Supplements · Metabolic & Cardiometabolic

MTHFR C677T decreases vitamin D

Contested Supplements 🔬 Includes disconfirming

RefutedContestedStrong support

consensus score 0.00

⚖️ Thin evidence — read the needle loosely. The score shows which way the studies lean, but there are too few independent, high-quality ones to place it firmly. Expect this to move as better evidence arrives.

📅 Last reviewed: 2026-07-15 ⓘ

Evidence ladder

How far up the ladder this claim has climbed. A high consensus on a low rung means "consistent so far," not "proven in people."

Top evidence so far: Population patterns (Observational)

MechanismIn-vitroAnimalObservationalRCTMeta-analysis

How the studies fall

1 support 1 contradict 0 tested null 2 mixed · 4 sources, 2 independent groups

What the evidence shows

The MTHFR C677T TT genotype is associated with lower serum vitamin D in women with PCOS; low vitamin D was in turn flagged as an independent risk factor for hyperhomocysteinaemia.

The evidence (4)

Source	Grade	Stance	Quality	Finding
Zhou R et al 2025 · study_type: observational	observational	supports	moderate	n=6344 infertility clinic: CT/TT higher vit-D-deficiency risk (p<0.001) BUT no sun/seasonal adjustment, single population, no direct MTHFR->vitD mechanism, Hcy mediates only 16-42% -> likely CONFOUNDED, not causal.
mazokopakis-2023 2023	observational	mixed	moderate	Cross-sectional healthy adults: 25(OH)D vs MTHFR genotype + folate/B12/Hcy - tests but does not cleanly confirm a genotype->vitamin-D depletion link.
epic-folate-2004 2004	observational	contradicts	moderate	EPIC-Potsdam: MTHFR 677TT had ELEVATED erythrocyte folate vs CT - disconfirms the simple 'TT depletes 1-carbon/fat-soluble cofactors' intuition behind a genotype->low-vitamin-D mechanism.
Zhao J, Li X, Chen Q 2024 · Gene	observational	mixed	low	Within PCOS: TT vitamin D < CC (P<0.001) BUT TT vs CT non-significant (P=0.172). The robust signal is vitamin D ↔ homocysteine (r=−0.281, P=0.004); paper frames LOW vitamin D as an independent risk factor FOR hyperhomocysteinaemia (adj OR 1.372), i.e. direction is not cleanly genotype→vitamin-D.

Disagree, or know a study we missed?

We grade by evidence, not opinions. The way to weigh in is to point us to a study we haven't cited (check the evidence table above first), or to flag a problem with one we have. Every submission is reviewed; if it holds up, the grade updates and shows in Science Changes Its Mind.

📚 Suggest a study ⚑ Flag / request reclassification

Opens a short form. You'll sign in with Google so submissions are tied to a real account — we don't display your identity, and we only accept a link we can verify (PubMed, DOI, ClinicalTrials.gov).

Educational only, not medical advice. Grades and scores reflect published evidence weighted by study design and quality; see the methodology.