In January, Rich asked people to share their 23andMe results for the MTHFS gene to see if we can sort out which SNP or SNPs may be detrimental in ME/CFS. I didn't see where anyone responded. (You can find your MTHFS results by going to https://www.23andme.com/you/explorer/ and logging in and entering "MTHFS" for the gene name.) It's important people contribute so we can try to figure out when folinic acid should be supplemented or avoided for certain people as part of a methylation protocol. I may be intolerant to folinic acid (seems to cause exacerbation of fatigue, irritation of taste buds) and so am providing my DNA results. We need MTHFS results from as many other people as possible, though, whether intolerant or not. If you could also include the one SHMT result that Yasko tests for, that may be helpful also. I'm heterozygous (AG) for that SNP (SHMT1 C1420T rs1979277), and the first day I took folinic acid it helped, as might be expected, but then I seemed to gradually get worse over several days (800-1600 mcg/day). Below are Rich's personal MTHFS results with mine next to his in parentheses (he volunteered to be the DNA "standard"). At the time Rich was tested, 23andMe only gave results for 22 SNPs. They gave 24 for me. (36 are known?) There was only one instance of a flip in homozygosity between Rich's results and mine, rs7177659, and I discuss it after: MTHFS rs8923 C or T CT (TT) [Rich is "CT"; I'm "TT"] MTHFS rs2733103 C or T CC (CT) MTHFS rs16971427 A or C AA (AA) MTHFS rs655473 A or G AA (AA) MTHFS rs17284990 C or T TT (CT) MTHFS rs16971450 A or G AA (AA) MTHFS rs6495446 C or T CT (CC) MTHFS rs7177659 A or C CC (AA)*** MTHFS rs6495449 A or G GG (GG) MTHFS rs17285431 A or C AC (AA) MTHFS rs6495451 C or T CT (CC) MTHFS rs2586154 A or G GG (AG) MTHFS rs12899781 G or T GT (TT) MTHFS rs16971478 A or G AA (AA) MTHFS rs2586153 C or T CC (CT) MTHFS rs2562744 A or C AA (AC) MTHFS rs2733106 A or G AA (AG) MTHFS rs12438477 A or C CC (CC) MTHFS rs12898642 C or T CT (TT) MTHFS rs2586182 A or C AA (AC) MTHFS rs2733088 A or G AG (AG) MTHFS rs12440798 C or T CC (CC) My two additional results: MTHFS rs685487 A or G (GG) MTHFS rs8033649 A or C (CC) We're not likely to be so lucky right away that rs7177659 is the "bad" SNP, but it's interesting because having the hetero version (AC) for that SNP actually seems to be "normal" (58% frequency according to openSNP) and apparently results in a 29% decrease in cardiovascular disease risk compared to the homo versions (AA/CC). (This is from a May 2012 publication: http://jn.nutrition.org/content/early/2012/05/28/jn.111.157180.abstract - I don't have access to the full text; it's not mentioned in the abstract.) So with respect to that SNP it might be that I have a detrimental down-regulation of MTHFS and Rich has a detrimental up-regulation (or vice versa). A down-reg would cause a build up of folinic acid and thus inhibition of SHMT (and several other enzymes outside the methylation cycle as well) and create an intolerance to supplementation. An up-reg can cause an increased turnover rate and depletion of cellular folate. Note: The C allele - what Rich has two copies of - is the ancestral (wild type) allele according to the NCBI data page. Hopefully, if enough people contribute, we can figure out which SNP(s) is/are problematic. Thanks!