Folate makes me feel worse
I totally empathize with your condition as I am also homozygous for MTHFR 1298 and I also have MAO, and COMT SNPs like yours as well as many of the others that you have including BMHT and CBS, MTR, MTRR and VDR. It is this constellation of SNPs that cause your mental illness.
I also have many SNPS in the serotonin pathway so I have chronic low serotonin and I have suffered with severe panic and OCD for most of my life until I started using nutrigenomics to treat myself including supplementing L-5-methyl folate. I now take a high dose of L-5-methyl folate every day and it is essential to my mental health. L-5-methyl folate is implicated directly in serotonin synthesis through the MTHFR 1298 B4 biopterin pathway so folate is needed for serotonin production. I humbly suggest you reconsider your stance on methylofalate is it's likely essential for you given your SNPs. This is the case for me anyway.
I have always felt that Walsh was somehow off base about folate and wonder if he doesn't confuse L-5-methylfolate with folic acid. Folic acid is definitely bad for those of us with low serotonin. I can't tolerate even trace amounts of synthetic folic acid or I get full blown panic attacks. So make sure you have a good understanding of the many different molecular forms of B9 as well as the other b-vitamins as they all have very different effects. For my low serotonin I also use 5-htp, B6 and tryptophan to help increase my serotonin synthesis.
I also used to take high dose SSRI. Roughly 15 years ago I was taking 40 mg of citalopram per day just to keep the panic at bay. I will say unequivocally that it did nothing for my health and may have done damage to my neurology and getting off of it was one of the worst experiences of my life. SSRI withdrawal is pure torture but the side effects and health problems caused by the drug made it absolutely necessary. I haven't touched a pharmaceutical product in over ten years since I got off the citalopram. That industry does not have your health or best interests at heart and is entirely driven by corporate profit. You should be aware that SSRIs may be high in oxalates, sulfites or bromine and many other potentially harmful substances. Bromine and oxalates can cause thyroid problems (happened to me) and oxalates are a major issue for some including me. More on this later when I talk diet.
There are many reasons why the folate makes you feel worse. One is the COMT ++ SNP you have that makes you sensitive to too many methyl groups that come from supplements like SAMe, and methyl folate. I can't handle any SAMe supplementation either or I get panicky.
Another reason may be the need for vitamin b12. Folate and b12 must always be taken together as well as riboflavin (B2) and pyridoxine (B6) in order for it to work. In fact, for folate to work properly the entire methylation cycle needs to be functioning.
You have MTR and MTRR SNPS so you might consider supplementing with methyl b12 but you could start with hydroxy b12 as this is great to control the COMT issue. I used methyl folate and hydroxocobalamin together with great success several years ago to reduce my anxiety while I slowly introduced and raised my methylcobalamin (mb12) intake.
NAC is also very good for anxiety if it is driven by glutamate excess. Glutamate is the most excitatory neurotransmitter and can be toxic when in excess and cause severe anxiety. I have GAD1 SNPs that suppress the conversion of glutamine to GABA in my body so that also adds to my problem with anxiety. Folate and detoxification will increase glutamate so this is another treatment conflict I had to deal with. I'm on the advanced methylation or Freddd's protocol now so I don't take NAC anymore and I don't need it as I'm converting glutamate to GABA well now because my methylation cycle is working. Mercury toxicity will also increase glutamate and aggravate your CBS SNP if it's active. B6 is vital for the conversion of glutamate to GABA.
Do you know if you have glutamate driven anxiety? If you do have issues with excess glutamate, I used Kava Kava for years to help with this and it was a revelation for my anxiety. Now that I'm on the advanced methylation protocol though I don't need that anymore either.
mentioned TMG, it is also helpful for the BMHT SNPs that you and I have and I have taken TMG with success for years and it doesn't seem to trigger the COMT SNP.
Yet another reason folate can cause problems is that folate will likely cause neurological methylation start-up and detoxification symptoms which includes anxiety as neurons heal and come back online and heavy metals are eliminated.
Your CBS SNP may mean you have problems with your Trans-sulfuration pathway which will cause major problems for detoxification and liver function and may cause problems with glutamate as it does for me. You may be high in sulfites which are also anxiety inducing so you could consider a sulfite free diet and investigate whether you need to supplement molybdenum or alpha-lipoic acid to correct sulfuration issues if you have them. You can test your sulfite load with urine test strips to see if you have high sulfites. B12 and molybdenum help the conversion of sulfite to sulfate which is vital for anxiety control and methylation.
I also use diet to treat my condition and it has been crucial to my success. I eat a grain free, (I'm celiac), dairy free, sulfite free, sugar free, alcohol free, low oxalate ketogenic paleo diet. I don't eat any processed food whatsoever because of my myriad sensitivities and there are a limited number of supplement manufactures I can use due to contamination or additives. I cook all my own food and use as much organic as possible.
If I were you I would reconsider my stance on beef and meat. The cancer studies done on red meat were very flawed as they didn't distinguish between processed red meat and unprocessed red meat. Undermethylators need lots of high quality protein, iron, zinc and bioavailable b-vitamins which beef and red meet provide much better than any other food source. I also eat 200-300 grams of grass fed organic beef liver every week. Certainly processed red meat like hotdogs, bacon, salami and bologna are carcinogens but plain meat is a very good food for me anyway and I eat a lot of meat. Many members of this forum are trying carnivore or Lion diets with success. Meat doesn't contain antinutrients like grains, legumes or some vegetables so some find it is better for those with autoimmune issues.
Along with diet, if I were you I would determine ASAP if you have a problem with oxalates. I have learned in the last year that oxalates have been a major driver of anxiety and depression for me all my life ( I really wish I had figured this one out sooner). I have SNPs that impair my ability to detox oxalates and I have SNPs that encourage endogenous oxalate production under certain conditions. Oxalate crystals can contain heavy metals such as mercury, cadmium and lead and can deposit in joints and tissues including the brain and amygdala and cause symptoms. Since I have gone low oxalate my mental health has improved dramatically and I have been able to reduce the dose of many supplements. This is a quote from the sulfation article linked below:
"The WHO (World Health Organization) and the AMA (American Medical Association) probably made the biggest medical mistake in world history by discounting the seriousness of oxalate overload because it impairs sulfation and sulfation is the key to life."
OK here are some good resources to help you and I've attached a PDF book by Amy Yasko that's been very helpful for me to understand my genetics and epigenetics.
- great explanations of SNPS and their impacts
- great resource on oxalates
- details problems caused by oxalates for people with methylation issues
- great resource for deficiency and toxicity symptoms of major nutrients as well as interactions between them
I hope you find this helpful and please don't hesitate to contact me directly if you want.