Balancing COMT & MAO Pathway Variant issues
Metabolic pathways are essential for life itself and dependent on nutrients, in proper balance, for their function. The COMT and MAO pathway are responsible for processing neurotransmitters and some hormones by transferring to them a methyl group, thus keeping proper balances of substrates in tissues, supplying energy to the body, as well as a multitude of other functions.
Epigenetic defects in genes called SNP defects can greatly affect the function of these pathways and testing for these SNPs may be beneficial. Lifestyle changes in diet and toxic exposure can greatly affect the function of these pathways as well. Balance is the key. The following diet can help bring such balance by regulating the foods that drive it.
It is VERY important to note that there are other reasons for these pathways to be imbalanced that include: toxic metals (HMT), chronic infections (Lyme, Candida, H. Pylori…), Gut dysbiosis (food allergies, consuming GMO foods, antibiotic use…), imbalanced diets, chronic stress, and many others. Addressing complete lifestyle changes is of UTMOST importance!
The chart below, though complicated, shows the COMT and MAO genes as they fit into the Biopterin pathway. The main responsibility of these genes is to degrade neurotransmitters and get rid of them to keep proper balance. A defect in one or both of these genes (COMT is a family of genes) can INCREASE or DECREASE its function though usually it results in a DECREASE function with symptoms as I list below.
Understand that these are metabolic pathways. Pathways may be likened to highways that can be flowing smoothly at times with no traffic delays. Gene defects (SNPs) may be likened to permanent road construction. Though road construction may block a single lane (as in a single allele defect) and may have little affect on traffic flow, and double lane closure (double allele defect) may cause more problems.
Even with a double (+, +) SNP defect, a person may experience little to no symptoms and live a normal, healthy life. It is important not to blame every disease or symptom on the “road construction” as there are other factors involved but knowing that the blockage exists may help the individual make better lifestyle choices and treat and prevent disease. Again, usually a MOA and/or COMT defect causes episodes of DECREASE in gene function and episodes of INCREASE function so the ‘diet’ below is simply intended to reduce or increase the substrates that feed that pathway and may change on a daily basis. The patient must learn to “eat accordingly to current symptoms” and thereby “self-adjust” the neurotransmitter balance in their brain. With practice, this can readily be accomplished.
There are 2 possibilities with a COMT/MAO defect:
- Common COMT/MAO pathway DOWN-regulation variant issues: (times when the epigenetic COMT/MAO SNP defects cause a DOWN regulation or a DECREASE in neurotransmitter breakdown) the patient may experience ONE or MORE (certainly NOT all) of the following:
- Increased Dopamine
- Digestive issues, nausea, vomiting, burning tongue, hiccups, muscle twitching, fidgeting, anxiety, nervousness, ADD-like, hyperactive, insomnia, increased drive, increased libido, mania, OCD, paranoia
- Increased Norepinephrine
- Increased blood pressure, sweating, headaches, heart palpitations, anxiety, nervousness, pallor, nausea
- Decreased Epinephrine
- Fatigue, weight gain, restlessness, anxiety
- Increased Estrogen
- Bloating, headaches, moody, breast tenderness
- Increased Serotonin
- Irritable, easily agitated, anxiety, quicker to anger
- General COMT/MAO DOWN regulation symptoms may be:
- Difficult respiration – shortness of breath, Asthma
- Cardiovascular disorders – hyper or hypotension, angina, bradycardia, ectopic beats, conduction issues, palpitations, tachycardia, vasoconstriction, arrhythmias
- Spectrum disorders – Autism, Asperger’s, ADD/ADHD, Dementia issues
- Other neurological disorders – agitation, disorientation, impaired memory, aggression, assaultive, hallucinations, psychosis
- Hormonal imbalances – adrenal fatigue, cortisol imbalances, glucose imbalances, low Thyroid hormone conversion (T4 to T3), low LH and GH, elevated BUN
Possible lifestyle changes to HELP a DOWN-regulated pathway:
- Avoid/limit foods high in tyrosine, tryptophan, phenylalanine and other amines since these amino acids are precursors in the pathway:
- Seeds and Nuts:
- Sunflower seed
- Chia seed
- Sesame seed
- Pumpkin seed
- Mung beans
- Lima beans
- Kidney beans
- Pork Loin
- Potatoes (all, even sweet potatoes)
- Green Coffee bean extract (in diet supplements)
- Avoid/limit the following nutrients/supplements:
- Green Tea Extract (EGCg)
- Chronic stress strongly inhibits COMT and MAO function – take a vacation
- “Bad” estrogens from exogenous sources (in food supply, plastics…), or created by the breakdown of other hormones – avoid plastics, start a mild exercise program
What to Do?
- Start with decreasing the FOODS in the above list that are in BOLD (turkey, chicken, beef, and cheese). Decrease stress loads and begin an exercise program. Reduce exposure to bad estrogens and stay away from processed foods. Report to us ANY change in symptoms. NOTE: this is NOT necessarily a diet to stay on long term (just for a few weeks while you watch your symptoms). You will then want to add ONE food back at a time and check for changes in symptoms.
- You may feel either better or worse – let us know immediately. If you feel better, you still do not need to continually eliminate ALL these foods for life. After a few weeks you want to add ONE food back to your diet and gauge symptoms. Then slowly add others over the next few weeks. If you feel worse, stop those foods.
- Consider (but get tested on) the following supplements:
- Support MTHF and Methionine pathways with B6, B1, B2, Niacin (B3) because SAM is a major co-factor for COMT – we typically use a product called B-Specific
- Magnesium and other minerals – another major co-factor - we typically use a product called Multi-Mins
- Adaptogenic herbs such as Eleuthero, Ashwaganda, Passion Flower, Lemon Balm, Valerian
- Vitamin C (ONLY if NOT autoimmune)
- Progesterone increases MAO production for those with an MAO defect
- Do NOT take too much MTHF (methyl Folate) or B12 (methylcobalamine) as it feeds this pathway too quickly and the patient can worsen quickly! Though B12 is essential, caution must be taken with the TYPE and dosage! I’ve seen many patients with COMT defects instructed to take high dose hydroxycobalamin, long-term. While this form of B12 is great for some people, its function is to consume methyl groups in patients who have too many, consume nitric oxide, and consume hydrogen sulfide. These are ALL essential metabolites that you do NOT want diminished long-term. I know this all gets pretty touchy but the only CORRECT way to treat is to monitor CONSTANTLY!
- For those with a COMT ++ (someone with a double allele defect) who are experiencing anxiety and insomnia - If you take a small amount of SAMe and increased magnesium (malate or glycinate) they may see a drastic improvement, however don’t do this without consulting with Dr. Conners.
REMEMBER: Since SAMe touches so many other enzymes, I find it best to support COMT by giving more magnesium, reducing tyrosine containing foods from the above list, reducing protein intake a bit, increasing healthy fats, reducing carbs, supporting liver and removing xenoestrogens (consider using DIM).
- What if my COMT/MAO defect causes an INCREASE function of the gene - Common COMT pathway UP-regulation variant issues: (this is also common and even more a common scenario of someone taking too high a dose of MAOI anti-depressant medication). Many, as stated, will “bounce” between too MUCH and to LITTLE neurotransmitter expression with days in category 1 above and days in this category. You will learn to “tweak” your diet to help your mood.
Symptoms of increased gene expression (and therefore a decrease in the neurotransmitters) may include: (remember, OTHER issues can cause these same symptoms (like a Histamine intolerance) which is COMPLETELY unrelated!)
- Sadness, blue, melancholy, depressed
- Lack of motivation, lack of DRIVE, lack of desire for life
- Hives, rashes
- Acute Chest pains
- Fast or slow heart beat
- Stiff neck
- Loss of sexual desire or ability
What to DO?
- Consider INCREASING Foods high in amines (meats, proteins, etc. from the above list)
- Consider using:
- Green Tea Extract (EGCg)
More on UP-regulated MAO and Depression
- When COMT and MAO are UP-regulated (particularly MAO) – this can lead to an INCREASE in the breakdown of Serotonin = LOW SEROTONIN with common symptoms of depression
- MAO inhibitors (EX: Cymbalta, Wellbutrin) are a class of medications commonly prescribed to people with depression. If you are on a MAOI, do NOT follow any of the recommendations in this paper as it may cause TOO HIGH a serotonin level – which, as you can see, is equally as bad!
Other natural substances/choices to help increase Serotonin and Dopamine levels (SLOW MAO pathway) if you have an UP-regulated gene pathway:
- Light exposure – get out in the sun
- High-dose Niacin (500mg) without methyl support
- B6 and Zinc
- John’s Wort
- Ura Ursi
- Evening Primrose
- Echinacea (if NOT autoimmune)
Our FOUR-STEP Protocol
1. What is the CAUSE and how are we going to get RID of it?
2. What specific Nutraceutical will work for YOUR condition?
3. What specific FREQUENCIES will work for YOUR condition?
4. What other SUPPORT is necessary (other organs, brain, diet…)?