Uncategorized Archives | Saul Marcus, ND

June 4, 2025June 4, 2025

Histamine – The Fast Summary

The following is a summary of key facts to know about histamine. In short form so you don’t need to read whole articles or books.

Histamine Receptors

There are 4 histamine receptors. For this reason histamine can cause a very wide range of different symptoms.

H1 – Allergy (vasodilatation). Causes traditionally allergy symptoms.
H2 – Gastric (HCL release). Causes digestive symptoms such as gastric reflux.
H3 – Neurological (brain). Causes fatigue and brain related symptoms.
H4 – Immune (bone marrow and WBC).

Symptoms that may be related to elevated histamine:

Migraines and Headeaches. Including trigeminal neuralgia
Mental symptoms due to neuroinflammation: ADHD, depression, anxiety.
Irritable bowel and acid reflux
Poor sleep, insomnia, waking up 3- 4 AM as histamine increases wakefullness
Restless leg syndrome
Hormonal conditions related to elevated estrogen.
Asthma
Bladder and prostate symptoms

Histamine Degradation

Histamine is degraded by these two pathways:

DAO
HNMT

Causes Of Low DAO

Digestive System Inflammation

Inflammation in the digestive system and increased permeability ("Leaky Gut") is thought to impair release of DAO, and increase histamine. So long term treatment should be focused on restoring digestive health, rather than just avoiding histamine food and taking anti-histamine medications or supplements.

Genetics

rs10156191. C/T or T/T reduces DAO.
rs2052129 T/T is associated with histamine and migraine.
rs1049748
rs1049793 C/G 35% reduced DAO. G/G 50% reduced DAO.
rs2071514.

Medications That Lower DAO

Proton Pump Inhibitors.Often Omeprazole.
NSAID such as aspirin and ibuprophen.
Tagamet and Pepcid. H2 blockers.
Antidepressants such as Cymbalta, Effexor, Prozac.
Immune modulators such as Humira, Plaqenil.
Hypertension medication such as Propanolol.
Amitriptyline.

Side effects of whatever medication someone is on should be checked.

Toxins That Lower DAO, and thus increase histamine

Glyphosphate.

Food colorings, especially tartrazine.

Food preservatives such as BHA (butylated hydroxyanisole), and BHT (butylated hydroxytoluene)

Foods High In Amines Low DAO

High tyramine foods: aged foods, cheeses and meat.

Sulfites: in dried fruits and red wine.

Nuts and seeds which have been stored for a long time.

Citrus fruits, bananas, strawberries.

Vegetables: Spinach, tomatoes, avocado, and eggplant.

High spermidine and spermine foods: aged cheeses, hazelnutes, chicken liver, peas, soy.

Fermented foods

Low HNMT

HNMT or Histamine N-mehtyltransferase is an enzyme which break down histamine. Less HNMT enzyme activity is associated with elevated histamine

Lower HNMT activity is associated with the following:

ADHD and hyperactivity due to food additives
Asthma
Eczema
Migraines
Poor cognition

Genetics which lower HNMT activity

rs105089 (G/G typical – lower risk of hyperactivity in ADHD due to food additives. A/G and A/A reduced brakdown of histamine)
rs11558538 (T/T reduced HNM activity, higher histamine, increased risk asthma. C/T increased risk asthma. C/C typical)
rs2071048 (T/T increased risk asthma (and higher histamine) common variant. C/T and C/C typical athma risk)

Drugs that impair HNMT include:

Chloroquine
Amodiaquine
Tacrine
Etoprine
Metoprine
Quinacrine
Dimaprit

Methylation, Genetics and low HNMT

The follwoing genetic may cause poor methylation and thus raise histamine

rs1801133 (G/G typical, A/G is one copy of MTHFR C677T and lowers MTHFR by 40%, A/A or two copies lowers MTHFR C677T by 70-80%)
rs1801131 (T/T typical, G/T is one ocpy of MTHFR A1298C slight less MTHFR, G/G two copies MTHFR A1298C – decreased enzyme by 20%)

HNMT enzyme breaks down histamine through methylation. This requires folate which is used in the production of S-adenosylmethionine (SAMe). Therefore, insufficient histamine can slow down HNMT activity and thus contribute to elevated histamine.

Foods, Probiotics and Histamine

Not all probiotics are the same with regards to histamine. Some may help. Others can actually make histamine reactions worse.

Probiotics which may increase histamine

No list is all comprehensive, as different sources vary. Additionally, not everyone will react the same to all probiotics. These are some probiotics which may make histamine worse for some people:

Lactobacillus casei
Lactobacillus reuteri - note all L. reuteri supplements are equal or the same strain
Streptococcus thermophilus

Sources differ about Lactobacillus plantarum and Lactobacillus bulgaricus. Some suggest it is helpful, others that it is harmful.

Foods and Probiotics associated with lowering histamine

Bifidobacterium infantis - many sources list. Often only available as a children's probiotic.
Bifidobacterium longum
Lactobacillus rhamnosus
Lactobacillus plantarum
Saccharomyces boulardii
Lactobacillus reteri - may be strain specific
Lactobacillus gasseri
Bifidobacterium breve
Lactobacilus salivarius
Bifidobacterium lactis
Lactobacillus casei - may be strain specific

Specific products

Specific products which are commonly used for histamine

Allergy Research Group Aller-Aid L92 - Consider high dose for seasonal allergies
Allergy Research Group GI Flora
Allergy Research Group Lactobacillus
Vitanica Flora Symmetry
Seeking Health ProBiota HistaminX

Foods that make histamine reactions better or worse

Yogurt

Most store bought yogurts have additives which give it a specific taste and texture. For a yogurt to be consumed as a medicinal food it needs to be made from the right type of bacteria, and fermented in the right way. Otherwise the amount of living probiotics may be very low, if not negligible. Therefore most yogurt can not be assumed to be very helpful, if at all.

Homemade yogurts fermented at 36 - 48 can be very strong medicinal foods. See the numerous youtube videos on Supergut Yogurt.

Sourkraut

Sourkraut is a fermented food, which is often high in histamine. Therefore it is not recommended for this purpose.

Foods commonly high in histamine

Leftovers
Meat that not eaten right after cooking
Seafood - best if frozen at sea
BBQ or smoked meats
Crock pot or slowly cooked foods

Pea sprouts and other foods that lower histamine

Pea sprouts are high in DAO so can be added to the died to lower histamine.

Other foods high in DAO

Kidney Beans
Fatty fish such as salmon or sardines - important for it to be fresh
Olive oil
Pineapple - high in the enzyme bromelain

Supplements For Histamine

Not all supplements will help everyone. Treatment plans need to be individualized.

Perilla
DAO
Copper
Vitamin B5 - often in form of P5P
Vitamin C
Luteolin
Quercetin- caution in people with slow COMT
Baicalin - from Skullcap - can take 30 minutes before a meal
Quail Egg - AllClear supplement from Integrative Therapeutics
SPM for mast cells
Vitamin D
Cordyceps
Resveratrol
Chicoric acid in eachinacea and chicory
EGCG from green tea - caution, makes some people worse
PEA - may help mood shifts and cognitive symptoms related to histamine
Curcumin
Saffron
Tulsi
Vitamin B2 (riboflavin) for itching
Homeopathic nosodes

How to put together a plan for someone with elevated histamine?

All the lists of foods to avoid for histamine, supplement and probiotics to take can be helpful. However, no two people are the same. What works for one person, may not work for all. Just taking supplement or making dietary changes because it is supposed to be good for histamine is not a very individualized approach. The purpose is going to a practitioner is not to learn what is good "for histamine." Rather, to help figure out what you specifically need to do.

Why you can't just use the same anti-histamine protocol for everyone

Histamine is just one inflammatory mediator. Other triggers of allergies and inflammation that work in conjunction with histamine include:

Mast cells
Eosinophils
IgG, IgA and IgE antibodies
This is not a complete list

Additionally, very sensitive people may react to almost anything. This is all supplements and even water.

Vitamin D

Most people have low vitamin D. Target range where people often feel best is 60-80 of 25-hydroxyvitamin D on blood test. Vitamin D works best with low dose of B vitamins (see work or Dr. Grominak). Take baseline vitamin D test and then supplement until reach target range on follow up blood test. Do not just take a random dose of vitamin D and assume you are getting enough. People can easily over dose, or under dose. Vitamin D also works much better with co-factors.

Vitamin D and B vitamins may work synergistically to feed healthy gut flora and thus offer a more permanent solution for people with choricra digestive issues.

Histamine Detoxificaiton pathways

There are numerous ways the body can detoxify histamine. This allows for specific supplementation to enhance clearance.

Histamine is converted with help of vitamin B1 to histadine (histadine decarboxylase enzyme).
Degraded via DAO enzyme. Uses nutrients vitamin B6, Magnesium, Copper.
Histamine is converted with help of vitamin B5 (pantothenic acid) to acetyl histamine (N-acetyltransferase)
Methyl histamine and histamine aldehydge pathway. This is a more complex, multi-step pathway. The important thing to to know is that more toxic forms of histamine are made mid-way through this pathway. If the body can not clear it, people will get worse from taking supplements.

Histamine is degraded with the help of folate and vitamin B12 to methyl histamine (histamine methyltransferase).
Methyl histamine is degraded with the help of magnesium, B6 and vitamin to to Histamine aldehyde (MAO). If histamine aldehydge is not cleared, symptoms will get worse.
Histamine aldehyde is cleared with the help of vitamins B1, and B3 (aldehyde dehydrogenase).

Heal The Digestive System

There are too many special diets and supplement promoted to fix the digestive system to list. There is no one sized fit's all answer. Often people take random supplements for "Leaky Gut". Digestive System supplements have their place. But should he used with appropriate diet and supplements targeting histamine.

Working with a practitioner

Anyone can do an online search for supplements or diets to treat histamine. The purpose of seeing a practitioner is for helping making a plan specific to your needs. Everyone is different. So the same histamine protocol will not help everyone. If it did, there would be no reason to see a practitioner. In the office I combine case history, with kinesiology muscle testing and other non invasive methodes to form an individualized and holistic assessment for each person. Functional labs tests may be used in some cases. This includes stool tests, candida antibodies, hair analysis, organic acids, hormones and other tests for environmental toxicity.

February 14, 2023February 14, 2023

Food Intolerance vs Food Allergy

Food Allergy Testing

The term “allergy” is often misleading. A lay person usually thinks of an allergy as an abnormal response to a food or substance that is well tolerated by most people. The medical definition, is an immune system response mediated by immunoglobulins.

Therefore, if you are having an adverse reaction to a food, for any reason other than immunoglobulins, it is not an “allergy.”

IgE Allergies

Usually allergists have looked for an immediate reaction to an allergen, such as tongue swelling, hives, or itching after eating a specific food. These symptoms indicate an IgE mediated immunoglobulin reaction.

Allergists typically test for IgE allergies with skin prick tests. Sometimes they run blood tests. These methods are excellent ways to uncover IgE mediated allergic responses. Unfortunately there are many other ways an offending food may cause symptoms. Nonetheless, for decades, allergists have been telling patients they are not allergic because they don’t have an IgE reaction against certain foods.

This is misleading. What patients want to know is not if they have an IgE mediated immune system response. They want to know what foods they are reacting to.

IgG Allergies

In holistic health, practitioners are taught that such tests miss many allergies. We are trained to look for delayed allergic reactions, such as eating an offending food followed by a headache the next day. These delayed food allergies are IgG mediated immunoglobulin reactions.

One of the most popular ways holistic practitioners test patients for food allergies is with blood tests against IgG antibodies. At times, these tests do help. But they are only testing for one type of food reaction. It is not uncommon for patients to spend hundreds of dollars on such food allergy panels just to see:

Almost no foods come up positive, which doesn’t help.
Conversely, it seems that half the panel comes up positive, which demonstrates a “leaky gut.” This however does not indicate which are the primary foods to avoid.
The foods they most commonly eat are positive, which is caused by repeated exposure of the immune system to that food. This thought, does not indicate if this food is the primary problem.

Although these tests can be useful in some cases, more often than not they don’t show anything significantly new, or particularly helpful.

The one exception I have seen to this is the client who has been eating a lot of gluten or dairy and doesn’t believe it is a problem. Blood tests for food allergies are a good way to prove to certain patients that they must avoid their favorite foods.

The Problem With Food Allergy Testing

Food allergies are only type of adverse reaction someone may be having against a particular food. What you need to know is not what foods allergies you have. Rather its what foods you are reacting to, regardless of underlining mechanism.

A food intolerance is a less specific terms which indicates that a food is adversely effecting health, regardless of the underlining mechanism.

Causes of food intolerances include:

Hypoglycemic reactions, usually to sugars and other carbohydrates.
Histamine reactions.
Deficiency in enzymes needed to digest particular foods, such as lactose intolerance, frutose intolerance and sensitivity to dietary amines.
Reaction to lectins, such as wheat lectins contributing to rheumatoid arthritis.
Neurotoxic substances such as glutamate.
Salicylate reactions.
Any other adverse reaction an individual may have to a particular food that is not currently known.

So, we can see that food allergy tests only look for one of many adverse food reactions someone may have.

A lab test may be technically right that you don’t have an “allergy” to a specific food, but at the same time it could totally miss another reason why you still have a lack of tolerance against the same food.

As far as skin prick tests, or IgE blood tests, I recommend those be used for seasonal allergies. If an IgE reaction is found for a food, then avoid that food. This is the best way to test for immediate IgE food reactions. But you can’t say a food is safe to eat, just because you don’t have an IgE reaction!

Allergy Elimination Diets

Allergy elimination diets are often taught as the best way to uncover food reactions. To do an allergy elimination diet, the patient eats a diet consisting of typically only non allergenic foods for a month or two. Then one by one, foods are reintroduced. Each day the patient charts off any symptoms they may have to uncover reactions.

This method is not practical for the real world because:

It can take months to properly do this.
Through experience I discovered that virtually no one complies with doing a proper allergy elimination / reintroduction protocol.
There many be typically non-allergenic foods the patient is reacting to.
The patient is unwittingly being exposed to foods which they think they are eliminating due to the large amounts of food additives.
Properly tracking symptom reactions each time a food is reintroduced into the diet takes meticulous work, which most patients do not have the time or energy to do.

In summation, the practitioner’s job is to identify foods which is important for their patient to avoid, not to give a nearly impossible job that involves a months long food homework assignment.

Applied Kinesiology Testing

I have been doing kinesiology muscle testing for 13 years now. It can help to uncover food reactions. However, in my experience it is often too sensitive. Testing weak against a food on a muscle test may mean you should never eat the food at all. It may also mean that it wont’ digest well with your last meal and you should not eat it right now. Or perhaps you have been eating too much of something and should not eat it for a week or two.

It is very common for people to test weak against some foods on one visit, and then weak against other foods on another visit.

If a food tests weak repeatedly on every visit, then it becomes more likely that it is a foundation problem that should be avoided all the time.

Ultimately there is just a lot of noise that can come up with muscle testing. It can be a useful tool when used well. But it can not be used to quickly identify a foundational food intolerance.

Carroll Food Intolerance Test

This is a long time used, traditional naturopathic technique for uncovering food intolerance. This is not a food allergy test. So if you have had food allergy testing done in the past, this results are probably different.

I have brought this method into my practice for several reasons:

There is a track record of it being used with great results by naturopathic doctors for 90 years.
It a way to discover foundational food intolerances.
Unlike the muscle testing I also do, the Carroll Food Intolerance Test eliminates much of the noise to uncover the most important foods to eliminate.
Helps to identify hidden sources of foods that may be a problem. Many processed foods have additives which can be hidden sources of exposure to offending foods.

December 28, 2022December 28, 2022

Making Melatonin Work For Sleep

Melatonin is one of the most commonly used supplements for sleep. Almost anyone I talk to who has dealt with insomnia has tried melatonin at some point. Sometimes with success. But more often than not it works poorly, or does not even do anything at all.

The available research studies show conflicting results as well. For example this meta-analysis on melatonin covers many studies, using different doses for jet lag, shift work, and improving sleep in otherwise healthy adults. The results are confusing, as some studies are very positive, and others don’t show much benefit. [1]

Drug, hormone or supplement?

Perhaps the problem is with the way people think about melatonin. It is not a pharmaceutical sleeping pill that drugs people to sleep. Melatonin is a hormone, which the body needs in specific amounts at the right time to initiate sleep. Like any other hormone, we need just the right amount. More is not necessarily better.

Usually people take melatonin supplements as they would a prescribed sleeping pill. At night, before bed. Some clients have told me this works very well for them. Usually it helps very little, or not at all.

Melatonin is also now being sold in doses as high as 10 – 20mg. These supra physiological doses were initially used for inflammatory health conditions, particularly cancer. They were not intended for insomnia. However, the supplement market being how it is, 20mg melatonin is now being sold for sleep. In reviewing the current research for this article, I could find nothing supporting the use of such high doses of melatonin for insomnia.

Regardless if it is a 3mg or 20mg pill before bed, these doses and timing of melatonin supplements often do no work well for sleep.

Sleep hygiene for melatonin

Another way people try to regulate melatonin in through sleep hygiene rituals, such as not looking at screens at night, wearing orange glasses to block out blue light. There are even black curtains some people use to seal off all light from entering their room. All this to promote the pineal gland’s natural release of melatonin.

Sometime these sleep strategies work. If you find them helpful, then go ahead and continue doing them. But just like taking a high dose melatonin pill at night, sleep hygiene rituals often don’t work. Nor does shutting off all the lights, computers and forcing yourself to sleep at an early time. At worst, sleep hygeine out of context creates it’s own problem. The stress from doing this may paradoxically make sleep even worse!

The Sleep Hormones, a very brief review

Melatonin is actually just one of several sleep hormones. The main job of melatonin is to regulate the circadian rhythm.

Sleep drive is regulated by another hormone, adenosine. The longer you are awake, the higher adenosine goes. When it gets high enough, it triggers sleep. Once of the reasons why it can be bad to take extended naps is that lowers adrenosine. Then at night when it’s time to go to sleep, you make not have enough adenosine to fall alseep.

There are only two way s we know of to raise adenosine: staying asleep longer, and exercise. One of the ways caffeine keeps people awake is by inhibiting adenosine.

Another hormone important for sleep is cortisol. This is our major stress hormone. It normally goes down at night, and then rises in the morning to help wake us up. Stress raises cortisol and this can lead to poor sleep.

Getting the hormones to work in sync with each other

So why may someone be very tired at night, but can’t fall asleep? Adenosine is slowly going up, making you sleepy. But if melatonin is too low, or cortisol too high, the sleep process isnt’ initiated. You lay down to fall asleep but can not. The mind is suddenly active with racing thoughts. This is feeling "tired but wired." Too exhausted to be up and active, but unable to sleep, even feeling even agitated once you go to bed.

How to use melatonin

Supplemental melatonin for sleep, should be used as an aid to get melatonin and the circadian rhythm in sync with the other sleep hormones.

Melatonin is not a sleeping pill like ambiem. For most people it’s not going to enter your bloodstream and knock you out. The key may be a small, physiological dose of melatonin several hours before bed to gently reset the circadium rhythm to help people fall asleep.

The easiest way to dose low dose melatonin is with a liquid supplement. This way you can find the right number of drops that work for you.

Typical supplement dose

2 to 5mg. Sold as high as 20mg.

Actual physiological dose

0.3 up to 1.0mg. [2]

My personal experience with sleep

Due to stress and lifestyle I through off my cirrcadium rrythm when I started college. For over 20 years nothing I did helped. And this includes anything I learned in naturopathic school and seeing different practitioners. I tried many of the the sleep supplements and sleep hygeine tips. It didn’t matter. No matter how little I slept I could not fall asleep until about 3 AM. Sometimes 4AM, or later.

This included a 3 year stretch when I was a mail carrier and at times had to be in to work at 7:30 AM. Months of working that job left me feeling like an exhausted zombie. My body never adjusted to waking up that early.

And yes, I tried melatonin. Many times. it didn’t work. In fact, it was the first thing I tried to fix my insomnia. Every few years I’d try it again. I tried up to 10mg, with absolutely no noticeable effect.

Finally I tried something different. A liquid melatonin which would allow me to take a very low dose melatonin. I didn’t take it before bed. Instead I took it 4 hours before I wanted to go to sleep. After a few days the melatonin was working so well that I was sleeping 10:00 to 4:30 AM!

At times I’ve used other products for sleep that would work a day or two and then stop. But the melatonin kept working for weeks, and then months, without ever stopping.

I’m not saying that everyone who can’t fall asleep needs melatonin. Also, it would be good to have some studies that used melatonin in low doses, and not right before bed, but those just simply have not been done. We do have these studies from 1999 and 2001 showing melatonin working well with doses as low as .3mg. [2, 3]

Blackout curtains and light box

Another way to to reset cirrcadium rhythem is through light. Blackout curtains around the windows at nigh, and shutting off electronic devices will promote the body’s natural production of melatonin.

A light-box, timed to go off in the morning will tell the body when to wake up.

If following this method, I recommend that these be done together. The blackout curtains may help to promote sleep at night, but then the body needs a light cue to learn when to wake up. If you state in total darkness, that won’t happen.

In theory, this system is more align with a truly natural approach. The blackout curtains and light-box simulate a day / night cycle we are designed to live in.

The problems with doing this is the expense of buy the material, and added stress of adding these to a daily routine. Supplemental melatonin is a step away from this more $quot;natural$quot; approach. However, considering how much more practical it is take melatonin, for many people this is going to be the better option.

Is melatonin for everyone?

There are numerous reaons why someone may not be able to fall asleep. Melatonin is not a panacea, nor should it be used for everyone. For some people who can not fall asleep due to a circadian rhythm problem, melatonin may be very helpful.

References

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4273450/

[2] https://news.mit.edu/1999/melatonin-1103

[3] https://news.mit.edu/2001/melatonin-1017

August 5, 2022August 5, 2022

Book Review: The Dangers of Celery Juice by Asa Hershoff

The Medical Medium and Celery Juice

This is a book review of the Dangers of Celery Juice. However, it is impossible to write about that book, without first commenting on the the series of Medical Medium books by Anthony William.

I have read Anthony William's first book,Medical Medium, and Thyroid Healing. In an age where it seems everyone is trying to declare how "scientific" they are, Anthony William is unique. Right from the start he explains that none of his ideas are based on research. He is a medical medium who simply recieves information on healing from "Spirit." William does not attempt to manipulate actual research to fit his claims. This is all from ""Spirit" and scientists simply have not discovered these facts yet. While I'm not sure how I feel about someone giving out so much health information based on advice from "Spirit" I do appreciate his honesty.

The good: whole food diet and basic health advice

William gives out a lot of basic health advice. Promoting whole food diets and juices. This is all fine, and I'm sure William is helping people by just giving them motivation to make positive changes. All health books agree on certain points. The most common causes of illness are stress, poor diet, over eating, and lack of exercise. Anyone who improves those problems is going to some good results.

I have no doubt that there are people who have healed themselves following William's advice. But all that proves is basic dietary and lifestyle changes works. It does not prove William's health theories. This is actually an important fact to be aware of in gereral. Just because a health treatment works, that does not mean it works in the way people think it does.

The bad: strange health theorie based on nothing other than "Spirit"

One of William's big ideas is how many diseases, such as hypothyroidism are cause by Epstein Barr Virus. Not only are these claims unfounded (as William openly admits), but it just does not fit what is seen in the real world. Autoimmune disease is multifactoral and can not be reduced down to just one factor, such as EBV. Diet, allergies, gut pathogens, toxic exposure all can play a role.

The ugly: potentially dangerous health advice

So far, even if what he says if theoretically questionable, if it's is just basic healthy lifestyle and dietary changes then what difference does it make if someone really has epstein barr virus causing their hypothyroidism?

The problem is when people start doing questionable treatments, like high dose celery juice.

Over the past 6 years or so, dozens of people have come to me telling me about how they were drinking lots of celery juice. The celery juice phenomena is heavily promoted by William as a sort of universal cure all. But what if high amounts of celery juice, instead of being an amazing medical cure, comes with side effects?

The dangers of celery juice

Hershoff does not directly mention the Medical Medium, although the book is a clear reply to the celery juice fad. He does spend some time differentiating between a food and a medicine. Celery is a medicinal herb and has traditionally been used such. It is ine to use it in reasonable amounts as a food. But juicing celery is not using food as medicine. It's is using a concentrated medicinal herb, as food.

Most of the book covers possible effects of high dose celery. This includes effects on detoxification, drug interactions, reproductive health, concentration of potentially toxic substances in celery, and the cardiovascular system.

He does go over potential benefits of celery. But the point is made that celery is just one plant. There are many other plants with healing properties. There is no reason to put celery on a special pedastal.

Final thoughts

As a naturopathic doctor I'm glad to have this book. So many people were coming to me already on celery juice, or asking me about it. It was something I needed to know more about. Hershoff writes from the perspective of a naturopathic doctor who believes in the tried and true methods of our field, as well as basic naturopathic philosophy. Which is also something I like to see, as this mindset is not universal amongst everyone writing natural health books.

August 2, 2019October 4, 2019

COMT, Anxiety, Folate and Genetic Testing

What is COMT

COMT stands for catechol-O-methyltransferase. This is an enzyme which is used to degrade catecholamines. We have three major catecholamines:

Dopamine
Epinephrine (also known as adrenaline)
Nor-epinephrine (also known as nor-adrenaline)

Dopamine

This is often called our "feel good" neurotransmitter. Dopamine triggers the brain’s "reward system."

But dopamine does not simply make us feel good. It is associated with repetitive behavior. Dopamine stimulates the brain to repeat behavior that triggers the release of more dopamine. This is why it is associated with addictive behavior. People do things that triggers the release of dopamine. They feel good for a movement and then seek to repeat the behavior to get more dopamine.

Dopamine is neither good nor bad. We need some of it for motivation, concentration and feeling pleasure. However, too much can become overly stimulating.

Epinephrine and Nor-epinephrine

Epinephrine is adrenaline. This is an emergency, stimulatory neurotransmitter. We need some epinephrine to respond to life events and provide energy to get us through true emergency situations.

On the other hand, if epinephrine is elevated all the time then it feels like we are in an emergency situation that never stops. This can lead to chronic feelings of anxiety.

COMT genetic types: Warrior Versus Worrier

COMT enzyme activity is regulated by several genes, most notably COMT v158m.

The "warrior" type has high production of COMT. These people can quickly degrade dopamine and epinephrine. This gives them an advantage in being able to calm down after a stressful event.

The "worrier" type has decreased production of COMT. These people are likely to stay stimulated longer after a stressful event. This may cause increase symptoms of stress and anxiety as.

Intermediate Types have neither high or low COMT activity. They are in the middle.

Genetic testing for COMT activity

Just because someone has a gene that predisposes them for a condition that does not mean they will have symptoms. Genetics are complicated. We have many genes, that work together, under the influence of environmental triggers to produce symptoms.

Having "worrier" COMT genes does not mean you will inevitably have symptoms of anxiety and go through life as a worrier. Likewise, having the "warrior" genes does not make you impervious to stress.

When working with clients my starting point is never genetics. In fact, for most cases I do not even bother with looking at genetics. We have many other factors that can influence mood such as the stress from life events and hormonal issues. Emotions should not be reduced down to a few genes.

However, it is important to recognize times when genetic testing may be helpful.

The several following issues may come up with slow COMT activity:

Increased sensitivity to stress and anxiety
Issues with estrogen metabolism. COMT is also needed to detoxify catechol estrogens. This can lead to hormonal effects as well. Supplement that help the liver detoxify estrogens may be needed
Sensitivity to folic acid supplements.

When genetic testing started to become popular, many people were told to supplement with folate based upon their MTHFR genetics. I can remember one particular case of a woman who had previously consulted with another naturopath who had made a name for himself as the folate/methylation expert. Based upon genetic testing he recommended a large dose of folate which made her anxiety symptoms much worse.

Folate increases production catecholamines. So for people with slow COMT and anxiety, taking a folate supplement is akin to putting fuel on the fire. They may have extreme symptoms with tiny doses.

This is true even if genetics and blood testing say someone needs more folate. None of that matters if COMT is slow. You then have to work on COMT first before doing anything with folate.

About the time I was in naturopathic school is when genetic testing for folate first became popular. Overnight everyone was talking about folate and how essential it is. How everyone has methylation issues and nutraceutical companies where brining out products with high doses.

This is often how the supplement industry works. Some promising research come out and then suddenly everyone is trying to make money off it it. We’ve seen this with folate, vitamin D, tumeric and now CBD. I don't wish to imply that these supplements do not help people. They are all good. That does not mean they are all miracle supplements that everyone needs to take either.

The point is that at first we were told so many people have genetic methylation issues and need large doses of methyl folate. A few years later and I go to same lectures and am told to be cautious of folate because some people with slow COMT production will not respond well to it.

The lesson to learn here is that genetic testing can be helpful, but it is not as simple as a single gene means you need to take so much of a specific nutrient. Single genes rarely cause diseases themselves. Testing COMT genetics is a tool. I have seen it be very helpful in some cases of anxiety. However, it is just one consideration.

Worrier genetics is not a disease

I believe that the more we know about genes, the more we will learn how supposed "bad" genes may have their own advantages.

Lower COMT activity is associated with positive factors such as better cognition, memory, brain plasticity and ability to feel more pleasure. The COMT types, "warrior" or "worrier" are not good or bad. This is just human variation.

How to get COMT testing done

23 and me

If you have already had your genes tested by a company such as 23 and me, you can download your raw data and send it to another company for interpretation.

Once such service I like is promethease. It's a cheap and simple way to find out what is in your genes.

Ask your doctor to do a blood test

See if your doctor can have the genetics tested on blood work. Doctors commonly run tests for MTHFR genes C677T and A1298C. Panels may be available which also include COMT. It is best to have both tested.

Doctors Data methylation Blood Spot Test

This is an advanced test that cover COMT, folate and much more. It only needs a small amount of blood from a skin prick, so there is no need to go to a lab. It is a somewhat expensive tests, but it only has to be done once and then you’ll have a lot of important information to know about your genes for the rest of your life.

Go here fore more information on the methylation blood spot test.

I keep these kits in the office and in certain cases just running a comprehensive genetic test such as this is best.