While trying to further optimize my diet, I recently noticed that I have a homozygous C677T (TT genotype) MTHFR enzyme.
Homozygous rs1801133(T;T) individuals have ~30% of the expected MTHFR enzyme activity, and rs1801133(C;T) heterozygotes have ~65% activity, compared to the most common genotype, rs1801133(C;C). This reduced activity (i.e. this SNP) has been linked at least once to each of the following disorders (though not necessarily reproducibly):
Smoking and having low folate levels (presumably from diets low in fruits and veggies) increased the risk for (T;T) individuals from ~1.5x to ~2x, whereas having high folate levels almost reduced the risk for (T;T) genotypes pretty much down to the (C;C) level, ie. the average risk. [PMID 18162478]
Another meta-analysis of three studies on rs1801133 stratified according to dietary folate intake showed an increased risk for individuals with low folate intake (OR=1.37, CI: 0.92-2.06 for head and neck cancer and OR=1.28, CI: 0.97-1.68 for lung) versus high folate intake (OR=0.85, CI: 0.63-1.16 for head and neck cancer, and OR=0.94, CI: 0.79-1.12 for lung).
So, it sounds like I want some more Folate in my diet. Besides eating dark green plants (I'm pretty good about that), I'm wondering if I should supplement and if so, how much / often / with what? Would I want folic acid? metafolin? Or maybe methylfolate? Would it be best to just get it from food? Can it be accurately measured by blood test?
Edit: I do get migraines with aura too.
Based on a study of 25,000 Caucasian women followed for 11 years (on average), the rs1801133(T;T) genotype individual was less likely to have migraine with aura (odds ratio 0.79, CI: 0.65-0.9 6, p = 0.02) and did not have increased risk for cardiovascular disease. However, if a (T;T) genotype did have migraine with aura, then the risk for cardiovascular disease was increased 3.66 fold (CI: 1.69-7.90, p = 0.001). This was apparently driven by a 4x increased risk for ischemic stroke (multivariable-adjusted relative risk 4.19, CI: 1.38-12.74, p = 0.01).
??? the more you know ???
Sounds like I need to find something that gets those headaches down better too. (Hey, maybe more folate?) I'm only ~3-4 months into the diet and still tweaking it.
asked bypaleot (995)
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on July 17, 2013
at 05:11 AM
Great question. ATM I can't really answer that well other than to suggest that if homocysteine levels are not suspiciously high then folate supplementation may not be necessary (as the gene may not be expressed if methylcation cycle is functioning normally, as evidenced by having normal homocysteine levels). Given the migraine issue though, probably you are right to think about this.
In relation to folate/folic acid etc, liver is fairly high in folate and there are potential negatives to folic acid - http://chriskresser.com/folate-vs-folic-acid