Trial reportThe American journal of clinical nutrition2009
A randomized trial on folic acid supplementation and risk of recurrent colorectal adenoma.
Trial report in The American journal of clinical nutrition, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00512850 (The Nurses' Health Study), which is not on this map. Cited by 48 papers, 10 of them syntheses that pooled 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.
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.
The Nurses' Health Study (NHS) and Health Professionals Follow-Up Study (HPFS) Folic Acid Prevention Trial
Who cites it
48 citing papers in PubMed, 10 syntheses or guidelines pooled it, 134 citations in OpenAlex.
- Pooled it
- Chemoprevention of colorectal cancer in individuals with previous colorectal neoplasia: systematic review and network meta-analysis.BMJ (Clinical research ed.) · 2016Pooled it
- Pooled it
- The effects of nutritional interventions on recurrence in survivors of colorectal adenomas and cancer: a systematic review of randomised controlled trials.European journal of clinical nutrition · 2016Pooled it
- Effects and safety of periconceptional oral folate supplementation for preventing birth defects.The Cochrane database of systematic reviews · 2015Pooled it
- Folic acid supplements and colorectal cancer risk: meta-analysis of randomized controlled trials.Scientific reports · 2015Pooled it
- Pooled it
- Meta-analysis: eating frequency and risk of colorectal cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals.Lancet (London, England) · 2013Pooled it
- Effects and safety of periconceptional folate supplementation for preventing birth defects.The Cochrane database of systematic reviews · 2010Pooled it
- Folic acid supplementation and risk of colorectal neoplasia during long-term follow-up of a randomized clinical trial.The American journal of clinical nutrition · 2019Trial
- The association between MTHFR 677C>T genotype and folate status and genomic and gene-specific DNA methylation in the colon of individuals without colorectal neoplasia.The American journal of clinical nutrition · 2013Trial
- Effect of combined folic acid, vitamin B(6), and vitamin B(12) on colorectal adenoma.Journal of the National Cancer Institute · 2012Trial
- Pro-Carcinogenic Implications of Folic Acid Supplementation During Chemically Induced Cutaneous Squamous Cell Carcinoma in Mice.Journal of biochemical and molecular toxicology · 2026Article
- Colorectal adenoma recurrence: an analysis of risk factors and gut microbiota characteristics.BMC gastroenterology · 2026Article
- Biological, dietetic and pharmacological properties of vitamin BNPJ science of food · 2025Review
- Recent Advances on the Role of B Vitamins in Cancer Prevention and Progression.International journal of molecular sciences · 2025Review
- High-dose folic acid use and cancer risk in women who have given birth: A register-based cohort study.Epilepsia · 2025Article
- The use of nutrigenomics and nutritional biomarkers with standard care of long-term recurrent metastatic rectal cancer: a case report.Frontiers in oncology · 2024Article
- Scientific opinion on the tolerable upper intake level for folate.EFSA journal. European Food Safety Authority · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
backgroundEvidence from observational studies suggests that inadequate folate status enhances colorectal carcinogenesis, but results from some randomized trials do not support this hypothesis.
objectiveTo assess the effect of folic acid supplementation on recurrent colorectal adenoma, we conducted a cost-efficient, double-blind, randomized trial among participants of 2 large prospective cohorts, the Health Professionals Follow-Up Study and the Nurses' Health Study.
designParticipants were randomly assigned to receive folic acid (1 mg/d) (n = 338) or placebo (n = 334) for 3-6.5 y. The primary endpoint was any new diagnosis of adenoma during the study period (May 1996-March 2004). Secondary outcomes were adenoma by site and stage and number of recurrent adenomas. Associations were also examined by plasma folate concentrations at baseline.
resultsIncidence of at least one recurrent adenoma was not significantly associated with folic acid supplementation [relative risk (RR): 0.82; 95% CI: 0.59,1.13; P = 0.22]. Among participants with low plasma folate concentrations at baseline (<or=7.5 ng/mL), those randomly assigned to receive folic acid experienced a significant decrease in adenoma recurrence (RR: 0.61; 95% CI: 0.42, 0.90; P = 0.01), whereas for subjects with high folate concentrations at baseline (>7.5 ng/mL), supplemental folic acid had no significant effect (RR: 1.28; 95% CI: 0.82, 1.99; P = 0.27, P(interaction) = 0.01). Contrary to findings from another clinical trial, there was no evidence for an increased risk of advanced or multiple adenomas.
conclusionsOur results do not support an overall protective effect of folic acid supplementation on adenoma recurrence. Folic acid supplementation may be beneficial among those with lower folate concentrations at baseline. This trial was registered at clinical trials.gov as NCT00512850.
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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.