Table 1

Characteristics of included RCTs

Study	Participants N: total (N_tot), folic acid (N_int); country	Population characteristics intervention/control group: sex (% females); age in years (mean ± SD); characteristics; % smokers	Intervention/control	Time of treatment/follow-up months	Outcomes
Logan (2008)22 (ukCAP)	N_tot: 939, N_int: 470; UK, Denmark	% F: 39/42; mean age: 58±9/58±9; colorectal adenoma^*; % smokers: not reported	Folic acid 0.5 mg/day ±aspirin/placebo ± aspirin	36^†/36	Total and site-specific cancer incidence
Wu (2009)23	N_tot: 672, N_int: 338; USA	% F: 61/62; mean age:65±7/66±7; colorectal adenoma^*; % smokers: 7/7	Folic acid 1 mg/day/placebo	Mean 64/64 + up to 12	Total and site-specific cancer incidence
Cole (2007)11 (AFPPS)	N_tot: 1021, N_int: 516; USA, Canada	% F: 36/36; mean age: 57±10/57±10; colorectal adenoma^*; % smokers: 15/14	Folic acid 1 mg/day ±aspirin/placebo ± aspirin	Mean 33 + mean 42^‡/75	Total and site-specific cancer incidence
Jamison (2007)24 (HOST)/Clarke (2010)3	N_tot: 2056, N_int: 1032; USA	% F: 2/2; mean age: 65±12/66±12; chronic renal disease; % smokers: 21/19	Folic acid 40 mg/day +vit B12+B6/placebo	Median 38/38	Total cancer incidence
Toole (2004)25 (VISP)/Clarke (2010)3	N_tot: 3680, N_int: 1827; USA, Canada, Scotland	% F: 38/37; mean age: 66±11/66±11; cardiovascular disease; % smokers: 18/16	Folic acid 2.5 mg/day +vitB6+vitB12/folic acid 20 μg +vitB6+vitB12	Mean 20/20	Total cancer incidence
Zhang (2008)26 (WAFACS)	N_tot: 5442, N_int: 2721; USA	% F: 100/100; mean age:63±9/63±9; cardiovascular disease; % smokers: 11/12	Folic acid 2.5 mg/day + vit B12+B6/placebo	Mean 88/88	Total and site-specific cancer incidence and mortality
Ebbing (2009)12 (WENBIT14 + NORVIT13)^§	N_tot 6837, N_int 3411; Norway	% F: 23/24; mean age: 63±11/62±11; cardiovascular disease; % smokers: 38/41	Folic acid 0.8 mg/day +vitB12±vit B6/placebo ±vit B6	Median 39/77	Total and site-specific cancer incidence and mortality
Lonn (2006)27 (HOPE-2)	N_tot: 5522, N_int: 2758; Europe, Canada, USA	% F: 29/28; mean age: 69±7/69±7; cardiovascular disease; % smokers: 11/12	Folic acid 2.5 mg/day + vit B12+B6/placebo	Mean 60/60	Total and site-specific cancer incidence and mortality
SEARCH (2010)28	N_tot 12 064, N_int 6033; UK	% F: 17/17; mean age: 64±9^¶; cardiovascular disease; % smokers: 12/12	Folic acid 2 mg/day + vit B12/placebo	Mean 80/80	Total and site-specific cancer incidence/total cancer mortality
Charles (2004)29/Charles (2005)30	N_tot: 2462, N_int: 485; Scotland	% F: 100/100; mean age: 26±5/26±6; pregnancy; % smokers: 45/46	Folic acid 5 mg/day/placebo	In pregnancy/36 years	Total and breast cancer mortality
Zhu (2003)31	N_tot: 98, N_int: 44; China	% F: 41/30; mean age 57±12/57±11; atrophic gastritis; % smokers: not reported	Folic acid 20 mg/day first year, 20 mg twice weekly second year +vit B12/placebo	12+12/mean 73	Gastrointestinal cancer incidence

↵* Colorectal adenoma: history of colorectal adenoma (removed before randomisation).
↵† Reported as 3 years, no mean given.
↵‡ Cole's study treatment: first period folic acid ± aspirin versus placebo ± aspirin, second period folic acid versus placebo.
↵§ Ebbing's study is a combined analysis with prolonged follow-up of two RCTs13 14 and we count them as two RCTs.
↵¶ SEARCH study mean age given for total participants.
RCT, randomised controlled trial.