Evidence map›Paper›PMID 27528407›Full record

SynthesisJournal of the American Heart Association2016

Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta-Analysis of Randomized Controlled Trials.

Yanping Li, Tianyi Huang, Yan Zheng, Tauland Muka, Jenna Troup, Frank B Hu

Open access · goldAbstract readMeta-AnalysisReview
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Journal of the American Heart Association, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
119citing papers in PubMed, 8 pooled it
19.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

119 citing papers in PubMed, 8 syntheses or guidelines pooled it, 261 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
  7. Pooled it
  8. Pooled it
  9. Trial
  10. Trial
  11. Article
  12. Article
  13. Article
  14. Review
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. Common Methylenetetrahydrofolate Reductase PolymorphismDiagnostics (Basel, Switzerland) · 2025
    Article

59 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 2 countries.

Yanping LiDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
Tianyi HuangDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Yan ZhengDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
Tauland MukaDepartment of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
Jenna TroupDepartment of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
Frank B HuDepartment of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA nhbfh@channing.harvard.edu.
Harvard University · USBrigham and Women's Hospital · USErasmus MC · NLErasmus University Rotterdam · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundResults from observational and genetic epidemiological studies suggest that lower serum homocysteine levels are associated with lower incidence of cardiovascular disease (CVD). Numerous randomized controlled trials have investigated the efficacy of lowering homocysteine with folic acid supplementation for CVD risk, but conflicting results have been reported. METHODS AND

resultsThree bibliographic databases (Medline, Embase, and the Cochrane Database of Systematic Reviews) were searched from database inception until December 1, 2015. Of the 1933 references reviewed for eligibility, 30 randomized controlled trials involving 82 334 participants were included in the final analysis. The pooled relative risks of folic acid supplementation compared with controls were 0.90 (95% CI 0.84-0.96; P=0.002) for stroke, 1.04 (95% CI 0.99-1.09; P=0.16) for coronary heart disease, and 0.96 (95% CI 0.92-0.99; P=0.02) for overall CVD. The intervention effects for both stroke and combined CVD were more pronounced among participants with lower plasma folate levels at baseline (both P<0.02 for interaction). In stratified analyses, a greater beneficial effect for overall CVD was seen in trials among participants without preexisting CVD (P=0.006 for interaction) or in trials with larger reduction in homocysteine levels (P=0.009 for interaction).

conclusionsOur meta-analysis indicated a 10% lower risk of stroke and a 4% lower risk of overall CVD with folic acid supplementation. A greater benefit for CVD was observed among participants with lower plasma folate levels and without preexisting CVD and in studies with larger decreases in homocysteine levels. Folic acid supplementation had no significant effect on risk of coronary heart disease.

Indexed as

AgedCardiovascular DiseasesCoronary DiseaseDietary SupplementsFemaleFolic AcidHumansHyperhomocysteinemiaMaleMiddle AgedRandomized Controlled Trials as TopicRisk FactorsStrokeFolic Acidcardiovascular disease preventionfolatestroke prevention

Identifiers

PMID27528407
PMCPMC5015297
OpenAlexW2514342691

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.