MTHFR gene and supplementation with 5-L-methylfolate | Tim Ferriss
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Gene polymorphisms, small changes in an organism's DNA sequence, can affect the absorption and metabolism of nutrients, including vitamins and minerals. A polymorphism in the MTHFR gene that decreases enzyme activity leads to inefficient folate metabolism. People with the modified version of this gene might benefit from supplementing with methylated forms of B vitamins. In this clip, Tim Ferriss discusses his MTHFR status and his experience with vitamin supplementation.
- Rhonda: So your biomarkers tend to be a lot of performance-related biomarkers.
- Tim: Yeah. And I've done the genetic stuff. So I know, let's just say that I'm a poor methylator, the motherfucker gene, as they say.
- Rhonda: Yes, MTHFR.
- Tim: Yeah. I'm not in an ideal spot. So taking, say, l-methylfolate could be a good option for me and I've experimented with that in the past, looking at how that can lower homocysteine or things like that.
- Rhonda: Have you noticed any differences after experimented with 5-methylfolate, L-5-methylfolate, methylcobalamin?
- Tim: Yeah. I haven't noticed many changes in blood markers and I haven't noticed subjective changes in, say, performance or clarity or anything like that.
- Rhonda: Yeah.
- Tim: It doesn't mean it isn't doing things.
- Rhonda: Yeah. I have an anecdotal story. So I'm very into looking at different gene polymorphisms. 23andMe is a great service that can do that. So my friends, family, etc., I'm telling everyone to do it. So my mother-in-law got genotyped and we found out that she is homozygous for MTHFR, meaning that her MTHFR enzyme only is working at about 10 to 20% efficiency. She's always had really high blood pressure, to the point where doctors were wanting to get her on medicine for it and she's always refused. Nothing she did . . . she's done various diets, lots of exercise, lots of things she's tried, nothing has gotten her into a normal range until we identified she had MTHFR, got her supplementing with 5-methylfolate and methylcobalamin. But she's been taking pretty high doses of it. But now her blood pressure for the first time is in like a normal range. So I was kind of curious if you had ever . . .
- Tim: I have very consistently what you would consider excellent blood pressure. So I haven't looked closely at that. The question that comes to mind for me always because I've noticed . . . so, I'm a big fan of Richard Feynman. Richard Feynman, and I'm not saying this is the case with your, you said mother-in-law?
- Rhonda: Yes.
- Tim: But the importance of not tricking yourself because you're the easiest person to fool, basically, is what he would say. I know that what I have initially thought were sort of causal relationships with high correlative value . . . for instance, I've talked to people who have gone on fill in the blank diet. They're like, "This thing changed. I'm so glad I found this diet." I'm like, "So you haven't changed anything else?" "No, no, no. I started running in the morning. I started doing this. I started doing that." I'm like, "Hell yeah" . . . because like one, it's so hard. That's where the observational data gets so challenging, when you look at, say anything, whether it's the China study or whatever. We don't need to get into that one. That's a sensitive one. But any observational self-reporting and so on, the data is almost always so flawed because humans almost never change just one thing.
- Rhonda: Yeah. I think that's why it's so important when you're looking at epi studies that are associative that are not a clinical, randomizable trial, coupling that data with mechanistic data done on animal models or lower organisms, I think coupling the two is very important because then you go, "Oh, okay. We've noticed this observational data and here we've done X, Y or Z to manipulate it in a worm or in a fly or a mouse."
- Tim: Right. So you have a plausible mechanism.
- Rhonda: Right. So you have a mechanism. That's where I think looking comprehensibly at the whole . . .
- Tim: At the intersection.
- Rhonda: Yeah, scientific is very important.
A measurable substance in an organism that is indicative of some phenomenon such as disease, infection, or environmental exposure.
Any of a group of complex proteins or conjugated proteins that are produced by living cells and act as catalyst in specific biochemical reactions.
A type of water-soluble B-vitamin, also called vitamin B9. Folate is critical in the metabolism of nucleic acid precursors and several amino acids, as well as in methylation reactions. Severe deficiency in folate can cause megaloblastic anemia, which causes fatigue, weakness, and shortness of breath. Certain genetic variations in folate metabolism, particularly those found in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene influences folate status. Inadequate folate status during early pregnancy increases the risk of certain birth defects called neural tube defects, or NTDs, such as spina bifida, anencephaly, and other similar conditions. Folate deficiency and elevated concentrations of homocysteine in the blood are associated with increased risk of cardiovascular disease. Low folate status and/or high homocysteine concentrations are associated with cognitive dysfunction in aging (from mild impairments to dementia). The synthetic form of folate is called folic acid. Sources of folate include most fruits and vegetables, especially green leafy vegetables.
The genetic constitution of an individual organism. The combination of genotype and environment determine an organism's physical characteristics – known as the phenotype.
An amino acid present in the blood. Homocysteine is produced during the metabolism of methionine. Abnormalities in methionine metabolism can lead to elevated homocysteine levels, a condition called hyperhomocysteinemia. Elevated homocysteine levels can contribute to arterial plaque formation and increase the risk of clot formation. Some evidence suggests that elevated homocysteine levels double the risk of developing Alzheimer’s disease. Homocysteine levels vary according to dietary intake, with highest levels associated with consumption of animal protein. Variants in the genes that encode for the enzymes that metabolize homocysteine, specifically MTHFR, or methylenetetrahydrofolate reductase, markedly increase the risk of developing a wide array of diseases, including cardiovascular disease, Alzheimer’s disease, and cancer. High intake of dietary folate (present in leafy greens and other fruits and vegetables) can modulate the harmful effects associated with MTHFR.
A gene coding for an enzyme that converts homocysteine into methionine; a critical step in the methyl cycle. Natural variation in this gene is common among healthy people, however, some variants have been reported to influence susceptibility to occlusive vascular disease, neural tube defects, Alzheimer’s disease and other forms of dementia, colon cancer, and acute leukemia.
A study in which people are randomly allocated to receive one of several clinical interventions. One of these interventions is the standard of comparison or control. The control may be a standard practice, a placebo, or no intervention at all.
A change in one nucleotide DNA sequence in a gene that may or may not alter the function of the gene. SNPs, commonly called "snips," can affect phenotype such as hair and eye color, but they can also affect a person's disease risk, absorption and metabolism of nutrients, and much more. SNPs differ from mutations in terms of their frequency within a population: SNPs are detectable in >1 percent of the population, while mutations are detectable in <1 percent.
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