MTHFR variants in up to 40% of population
Up to 40% of people carry one or two copies of common MTHFR variants, making them so prevalent that their average clinical effect is likely very small.
Snapshot · The Peter Attia Drive
#392 - Genetic testing: when it's valuable, how to choose the right test, and what to do with the results
Explore episode
May 18, 2026
Where this was said
Functional medicine genetic testing: the gap between biological plausibility and clinical evidence
At 33:05 · chapter starts 32:45
Peter turns to one of the most pointed critiques in the episode: the world of functional medicine genetic panels. MTHFR is his central example. The variants are real and do alter folate metabolism, but they are so common — carried by up to 40% of the population — that natural selection's failure to eliminate them is itself strong evidence that their average effect is small [1] — Peter Attia "Up to 40% of people carry MTHFR variants — which is exactly why they can't be driving serious disease. Natural selection weeds out harmful …" 32:40 . Yet patients are routinely told by functional medicine practitioners that MTHFR explains their fatigue, brain fog, or anxiety, and placed on aggressive methylation supplement protocols with no meaningful clinical evidence. Peter identifies a repeating playbook: find a common variant with at least some scientific basis, inflate its importance, and sell a bespoke supplement stack. COMT variants are used to tell patients they are fast or slow metabolizers of dopamine, and that this explains their personality and stress response. So-called detox panels assess cytochrome P450 variants and present color-coded charts implying that the liver's detoxification pathways are compromised — when in reality the liver's machinery is extraordinarily redundant and compensatory. Nutrigenomic tests promise personalized diets from DNA, but the evidence shows these diets typically perform no better than conventional dietary advice. The through-line is that a mutation can be biologically interesting without being clinically actionable.
Pharmacogenetics: The Most Defensible Use of Genetics in Medicine
Pharmacogenetics sidesteps the uncertainty of disease prediction and asks a far more tractable question: how will you respond to this specific medication? From Plavix and CYP2C19 to allopurinol and HLA-B58, these tests can prevent serious harm and guide drug selection with real clinical evidence.
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