Some in the chronic fatigue syndrome community theorized that the debilitating symptoms of fatigue may be blamed on in-born errors of metabolism. These in-born errors are due to simple genetic alterations (single nucleotide polymorphisms; SNPs) that can result in poorly functioning enzymes that block or disrupt biochemical pathways.
The late Rich Van Konynenburg popularized the idea that CFS patients may have certain SNPs in methylation pathways; when addressed nutritionally can improve symptom severity. His theory was born out of the work of Amy Yasko, PhD who looks for in-born metabolic errors in her autism work. I studied Yasko's and Koynenburg’s work very closely over the past year and wanted to collect SNP data on myself. My results are in:
Based on the raw data from my 23andMe analysis, these are my homozygous mutations. Homozygous mutations (+/+) indicate that 100% of these enzymes are genetically altered, which likely slows down metabolic reactions.
Below are my heterozygous mutations. Heterozygous mutations (+/-) may differ from homozygous mutations (+/+) in associated metabolic abnormalities since a person with a heterozygous mutation will often still have one fully functioning copy of the gene.
COMT V158M & COMT H62H
CBS C699T & CBS A360A
Now that I know my SNPs, what changes did I make to my supplement protocol or diet?
Based on the homozygous (+/+) MTRR A66G SNP, I make sure to only use methyl-forms of B12. MTTR is the enzyme Methionine Synthase which is responsible for regenerating B12 needed to recycle homocysteine back to methionine. With this SNP, my metabolism may be slow/inefficient when utilizing B12, leading to a back-up in homocysteine (a finding that has been confirmed by past labwork).
I have several heterozygous alterations in key methylation pathway enzymes. Let’s tackle the COMT enzymes first. catechol-O-methyltransferase (COMT) is a key enzyme involved in the production of “feel good” neurotransmitters like dopamine and adrenaline. With sluggish/inefficient COMT enzymes there may be lowered neurotransmitters leading to depressive symptoms. With this finding I have implemented two new supplements to give the pathway a boost. First, I added Royal Jelly, a natural source of BH4 (according to Yasko), which is necessary to convert amino acids into these beneficial neurotransmitters. I’ve also added SAMe, S-Adenosyl-L-Methionine, which provides the methyl group needed to assist COMT enzymes. Both interventions sustainably improved my mood and sense of well-being.
Next is betaine-homocysteine methyltransferase (BHMT) which is an enzyme that serves to recycle homocysteine back into methionine. This pathway is not the primary means to recycle homocysteine, but acts as a secondary short-cut pathway. The enzyme BHMT requires trimethylglycine (TMG) to function. TMG is commonly found in supplements in the form of Betaine, and is readily available in the diet.
The last heterozygous alteration in my methylation pathway is the enzyme cystathione B-synthase (CBS). This enzyme functions to convert homocysteine to the antioxidant glutathione. CBS requires a B vitamin for proper function—thus adding this vitamin would theoretically improve functioning of my sluggish CBS enzymes. Vitamin B6 in the active form of pyridoxal 5'-phosphate activates CBS enzymes pushing homocysteine toward glutathione.
Using genetic data to design nutrition and supplement recommendations is far from an exact science. What works for one may not work for another. Currently a crowd-funded study hopes to uncover the role of methylation cycle SNPs in ME/CFS. Until then, we can only speculate if these simple interventions, like B12 and active folate, will make a major difference in symptoms.
Have you checked your methylation SNPs and changed your treatment approach based on the findings? If so, let us know in the comments.