I have many heterozygous conditions for numerous genes in COMT and homozygous for MAO-A. There are 24 versions of MAO-A genes that I can see from 23andme test results, which I think can vary based on the version of 23andme test. I am homozygous for many of them, but there has not been much research on specific gene within MAO-A. Two specific genes that result in downregulation of MAO-A activity are rs6323 and rs1137070 while rs2072743 results in upregulation of MAO-A activity according to this thread, which also coincides with what Nutrahacker result says. FYI, I think Nutrahacker has a lot of conflicting information and their report is not thorough at all. As pointed out by many members on the forum, genetic defects work in combination, which is why each individual responds so differently to various treatments and protocols. Having homozygous MAO-A could be compensated by other SNP's, and it's the combination of SNP's that matters at the end. Unfortunately, my genetic profile is full of defective genes that slows down breakdown and conversion of neurotransmitters. For instance, the lab results showed that I am high in glutamate level and low in GABA level, even though I have not been supplementing with any glutamate or gluatmine recently. The fact that my GABA level is low explains why I could never fall asleep or have deep sleep for the past decade. Because of slow breakdown and conversion of neurotransmitters, my body reacts very negatively to methyl donor supplements. I have only tried mb12 (horrible body rashes everywhere, insomnia, restless syndrome) as a methyl donor, but the side effects I have gotten from it were so extreme that I am hesitant to try other methyl donor supplements. The negative reaction is somewhat countered when I take high doses of B2 or activated B2 in the form of FMN. This is because FMN can be converted to FAD, which increases MAO-A activity. Also, the combination of my MAT1 genes is defective as well, revealed by low SAM-e level. Defective MAT1 combination makes my body unable to convert methionine properly into SAM-e. So in addition to high sensitivity to methyl groups, I have an innate block in the methylation cycle. I would love to increase my SAM-e level as it is an important factor in many biosynthesis and conversion processes like creatine conversion process. I feel a bit overwhelmed to have such strange combination of genes . Should I bite my tongue and try SAM-e at a low dose? Please share your thoughts and suggestion. Thank you so much.