The power and pitfalls of omics part 2: epigenomics, transcriptomics and ME/CFS
Simon McGrath concludes his blog about the remarkable Prof George Davey Smith's smart ideas for understanding diseases, which may soon be applied to ME/CFS.
Discuss the article on the Forums.

NutraHacker Report (Rare FOCM SNP)

Discussion in 'Genetic Testing and SNPs' started by Journeyman, Nov 25, 2016.

  1. Journeyman

    Journeyman Senior Member

    Messages:
    152
    Likes:
    41
    Hi Folks,

    I understand that NutraHacker is frowned upon somewhat for its alleged inaccuracies, but I can't help but notice a lot of its interpretations are correct and thus useful for implementing solutions to SNP polymorphisms.

    I recently used its report for the first time to analyse my old V3 23 & Me results and my attention was drawn to the red tab (homozygous mutation?) for rs1801131. This is new for me and I read with interest the 'Consequences' and 'Encourage' and 'Avoid' tabs for rs1801131 where apparently I've got a RED 0.0071% mutation that relates to my conversion of folic acid to 5-MTHF.

    Now from what I understand rs1801131 is another way of describing the A1298 SNP, however my genetic genie results only indicated that I was heterozygous for that SNP so what is the SNP that rs1801131 relates to and if it is A1298 as I suspect, then why is Nutrahacker indicating I'm homozygous for the mutation where as Genetic Genie is indicating just heterozygous...?

    It says that one of the key consequences of this rs1801131 mutation is low BH4 which might be more significant for me since I already have a mutation for BH8??? with the implication being lower serotonin (might explain the anxiety??)
    However it also mentions that it results in excess Ammonia. Now I always assumed that since I don't have a CBS mutation I would have no ammonia issues. How significant is the 'ammonia' effect of this polymorphism??

    It also indicates decreased glutathione which taking into account my absent GSTT1 SNP and hetero SOD2 means I'm at great risk of toxicity issues? (from the lack of glutathione) Which kinds of toxicities should I be looking to fight off here?? What might be the best way to do that (Glutathion supplementation??)

    What does 'high sulfate' and higher 'ammonia' risk translate to in terms of diet noting I eat a lot of cruciferous vegetables (and fruit generally) and also noting the alleged consequence of 'poor conversion of folic acid to 5-MTHF. Is it referring to the synthetic folate or the folate I'd be getting from the high amount of fruit/vegs I'm eating....

    Any clarification on these points would be most appreciated and I've upped the nutrahacker report in case you can see any other things that might tie together that I should be aware of!

    Regards

    Journeyman
     

    Attached Files:

  2. Valentijn

    Valentijn Senior Member

    Messages:
    14,281
    Likes:
    45,812
    The mutation is quite common, even when homozygous. Nutrahacker has made (another) error here.

    Genetic Genie has always reported the right alleles at least. No idea why Nutrahacker is reporting the wrong ones. Either way, MTHFR A1298C is a mild down-regulation, which brings enzyme activity down to levels which are completely on par with the general (healthy) population.

    Nutrahacker has no understanding of genetics or methylation, but is merely exploiting an ill population. They cut and paste their information and advice from random places on the internet, including plagiarizing my own comments from this forum until a moderator made them remove their plagiarized content.
     
  3. alicec

    alicec Senior Member

    Messages:
    1,405
    Likes:
    2,716
    Australia
    Yes rs1801131is A1298C. Just browse your raw data in 23andme and you will soon find out if you are +/- or +/+.

    That incidence figure is way off, it is a very common variant. About 9% globally are +/+ for this SNP, about 42% +/-.

    The enzyme MTHFR does not act on folic acid, it converts 5,10 methylene THF to methyl THF. The enzyme dihydrofolate reductase (DHFR) acts on folic.

    Here is a post about how difficulties in processing folic acid by this enzyme affect other aspects of the folate cycle.

    The stuff about this SNP affecting the reverse reaction of MTHFR which supposedly regenerates BH4 is one of Yasko's serious errors. The enzyme does not run backwards nor is it involved in BH4 regeneration. Here and here are posts relevant to this question.

    The ammonia stuff is an even more serious error from Yasko. BH4 has nothing to do with ammonia. I don't know where Yasko got this idea but I suspect she simply misread metabolic diagrams which show the NOS (which uses BH4) and urea cycle (which uses ammonia) pathways side by side because they share arginine and citrulline as reactants. She somehow conflated the two independent pathways.

    NOS converts arginine to citrulline plus nitric oxide (NO). It uses BH4 as a cofactor (5 cofactors in total - a complicated enzyme). Ammonia has no part in this reaction.

    Ammonia is processed in the urea cycle. This is a more complicated cycle of interconversion which includes arginine and citrulline (though in a different sequence) along with other intermediates. Ammonia is incorporated into the cycle and the less toxic waste product urea is produced as a by-product.

    Finally I am not sure what BH8 is I don't think it is related to BH4. The latter is tetrahydrobiopterin, a cofactor for NOS and for the three aromatic amino acid hydrolases (phenylalanine, tyrosine and tryptophan) which are involved in synthesis of the neurotransmitters dopamine and serotonin.

    I wouldn't worry too much about their so-called recommendations, they are based on a lot of wrong ideas.
     
  4. aaron_c

    aaron_c Senior Member

    Messages:
    642
    Likes:
    1,000
    As I understand it methylfolate is a peroxynitrite scavenger, and perhaps more importantly improves eNOS coupling, which decreases peroxynitrite formation. So low(er) methylfolate might conceivably cause an increase in peroxynitrite. Peroxynitrite reacts with BH4 to form BH3.

    Without supplements do we have enough methylfolate floating around in our blood to make a difference? I'm not sure. Would the somewhat slower version of MTHFR that you have make any difference? I don't know enough to say. Even if your mood were to improve on methylfolate or BH4, we wouldn't know whether your MTHFR SNP was the reason you needed it. Nonetheless, I think there is reason to believe that supplemental 5MTHF can benefit BH4 levels--although not in the way that Yasko suggests.
     
  5. alicec

    alicec Senior Member

    Messages:
    1,405
    Likes:
    2,716
    Australia
    I agree. This is discussed in the links.
     
  6. aaron_c

    aaron_c Senior Member

    Messages:
    642
    Likes:
    1,000
    My bad for not reading all the way through them!
     
  7. alicec

    alicec Senior Member

    Messages:
    1,405
    Likes:
    2,716
    Australia
    Well I didn't canvas methylfolate supplementation, just the peroxynitrile scavenging and protective effect on NOS.

    So between us we have covered all bases.
     
  8. Critterina

    Critterina Senior Member

    Messages:
    1,202
    Likes:
    700
    Arizona, USA
    Do you maybe mean BHMT-8?
     
    Journeyman likes this.
  9. Journeyman

    Journeyman Senior Member

    Messages:
    152
    Likes:
    41
    Yup, per my signature block...
     

See more popular forum discussions.

Share This Page