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Reducing CVD risk with Vitamin E & reducing caffeine based on COMT genotype.

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  • Reducing CVD risk with Vitamin E & reducing caffeine based on COMT genotype.

    After finding that I have several genes (SNPs) that reduce the activity of the COMT enzyme, I decided to look into the implications of this some. Just sharing here some of the things Ive come across. COMT is an enzyme that breaks down many important chemicals - catecholamines, neurotransmitters, etc (examples: dopamine, epinephrine, norepinephrine). Given this important role, there's a lot of research on it, but the research is very varied because of how many impacts these compounds have physiologically and psychologically. I found several studies that linked some of the COMT SNPs to cardiovascular diseases, but I'm going to focus here on some (*potential*) takeaways / action steps.

    There are several genes/SNPs that have been researched in association w/ COMT and CVD, including rs4680, rs4633, rs4818, rs6269. These are names for 'individual genes', and you can find out which you have if you have done a 23andMe, Ancestry, or the like test (You will need to download the 'Raw SNP data' from 23 / ancestry, and then pay ~$15 to upload your SNP data to 'Promethease'. With SNP data and Promethease, can search for these SNPs in Promethease to see what genes you carry.). The SNP / gene that has been researched the most is rs4680. People who are A/A for rs4680 have very reduced activity of the COMT enzyme. Other SNPs can further slow its activity. Slower activity of SNP means that the chemicals it breaks down are broken down slower.

    So, to the point:

    Vit E
    It seems that rs4680 A/A (a.k.a. met/met) carriers might see significant benefit from vitamin E. In a cohort from the Womens Health Study (so, note, this cohort was all women), val/val and val/met carriers showed increased CVD incidence from Vit E, but met/met carriers showed very reduced incidence (CI 0.34 - 0.84 for major CVD) - see the life table on p.2165 here -- https://www.ahajournals.org/doi/pdf/...aha.114.303845 This SNP is part of 23andMe and other consumer tests, so many people may be able to identify their status.

    A few other interesting findings that I'm wading through:

    Caffeine
    "In logistic regression adjusting for age, smoking, family history of CHD, vitamin C deficiency, blood pressure, plasma cholesterol concentration, and diabetes, the odds ratio [of CHD] (90% confidence interval) comparing heavy coffee drinkers with the low activity COMT genotype with those with the high activity or heterozygotic genotypes was 3.2 (1.2–8.4). Urinary adrenaline excretion increased with increasing coffee intake, being over two-fold in heavy drinkers compared with nondrinkers (p = 0.008 for trend)."
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1762420/

    Well this one wasn't too fun to discover -- tea and coffee are two of my hobbies -- I easily have over 150 types of tea!

    Homocysteine
    "When comparing the COMT low activity genotype with the others, we found... an age, examination year, serum LDL and HDL cholesterol, and triglyceride concentration, systolic blood pressure and smoking adjusted HRR [hazard rate ratio of CHD] of 1.77 (95% CI, 1.05–2.77). Although serum tHcy [total homocysteine] concentration was not statistically significantly associated with acute coronary events (HRR for the highest third versus others 1.52, 95% CI, 0.93–2.49), subjects with both high serum tHcy [total homocysteine] and the COMT low activity genotype had an additionally increased adjusted risk of HRR 2.94 (95% CI 1.50–5.76) as compared with other men.... hyperhomocysteinemia [high homocysteine] may exert its pathogenic effects largely through metabolic accumulation of SAH, a potent non-competitive inhibitor of COMT-mediated methylation metabolism of various catechol substrates was recently proposed"
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779620/

    In other words, they think high homocysteine -> high SAH -> inhibition of COMT -> further reduction in COMT activity.
    I have several genes/factors that are risk factors for low homocysteine, so this is news to me as well!

    I've also read some info about EGCG, a compound in Green Tea, may also be a potent COMT inhibitor.
    Last edited by mtbizzle; 03-28-2019, 10:53 PM.

  • #2
    Well this is very geeky!

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    • #3
      Ha! That's me! I was in academia for a while and am in the process of a career change over to healthcare, so... that's what you see here

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      • #4
        Originally posted by mtbizzle View Post
        Ha! That's me! I was in academia for a while and am in the process of a career change over to healthcare, so... that's what you see here
        Well that explains why you write so well! I enjoy your work.

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        • mtbizzle
          mtbizzle commented
          Editing a comment
          Thanks David! Appreciate the kind words. Hopefully some of the skills I've picked up in academia, like being able to think carefully / communicate clearly, will serve me well in healthcare.
          Last edited by mtbizzle; 03-31-2019, 01:22 AM.

      • #5
        On the other hand, there is another SNP that indicates a person should not take vitamin E.

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        • #6
          I'm not very clear on this, but I think what I recall from what I've read is that (a) Vit E did not show benefit in the general population, and (b) Vit E was beneficial for certain Haptoglobin genotypes.

          Do you by chance recall what gene (s) indicate avoiding Vit E? Unfortunately Haptoglobin is not part of the ancestry/23andMe tests.

          Just did a quick search -- "in individuals with diabetes and the Hp2-2 genotype, vitamin E has been shown to be associated with an approximately 35% reduction in CVD."

          But they specify in diabetics. The met/met genotype doesn't seem to have that qualification, so that's noteworthy. Of course this is all preliminary data also.

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          • #7
            From Dr Rhonda Patrick's app:

            GSTP1 rs1695(A;G) Supplemental vitamin e may be harmful

            The glutathione transferase enzyme plays an important role in detoxification of many compounds that are harmful to cells from the environment and generated from normal metabolism and immune function. This version of the glutathione transferase enzyme seems to have normal activity and is found in around half of the population. Glutathione is one of the most potent antioxidant systems that the body has and is orders of magnitude more powerful than supplemental vitamin E (alpha tocopherol). Supplemental vitamin E has been shown to have a negative impact on individuals with the rs1695(A;G) genotype by raising the levels of pro-inflammatory cytokines in the blood. However, people that have the less active version of GSTP1, rs1695(G;G), may possibly have an anti-inflammatory benefit from a low dose (75 IU) supplemental vitamin E.

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            • #8
              That's what the geneticists & biochemists have said. MyGenetx uses that concept as a reason or marketing their Haptoglobin 2 test.

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