Folate and global health umbrella review series, part 2: syntheses on cancers

TY - JOUR

T1 - Folate and global health umbrella review series, part 2

T2 - syntheses on cancers

AU - Yoo, Samantha

AU - Montazeri, Azita

AU - Bennett, Derrick

AU - Bo, Yacong

AU - Chen, Peizhan

AU - Duthie, Susan

AU - Jensen, Natalie

AU - Kaminga, Atipatsa

AU - Lai, Jun Shi

AU - Li, Xue

AU - MacFarlane, Amanda J.

AU - Martinez, Homero

AU - McNulty, Helene

AU - Momoli, Franco

AU - Mossey, Peter

AU - Mullie, Patrick

AU - Munger, Ron

AU - Parajuli, Rajendra Prasad

AU - Kent, Monique Potvin

AU - Rubini, Michele

AU - Senekal, Marjanne

AU - Sikora, Lindsey

AU - Stintzi, Alain

AU - Theodoratou, Evropi

AU - Wang, Hui

AU - Yajnik, Chittaranjan

AU - Yaktine, Ann

AU - Little, Julian

N1 - Publisher Copyright: Copyright © 2026 by the Journal of Global Health. All rights reserved.

PY - 2026/2/20

Y1 - 2026/2/20

N2 - Background: Folate has been examined extensively in relation to carcinogenesis due to its role in one-carbon metabolism impacting the synthesis of DNA and RNA, methylation processes, and genomic integrity. Current evidence on the relationship between folate status and the risk of cancer is equivocal: low or deficient folate status may contribute to an increased risk of cancers, while high-dose folic acid supplementation may have adverse effects on carcinogenesis. Methods: We searched MEDLINE, Embase, CINAHL, the Cochrane Library, and the Database of Abstracts of Reviews of Effects up to February 2024 for systematic reviews and meta-analyses investigating the associations of folate (measured as dietary intake, supplementation, or blood concentrations) with any specific cancer outcome. Screening, data extraction, and risk of bias assessment were performed in duplicate. We assessed the credibility of the evidence using predefined criteria. Results: We found 67 syntheses, of which 57 provided meta-analyses. Over half of the syntheses had a high risk of bias. We identified 168 unique associations (unique exposure - unique outcome - unique setting) across 10 cancer types, 3 system cancers, and total cancer. Of these, we assessed 15 directional associations (colorectal, oesophageal, and total cancers) to be at a highly suggestive level of credibility, and 17 directional and 10 null associations to be at a suggestive level of credibility. Conclusions: The available evidence for each category of unique association was generally limited. Highly suggestive associations were found for oesophageal, colorectal, childhood brain and spinal tumours and total cancers. More robust primary studies are warranted to follow-up the signal of a positive relationship reported for prostate cancer warranting further research. Evidence was weak for all but colorectal and oesophageal cancers, or the central nervous system cancers in children. Registration: PROSPERO: CRD42021265041.

AB - Background: Folate has been examined extensively in relation to carcinogenesis due to its role in one-carbon metabolism impacting the synthesis of DNA and RNA, methylation processes, and genomic integrity. Current evidence on the relationship between folate status and the risk of cancer is equivocal: low or deficient folate status may contribute to an increased risk of cancers, while high-dose folic acid supplementation may have adverse effects on carcinogenesis. Methods: We searched MEDLINE, Embase, CINAHL, the Cochrane Library, and the Database of Abstracts of Reviews of Effects up to February 2024 for systematic reviews and meta-analyses investigating the associations of folate (measured as dietary intake, supplementation, or blood concentrations) with any specific cancer outcome. Screening, data extraction, and risk of bias assessment were performed in duplicate. We assessed the credibility of the evidence using predefined criteria. Results: We found 67 syntheses, of which 57 provided meta-analyses. Over half of the syntheses had a high risk of bias. We identified 168 unique associations (unique exposure - unique outcome - unique setting) across 10 cancer types, 3 system cancers, and total cancer. Of these, we assessed 15 directional associations (colorectal, oesophageal, and total cancers) to be at a highly suggestive level of credibility, and 17 directional and 10 null associations to be at a suggestive level of credibility. Conclusions: The available evidence for each category of unique association was generally limited. Highly suggestive associations were found for oesophageal, colorectal, childhood brain and spinal tumours and total cancers. More robust primary studies are warranted to follow-up the signal of a positive relationship reported for prostate cancer warranting further research. Evidence was weak for all but colorectal and oesophageal cancers, or the central nervous system cancers in children. Registration: PROSPERO: CRD42021265041.

UR - https://www.scopus.com/pages/publications/105030785804

U2 - 10.7189/jogh.16.04102

DO - 10.7189/jogh.16.04102

M3 - Article

C2 - 41718012

AN - SCOPUS:105030785804

SN - 2047-2978

VL - 16

SP - 4102

JO - Journal of Global Health

JF - Journal of Global Health

ER -