Vitamin B6 (Pyridoxine / Pyridoxal-5'-Phosphate) for Homocysteine
Verdict: Does not work; lowers homocysteine but not cardiovascular risk
Vitamin B6 does not prevent heart attacks, strokes, or cardiovascular death by lowering homocysteine, and on its own it barely lowers homocysteine at all. Large, high-quality trials and meta-analyses consistently find no clinical benefit, so this use is not supported.
D 🔴 D Counter-Evidence Counter-Evidence
Why this grade7-layer evidence engine
This earns a counter-evidence (D) grade because it is a textbook case of a moved biomarker that does not translate into better outcomes. B-vitamin regimens lower plasma homocysteine by roughly 25%, but B6 is not the active agent: in the NORVIT trial (PMID 16531613) the B6-alone arm (40 mg) produced essentially no homocysteine drop, and the SEARCH trial (PMID 20571015) achieved a 28% reduction using folate plus B12 with no B6 at all.
On hard clinical endpoints the evidence is uniformly null. The largest B6-containing stroke trial, VITATOPS (PMID 20688574, n=8,164), showed only a borderline composite result (RR 0.91, CI 0.82-1.00) with every individual endpoint non-significant; VISP (PMID 14762035) and HOPE-2 (PMID 16531614) were also null. Two of the strongest syntheses seal the verdict: Clarke's individual-participant meta-analysis (PMID 20937919, n=37,485, RR 1.01) and the 2017 Cochrane review (PMID 28816346, n=71,422, MI RR 1.02).
Regulators and major clinics agree. The American Heart Association and allied guidelines (cited via L5e) recommend neither B-vitamin supplementation nor homocysteine screening for cardiovascular prevention, and the NHS does not endorse B6 for cardiovascular claims. There is also a real safety caveat: HOPE-2's high-dose 50 mg B6 arm showed a significant rise in unstable-angina hospitalisation (RR 1.24), and chronic high-dose B6 can cause sensory peripheral neuropathy, which is why EFSA and the NHS set conservative upper limits.
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Scoring transparency
All scores computed by a 7-layer evidence engine — fully auditableRaw score 0.29
D
C
B
A
S
← counter-evidence / ineffectiveeffective / strong evidence →
Final grade
D · Counter-Evidence
Confidence
76%
Broadly consistent
Evidence level
E1
Cochrane high-quality SR/MA
▸View the full decision path (audit trail)
- compute_raw_score — 加權公式: L2×0.30 + L3×0.25 + L5×0.25 + L11×0.10 + L1×0.10 = 0.286
- tier_from_score — 依分數區間映射至 tier letter
- apply_hec_rules — 高階證據未達主導 (0 positive vs 1 negative)，由 raw_score 決定
- tier_strict_requirement_check — Tier 條件達標，未降階
- detect_disputes — 偵測到 0 個 hard + 0 個 soft dispute
- decide_status — 依 tier + dispute 結果決定 status
PubMed studies (7)L2 · primary research & systematic reviews
B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial
Finding: Daily B6 25 mg + folate 2 mg + B12 0.5 mg lowered homocysteine but did not reduce the primary composite of stroke, MI, or vascular death (15% B-vitamin arm vs 17% placebo; RR 0.91, 95% CI 0.82-1.00, p=0.05). Individual endpoints (stroke, MI, vascular death) all non-significant on their own. Largest stroke-specific trial of B6-containing regimen; net result null on hard outcomes despite Hcy reduction.
View on PubMed Homocysteine lowering and cardiovascular events after acute myocardial infarction (NORVIT trial, Bonaa et al., NEJM)
Finding: Critical for B6-alone evidence: the B6-monotherapy arm (40 mg pyridoxine alone, no folate/B12) produced essentially NO homocysteine lowering and showed no benefit on the primary composite (17.1% B6-alone vs 16.2% placebo; RR 1.14, 95% CI 0.93-1.39). The triple-combination arm (folate + B12 + B6) showed a borderline harmful signal (RR 1.22, p=0.05). Conclusion: B6 alone is biochemically ineffective at lowering Hcy and provides no CV benefit; adding high-dose B6 to folate + B12 does not improve clinical outcomes and may worsen them.
View on PubMed Homocysteine lowering with folic acid and B vitamins in vascular disease (HOPE-2 trial, Lonn et al., NEJM)
Finding: Combination including B6 50 mg reduced mean plasma homocysteine 2.4 µmol/L. Primary composite RR 0.95 (95% CI 0.84-1.07, p=0.41) - null. Stroke modestly reduced (RR 0.75, 95% CI 0.59-0.97) but hospitalization for unstable angina significantly increased (RR 1.24, 95% CI 1.04-1.49). B6 contribution to net effect cannot be isolated from folate/B12 in this design. Trial included high-dose B6 (50 mg) without evidence of clear benefit on hard endpoints.
View on PubMed Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death (VISP trial, Toole et al., JAMA)
Finding: High-dose regimen including B6 25 mg lowered homocysteine ~2 µmol/L more than low-dose arm. Recurrent ischemic stroke equivalent between arms (HR 1.0, 95% CI 0.8-1.3); composite vascular endpoint also null (HR 1.0, 95% CI 0.8-1.1). The B6 dose differential (25 mg vs 0.2 mg) is large but contributed minimally to Hcy lowering (folate is the dominant Hcy-lowering agent). No clinical benefit attributable to B6 dose.
View on PubMed Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors (SEARCH trial, Armitage et al., JAMA)
Finding: Included as comparison: SEARCH used folate + B12 WITHOUT B6 and reduced homocysteine by 28% (3.8 µmol/L) - confirming folate + B12 (not B6) is the active Hcy-lowering combination. Primary major vascular event RR 1.04 (95% CI 0.97-1.12, p=0.28) - null. This trial demonstrates that excluding B6 does not reduce Hcy-lowering effect, reinforcing that B6 contributes negligibly to homocysteine reduction in repleted populations.
View on PubMed Effects of lowering homocysteine levels with B vitamins on cardiovascular disease, cancer, and cause-specific mortality: Meta-analysis of 8 randomized trials involving 37 485 individuals
Finding: Allocation to B-vitamin supplementation (most regimens included B6 20-50 mg) reduced homocysteine 25% on average. No effect on major vascular events (RR 1.01, 95% CI 0.96-1.07), coronary events (RR 1.01, 95% CI 0.95-1.07), stroke (RR 0.96, 95% CI 0.87-1.06), cancer (RR 1.05, 95% CI 0.98-1.13), or all-cause mortality (RR 1.02). Subgroup analysis: no benefit detected for any trial regimen variant including those with high-dose B6. Definitive null result across 37,485 participants.
View on PubMed Homocysteine-lowering interventions for preventing cardiovascular events (Cochrane systematic review, Marti-Carvajal et al.)
Finding: Pooled 15 RCTs (n=71,422) including all major B6-containing regimens: no effect on non-fatal/fatal MI (RR 1.02, 95% CI 0.95-1.10; high-quality evidence), all-cause mortality (RR 1.01, 95% CI 0.96-1.06), or cardiovascular mortality. Borderline stroke reduction (RR 0.90, 95% CI 0.82-0.99) driven by trials in non-fortified regions (especially Chinese CSPPT, which used folate alone WITHOUT B6). Authors conclude no convincing evidence supporting homocysteine-lowering (including B6-containing regimens) for CV event prevention.
View on PubMed Regulatory & authoritative positionsL4/L5 · FDA / EMA / NIH ODS / Cochrane / Mayo …
L4a US FDA
Supportive
PYRIDOXINE — CAS 65-23-6 — SCOGS no. 100 — 21 CFR 101.9, 170.3(o) — Generally Recognized as Safe (referenced via SCOGS); permitted use: NUTRIENT SUPPLEMENT. source↗
L4b EU EFSA
Supportive
the Panel established a tolerable upper intake level (UL) for vitamin B6 of 12.5 mg/day for adults, including pregnant and lactating women source↗
L4c UK NHS
Cautious
Taking 200mg or more a day of vitamin B6 can lead to a loss of feeling in the arms and legs known as peripheral neuropathy. ... Do not take more than 10mg of vitamin B6 a day in supplements unless advised to by a doctor. source↗
L4d TW TFDA / 衛福部
Supportive
維生素B6成人每日建議攝取量為1.5毫克，上限攝取量為80毫克 source↗
L4e WHO
Cautious
From 1 June 2027, oral preparations containing 50 mg or less per recommended daily dose will continue to be available for general retail sale. Oral preparations containing more than 50 mg but not more than 200 mg per recommended daily dose will be available over the counter with the advice of a pharmacist. Oral preparations containing more than 200 mg per recommended daily dose will continue to… source↗
L5a NIH Office of Dietary Supplements
Supportive
The American College of Obstetrics and Gynecology (ACOG) recommends monotherapy with 10–25 mg of vitamin B6 three or four times a day to treat nausea and vomiting in pregnancy. source↗
L5c Cleveland Clinic
Cautious
L5d Harvard Health
Neutral
L5e Specialty Society (condition-mapped)
Against
Current guidelines, such as the American Heart Association (AHA), do not recommend neither B-vitamin supplementation nor routine screening for elevated homocysteine levels. source↗