You may have heard of the term “MTHFR gene mutation” and be wondering what it is. First, I’d like to say that I prefer the term MTHFR gene variation rather than mutation. The word variation is more empowering, and in my opinion, also more accurate.
While the word mutation implies an occurrence that is rare, unnatural or flawed, the MTHFR gene variation is common. In fact, it’s present in up to 55 percent of the European population, is naturally occurring, and often has no negative health consequences – unless expressed.
The reason we do tests and learn about our genes is to feel empowered. While we can’t change our genes, I can tell you that we can absolutely change their expression! So if you have the MTHFR gene variation, or are thinking of testing for it, I hope that this overview empowers you.
Understanding the MTHFR Gene Variation
It’s important to understand what it means to have the MTHFR gene variation in order to determine if it may be contributing to some of the symptoms you’ve been experiencing.
The gene involved is the MTHFR (Methylenetetrahydrofolate Reductase) gene. This gene codes for the MTHFR enzyme, the enzyme that converts the amino acid homocysteine to methionine, a building block for proteins.
As a result, individuals with a genetic variation and low activity of the MTHFR enzyme may present with elevated homocysteine levels, which have been associated with inflammation, heart disease, pregnancy complications, and even miscarriages. It has also been associated with higher rates of Down syndrome and birth defects in offspring, as well as other issues later such as depression, an increased risk of blood clots, and a higher risk of certain cancers.
One of the key things to note is that this gene variation also prevents people from properly methylating, which is one of the body’s key detox processes that helps them get rid of toxins. Methylation impairment can result in an impaired ability to clear out certain toxins such as mercury and arsenic, and may lead to estrogen dominance. Symptoms like brain fog, multiple chemical sensitivities, depression, irritability and anxiety are related to impaired methylation.
It’s not all doom and gloom, however – Dr. Ben Lynch (author of the book Dirty Genes) reports that those who are born with the MTHFR gene variation may also have some advantages, such as being more alert, productive, and focused. As the owner of two MTHFR gene variations, I can surely attest to this!
Genetic Effects on Nutrient Extraction
The genetic variation can also play a role in vitamin deficiencies. Specifically, elevated homocysteine levels often caused by the MTHFR gene variation have been associated with nutrient deficiencies in vitamin B9 (folate), B6, and B12.
It may seem like common sense to take a supplement to address a deficiency in folate, but not all sources of vitamin B9 are created equally. While vitamin B9 can be found naturally in foods in the form of folate, it can also be found in the form of folic acid, a manufactured version of folate that is present in most bargain priced multivitamins and often added to processed foods.
Unfortunately, folic acid can be highly problematic for individuals with the MTHFR gene variation, as they may have a difficult time processing this form of folate. Some professionals claim that this type of synthetic folate may even cause a build-up in the body, leading to toxicity. Studies have been done that showed folic acid supplements increased cancer risk ─ one more reason to ditch processed foods and your multivitamin. (By the way, if you’re looking for a better multivitamin, I recommend Primal Multi by Designs for Health, which contains the active version of folate.). The MTHFR gene variation does appear more commonly in those with hypothyroidism.
Testing for the MTHFR Gene and High Homocysteine Levels
You can take genetic tests to find out whether you have this gene, as well as high homocysteine levels.
It’s important to test for both homocysteine levels and the MTHFR gene variation because, while you may not have the gene that affects the methylation pathways, you may still have elevated homocysteine levels, which tell us the level of inflammation in our bodies. Elevated homocysteine levels may also indicate a deficiency in B vitamins.
Testing for homocysteine levels is now available through many labs and can be assessed with a blood test.
Please note, the optimal reference ranges for homocysteine are somewhat of an emerging science. While higher levels of homocysteine have been associated with numerous health complications, levels of homocysteine that are too low can also be problematic and have been associated with peripheral neuropathy (often felt as hand and arm tingling), and an impaired ability to make glutathione, an important antioxidant that reduces inflammation in the body.
Depending on the lab, some reference ranges may define homocysteine excess as >10 or 11 µmol/L, while levels under 6 µmol/L may be considered too low.
Other reference ranges, such as the one reported by Medscape, break down homocysteine levels by age and gender. (Levels of homocysteine generally increase with age.)
As for testing for the MTHFR genetic variation, many labs also offer tests for this gene. For example, you can order a saliva test kit from 23andme.com, and many individuals can get the tests from their physicians covered by insurance. You can upload your results to geneticgenie.org, which will then tell you if you have the genetic variation.
However, some may be concerned with this genetic information getting reported on insurance or to employers. There have been concerns that having a MTHFR variation or elevated homocysteine levels could potentially interfere with future insurance coverage that may limit pre-existing conditions.
Fortunately, one can order confidential tests that will not be reported to insurance by using online lab testing services, like Ulta Labs for Homocysteine or Ulta Labs MTHFR gene variation test.
There are two possible MTHFR variations that you may have. Both the 677 gene and the 1298 gene can carry the MTHFR variations.
These are the different types of potential variations to look for:
Food as Medicine
If you do have this gene variation, remember: genes are NOT your destiny! In fact, I personally have two copies of the MTHFR gene variation, but I’m alive and well. In other words, the presence of a gene does not always imply gene expression. It all depends on your unique genetic makeup, lifestyle choices, and interventions. There are many things you can do to support and optimize your methylation pathways.
First, I recommend eating a diet that will lower the overall inflammation in your body, such as the Paleo diet. (The plan I recommend doesn’t just eliminate processed foods, but it also focuses on a high intake of veggies).
As for addressing high homocysteine levels, there are two main nutrient pathways of breaking down homocysteine. Nutrient deficiencies along either of the pathways may result in elevated homocysteine levels.
One of the pathways involves the use of the B vitamins, while the other one uses trimethylglycine (Betaine) to help with metabolizing homocysteine. The following nutrients may support methylation and homocysteine levels:
Folate (B9) – You can find folate present in its activated form in real foods such as green leafy vegetables (spinach, collard greens, and romaine are some examples), asparagus, papaya, beans (especially lentils), avocados, brussels sprouts, nuts, seeds, and beets.
Vitamin B6 – Rich sources include meats, beans, avocados, and nuts and seeds.
Vitamin B12 – This is primarily found in meats, and may be deficient in a vegan and vegetarian diet.
Riboflavin (B2) – Rich sources include lamb, eggs, liver, salmon, and mushrooms.
Betaine AKA trimethylglycine – Betaine can be found in beets, whole grains like quinoa (which some individuals may not be able to eat), and spinach.
Supplements to Support Methylation
Of course, we may not be able to get enough of the needed nutrients from food alone. Individuals with the MTHFR gene variation and high homocysteine levels may also benefit from activated versions of folate, B6, and B12, such as methylated folate (also known as L-5-MTHF Folate, methylfolate, 5-formyltetrahydrofolate or NatureFolate), Pyridoxyl-5-Phosphate (P5P), and methylcobalamin, respectively.
In the survey of 2232 patients with chronic disease, 45 percent of participants said they felt better after adding methylation supporting supplements like methylated folate, B12 and B6 to their regimen.
Another 59 percent reported feeling better with adding the digestive enzyme betaine with pepsin as well, and I suspect this may in part be due to improved methylation. The top symptoms that improved included energy, pain, and mood.
Thus, if you also happen to have low stomach acid, taking the protein digestive enzyme Betaine with Pepsin is another great way to get extra trimethylglycine. Betaine HCl and pepsin are necessary for adequate absorption of Vitamin B12, as well as protein, calcium, and iron. Designs for Health developed the Homocysteine Supreme supplement to contain synergistic nutrients that support homocysteine pathways, including activated forms of folate, B2, B6, and B12, and trimethylglycine (Betaine).
This combination may help to facilitate the efficient metabolism of homocysteine and maintain a healthy homocysteine pathway, allowing for the normal production of its necessary and important end products, including the sulfur-containing amino acids taurine and cysteine, and the neurotransmitters norepinephrine and dopamine.
An optimally functioning homocysteine pathway provides methyl and sulfur groups for biochemical reactions such as detoxification, healthy immune function, ideal joint and cartilage structure, and brain and cardiovascular health – so it’s important to metabolize homocysteine effectively.
I recommend supplementing as follows, based on your homocysteine level test results:
Homocysteine Test Results Number of Capsules per Day
<6 µmol/L 1
6-9 µmol/L 2
9-15 µmol/L 3
>15 µmol/L 5
What if you feel worse after taking MTHFR Support Supplements or Betaine?
First and foremost, you’re not crazy, and you’re not alone. While most people with chronic disease tend to feel better, about 8 percent of people will feel worse with MTHFR Pathways. Some of the people who feel slightly worse (i.e. who may experience more anxiety and irritability) may benefit from a dosage reduction, in the case that their pathways are moving too quickly. However, if “feeling worse” lasts more than a few days, this could be due to overmethylation, other gene variations, or a sensitivity to the supplements, and the supplements should be discontinued. As always, listen to your body and to your knowledgeable practitioners.
Some people have a genetic variation that may impair their detox abilities, affect how they absorb certain B vitamins, and contribute to their symptoms. Nonetheless, knowledge leads to empowerment. Again, while we can’t change our genes, we can absolutely change their expression!
You can support your methylation pathways with dietary interventions and supplements. To kick-start your path to wellness, I recommend testing your homocysteine levels and checking to see if you have markers for the MTHFR gene variation. If you do, supporting your methylation pathways with supplements may help reduce some of the symptoms you’re experiencing.
If you’ve been following me for a while, you’ll likely have heard of betaine with pepsin — betaine with pepsin is one of the most helpful supplements I came across during my health journey.
You may have been told that you have too much stomach acid, and that you need to go on medication to help reduce the acid your stomach is producing…. And chances are that, if you’re like me, you’ve taken the advice of mainstream doctors and websites, but still don’t feel well or “human.” What if I told you that it may actually be the opposite; that you may not be producing enough stomach acid? What if I told you that there is a supplement that can help you on your health journey to feel human again and get your energy back?
Low Stomach Acid and Chronic Disease
Studies have found that people with chronic diseases and hypothyroidism often have hypochlorhydria (low stomach acid) or achlorhydria (lack of stomach acid). When we have low stomach acid, we are at greater risk for many undesirable health consequences:
Symptoms of Achlorhydria or Hypochlorhydria
There aren’t too many tell-tale signs of low stomach acid, other than perhaps feeling full and tired after meals, as well as experiencing acid reflux-like symptoms. Nonetheless, low stomach acid is very common in chronic disease. Signs and symptoms that would lead me to believe that a person with chronic disease has low stomach acid include: acid reflux (this condition, that is conventionally treated with acid suppressant, can actually be caused by low stomach acid), low B12, ferritin, or iron levels, fatigue despite thyroid medications, and constipation/diarrhea.
What is Betaine HCl and Pepsin?
Betaine HCl and pepsin are naturally occurring components of gastric juice that make nutrients and amino acids from our protein-containing foods more bio-available, by breaking down protein bonds. They are especially important for proper absorption of protein, calcium, B12, and iron.
Betaine, also known as trimethylglycine, is a naturally occurring amino acid derivative that is isolated from beets, and the acidic HCl version of it promotes acidity in the gastric opening. Betaine HCl used to be available as an over-the-counter (OTC) drug, marketed as a stomach acidifier and digestive aid. However, it was removed from OTC use in 1993 due to insufficient evidence of it working, and was banished to being a dietary supplement by the FDA. (Dietary supplement companies cannot make claims of the effectiveness of their products, while drug companies can make specific claims.) However, studies done in 2014 did indeed find that betaine HCl can re-acidify gastric pH.
Pepsin is a naturally occurring digestive enzyme that breaks apart proteins into smaller pieces so they can be properly absorbed by the small intestine. In supplements, pepsin is usually derived from porcine sources.
How Betaine with Pepsin Can Help with chronic diseases
In a 2015 survey of 2232 people with chronic diseases out of 627 people who took betaine HCl and pepsin, 59 percent said that it made them feel better, 33 percent said that it made them feel worse, while 7 percent saw no difference in symptoms. Based on the improvement rates, this leads me to believe that 50-70 percent of people with chronic diseases are likely deficient in stomach acid. Those that felt worse were likely not deficient, as taking the supplement can make a person with adequate stomach amounts feel worse for a short time (burning in the throat and stomach upset may occur). Those that did not see improvement may not have been dosed adequately, as betaine with pepsin dosage needs to be individualized.
The biggest improvements seen after taking this supplement were improved energy levels (58 percent), reduced pain (40 percent), and improved mood (35 percent). One fourth of people felt that this supplement also helped them with losing weight.
Betaine HCl and pepsin can make a tremendous difference in a person’s symptoms because, once we begin to digest our proteins correctly, a few great things can happen:
When we assist our digestion with the use of betaine with pepsin, it is possible to reduce pain. As I mentioned above, forty percent of people with chronic diseases reported a reduction in pain with the use of betaine with pepsin. Why does betaine with pepsin reduce pain? At first, this caught me a bit off guard, but the more I thought about the mechanism of action, the more it made perfect sense. Betaine and pepsin break down protein bonds in food, thereby aiding digestion, reducing intestinal inflammation, and even leading to reduced systemic inflammation and less pain for many people.
Trimethylglycine (betaine) can also be helpful for breaking down homocysteine, which has been associated with inflammation. Furthermore, it can increase the amount of SAMe, a naturally occurring substance with mood-boosting and pain-relieving properties, within the body.
Who Should Avoid Betaine with Pepsin?
Some people should NOT take betaine with pepsin. For example, people who have a history of peptic ulcers or gastritis, or those who take NSAIDs, steroids, or other medications that can cause an ulcer, should not take betaine with pepsin.
Signs and symptoms of an ulcer include a dull pain in the stomach, weight loss, nausea/vomiting, acid reflux, bloating, and burping. Pain improves when you eat, drink, or take antacids.
Signs and symptoms of gastritis include a gnawing/burning in your upper abdomen, nausea/vomiting, and fullness after eating. Symptoms can improve or get worse after eating.
Using this supplement in excess can lead to stomach irritation, and I always recommend a slow dose titration to determine your optimal dose.
A person using proton pump inhibitor medications would not likely want to take betaine with pepsin, as these medications and betaine with pepsin have opposing effects. Additionally, while having hypothyroidism or chronic disease in itself can cause low stomach acid, as can aging and genetics, there are other root causes of low stomach acid that need to be considered.
Addressing these root causes should always be done in conjunction with betaine HCl with pepsin supplementation:
Betaine HCl and pepsin should be taken with a protein-rich meal, starting with one capsule per meal. The dose should be increased by one more capsule at each meal, until symptoms of too much acid are felt (burping, burning, warming in the stomach region, etc.). At that point, you will know that your dose is one capsule less than what resulted in symptoms.
Drinking a mixture of one teaspoon of baking soda in a glass of water can reduce these temporary symptoms.
In my research, I came across the work of Dr. Alessio Fasano, a physician and researcher whose work has uncovered the idea that all autoimmune conditions involve some degree of intestinal permeability, also referred to as “leaky gut”. His research led him to discover the three-legged stool of autoimmunity that has revolutionized the way we understand autoimmune disease.
The three legs consist of:
What is Leaky Gut?
When functioning as they are designed to function, our healthy human intestines serve the role as both a barrier and a filter. A layer of cells form a mucus barrier, consisting of inter-cellular tight junctions similar to thread fibers that come together to form a piece of cloth. The intestines open and close their tight little junctions to allow nutrients to be absorbed from the food that passes through our gut and blocks the absorption of toxins like partially digested food, pollen, feces, dead cells, and bacteria that we certainly don’t want circulating around our bodies.
But what happens when those intestinal tight junctions become damaged and loose?
Those toxic substances become absorbed into the bloodstream, causing the body to recognize them as foreign invaders. This causes inflammation in the body as it begins to attack the intruders, and eventually leads to autoimmunity.
There are numerous factors that can cause intestinal permeability, and discovering which trigger (or triggers) is damaging your gut is key to restoring its function. These factors include:
This long list of potential triggers can seem daunting, but the most common triggers that cause leaky gut are stress, food sensitivities, nutrient deficiencies, a deficiency in digestive enzymes, an imbalance of gut bacteria, and intestinal infections (including SIBO).
By addressing and managing stress and then tackling potential gut irritants, we can oftentimes reverse leaky gut and stop autoimmunity in its tracks!
There are four steps to removing some of the triggers and putting an end to leaky gut and its symptoms.
Step 1: Remove Reactive Foods
In some conditions, a single food can act as a trigger and induce intestinal permeability. This is the case with gluten (a protein found in wheat, barley and rye) and Celiac disease. Dr. Fasano estimates that for up to 20 percent of people with autoimmune conditions, the trigger may be gluten, and removing gluten will reverse the autoimmunity.
Even in a person without Celiac disease or any apparent gluten sensitivity, gluten can lead to a leaky gut because it is a protein that is difficult to digest for humans. While some people with chronic diseases go into remission just by removing gluten from their diet, others will need to search for additional “root causes”. These additional food sensitivities are likely to include dairy, soy, and grains, but might also include nuts, seeds, eggs or nightshades (potatoes, tomatoes, bell peppers and eggplant). The Autoimmune Paleo diet can be helpful with this.
I suggest that to discover the food triggers that are causing your leaky gut, begin by eliminating gluten, dairy, soy and grains for a period of 4 weeks. If you begin to feel a relief of gut symptoms after that trial period, you can slowly add each food group back into your diet, one at a time, allowing a few days between foods to see if you get a reaction.
If after eliminating each of these food groups you are still experiencing gut symptoms, it might be time to eliminate a wider group of possible food irritants.
This elimination diet would exclude:
Step 2: Supplement with Enzymes
Several studies have found that people with chronic diseases and hypothyroidism often have a deficiency in hydrochloric acid, resulting in low levels or even a complete absence of stomach acid.
Digestion is one of the biggest energy-requiring processes of our bodies. When extra effort is required to break down the proteins we eat, it takes a huge toll on our bodies and can often lead to extreme fatigue – a common symptom for those dealing with thyroid and other autoimmune conditions.
A digestive system that is weakened by difficulty with digesting proteins can set off a chain reaction of greater digestive trouble as it struggles to digest the more complex protein molecules found in gluten, dairy and soy. When proteins are poorly digested, we are more likely to become sensitive to them, leading many people with chronic diseases to become sensitive to gluten, dairy and soy, among other foods.
It’s a vicious cycle, but one that can be slowed by supplementing with hydrochloric acid and digestive enzymes, which can assist the body in breaking down these difficult to digest proteins and improving overall intestinal function and vitality. My research and personal experience have led me to recommend a few supplements to help restore proper gut function.
1. Betaine HCL with Pepsin – When I first took Betaine HCL after struggling for a decade with debilitating fatigue, I was amazed at how my energy returned almost overnight! I no longer needed to sleep for 12 hours, and my bloating was significantly reduced. All because I was finally able to digest my food.
Betaine HCl and Pepsin are naturally occurring components of the gastric juices that break down protein bonds in our food to make nutrients and amino acids more bio-available. They are especially important for proper absorption of protein, calcium, B12, and iron. Taking Betaine HCL with Pepsin after every protein-containing meal can assist with digestion and greatly improve energy levels. I recommend the Betaine with Pepsin supplement by Designs for Health.
2. Proteolytic Enzymes – Also known as systemic enzymes, proteolytic enzymes can help bring our immune system back into balance by breaking down pathogens and reducing inflammation that can lead to autoimmunity. In Europe, these systemic enzymes have been studied extensively and have become a popular alternative to pain medications for many inflammatory conditions.
3. Fat Digestive Enzymes – Fat malabsorption is easily overlooked by patients and practitioners alike, but is a common occurrence. Some signs and symptoms of fat malabsorption include greasy, smelly, floating, light-colored stools, gas or belching after eating, diarrhea, dry skin, stomach pain, gallbladder pain (which is on the right side, under the ribs), gallstones, gallbladder removal, nausea, weight loss, hormonal imbalances, and adrenal issues. A low fecal elastase test on functional medicine stool testing can also indicate fat malabsorption.
Potential reasons why a person may have difficulty with fat malabsorption include bile deficiency, pancreatic enzymes deficiency, liver backlog, and small intestinal bacterial overgrowth (SIBO).
The Designs for Health Liver & Gallbladder Support (LV-GB) supplement can help fat digestion in three different ways: it can support the liver’s ability to process fat with milk thistle, give us extra bile via ox bile, and support our bile flow with dandelion, artichoke, and beets. If you have issues with fat malabsorption, this is life-changing support.
4. Vegetable Digestive Enzymes (Plant Enzymes) – Many people with chronic diseases may also have an impaired ability to digest vegetables due to fiber and starch content. In some cases of hypothyroidism, an indigestible ball of plant fiber material known as a phytobezoar has been found to cause bowel obstruction. In the case of poor fiber absorption, undigested vegetables fibers may be found in the stools, and high-fiber meals may cause bloating. A vegetable digestive enzyme that contains fiber-digesting enzymes like cellulase, and/or starch digesting enzymes like amylases, may help with digesting vegetables. I formulated the Designs for Health Plant Enzymes with a specific combination of enzymes, including cellulase and amylase, to help support this digestive process.
5. Broad Spectrum Digestive Enzymes – A broad spectrum digestive enzyme may also be helpful with decreasing symptoms of nutrient deficiencies and increasing energy. Broad spectrum enzymes, like Digestive Enzymes Ultra from Pure Encapsulations, promote optimal digestion of proteins, fats, and carbohydrates. Digestzymes is comprised of a mixture of enzymes, to support enhanced digestion for optimal nutrient bio-availability and absorption.
Step 3: Balance the Gut Flora
The gut is home to trillions of bacteria, and studies have shown that autoimmune disorders can be brought on by an overabundance of the wrong type of bacteria, and can be reversed by an increase in beneficial bacteria. So, you can see how important it is to make sure our gut flora is well balanced.
Gut flora balance is achieved in large part through eating a wide variety of healthy foods, but for those on restrictive diets to help get to the root cause of their autoimmunity, this might be difficult. For that reason, it is often necessary to supplement with fermented foods and probiotics.
Fermented foods – Sauerkraut and similar fermented vegetables are a wonderful source of beneficial bacteria and can help to restore proper gut flora when consumed regularly. Similarly, kefir and yogurt offer an abundance of good bacteria, but should be avoided by those who have been determined to have a sensitivity to dairy. Coconut yogurt and fermented coconut water are great alternatives.
Probiotics – Widely used to rebalance gut bacteria, probiotics can be a powerful tool for those dealing with leaky gut, as they can help restore healthy gut flora by displacing the pathogenic bacteria.
It is important to note that not all probiotics are created equally, and it’s crucial to start slowly and build up from there. As the “good” bacteria begins to take up residence in your intestines and displace the “bad” bacteria, the die-off can sometimes create what’s called a Herxheimer reaction. This can include lethargy, difficulty concentrating, cravings for sweets, diarrhea, rashes, irritability, gas, bloating, headache, nausea, vomiting, congestion, and increased autoimmune symptoms. This type of reaction usually clears within three to five days and leaves the person feeling much better in the end.
There are several different types of probiotics that can be beneficial for those dealing with chronic disease. Lactic acid-based probiotic recommendations include VSL#3, Probiotic Synergy, and Probiomed 50B . Yeast-based probiotics are a safer option for those combating SIBO (small intestine bacterial overgrowth), in which case I recommend Saccharomyces boulardii based probiotics like Floramyces by Designs for Health.
Finally, spore-based probiotics have recently been shown to reduce allergies and asthma, in addition to helping recovery from autoimmune disease and reducing SIBO. I recommend ProbioSpore.
Step 4: Nourish the Gut
Providing nourishing food and supplements is an important last step to give your gut long term support. By adding a few critical nutrients, we can both heal and help prevent leaky gut.
One of the easiest ways to soothe and heal the lining of the gut is to have a delicious cup of bone broth. Bone broth is a traditional food that we hear a lot about these days because it really is one of the most nourishing foods we can feed our bodies.
The reported benefits of bone broth include boosting immunity, relieving joint pain, increasing energy, improving digestion, and giving you a more youthful appearance. Most importantly, for those suffering from leaky gut, the gelatin in bone broth actually helps to seal the junctions in the intestines so they are no longer permeable; and so that toxic substances can no longer pass through the intestinal wall.
Best of all, bone broth is cheap and easy to make and makes a delicious beverage or soup to sip any time of day.
Here’s an easy bone broth recipe that can be thrown together in a slow cooker before bed and enjoyed the next day:
Easy Bone Broth
5 chicken legs
2 cups mixed chopped carrots, onions, and celery
1 tablespoon apple cider vinegar
Sea salt to taste
Add all ingredients to a slow cooker and cook overnight, or for 8-24 hours. You’ll wake up to a delicious smell!
Acute or chronic stress can trigger an overactive sympathetic nervous system, resulting in high oxidative stress. The immune system functions at its best in the parasympathetic state so when it switches to a sympathetic state, the body is vulnerable to disease. Chronic release of hormones such as cortisol, catecholamines and neuropeptides due to stress also has a deleterious effect on the immune system, which impacts the sleep cycle and circadian rhythm. Psychological stress can also have a negative effect on the skin, triggering or exacerbating immune-mediated dermatological disorders.
New scientific discoveries have explored the connection between melatonin and stress. In this article, we’ll review these findings and discuss 4 ways melatonin regulates the stress response.
What is Melatonin?
Melatonin (N-acetyl-5-methoxytryptamine) is a hormone that is released by the pineal gland and the skin. In addition to regulating the sleep-wake cycle, it is intricately linked to the fight or flight response (and digestion). Melatonin plays a role in mitigating stress, as well as controlling the sleep-wake cycle and can, therefore, significantly alter mood.
Melatonin is produced when light hits the retina and subsequently, the pineal gland, which influences the circadian rhythm. It also stimulates γ-aminobutyric acid (GABA) and reduces catecholamine levels.
Skin is Especially Responsive to Psychological Stressors
Melatonin is a methoxyindole produced by the skin and has both receptor-dependent and receptor-independent effects that protect the skin against UV rays and oxidative stress. The skin is the largest bodily organ and has its own innate and adaptive immune system, protecting the body from the stressor of daily toxins.
Because the skin and brain interact through psychoneuroimmunoendocrine mechanisms, there’s a clear connection between stress, psychiatric disorders and skin disorders. In fact, 30% of patients with a skin disorder have a co-occurring psychiatric disorder. Melatonin plays a major role in the stress response of the skin and can counter or buffer stressors to keep the skin intact. Excessive stress can, therefore, appear on the surface of the skin as a dermatological disorder.
1. Melatonin Helps You Sleep Better
Sleep and mood are intrinsically linked. When we’re feeling stressed or worked up it’s difficult to sleep, due in part, to the activation of the HPA axis and the sympathetic nervous system.
In one randomized, double-blind, placebo-controlled, crossover trial designed to evaluate the effects of melatonin on sleep and behavioural disorders, researchers found that melatonin supplementation significantly improved sleep quality. Their mood-related disorders also improved. The researchers concluded that “melatonin administration significantly improves sleep and, therefore, behavior.”
2. Melatonin Protects the Central Nervous System (CNS)
Melatonin protects the CNS in a variety of ways. It supports healthy inflammation, shifts the balance of the sympathetic nervous system over to the parasympathetic nervous system and reduces free radical burden while improving cellular and organismal physiology. Melatonin also improves endothelial dysfunction and supports healthy blood pressure levels.
High blood pressure may be the result of an imbalance between the sympathetic and parasympathetic systems and heightened inflammation. Melatonin plays an important role in allostasis, synchronizing daily rhythms as well as regulating parameters of the cardiovascular system.
3. Melatonin is an Antioxidant
Stress shows up physically in the body through the speeding up of the metabolism and the HPA axis, which creates cellular and toxic waste by-products. These waste products create a vicious cycle, adding additional stress to the body.
Melatonin supports healthy inflammation pathways and stimulates various antioxidative enzymes, which increases its efficiency as an antioxidant. Additionally, it potentiates the antioxidant activity of other molecules like glutathione, vitamin E and vitamin C.
Melatonin has a lipophilic effect on cells, which allows it to cross cell membranes and reach subcellular structures. This means that it can successfully scavenge free radicals deep inside the cells. The lipophilic properties of melatonin can also decrease lipid profiles. Administration of melatonin for two months has been found to increase catalase activity, which helps reduce oxidative stress.
4. Melatonin and Cellular Bioenergetics
Aging and disease can impair the body's ability to produce ATP, the energy molecule of the body. This can be due, in part, to excessive free radical build-up, particularly the superoxide anion, which is a free radical produced by mitochondrial metabolization.
Melatonin has also been shown to support the neurological response, calming the mind and allowing the body to rest.
The Bottom Line
Melatonin regulates the parasympathetic (fight or flight) and sympathetic (rest and digest) systems. This allows the body to rest and the circadian rhythm to be kept in check. Additionally, melatonin acts on many levels to promote free radical scavenging, which helps the body detoxify acidic cellular waste.
For many people with chronic disease, the underlying cause of their disease can be linked to dietary triggers. Often times, eliminating problematic foods is key to finding healing and eventual remission. However, there are other toxins that can contribute to the autoimmune response, some of them less obvious than others. One such trigger that we hear about less often is mold.
Though not everyone is sensitive to mold, a surprising number of people will find that their deteriorating health, including respiratory, digestive and cognitive issues, can be linked to exposure to toxic mold.
What is Mold?
Molds are a form of fungi and are a natural part of the environment we live in. They can be found almost anywhere, wherever oxygen and moisture are present, and can spread through the air by way of spores, their reproductive cells.
Mold often lurks in damp, dark environments within the home, such as bathrooms, kitchens, recently flooded areas, and basement areas. It can also be found under sinks and in areas with poor ventilation.
Outdoors, mold is often found in moist soil and decaying organic matter. High levels of mold spores in the air are often to blame for environmental allergic reactions. Indoors, when moisture is present, mold can be found in building materials, carpeting, and even foods. Mold can often accumulate when a home is flooded or if there is a hidden water leak that is left unaddressed.
Though molds are all around us, it’s exposure in large quantities that can sometimes lead to serious health problems. Indoors, the most common types of mold typically found are Cladosporium, Penicillium, Alternaria, and Aspergillus. Common health complications related to indoor mold exposure include asthma attacks, headaches, dizziness, sinus infections, and skin rashes.
Some molds produce toxic secondary metabolites called mycotoxins. We call these “toxic molds,” as their mycotoxins can cause serious health problems for both humans and animals. Exposure to mycotoxins has been linked to neurological problems and even death.
Stachybotrys chartarum (sometimes referred to as “black mold”), which grows on household surfaces such as wood, fiberboard, gypsum board, paper, dust, and lint, is one of the most commonly known toxic molds.
Mold: The Potential Root Cause of Chronic Symtoms
There are hundreds of peer-reviewed articles discussing the harm that “black molds” are capable of causing to the brain and immune system. The work by mold researcher Dr. Enusha Karunasena has demonstrated that the endothelial cells that make up the blood-brain barrier can become compromised by these molds. Since the endothelial cells make up the brain’s primary protection mechanism against outside threats, damage to them means that the toxic molds can easily get into the brain and damage the neurons.
Additionally, the damage to the blood-brain barrier can allow substances (which are otherwise harmless to the rest of our systems) to cross into the brain and further damage the delicate neurons. This makes it possible for individuals who have suffered damage to the blood-brain barrier due to toxic mold, to develop sensitivities and become affected by exposure to a variety of other substances, from wood smoke to air fresheners.
It’s important to note, however, that not all molds are harmful. In fact, molds have many valuable functions, including pharmaceutical and food production uses. After all, penicillin, soy sauce, and blue cheese wouldn’t exist without the presence of mold! However, those who are sensitive to mold may find that even the small amounts of mold present in cheese, nuts, or coffee may be enough to create an adverse reaction.
Symptoms of Mold Toxicity
When it comes to mold exposure, not everyone is affected in the same way. Even those living in the same home may develop different symptoms depending on their genes. Sometimes, multiple family members in the same household may have varying levels of immune-related diseases, but others may not exhibit any symptoms.
That said, common symptoms of mold exposure include brain fog, respiratory issues, cognitive impairment, immune suppression, fatigue, depression, arthritis, digestive problems, poor sleep, inflammation, and joint pain.
Those who have an allergy to mold may experience watery, itchy eyes, a chronic cough, headaches or migraines, difficulty breathing, rashes, fatigue, sinus problems, nasal blockages, and sneezing.
Some of the clients that I’ve seen affected by mold have shown me unbelievable before and after photos. People who were once thin and athletic can put on weight and collect so much inflammation in their bodies that they become virtually unrecognizable within months of mold exposure.
Testing for Mold
If you suspect that you have been exposed to mold, like many of my patients have been, it’s important that you test both your home environment and your body to see if molds are present.
Mold in the Home
As I mentioned earlier, the most common places for mold to exist in the home are dark, damp places that get limited ventilation, such as bathrooms, basements, and any areas that have been flooded in the past. Many affected homes may have a stale, moldy smell. Though a visual inspection may alert you to the presence of mold, not all mold spores are visible to the human eye. Mold can also be lurking behind walls and under flooring, so it will be important to perform an air quality to test to find out if mold is present in your home.
Additional places that can harbor mold in the home include:
To determine if mold is present in a building space, an air sample is taken by using a specialized pump to collect airborne spores. A lab will then determine both the amount of mold spores present in the air, as well as the species of molds.
Mold testing can be conducted by a professional service; however, there are also home kits available that allow you to test for the presence of mold in your home yourself. Kits can be purchased through Real Time Laboratories, and results will be sent directly to you.
To prevent mold growth in your home or workspace, there are several steps that can be taken:
Testing for mold in your home environment is just as important as testing your body for the presence of molds.
Functional medicine testing can help you determine whether the mold from your environment has moved into your intestines. I recommend the GI Effects Gastrointestinal Function Comprehensive Profile (One day collection) METAMETRIX KIT, which can be ordered by a functional medicine physician. Alternately, you can order the test yourself through a company such as Direct Labs use code THUTH.
You can also run a RealTime Laboratories test for mold metabolites in your urine to determine if mold has taken up residence in your body. Additionally, it may be helpful to have your doctor run a mold panel from ALCAT labs to see which molds are reactive in your body. If you’ve done stool testing, sometimes the tests may reveal mold overgrowing in your gut. The mold will show up as “yeast present—taxonomy unavailable.”
A third test that can be ordered online is the MycoTOX Profile. This comprehensive test screens for 11 different mycotoxins, from 40 species of mold, in one urine sample. It uses advanced mass spectrometry (MS/MS) to detect lower levels of these fungal toxins. This test is optimal for follow up testing to ensure that detoxification therapies have been successful.
Treatments to Eliminate Mold
If you’ve been exposed to mold, it is quite possible that the mold has taken up residence in your body. Eliminating your exposure is a critical first step to recovery from mold toxicity.
In addition to removing the source of the mold, you will most likely need additional interventions to clear the mold from your body.
The presence of mold in the sinuses and intestines can lead to intestinal permeability (leaky gut) and become a trigger for autoimmune disease. Sinus infections (sinusitis), which are often triggered by mold, can also be a root cause of chronic disease. In fact, a study conducted by the Mayo Clinic showed that moldy home and work environments were responsible for 9 out of 10 cases of chronic sinus issues.
For years, researchers believed that all sinus infections were the result of either bacteria or viruses. Now, they are coming to realize that when fungi like mold enters the sinus cavity, a suppressed immune system can react and result in fungal sinusitis. Fungi love damp, dark conditions, making the sinus cavity a perfect place to grow.
There is almost no way to tell the difference between sinus infections caused by fungi and those caused by viruses or bacteria. Additionally, sinus infections can often have a combination of causes. Symptoms of all three types of sinus infections look the same: headaches, sinus pressure, congestion, and discolored discharge.
Allergic fungal sinusitis was first recognized as a disease about a decade ago. It accounts for approximately 6-8 percent of all chronic sinusitis diagnoses that require surgical intervention. Although certain signs and symptoms may cause a physician to suspect allergic fungal sinusitis, no standards have been defined for establishing the diagnosis. However, it is extremely important to recognize allergic fungal sinusitis and differentiate it from chronic bacterial sinusitis, because the treatments and prognosis for these disorders may vary significantly.
Fluconazole, in particular, is a promising treatment for persistent fungal sinusitis infections. One recent study looked at 16 patients with a history of allergic fungal sinusitis. The patients were given fluconazole nasal spray and were followed for three months. Improvement of disease, without significant side effects, was observed in 12 of the 16 patients. Though larger studies are needed to confirm these results, these preliminary findings show that people with allergic fungal sinusitis may benefit from this course of treatment.
The only way to know for sure whether your sinus infection is caused by mold is to get tested for fungal sinusitis by your doctor. There is a test called MARCoNS (Multiple Antibiotic Resistant Coagulase Negative Staphylococci) that can test for mold related bacterial infections, as well as fungi in the sinuses.
A CT scan (which combines x-rays to view cross sections of the body) with an ear, nose and throat specialist can also help determine if a fungal or bacterial infection is present in the sinuses.
Symptoms of chronic sinusitis include pain in the sinuses, nose, ear, face, or throat, as well as drainage from the nose, headaches, chronic cough, post-nasal drip, sneezing, congestion, throat irritation, loss of smell, and ear inflammation. A person may also have a fever, but that may be missed in thyroid disease.
Supplements to help clear mold from the sinuses and gut include:
Please note: Candida yeast can often co-occur with mold toxicity, especially when a sinus infection is present, so it may be necessary to follow protocols to eliminate Candida overgrowth along with the mold. You can read more about my recommendations for addressing Candida overgrowth here.
It may be helpful to work with a practitioner who is specifically qualified to treat fungal infections. For more information on what to look for in a doctor and a few resources for finding a mold doctor near you, please visit the Biotoxin Journey website.
Additional Lifestyle Interventions
Whether you’ve experienced mold toxicity yourself, or you simply want to avoid toxic mold exposure as much as possible, there are several ways you can protect both your living environment and your body from excessive amounts of mold.
Many commonly consumed foods can be contaminated with molds that will increase the toxic burden on the body. Some food-borne molds are obvious. White fuzz on the casserole you found in the back of the refrigerator should probably be avoided! But other foods may contain molds that aren’t visible to the eye. If consumed regularly, these molds can be problematic.
Common mold-contaminated foods include:
Additionally, following a diet that is low in mold-containing foods (such as the one outlined in Dave Asprey’s The Bulletproof Diet book, which avoids many of the commonly mold-contaminated foods above) can be helpful when you are trying to eliminate molds from your body.
If you’ve discovered mold in your home, it’s likely that you will need to call in a professional mold remediation service to safely remove the contaminated parts of your home. It is critical that the source of exposure be removed in order to heal from mold toxicity. Otherwise, you will be recontaminated and the vicious cycle will continue.
The Environmental Protection Agency website provides more information and a number of resources for detecting mold in your home, methods to clean the mold yourself, and how to find a professional agency to remove mold from your home.
In extreme cases of mold within a home, it may be necessary to move and discard any belongings that have been contaminated with mold. Otherwise, the risk of re-contamination can be too great. While this may seem extreme, remember that your health is worth the sacrifice and you will feel so much better once you have eliminated this trigger from your life.
If you are shopping for a new home or work-space, I suggest having the space inspected by a professional mold detection service so that there are no surprises down the road.
It’s also critical that you keep your living space dry and ventilated. Any flooding or water leaks should be immediately addressed to avoid the opportunity for mold to flourish.
Additionally, you will want to have your air ducts cleaned on a semi-annual basis to ensure they remain clear of mold spores.
Using a silver sol cleaning spray, such as Silvercillin, will help kill mold and bacteria on household surfaces. This spray is naturally derived, and safe to use around children and pets.
I also highly recommend investing in a quality air filter, such as the Air Doctor, to help purify your living environment of airborne molds and other allergens. My mother, who has asthma, has seen a reduction in her asthmatic symptoms with it!
The TakeawayThough mold is one of those unpleasant substances that we’d rather not believe is lurking inside our walls (or inside our bodies!), uncovering the mold in your life could be an important step toward recovering your health and putting your Hashimoto’s into remission.
Testing your home and workspace, eliminating any molds that are present, and being vigilant about preventing mold from forming in your living space are important first steps to becoming free of mold toxicity. Further testing to see if mold is present in your body, followed by implementing a protocol of supplements and pharmaceuticals, may be next steps to ensuring that you eradicate the mold completely.
As always, I encourage you to keep digging for the root cause of your thyroid condition and take the necessary steps to recover your health and vitality!
Consider Additional Supplements
You may have heard the term “nootropics,” which refers to a broad range of drugs, supplements and other substances that are taken to improve cognitive performance. Sometimes referred to as “smart drugs” or “cognitive enhancers,” these substances can range from caffeine and adaptogens, to amphetamines. While the list of nootropics is long, there are few that I like that are science-backed for improving brain fog, and safe for those of us with chronic disease.
If you are still experiencing brain fog after tackling the fundamental strategies I’ve outlined above, you may want to dig a little bit further and incorporate one or more additional steps to uncover your root causes.
Brain fog is an incredibly common symptom in Chronic Disease and can leave a person feeling unable to function in their day-to-day life. Confusion, lack of focus, memory loss… these can all sap a person’s self-confidence and greatly impact their quality of life. I know this to be true, as it was my own experience!
The good news is that, by making sure our thyroid hormones are optimized, and by addressing gut health, we can eliminate most of the underlying causes of brain fog and regain mental clarity. It might take some work; after all, healing from chronic disease involves some detective work to get the bottom of everyone’s underlying causes. But I have no doubt that you can get there. When brain fog is eliminated, there is no limit to what you can accomplish!
Look for my article on Mold and Mold Exposure tomorrow!!
Addressing the Underlying Cause of Brain Fog
To get to the root cause of brain fog in chronic disease, we must start with the basics. Optimizing thyroid hormones should be the first item to check off in addressing brain fog for most people. Next, since so many of the causes of brain fog are based in poor gut health, we must eliminate food intolerance that may lead to intestinal permeability (leaky gut), support proper digestion of the food we eat, and address nutrient deficiencies that may be contributing to symptoms of brain fog.
Checklist of What Needs to be Looked at
1. Optimize TSH Levels
TSH (Thyroid Stimulating Hormone) is a pituitary hormone that responds to low/high amounts of circulating thyroid hormone. While the standard reference range for TSH is 0.2-8.0 μIU/mL, a new normal reference range was defined by the American College of Clinical Endocrinologists to be between 0.3-3.0 μIU/mL. Functional medicine practitioners have defined that normal reference ranges should be between 1 and 2 μIU/mL, for a healthy person not taking thyroid medications. Anecdotally, most patients feel best with a TSH between 0.5-2.0 μIU/mL. Get your TSH checked with UltaLab Tests or your primary care provider.
If your TSH test shows a TSH level above 2.0 μIU/mL, even when all other thyroid tests fall within normal ranges, this is considered subclinical hypothyroidism. This means your thyroid is losing its ability to make enough thyroid hormone. At this point, you may benefit from starting on a thyroid medication (or increasing your current dose). For many, getting your TSH levels within optimal ranges will relieve many of the common hypothyroid symptoms, including brain fog.
2. Optimize T3
Some people may not properly convert T4 to T3 (the active thyroid hormone). (There are many factors that may contribute to a person not being able to properly convert thyroid hormone, including liver congestion, stress, low zinc levels, and other nutrient deficiencies… which are all common in those with chronic disease!) This is why many people continue to struggle with thyroid symptoms such as hair loss, brain fog, weight gain, depression and fatigue, even after they’ve started taking thyroid medication.
Studies have suggested that T4-only therapy might not be enough to address the symptoms of hypothyroid patients, especially those related to mental well-being, such as brain fog and depression; and people who continue to have thyroid symptoms despite having normal TSH levels may benefit from a trial of T3, in addition to T4 medication. Get your T3 checked with UltaLab Tests or your primary care provider.
If this sounds like something you may benefit from, you do have a few options when it comes to T3-containing medications:
3. Eliminate Food Intolerances
I have found that most people with chronic disease will need to give up gluten, dairy, and soy, as they are the primary food sensitivities affecting people with chronic disorders. However, undergoing an elimination diet and food sensitivity testing will help you to pinpoint the foods that are problematic for you and lead to intestinal permeability, leaky gut.
4. Address Adrenals
Healthy adrenal hormones tame inflammation (including inflammation in the brain), and the most important strategy for combating adrenal hormone dysfunction is stress reduction. In the early stages of adrenal fatigue, the adrenals secrete excessive levels of cortisol; in the later stages, they secrete less and less, leading to inadequate levels of the anti-inflammatory hormone in the body. This can be a major contributing factor to brain fog.
Stress reduction, adequate sleep, taking the ABC’s (adaptogenic herbs, B vitamins and vitamin C) are great starting points for addressing adrenal hormone imbalances. Adrenotone is a formulation of adaptogenic herbs and vitamins that is designed to support stress levels and brain health, by promoting healthy cortisol levels and hypothalamic and pituitary function (HPA axis), as well as dopamine, norepinephrine, and epinephrine production. Taking three capsules per day can help with brain fog due to adrenal issues.
For additional ideas on how to reduce stress and support your adrenals, please take a look at my article on adrenal health.
5. Support Digestion
A lack of digestive enzymes and stomach acid are common in chronic disease, and can allow undigested food particles to enter the bloodstream through a leaky gut. This can often be the cause of food sensitivities and nutrient depletions, which can lead to brain fog (among other symptoms). I recommend using betaine with pepsin (Betaine HCL) and digestive enzymes, to help your body break down the foods you consume, so that they can be readily utilized by your body and reduce damage to your gut. Additionally, taking a quality probiotic can help restore the balance of bacteria in the intestines, and help prevent leaky gut.
My theory is that the body is focused on the backlog of undigested foods, instead of on creating luxuries like, brain power and energy.
6. Address Nutrient Deficiencies
Nutrient deficiencies can occur as a result of eating nutrient-poor foods, having inflammation from infections or food sensitivities, taking certain medications, or having an imbalance of gut bacteria. A lack of sufficient thyroid hormones can also lead to nutrient deficiencies, as it makes nutrient extraction from food more difficult and less efficient.
The nutrient deficiencies that we see with Hashimoto’s that can lead to brain fog include:
If you find that you are still experiencing symptoms, I recommend a few additional supplements that have been shown to support brain function. I will address these additional supplements tomorrow!! So Stay Tuned!!