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The Complete Guide to the COMT Mutation and Adrenal Fatigue

An image of a strand of DNA with a piece floating away from the wholeYour body’s ability to rid itself of toxins and other contaminants is absolutely essential to your health. It’s also an essential part of your ability to recover from stress. Most of the time, your body performs these processes in the background, and you probably aren’t even aware of them. But this isn’t always the case. There are certain issues such as the COMT mutation that can impede these processes. And if you aren’t aware of the issue, then you may experience long periods of ill health without any obvious cause. This, paired with chronic stress, can create the conditions for long-term health problems like Adrenal Fatigue Syndrome (AFS).

What is the COMT Mutation?

The COMT gene helps make an essential enzyme known as catechol-O-methyltransferase. This enzyme helps to degrade catecholamines like dopamine, norepinephrine, and epinephrine as well as drugs and substances that have the same catechol structure. So, if you have a mutation in this gene, your body will struggle to process and rid itself of these chemicals. This means you might experience higher than usual levels of these chemicals as well as the metabolites they help create.

The COMT gene is also essential in methylation. This is a biochemical process where atoms are transferred from one substance to another. It helps manage or contribute to several vital processes including:

  • Inflammation
  • Neurotransmitter synthesis
  • Cardiovascular function
  • Detoxification of certain chemicals and substances
  • Energy production
  • The expression of DNA and certain genes
  • Immune function

Between 20 and 30 percent of Caucasians with European ancestry have a COMT mutation. This mutation limits the body’s ability to break down and remove neurotransmitters (NTs) by 3-4 times. These NTs are responsible for planning, behavioral inhibitions, short-term memory, and stress reactions. So, if you have this COMT mutation, your body will struggle to cope with the high NT levels that occur during stressful periods. Your NT levels may also remain higher than normal for a longer period, so you experience more stress for longer. In this way, COMT genes can determine:

  • Your stress levels
  • How you respond to both negative and positive emotions
  • How you react to stress.
  • Your stress resiliency

COMT is also associated with high cortisol levels and HPA axis dysfunction. This mutation has a powerful impact on your stress reactivity and your ability to de-stress. It may also have an important role in AFS and in your recovery from it.

Symptoms of COMT Mutation

The symptoms of the COMT mutation can vary widely between people. Also, research is still in its infancy regarding this issue. This means that there is no agreement in the medical field about the symptoms of COMT gene mutations. However, some common problems associated with this mutation are:

Estrogen Imbalances

Both estrogen dominance and imbalances are very common with COMT mutations. This can cause a range of symptoms such as:

  • Psychological problems like anxiety, bipolar disorder, or depression
  • Fatigue
  • Thyroid abnormalities
  • An image of a human head with a cloud where the brain is locatedAllergies
  • Hormonal imbalances, a low libido, or infertility
  • Memory problems or 'brain fog'
  • Early menopause symptoms
  • Breast tenderness
  • Fibromyalgia
  • Cancer
  • Neurological disorders

Dopamine Imbalances

Problems with the COMT gene can also cause low or high dopamine levels. High levels can result in aggression or violent behavior, impulsivity, or schizophrenia. Low levels, on the other hand, are associated with:

  • Addiction
  • Low libido
  • Depression
  • Tremors
  • Mental and physical fatigue

Poor Detoxification

This mutation also slows down the processing and expulsion of NTs and other related chemicals, which can make issues related to the processing of these chemicals worse than normal.

These problems can be made worse by another common gene mutation known as MTHFR.

The COMT Mutation and MTHFR

The COMT mutation is closely related to MTHFR. Methylenetetrahydrofolate reductase or MTHFR is another fairly common gene mutation that comes in two main variations:

  • C677T
  • A1298C

It’s possible to have one or the other of these mutations or to inherit both. You may also have MTHFR and COMT mutations at the same time.

It’s important that you get tests for both of these mutations if possible, as they are closely related and may have an important impact on each other and on AFS. Both COMT and MTHFR genes are involved in the methylation pathway, and MTHFR may affect how COMT functions. For instance, if MTHFR activity is lower than normal, then it will lower COMT processes as well. And if the activity of both are lowered because of mutations, then it could have serious health consequences.

It’s actually quite simple to test for COMT and MTHFR gene mutations. Talk to your doctor about a cheek swab test. This will give you the information you need to better manage any mutations in your DNA. This is even more important if you have AFS and need to find better ways to manage your condition.

The COMT Mutation and Adrenal Fatigue

The COMT mutation can have a major impact on adrenal fatigue because it changes the way your body reacts to stress. AFS occurs when you’re under stress over a long period.

Usually, your NeuroEndoMetabolic (NEM) Stress Response does its work behind the scenes to help you cope with stress, and then it shuts down once your stress levels go down again. But, if you’re like many people in the modern world, then you’re under chronic stress because of lifestyle and environmental factors. This can result in ongoing activation of the NEM stress response.

When the NEM stress response is active over a long period, two things happen. Firstly, the adrenal glands become fatigued. This occurs when your body needs high levels of cortisol in order to cope with the stress. Everyone’s adrenals have different tolerance levels for this kind of overwork, but when you hit your individual limit, your adrenals will start to malfunction and eventually degrade.

The second thing that happens is that the six circuits that make up the NEM stress response start to become unbalanced when your NEM stress response is active for too long. The unnatural level of activity causes the individual components to degrade in health, affecting the circuit overall. This applies to all of the body’s circuits, including the Detoxification circuit.

Detoxification Circuit Dysfunction and the COMT Mutation

An image of the extracellular matrixThe Detoxification circuit includes the immune system, the liver, and the extracellular matrix (ECM) or the fluid-filled spaces outside of cell walls. These three components work together to clear your body of toxins and metabolites, the harmful by-products of metabolism.

When you’re stressed, cortisol causes extra activity in your body and creates more metabolites for your body to deal with. Ordinarily, your Detoxification circuit would deactivate these metabolites and expel them. But when this circuit is unbalanced and malfunctioning, this process can slow considerably, leaving your body awash in a sea of harmful substances.

The COMT mutation worsens this situation. When you’re stressed, your body naturally produces more of the NTs epinephrine and norepinephrine to make you alert and prepare you to respond to a threat. The imbalances that occur with AFS will only worsen this situation. As AFS progresses and your stress levels increase, your body will produce more of these NTs to keep you alert and ready to face a threat. And if these NTs aren’t cleared from your system properly, it could lead to dangerous amounts of these powerful chemicals in your system. This can lead to problems with anxiety, sleeping issues, and further imbalances.

These problems in turn will lead to more stress, which will prompt the release of more NTs and the creation of more metabolites. Over time, this can be a vicious circle that leaves your body awash in a sea of NTs and toxic metabolites that worsen your AFS and have a negative impact on your health overall.

What To Do About the COMT Mutation?

You obviously can’t change your genes, so you can’t eliminate a COMT mutation. However, there are things that you can do to support your body’s natural detoxification processes. Here are some simple changes that will help:


COMT is a methylation gene, which means you can take supplements to support its function. The most helpful are:

  • B vitamins, particularly B2, B6, B9, and B12. But always be aware of the possibility of overstimulation if you have AFS and are very sensitive. If you have the COMT mutation, consider the adenosyl/hydroxy form of vitamin B12. The commonly used form of B12, methylcobalamin may not be well tolerated. Often times a combination of various forms of vitamin B12 is required.
  • Magnesium
  • S-Adenosyl methionine (SAMe), which is essential for methylation. Those who are very weak or sensitive may not do well with this supplementation. Be on the alert for paradoxical reactions.
  • Fluvic acid
  • Marine phytonutrients

Avoid Catechols

If you have a COMT mutation, then your body will have trouble removing catechols. These are found in NTs as well as in certain foods. So it’s important to eliminate anything that will increase catechol levels in your body such as:

  • Caffeine, which triggers a release of catechols in the body
  • Alcohol, since it can trigger a dopamine release in your body
  • High protein foods that contain the amino acids tryptophan, tyrosine, or phenylalanine, as these can trigger a release of catechol and be converted into dopamine in the body
  • Smoking, as it may have a negative effect on COMT

Eliminate Catechol Estrogens

When you have excess estrogen in your body, it slows COMT processes. COMT is essential for ridding your body of harmful estrogen metabolites. So, if you have excess estrogen in your body, then it will slow COMT activity, which will lead to a build-up of even more estrogen. This is a dangerous cascade that you should try to avoid by eliminating estrogen-heavy influences such as:

  • Dairy
  • Soy
  • Parabens
  • Bath products that mimic estrogen.

You can also speed up your liver detoxification and the removal of estrogen metabolites by eating more:An image of broccoli and cauliflower heads

  • Broccoli
  • Cauliflower
  • Cabbage
  • Flaxseed

This will not only help remove estrogen metabolites from your body, but it will also help detoxify your liver. If you have AFS and Detoxification circuit imbalances, your liver will benefit from this boost. Making this dietary change may help return your liver to a better state of health, which should improve the health and functioning of the Detoxification circuit as a whole.


You must strike a careful balance when it comes to phytonutrients, which are the chemicals produced by plants. Certain types of phytonutrients should be avoided as they contain catechols and will impact your COMT mutation.

Phytonutrients to avoid include:

  • EGCG
  • Fisetin
  • Quercetin
  • Ferulic acid
  • Rutin
  • Epicatechins
  • Luteolin
  • Catechins
  • Hydroxytyrosol

These catechol-containing flavonoids can be found in foods like capers, berries, apples, green tea, and cilantro.

However, you still need to stay healthy overall and limit oxidative damage in your body by eating a healthy balance of plant nutrients. You can do this by eating flavonoids that don’t have the catechol structure.

Phytonutrients to get more of include:

  • Flavones, which includes tangeritin, apigenin, baicalein, wogonin, scutellarein, and chrysin
  • Myricetin
  • Genistein

These can be found in foods like onions, parsley, celery, chamomile, and grapefruit.


Exercise is important for good health. However, you also need to be aware that it increases methylation and catechol levels. So, if you really struggle because of a COMT mutation, it might be best to limit strenuous exercise and stick to gentler forms like walking or yoga.

This is good advice when you have AFS as well, as strenuous exercise can overwhelm your already overtaxed body and cause further adrenal fatigue and even an adrenal crash.

Eat Regularly

Going for long periods without food can increase catechol levels in your body. So, it’s important that you eat regularly to maintain steady blood sugar levels. This is another strategy that will benefit AFS as well by helping to limit blood sugar spikes and giving your body the nutrients it needs to function properly.


When you have a COMT mutation, your body will be slower to get rid of many of the hormones that are produced when you’re under stress. So, if you have this mutation, then you may be more sensitive to stress and find that its effects last longer. That’s why it’s important that you practice stress reduction strategies regularly and do everything you can to support your body in its fight against stress and the damage it can do.

For AFS sufferers, this is obviously a very beneficial strategy. Adopting strategies to lower your stress levels will decrease your body’s demand for cortisol and lower adrenal activity. This will help lessen the impact of AFS. Some of the best strategies for stress management are:

  • Yoga
  • Meditation
  • Implementing a healthy diet
  • An image of a woman holding her hand up to refuse a glass of wineRegular exercise
  • Make times for hobbies and interests that you enjoy
  • Get plenty of sleep
  • Avoid alcohol and other drugs that may just mask the problem
  • Spend time with people who you love and who support you

Support Your Liver

Supporting your liver is one of the best things you can do when you have a COMT mutation. Your liver is essential for deactivating and expelling metabolites, so you need to keep it healthy. This may be difficult if you have AFS and Detoxification circuit imbalances, but it will also help lower your stress levels overall, which will naturally help alleviate adrenal fatigue.

Some helpful foods to eat for liver detox and support are:

  • Cruciferous vegetables like broccoli and cauliflower.
  • Citrus foods
  • Dandelion
  • Honeybush tea
  • Rosemary
  • Rooibos tea
  • Yeast, trout, microalgae, and shrimp, which contain astaxanthin
  • Turmeric
  • Plant foods like wheat, oats, rice, pineapple, vegetables, nuts, fruits, and beans, which contain ferulic acid
  • Strawberries, cherries, raspberries, walnuts, and blackberries, which contain Ellagic acid

All of these foods and nutrients can be helpful in promoting liver health and detox. Improving the health of your liver in this way will also improve the balance of your Detoxification circuit. The three components in this circuit are tightly interconnected, so when one improves, the others do as well.

Lifestyle Changes with AFS

Don’t try to make any of these changes alone or without professional help when you have AFS or other serious health conditions. Even healthy changes can increase your stress levels and strain your NEM stress response systems, so you need to be careful.

When you do begin to make changes, do so slowly and stop if you notice any adverse effects. Causing additional strain in the service of trying to improve your health will only delay or derail your recovery. Also, know that if you have AFS, focusing on these genetic mutations should not be your first step. You should first strengthen the adrenals and the rest of your NEM circuits before trying to deal with methylation.

The Takeaway

There are lots of factors that can influence how your body reacts to stress, including a COMT mutation. That’s why you need to be vigilant about your health and seek out expert help when necessary. If you’re one of the many people with this type of gene mutation, then here’s what to do:

An image of a woman holding either side of her liver area

  1. Change your diet to avoid substances such as milk and dairy, which contain estrogen as well as substances that contain extra catechols such as alcohol and high protein foods.
  2. Support your liver health and detox with cruciferous vegetables and supplements if necessary.
  3. Talk to your doctor and get tested for this mutation.

If you’re concerned about how your body reacts to stress, our team at Dr. Lam offers a free consultation at (626) 571 1234, or you can access our Ask the Doctor system by clicking here.

© Copyright 2020 Michael Lam, M.D. All Rights Reserved.

Dr. Lam's Key Question

Between 20 and 30 percent of Caucasians of European descent have a COMT mutation. This means that the gene that produces an enzyme to break down certain substances and toxins doesn’t work the way it should, causing a range of health, hormone, and stress-related issues.

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