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 · Front Nutr	observational	supports	moderate	n=6,344 infertility clinic (Guangzhou): vitamin-D deficiency 23.9% (CC) / 27.8% (CT) / 29.7% (TT), p<0.001; adjusted OR CT 1.229 (1.089-1.386) and TT 1.355 (1.109-1.657) in model 2, which DID adjust for season of blood collection plus age, BMI, AMH, infertility type/cause and haemoglobin. Effect is small in absolute terms (median 25(OH)D 62.4 -> 61.0 nmol/L) and absent in women >=35y. Residual objections: no measured sun exposure, dietary/supplemental vitamin D intake, smoking or physical activity; all participants already on folic acid of unknown dose; single centre, single ethnicity.
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 was 'less than that in the CC (P < 0.001) and CT (P = 0.172) groups' — significant only at the TT-vs-CC extreme and null at TT-vs-CT, while the paper's Conclusions overstate both contrasts as significant. The robust signal is the vitamin-D/homocysteine correlation: vitamin D 'correlated with homocysteine levels in all PCOS patients (r = -0.281,' P = 0.004). The multivariate line reads 'for hyperhomocysteinaemia (adjusted OR 1.372, 95 % CI: 1.100-1.712).' for vitamin D concentration, but the exposure coding is not given, so the direction of that OR cannot be told from the abstract — the earlier gloss of it as 'LOW vitamin D is the risk factor' is an interpretation the text does not carry. Stance stays mixed, quality low (abstract-only).

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