TABLE E.1 Overview of the identified systematic reviews and meta‐analyses of RCTS on the association between folic acid and cancer risk.
| Study Name Ref | Comparison | Vollset et al. (2013) a | Qin et al. (2013) | Wien et al. (2012) | AHRQ, 2021 b | ||||
|---|---|---|---|---|---|---|---|---|---|
| FA | FA + B12 | FA + B12 + B6 | FA + A | P | |||||
|
SEARCH Armitage 2010 |
x | x | x | – | |||||
|
NORVIT Bønaa 2006 |
x | x | x | – | |||||
|
AFPPS Cole 2007 |
x | x | x | x | |||||
|
VITRO e den Heijer 2007 |
x | – | – | – | |||||
|
NORVIT, WENBIT Ebbing 2008 |
x | x | x | – | |||||
|
SU‐FOL‐OM3 f Galan 2010/Andreeva 2012 |
x | x | – (c) | – | |||||
|
VITATOPS Hankey 2012 |
x | x | – | – | |||||
|
BVAIT Hodis 2009 |
‐ | x | – | – | |||||
|
HOST e Jamison 2007 |
x | x | x | – | |||||
|
UkCAP Logan 2008 |
x | x | x | – | |||||
|
HOPE−2 Lonn 2006 |
x | x | x | – | |||||
|
Toole 2004 |
x | x | x | – | |||||
|
B‐PROOF van Wijngaarden, 2014 |
– | – | – | x | |||||
|
NHS/HPFS Wu 2009 |
x | x | x | x | |||||
|
WAFACS Zhang 2008 |
x | x | x | – | |||||
| N studies included | 13 | 13 | 10 | 3 | |||||
| FA arms: Cases/total (%) | 1904/24,799 (7.7%) | 1914/24,692 (7.8%) | 1639/19,107 (8.6%) | 144/2315 (6.2%) | |||||
| P arms: Cases/total (%) | 1809/24,822 (7.3%) | 1827/24,714 (7.4%) | 1545/19,128 (8.1%) | 102/2297 (4.4%) | |||||
| Pooled RR (95% CI) | 1.06, 95% CI 0.99–1.13, p = 0.10, I 2 15.26% | 1.05, 95% CI 0.99–1.11, p = 0.13 | 1.07, 95% CI 1.00 to 1.14, I 2 0% | 1.42, 95% CI 1.10 to 1.84, I2 0% | |||||
Abbreviations: A, aspirin; B6, vitamin B6; B12, vitamin B12/cobalamin CI, confidence interval; FA, folic acid (except in SU‐FOL‐OM3, in which 5‐MTHF was used); I2, heterogeneity index; MI, Myocardial infraction; N, count; P, placebo; RCT, randomised controlled trial; RR, relative risk.
Pooled analysis of individual data by the B‐Vitamin Treatment Trialists' Collaboration.
Included studies with FA alone or in combination with cobalamin (combinations with other nutrients excluded); excluded studies with dose >UL or in which >10% individuals had active/current cardiovascular disease, diabetes mellitus or cancer
Included in a sensitivity analysis: RR 1.08, 95% CI 1.01–1.1.
Compared combination of FA + vitamin B6 + cobalamin at high versus low doses.
Data unpublished.
Also included concomitant supplementation with Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA).