MAO-A/COMT Issues

[Tigger]

Hi all,

Not sure if I'm posting this in the right forum given that just about everything overlaps but here goes. I've posted on and mostly focused on methylation with some success. My SNP's are in my signature. After seemingly never-ending research, I've come to the conclusion that my main problems lie within MAO-A/COMT mutations. This has, by far, been the most spot on article I've found yet: http://www.connersclinic.com/balancing-comt-and-mao-defects/.

My most frustrating issues have been socially-based (extreme panic, low confidence, etc.). Strangely, many of my symptoms are in line with Asperger's (inability to empathize, failure/extreme difficulty developing and maintaining friendships, repetitive behaviors, narrowed interests, routine-oriented, depression/anxiety). This is all in addition to other symptoms listed below. Much of the following portion applies to me:

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:
  • Seaweed
  • Spirulina
  • Seeds and Nuts:
    • Almonds
    • Sunflower seed
    • Pistachio
    • Walnuts
    • Chia seed
    • Sesame seed
    • Soy
    • Peanut
    • Pumpkin seed
  • Beans:
    • Mung beans
    • Lima beans
    • Kidney beans
    • Lentils
  • Meats:
    • Turkey
    • Chicken
    • Beef
    • Cod
    • Mollusks
    • Tuna
    • Salmon
    • Bacon
    • Pork Loin
  • Dairy:
    • Cheese
  • Other:
    • Gelatin
    • Chocolate
    • Eggs
    • Potatoes (all, even sweet potatoes)
    • Coffee
    • Green Coffee bean extract (in diet supplements)
    • Blueberries
  • Avoid/limit the following nutrients/supplements:
    • Rhodiola
    • Green Tea Extract (EGCg)
    • Quercitin
  • 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?

1. 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.
2. 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.
3. 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!

1. 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).


Has/does anyone have similar experiences and, if so, have you found any solutions?

@Changexpert @Gondwanaland @LisaGoddard @ahmo @caledonia @Wishful @stridor @alicec

 

[caledonia]

You might enjoy Ben Lynch's new book "Dirty Genes". He's selected the 7 most important genes based on two years of researching the scientific literature. Two of those are COMT and MAO-A.

The book focuses on epigenetics vs. genetics. In other words, how do environmental factors make genes express, and what you can do about it.

Beyond that, Asperger's/autism could suggest that mercury is affecting gene expression. He mentions metals briefly, but in my opinion doesn't have a very good program for eliminating them.

In my opinion, the Cutler chelation protocol would give better results.

I have links to Ben Lynch's book, and the Cutler protocol in my signature link.

 

[Tigger]

@caledonia
Thank you as always for a thorough reply. I will absolutely check his book out.

I've actually done close to 50 rounds of ALA chelation with supports via Cutler's protocol with no real change. I'm not sure on the reliability of the hair test (Doctor's Data) but had very low readings for Mercury.

 

[caledonia]

@caledonia
Thank you as always for a thorough reply. I will absolutely check his book out.

I've actually done close to 50 rounds of ALA chelation with supports via Cutler's protocol with no real change. I'm not sure on the reliability of the hair test (Doctor's Data) but had very low readings for Mercury.

Yay for you for 50 rounds!

The toxic metals section of the Doctor's Data hair test is typically low for mercury, even if you have a bunch of it. That's why Cutler says to look at the essential elements section for disordered/deranged mineral transport via his counting rules.

Have you had any sort of changes at all, good or bad? For example, with 26 rounds, my balance is improved, and one more thing I can't remember right now, but I've developed a mild case of EMF sensitivity. I did have some really big changes sometime after I got my last mercury filling out - no more autoimmune thyroiditis or candida, and a 50% improvement in adrenal fatigue.

You can refer to Cutler's list of mercury symptoms in his Amalgam Illness book, and the Hair Test Interpretation book has lists of symptoms for other metals like lead, arsenic, etc.

I had made up a list of symptoms I had before chelating, so I could track any changes over time.

 

[alicec]

I've come to the conclusion that my main problems lie within MAO-A/COMT mutations.

I'm sorry, that MAO A SNP has no effect and the protein produced by the variant gene is identical to the one produced by the wild-type gene.

An enormous amount of nonsense is propagated on the internet about this SNP which is simply wrong. Here, here and here are some relevant posts.

The COMT V158M SNP does have the effect of slowing the enzyme but the variant nucleotide A has a frequency of just under 50%. The most common genotype is +/-, which you have. Clearly this doesn't carry risk for disease since it is carried by the majority of the population.

The SNP has been studied extensively and the wildtype and variant have each been shown to have advantages and disadvantages.

As for the article you linked, I couldn't get past the second paragraph. The author confuses epigenetic change - the new trendy buzzword - with the genetic changes indicated by SNPs. S/he clearly doesn't know what s/he is talking about.

 

[Tigger]

@alicec

Thank you so much for this information. Based on my description of symptoms above, do you have any idea what the root cause of my issues could be?

 

[alicec]

@alicec

Thank you so much for this information. Based on my description of symptoms above, do you have any idea what the root cause of my issues could be?

Sorry you would need a skilled diagnostician to help with that. I can only help with information about some of the science.

 

[Tigger]

Well thank you both nonetheless.

 

[Tigger]

@alicec

Any comments on pyroluria? I've tried various dosages and forms of Zinc and P5P with mostly overstimulating and panic type responses.

 

[alicec]

@alicec

Any comments on pyroluria? I've tried various dosages and forms of Zinc and P5P with mostly overstimulating and panic type responses.

I've made some comments about that here, here, here and here.

 

[Tigger]

Perfect. Thank you. While I was always skeptical about the idea of it (seemed too good to be true), I certainly didn't and don't understand the technicalities so it's good to read information from people who have a much better idea. I've been tested before and was borderline but fit many of the seemingly unrelated symptoms. Perhaps I will try again and give it some more time. Thanks again.

 

[Tigger]

@alicec One more question if you don't mind. Back to the MAO-A topic. I'm clearly missing something but even if the variant and wild type genes produce the same protein and function the same, does that rule out supporting the gene completely? Given that MAO Inhibitors even exist would suggest that supporting may still be a helpful option. Please fill me in if I'm missing something.

 

[alicec]

even if the variant and wild type genes produce the same protein and function the same, does that rule out supporting the gene completely?

It just means that potential problems with MAOA activity are not due to genetic change in the gene.

Similarly use of MAOA inhibitors to manipulate neurotransmitter levels doesn't imply that the latter are due to genetic problems with MAOA.

Just be careful about claims for "supporting" the gene. These are often as flawed as the claims that the gene is faulty and thus in need of support.

The enzyme uses a flavin cofactor so ensuring adequate intake of riboflavin is important for enzyme function.

 

[Tigger]

Ahh! Gotcha! Thank you much. I will continue to support it (already have had good success with B2) with the knowledge that they perform roughly the same but additional support may still be beneficial.