Evidence map›Paper›PMID 9569395›Full record

SynthesisBMJ (Clinical research ed.)1998

Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists' Collaboration.

3 registry-linked trialsOpen access · greenAbstract readMeta-Analysis
PubMed Full text at PMC
In one paragraph

Synthesis in BMJ (Clinical research ed.), 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 190 papers, 21 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
190citing papers in PubMed, 21 pooled it
3.6field-weighted citation impact, top 7% 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.

NCT03472508 phase4unknown statusnot on this mapstarted 2018, after this paper: background citation

A Randomized, Double-Blind, Controlled Trial on the Homocysteine-Lowering Effects of Different Doses of Folic Acid Among Patients With Hypertension According to Methylenetetrahydrofolate Reductase C677T Genotypes

TypeinterventionalSponsorShenzhen Ausa Pharmed Co.,LtdRan2018 to 2019Enrolled3,600ConditionsHypertensionArmsFolic Acid, Enalapril Maleate and Folic Acid Tablets (Yiye), Enalapril
NCT04974138 phase4recruitingnot on this mapstarted 2024, after this paper: background citation

Comparative Efficacy of Amlodipine Folic Acid vs. Amlodipine on the Risk of First Ischemic Stroke Among Participants With H-type Hypertension and MTHFR 677 CC/CT Genotype: A Multi-center, Randomized, Double-blind, Double-dummy, Controlled Clinical Trial

TypeinterventionalSponsorShenzhen Ausa Pharmed Co.,LtdRan2024 to 2030Enrolled32,000ConditionsHypertension, MTHFR 677 CC or CT Genotype, Elevated Plasma Homocysteine (Hcy≥10µmol/L), Insufficient Plasma Folate Levels (<12ng/mL)ArmsAmlodipine besylate, Amlodipine besylate and folic acid, Amlodipine placebos, Amlodipine-folic acid placebos
NCT04974151 phase4recruitingnot on this mapstarted 2024, after this paper: background citation

Comparative Efficacy of Amlodipine Folic Acid vs. Amlodipine on the Risk of First Ischemic Stroke Among Participants With Hypertension and MTHFR 677 TT Genotype: A Multi-center, Randomized, Double-blind, Triple-dummy, Controlled Clinical Trial

TypeinterventionalSponsorShenzhen Ausa Pharmed Co.,LtdRan2024 to 2029Enrolled24,000ConditionsHypertension, MTHFR 677 TT GenotypeArmsAmlodipine besylate, Amlodipine besylate And Folic Acid, 5-methyltetrahydrofolate (5-MTHF), Amlodipine placebo, Amlodipine folic acid placebo
3 · Its place in the literature

Who cites it

190 citing papers in PubMed, 21 syntheses or guidelines pooled it, 181 citations in OpenAlex.

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  6. Folate supplementation in people with sickle cell disease.The Cochrane database of systematic reviews · 2018
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  8. Folate supplementation in people with sickle cell disease.The Cochrane database of systematic reviews · 2016
    Pooled it
  9. Individually modifiable risk factors to ameliorate cognitive aging: a systematic review and meta-analysis.Climacteric : the journal of the International Menopause Society · 2015
    Pooled it
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  11. Effect of B vitamin (folate, B6, and B12) supplementation on osteoporotic fracture and bone turnover markers: a meta-analysis.Medical science monitor : international medical journal of experimental and clinical research · 2015
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  19. A strategy to reduce cardiovascular disease by more than 80%.BMJ (Clinical research ed.) · 2003 · on this map
    Pooled it
  20. Folate for depressive disorders.The Cochrane database of systematic reviews · 2003
    Pooled it

130 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

0 authors.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveTo determine the size of reduction in homocysteine concentrations produced by dietary supplementation with folic acid and with vitamins B-12 or B-6.

designMeta-analysis of randomised controlled trials that assessed the effects of folic acid based supplements on blood homocysteine concentrations. Multivariate regression analysis was used to determine the effects on homocysteine concentrations of different doses of folic acid and of the addition of vitamin B-12 or B-6. SUBJECTS: Individual data on 1114 people included in 12 trials.

findingsThe proportional and absolute reductions in blood homocysteine produced by folic acid supplements were greater at higher pretreatment blood homocysteine concentrations (P < 0.001) and at lower pretreatment blood folate concentrations (P < 0.001). After standardisation to pretreatment blood concentrations of homocysteine of 12 mumol/l and of folate of 12 nmol/l (approximate average concentrations for Western populations), dietary folic acid reduced blood homocysteine concentrations by 25% (95% confidence interval 23% to 28%; P < 0.001), with similar effects in the range of 0.5-5 mg folic acid daily. Vitamin B-12 (mean 0.5 mg daily) produced an additional 7% (3% to 10%) reduction in blood homocysteine. Vitamin B-6 (mean 16.5 mg daily) did not have a significant additional effect.

conclusionsTypically in Western populations, daily supplementation with both 0.5-5 mg folic acid and about 0.5 mg vitamin B-12 would be expected to reduce blood homocysteine concentrations by about a quarter to a third (for example, from about 12 mumol/l to 8-9 mumol/l). Large scale randomised trials of such regimens in high risk populations are now needed to determine whether lowering blood homocysteine concentrations reduces the risk of vascular disease.

Indexed as

Food, FormulatedAdultAgedDose-Response Relationship, DrugFemaleFolic AcidHematinicsHomocysteineHumansMaleMiddle AgedMultivariate AnalysisPyridoxineRandomized Controlled Trials as TopicVitamin B 12Folic AcidHematinicsHomocysteinePyridoxineVitamin B 12

Identifiers

PMID9569395
PMCPMC28491
OpenAlexW4300941274

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.