Folate for Cardiovascular Disease
Verdict: Insufficient Evidence
Across 6 PubMed studies, the evidence for Folate in Cardiovascular Disease grades Tier D — counter-evidence. Research is still too limited to draw a firm conclusion.
D 🔴 D Counter-Evidence Insufficient Evidence
Why this grade7-layer evidence engine
⚖️
Scoring transparency
All scores computed by a 7-layer evidence engine — fully auditableRaw score 0.45
D
C
B
A
S
← counter-evidence / ineffectiveeffective / strong evidence →
Final grade
D · Insufficient Evidence
Confidence
86%
Highly consistent evidence
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 = 0.448
- tier_from_score — 依分數區間映射至 tier letter
- apply_hec_rules — 高品質 SR/MA 顯示 negative 主導 (2 negative > 1 positive)，下層 RCT 不能推翻
- apply_hec_override — HEC-1 高階證據 negative — 強制由 C 改為 D
- 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 (6)L2 · primary research & systematic reviews
Homocysteine-lowering interventions for preventing cardiovascular events
Finding: B-vitamin/folic acid supplementation showed no effect on myocardial infarction (RR 1.02, 95% CI 0.95-1.10) or all-cause mortality (RR 1.01, 95% CI 0.96-1.06), with only a modest reduction in stroke (RR 0.90, 95% CI 0.82-0.99); all three outcomes graded high-quality evidence.
View on PubMed Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial
Finding: Adding 0.8 mg folic acid to enalapril significantly reduced first stroke versus enalapril alone over 4.5 years (2.7% vs 3.4%; HR 0.79, 95% CI 0.68-0.93), in a low-folate, non-grain-fortified population.
View on PubMed Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials
Finding: Folic acid produced a small overall CVD reduction (RR 0.96, 95% CI 0.92-0.99, P=0.02) driven by stroke (RR 0.90, 95% CI 0.84-0.96, P=0.002), with no effect on coronary heart disease (RR 1.04, 95% CI 0.99-1.09, P=0.16).
View on PubMed Effect of folic acid supplementation on cardiovascular outcomes: a systematic review and meta-analysis
Finding: Folic acid supplementation had no significant effect on major cardiovascular events (RR 0.98, 95% CI 0.93-1.04), stroke (RR 0.89, 95% CI 0.78-1.01), myocardial infarction (RR 1.00, 95% CI 0.93-1.07), or all-cause mortality (RR 1.00, 95% CI 0.96-1.05).
View on PubMed Folic acid for the primary prevention of stroke: a systematic review and meta-analysis
Finding: Folic acid supplementation overall did not significantly prevent first stroke (RR 0.92, 95% CI 0.80-1.05), but was effective in regions without grain fortification (RR 0.78, 95% CI 0.68-0.89).
View on PubMed Efficacy of folic acid supplementation in the prevention of cardiovascular disease - a systematic review and meta-analysis
Finding: Folic acid produced a modest CVD reduction (RR 0.95, 95% CI 0.90-0.99, P=0.04) and a stroke reduction (RR 0.85, 95% CI 0.76-0.96, P<0.01), with no benefit for mortality, coronary heart disease, peripheral arterial disease, or lipid profile.
View on PubMed Regulatory & authoritative positionsL4/L5 · FDA / EMA / NIH ODS / Cochrane / Mayo …
L4a US FDA
Supportive
Health claims relating folate to risk of neural tube defects may be made on the label or in labeling of foods, including dietary supplements, provided that the requirements in this section are met. source↗
L4b EU EFSA
Supportive
L4c UK NHS
Neutral
It's recommended that all women who could get pregnant should take a 400 microgram folic acid supplement daily before pregnancy and until they're 12 weeks pregnant. source↗
L4d TW TFDA / 衛福部
Supportive
孕期缺乏葉酸，會增加胎兒腦及脊髓先天性神經管缺陷的風險。育齡婦女及準備懷孕婦女可在準備階段每日攝取400微克，懷孕期間每日攝取600微克。 source↗
L4e WHO
Neutral
Current evidence suggests that folic acid supplementation in the periconceptional period, either alone or in combination with other vitamins and minerals, can prevent neural tube defects. source↗
L5a NIH Office of Dietary Supplements
Supportive
L5b Mayo Clinic
Cautious
High levels of homocysteine are associated with an increased risk of cardiovascular disease, which led researchers to theorize that reducing homocysteine with folic acid therapy would also reduce cardiovascular risk. However, although taking folic acid reduces the level of homocysteine and provides protection against stroke, it doesn't appear to decrease deaths from heart attack or other cardio… source↗
L5c Cleveland Clinic
Cautious
Healthcare providers may prescribe B9 to lower high blood levels of homocysteine, a chemical that builds proteins (amino acids) that can harden your arteries. Both high and low levels of homocysteine (compared with moderate levels) have been associated with an increased risk of death from cardiovascular disease. But the exact link between folic acid and heart disease remains unclear. source↗
L5d Harvard Health
Cautious
Until recently, experts hoped that lowering homocysteine with folic acid and vitamin B6 and B12 supplements would lead to fewer heart attacks and cardiovascular events. But several large trials have been disappointing. For now, the American Heart Association doesn't recommend folic acid and B vitamin supplements to reduce the risk of heart attack or stroke. source↗
L5e Specialty Society (condition-mapped)
Cautious
treatment with folic acid was not associated with a reduction in the primary composite endpoint of all-cause mortality or vascular event. Based on the totality of the randomized trial data to date, homocysteine lowering with vitamin B and folic acid supplementation does not appear to be an effective secondary prevention strategy for patients with coronary heart disease. source↗