted in “significant clinical improvement” in 75%, and complete remission in 25% of patients.
Another clinical study involves close to 600 inflammatory bowel patients. Among the 250 or so patients who became persistent LDN takers, there were reductions in the number of users of all previously consumed drugs (down by 12%), intestinal anti-inflammatory agents (down by 17%), other immunosuppressants (down by a whopping 29%), intestinal corticosteroids (also markedly decreased by 32%), and aminosalicylates (decreased by 17%). Of importance: this study did not manipulate diet or use any other gut-healing agents. Not even any probiotics!
The most recent clinical study assessing LDN in IBD involved 28 patients affected by Crohn’s disease and 19 by ulcerative colitis. Patients with an intractable (meaning basically untreatable by conventional methods) active phase of IBD received a daily dose of LDN in addition to standard treatment. Follow-up lasted for approximately 3 months and 35 patients (75%!) responded to therapy with a decrease in disease activity which lasted for at least a month. Six patients achieved full clinical remission, including five of them having a complete endoscopic remission.
Just imagine if the above patients had been put on my autoimmune diet, given peptides, vitamin D, sporulating probiotics with good prebiotics- along with their LDN? And just imagine that we could add in some supplements? What, then would the response rate be? Let’s finish up with some possibly helpful supplements.
“Conventional medicine” offers Crohn’s and U.C. patients “biologics,” which come with an array of potentially fatal side effects. I’m not saying they don’t work, and I also don’t suggest that you stop anything “cold-turkey.” We know that these drugs all lower a laboratory biomarker called TNF-alpha. Disease activity appears to correlate with the level of this marker. We don’t yet know if reducing this marker will reduce disease activity in humans. However we know that TNF-alpha is likely a toxic lab value that we’d probably prefer to get as low as possible, no matter what. If that’s the case, then the following “in vitro” information is relevant.
We know that nutritional ketosis will inhibit TNF-alpha. Resveratrol, curcumin, melatonin, PQQ and vitamin D will also all inhibit TNF-alpha. We understand that some activities (ice baths, FIR saunas, and even cold showers, and baths) will suppress TNF-alpha, and have other beneficial physiologic effects. So, as a last thought on these things, why not?
Finally, this article contains a great deal of information that can inform you- the patient and can also inform your doctor. It is not information that is intended to diagnose or treat patients who have inflammatory bowel disease. As with all procedures and “meds” used in the practice of medicine, the dose, timing, mixture, and monitoring of symptoms and laboratory tests is crucial to obtain optimal results. Not to mention the cooperation between the patient and an experienced, board-certified Functional doctor.
You may have “heard” that premenstrual syndrome; PMS, or even the worse premenstrual dysphoric disorder (PMDD) is due to low progesterone. You might have read that one of the common signs of progesterone deficiency is premenstrual bloating. However, this article will review the common symptoms and then the signs of progesterone deficiency that are not often discussed. In fact, many symptoms (complaints) and signs (physical findings) related to low progesterone levels are simply not widely known, even amongst even the most knowledgeable Ob-Gyns or Endocrinologists. Many of the patients I personally see have been to an array of doctors who haven’t picked up on the fact that they are dealing with simple cases of low progesterone symptoms, which, in turn, cause a host of problems. All reversible. And yes, a Functional Internist who is an expert in female hormones is your best bet. Let’s start with the obvious.
Women often attribute all of their premenstrual symptoms to what they call PMS. There are a host of symptoms, with low progesterone as the root cause, but they are not all categorized together. I’ll explain. You might be having fertility issues. You might develop ovarian cysts. Most women and even most doctors believe that fibroids and endometriosis are estrogen-dependent. Not so. It’s the ratio of estrogen to progesterone that is important, so low progesterone can cause these issues too. Similarly, fibrocystic breast disorder can be caused by low progesterone.
Your libido is (mostly) controlled by your free testosterone level but progesterone also plays a role. Estrogen deficiency isn’t the only hormone that can cause hot flushes. Progesterone deficiency or cortisol excess (early adrenal fatigue) can also cause hot flushes. Lastly, mold and mycotoxin exposure can also cause hot flushes. I won’t go into these other little “nuggets of information” on this article, as they are off-topic. Let’s get started with the major gynecologic issues.
During the luteal (second) phase of your menstrual cycle, your uterine lining (endometrium) is building up to receive a fertilized egg. This phase becomes shortened when you are progesterone deficient. Your periods might then be irregular due to progesterone deficiency. You might have some spotting right before your period and then some clots during your period.
The principal cause of irregular periods is the lack of normal ovulation. Lack of normal ovulation, where the egg is not released from the ovary- causes low progesterone because your body is not preparing for pregnancy by building up the endometrium. Other reasons for irregular periods can be PCOS, stress (high cortisol), or simply coming off of oral contraceptives. However, remember that an early “pre-menopause” can mean that you have lower-than-normal progesterone levels, with or without significant symptoms.
Approximately 50% of females who report heavy menstrual bleeding, do not meet the requirements of 80 mls (about 1/3 cup) or more of blood “release” per menstrual cycle. Heavy menstrual blood loss usually includes clotting and having to change pads or tampons every two hours or more. Heavy bleeding is thought to result from imbalances in estrogen and progesterone, and is generally successfully treated with supplemental progesterone. If you are experiencing heavy periods, you will need a full work-up to exclude other causes of heavy menstrual flow such as polyps, endometriosis or adenomyosis (endometrium growing in the uterine wall), as well as other (less common) issues including bleeding or clotting disorders.
Another one of the signs of progesterone deficiency is premenstrual syndrome- PMS. Premenstrual syndrome is defined as life-disrupting physiological and/or psychological signs or symptoms which occur in the luteal phase of the cycle. Symptoms include headaches, cramps, fatigue, bloating, nausea and mood swings. When menses begins, symptoms will generally disappear. The reason PMS is thought to occur is due to the difference in hormone levels between estrogen and progesterone. Many women respond to progesterone supplementation, while others need a more varied approach-similar to women suffering from the more severe variant- PMDD.
Most women are aware of the typical symptoms of PMS. In fact, how many of us have experienced fluid retention (bloating), breast tenderness, or even a little bit of a mood swing? However, women with PMDD (less than an estimated 10% of the female menstruating population) have symptoms that can last all month. Not only that-the symptoms are a gross exaggeration of PMS symptoms. Mood swings are prevalent and severe. Depression brings on “fits” of crying or feelings of hopelessness. Often the most reasonable women experience intense anger and conflict with other people. Tension, anxiety, and irritability. No interest in your usual activities. Trouble concentrating. Fatigue. Appetite changes with binge eating. Not your ordinary PMS. This disorder is associated with measurable drops in serotonin levels, as well as exaggerated estrogen to progesterone dips and drops. Treatment includes serotonin precursors, progesterone and more.
Another sign of low progesterone is breast tenderness. This is a PMS symptom that will typically occur and then worsen during the mid to late luteal phase. Imbalances in estrogen and progesterone can worsen breast tenderness and pain.
Cyclic mastalgia is not considered as a part of PMS, even though it is indeed related to the menstrual cycle. It is bilateral, diffuse, poorly localized, and generally described as soreness that often radiates to the underarms and even down the arms. It occurs mostly during the luteal phase of the menstrual cycle due to increased water content in breast stroma caused by increasing hormone levels. Cyclic breast pain occurs more commonly in younger women, often will resolve spontaneously, and is classified differently than as being a part of premenstrual syndrome.
Bloating is a common sign of low progesterone. Studies have shown that, during the luteal phase, water and sodium retention increase with low levels of progesterone and high levels of estrogen. This occurs because the estrogen lowers what is called the “osmotic threshold,” for which water is reabsorbed in the body. The hormone ADH (arginine vasopressin) is responsible for the reabsorption of water into the bloodstream. When estrogen levels are high, this threshold is lowered, and therefore less water will be excreted through urine. This then causes the body to retain water and creates the sensation of bloating. It could be as little as noticing your rings are tight or as much as being unable to zip up your jeans. This looks and feels differently than the belly fat you start accumulating during pre-menopause.
Dysmenorrhea (painful periods) is typically experienced as painful cramps before or during menstruation. Secondary dysmenorrhea is due to gynecological issues such as endometriosis or adenomyosis. What we’re discussing here is simply primary dysmenorrhea as a result of “normal” female anatomy. The cramps in the uterus are caused by high levels of prostaglandins. Prostaglandins are a group of fatty molecules made at sites of tissue damage or infection. They control processes such as blood flow, the formation of blood clots, degree of inflammation, and even the induction of labor. Prostaglandins work in opposition to progesterone, so when progesterone decreases right before menstruation, prostaglandin levels will increase. This then causes uterine contractions, cramps and pain. Treatment is not necessary for “mild cramps”, but more severe cramps usually require prostaglandin inhibition. “Natural” ways to do this are with fish oils and curcumin supplements.
Ovarian cysts are sacs filled with fluid that are attached to or adjacent to the ovaries. Ten percent of women have ovarian cysts, which can be an “incidental finding” on pelvic exam or ultrasound, or a cause for pelvic pain and other symptoms. Cysts are usually classified according to whether they are a variant of the normal menstrual cycle, referred to as a functional or follicular cyst. Frequent follicular cysts can be one of the signs of low progesterone.
Ovarian cysts are considered “large” when they are over 5 cm and giant when they are over 15 cm. Most cysts are benign and cause no pain, but others do cause pain as they sometimes don’t resolve with the menstrual cycle and then grow larger over time. Symptoms of an ovarian cyst are heavy cramping with abdominal pain, irregular periods, and pain during bowel movements. In some studies, progesterone supplementation in the early stages of cyst growth reduced its size, ability to grow and sometimes induced ovulation.
Adequate progesterone is necessary for healthy fertility. Progesterone helps to maintain the integrity of the uterine lining so that a fertilized egg can implant. Without optimal progesterone, you are at a higher risk of miscarriage. Many studies have documented the benefits of administering progesterone to patients who are experiencing infertility to increase conception as well as to-term pregnancy rates. This leads us to the next logical topic; miscarriage.
It is critically important to have optimal progesterone levels for a healthy pregnancy. The first trimester of pregnancy is typically when most miscarriages occur. If progesterone levels are low, studies have found that those who are administered progesterone in the first trimester have a better chance of reducing their chances of miscarriage.
Chronically low progesterone levels are often associated with low-grade depression, a topic we’ll cover soon. Low progesterone will lower serotonin levels. If you get sugar cravings, they are often due to low serotonin levels. If you crave sugar and feel happier after you eat an ice cream cone or cookie, this is likely a physiological fact. If you self-medicate your low serotonin levels with too much sugary food, you’ll gain weight, raise your blood sugar, and levels of inflammation in your body.
And it’s not just the serotonin. Low progesterone (in and of itself) is the beginning of the rise in the hunger hormones leptin and ghrelin. Ghrelin is an actual “hunger hormone”, stimulating your appetite but leptin is a bigger problem for most women. As leptin rises, your fat cells will “hold onto fat”, starting often with belly fat. This makes fat loss much more difficult if you are progesterone deficient.
Since progesterone helps to normalize thyroid hormones, it can lower those, causing your metabolic rate to drop. This will often be reflected in a lowering of your morning basal temperature as well as your energy levels. However, fatigue is more likely to occur due to another problem which I’ll discuss next.
You need two brain chemicals (neurotransmitters) to help you fall asleep and then stay asleep for the night. The fall-asleep brain chemical you need is called GABA, and the stay-asleep chemical is our good friend, serotonin. When progesterone levels fall, so do levels of both GABA and serotonin. This then makes both falling and staying asleep more difficult. When these two neurotransmitters drop, women often get a poor night’s sleep which leads to daytime fatigue and, eventually, all sorts of other problems. Women’s sleep cycles have been studied in depth.
Many studies have found changes in sleep architecture across the phases of the menstrual cycle, with most sleep disturbances occurring in the luteal phase. In the luteal phase, women experience increased sleep onset and awakenings and lower sleep efficiency and quality compared to the follicular phase. Women in the luteal phase have less REM sleep and more non-rapid-eye-movement (NREM) sleep, with an increase in slow wave sleep (SWS) in particular. EEG (electroencephalogram) power density varies throughout the menstrual cycle, with the highest density of sleep spindles occurring in the luteal phase.
The luteal phase is also associated with elevated core body temperature, which could potentially interact with sleep processes to impact sleep quality. During the luteal phase, some women experience nocturnal PMS symptoms of discomfort, such as stomachache, backache, headaches, and nausea. And as a corollary, those with PMS are more vulnerable to sleep disruptions during the luteal phase. Women with PMS report having more unpleasant dreams, nocturnal awakenings, morning tiredness, and increased mental activity at night in comparison with women without PMS.
Several studies have shown that progesterone supplementation has a better ability to restore normal sleep when there was a disturbance in the night compared to the control groups. Progesterone administration seems to enhance sleep duration and sleep quality, mainly by improving slow-wave sleep (SWS). As an aside, let me mention that disturbed sleep and daytime fatigue are very common issues for all of my women patients. I usually end up giving at least half of my patients integratives to raise their GABA and serotonin levels; not just supplemental progesterone. As a final note in this section; ongoing research is pointing to the increasing role of progesterone in regard to growth hormone and melatonin secretion as well. And yes, both of these carry implications for sleep as well.
We touched on the topic of mood swings during the discussion of PMDD. You might recall that as your progesterone levels drop, so too, do your serotonin levels. Serotonin is one of your happy neurotransmitters, so for some, this drop is enough to cause depressive symptoms. Don’t think that anti-depressants are the answer. Why wouldn’t you want to treat your mood issues more physiologically with progesterone and some serotonin precursors?
We also discussed the diminution of GABA levels in regard to sleep initiation. But GABA levels also control how much anxiety and even panic you’ll have to deal with as you move through peri-menopause and then menopause. However, the degree of symptoms you’ll experience as a result of decreased serotonin and GABA levels is a reflection of your “baseline” levels.
Anxiety is the experience of feelings of worry, fear, or at worst-panic attacks that can completely overpower aspects of your day. Progesterone has anti-anxiety effects due to its boosting relationship with GABA, your natural relaxation mood chemical. If your progesterone is low or you are not producing enough each cycle this can show up as anxiety because you are not producing as much GABA. This is often corrected with supplemental progesterone and pure GABA. A word of warning: if your doctor prescribes an anti-anxiety medication such as Xanax, run, don’t walk, to find a Functional Specialist that won’t give you prescriptions for highly addictive drugs.
Pain and discomfort cause feelings of stress and elevated cortisol levels. As described above, there are many ways that having low progesterone levels cause you discomfort- from cysts, to cramps, to PMS, to sleep disruption. Stress will lower dopamine levels, and this then causes irritability and can even contribute to a depressed mood. Low dopamine lowers GABA even further, thus compounding any anxiety issues you might have. We’re talking about close to half of a month of distressing symptoms, all due to a simple lack of progesterone! Studies have found that there were significant improvements in mood and irritability due to progesterone administration compared to a placebo. And please do note: there are ways to naturally increase dopamine levels as well. Also note: oral GABA is destroyed by stomach acid and rendered ineffective.
Cyclical headaches are defined as recurrent headaches which occur during the same time with each menstrual cycle. They are classified as a complication of PMS, and are one of the less common signs of low progesterone. When progesterone is low, you are in (by definition) an estrogen-dominant state. Early to mid-luteal cyclical headaches are thought to be caused by the estrogen-dominant effect on cerebral blood vessels. These cyclical headaches are successfully treated with progestins (synthetic progesterone) in clinical studies. It would make sense that the more safe, bioidentical progesterone would be effective for these types of headaches. To make matters just that much more complicated, a small percentage of women get “estrogen-drop” headaches at the very end of their luteal phase, just as menses starts.
Speaking of headaches, we must differentiate cyclical headaches from migraine headaches which are also associated with low progesterone levels. Low levels of brain serotonin have been linked to migraines, accounting for the statistical increase in migraines reported by women with documented low progesterone levels. Indeed, bioidentical progesterone is an effective (partial) treatment for a select group of migraine sufferers. Recent studies have shown that, compared to a regular diet, a nutritional ketosis diet might also help to ears to be great for keeping migraines at bay. And speaking of headaches……
This is one I’ll bet you didn’t know about. While normal levels of progesterone and indeed the progesterone spike a week before your period can cause constipation which is immediately relieved when you get your period, if progesterone levels are low for your entire luteal phase, it’s a different story. It’s also a different story if you are pre-menopausal, with constantly low progesterone levels or post-menopausal, with inadequate progesterone replacement dosing.
Numerous studies suggest that the interplay between progesterone and the serotoninergic system could underlie altered bowel habits in women. Serotonin (5-hydroxytryptamine or 5-HT) is known to play a key role in the motor function of the GI tract by stimulating smooth muscle contractility. It has been shown that progesterone administration increases 5-HT levels by decreasing the level of 5-HT reuptake, monoamine oxidase mRNA expression, and increasing the availability of 5-HT precursor, tryptophan. This effect of progesterone on the serotoninergic system is not surprising because 5-HT promotes peristalsis. The moral of this story is that curing chronic constipation in women is often a matter of simply restoring progesterone and serotoninergic balance.
It astounds me that so many women who I speak with about hormones think that it is “normal” to start becoming forgetful and foggy-brained at age 40! However, being foggy-brained and having memory lapses can indeed by directly caused by progesterone deficiency. We don’t think of progesterone as a sleep supplement or a brain supplement, but in fact, BI progesterone is just that. As with so many hormonal issues, this is also complex.
Studies demonstrate that increased levels of GABA increase our cognitive performance. Other studies demonstrate that serotonin is important for memory consolidation and storage in the hippocampus. In fact, there is a higher incidence of dementia in people with chronically low serotonin levels. And finally, progesterone is neuroprotective in animals and women. There is a firm biological rationale for the view that progesterone plays an important role in brain function and there are discernible effects on cognition in animals. Moreover, progesterone exposures are linked to patterns of brain activation during cognitive processing in women.
However, if I am to be scientifically accurate; despite my bias, it remains to be shown that endogenous progesterone or exogenous progestogens exert clinically meaningful effects on short-term or long-term cognitive function in healthy women.
Studies are ongoing to investigate the role that progesterone may have in preventing or lessening seizure activity. As noted above, it is thought to be neuroprotective in animals and in women. As such, it is being investigated as a modality to aid in the treatment of traumatic brain injury.
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