Document Detail


Effects of folic acid supplementation on overall and site-specific cancer incidence during the randomised trials: meta-analyses of data on 50,000 individuals.
MedLine Citation:
PMID:  23352552     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Some countries fortify flour with folic acid to prevent neural tube defects but others do not, partly because of concerns about possible cancer risks. We aimed to assess any effects on site-specific cancer rates in the randomised trials of folic acid supplementation, at doses higher than those from fortification.
METHODS: In these meta-analyses, we sought all trials completed before 2011 that compared folic acid versus placebo, had scheduled treatment duration at least 1 year, included at least 500 participants, and recorded data on cancer incidence. We obtained individual participant datasets that included 49,621 participants in all 13 such trials (ten trials of folic acid for prevention of cardiovascular disease [n=46,969] and three trials in patients with colorectal adenoma [n=2652]). All these trials were evenly randomised. The main outcome was incident cancer (ignoring non-melanoma skin cancer) during the scheduled treatment period (among participants who were still free of cancer). We compared those allocated folic acid with those allocated placebo, and used log-rank analyses to calculate the cancer incidence rate ratio (RR).
FINDINGS: During a weighted average scheduled treatment duration of 5·2 years, allocation to folic acid quadrupled plasma concentrations of folic acid (57·3 nmol/L for the folic acid groups vs 13·5 nmol/L for the placebo groups), but had no significant effect on overall cancer incidence (1904 cancers in the folic acid groups vs 1809 cancers in the placebo groups, RR 1·06, 95% CI 0·99–1·13, p=0·10). There was no trend towards greater effect with longer treatment. There was no significant heterogeneity between the results of the 13 individual trials (p=0·23), or between the two overall results in the cadiovascular prevention trials and the adenoma trials (p=0·13). Moreover, there was no significant effect of folic acid supplementation on the incidence of cancer of the large intestine, prostate, lung, breast, or any other specific site.
INTERPRETATION: Folic acid supplementation does not substantially increase or decrease incidence of site-specific cancer during the first 5 years of treatment. Fortification of flour and other cereal products involves doses of folic acid that are, on average, an order of magnitude smaller than the doses used in these trials.
FUNDING: British Heart Foundation, Medical Research Council, Cancer Research UK, Food Standards Agency.
Authors:
Stein Emil Vollset; Robert Clarke; Sarah Lewington; Marta Ebbing; Jim Halsey; Eva Lonn; Jane Armitage; JoAnn E Manson; Graeme J Hankey; J David Spence; Pilar Galan; Kaare H Bønaa; Rex Jamison; J Michael Gaziano; Peter Guarino; John A Baron; Richard F A Logan; Edward L Giovannucci; Martin den Heijer; Per M Ueland; Derrick Bennett; Rory Collins; Richard Peto;
Publication Detail:
Type:  Journal Article; Meta-Analysis; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Lancet     Volume:  381     ISSN:  1474-547X     ISO Abbreviation:  Lancet     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-06-17     Completed Date:  2013-06-27     Revised Date:  2014-02-20    
Medline Journal Info:
Nlm Unique ID:  2985213R     Medline TA:  Lancet     Country:  England    
Other Details:
Languages:  eng     Pagination:  1029-36     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Carcinogens / administration & dosage*
Dietary Supplements / adverse effects*
Female
Folic Acid / administration & dosage,  adverse effects*
Humans
Incidence
Male
Middle Aged
Neoplasms / chemically induced*,  epidemiology
Randomized Controlled Trials as Topic
Grant Support
ID/Acronym/Agency:
MC_U137686861//Medical Research Council; R01 CA059005/CA/NCI NIH HHS; //British Heart Foundation; //Cancer Research UK; //Medical Research Council
Chemical
Reg. No./Substance:
0/Carcinogens; 935E97BOY8/Folic Acid
Investigator
Investigator/Affiliation:
J Armitage / ; L Bowman / ; R Clarke / ; S Parish / ; R Peto / ; R Collins / ; E Lonn / ; S Yusuf / ; J E Manson / ; R Glynn / ; F Grodstein / ; C M Albert / ; N R Cook / ; G Hankey / ; J W Eikelboom / ; J Toole / ; M R Malinow / ; L E Chambless / ; J D Spence / ; L C Pettigrew / ; V J Howard / ; E G Sides / ; C H Wang / ; M Stampfer / ; P Galan / ; S Hercberg / ; O Nygård / ; M Ebbing / ; J E Nordrehaug / ; D W T Nilsen / ; P M Ueland / ; H Refsum / ; S E Vollset / ; K H Bønaa / ; I Njølstad / ; R Jamison / ; J M Gaziano / ; P Guarino / ; J A Baron / ; E A Giovannucci / ; R F A Logan / ; M denHeijer / ; H Blom / ; G Bos / ; R Clarke / ; J Halsey / ; S Lewington / ; D Bennett / ; R Collins / ; R Peto /
Comments/Corrections
Comment In:
Lancet. 2013 Mar 23;381(9871):974-6   [PMID:  23352551 ]

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