Reference Study Country Duration Funding	Design	Subject characteristics at baseline a	Intervention a	Endpoint assessed	Results
Qin et al. (2017) CSPPT China 4.5 yrs 2008–2013 Mixed	RCT, multi‐community Inclusion criteria: cancer free 45–75 yrs with hypertension Exclusion: overt CVD, pregnant/breast feeding etc long‐term use of folic acid, cobalamin, B6 Eligible participants were stratified by MTHFR C677T genotype (CC, CT, TT) (CC = 27%, CT = 49%, TT = 23%) Number participants randomised/completed/analysed G1: 10348/10276/10348 G2: 10354/10354/10354	Sex (% women) G1: 59% G2: 58.9% Age G1: 60 ± 7.5 G2: 60 ± 7.6 Nutrient status marker: S‐folate; median (interquartile range) baseline S‐folate was 8.1 (5.6–10.4) ng/mL (~18; 12–23 nmol/L). Extracted from Huo et al. (2015)	Folic acid Doses: G1: 800 μg folic acid+10 mg Enalapril G2: 10 mg Enalapril Background nutrient intake: NR Compliance: Assessed every third months Around 70% took at least 70% of the study medication throughout the trial	CRC (physician or oncologist diagnosed)	Number of CRC cases (%) G1: 13 (0.13%) G2: 6 (0.06%) HR 2.17 (95% CI 0.82–5.70) p = 0.117

Abbreviations: CI, confidence Interval; CRC, colorectal cancer; CSPPT, China Stroke Primary Prevention Trial; CVD, cardiovascular disease; HR, hazard Ratio; G, group; MTHFR, methylenetetrahydrofolate reductase; NR, not reported; RCT, randomised controlled trial; S, serum; SD, standard deviation; yrs, years.

^a Values reported as mean ± standard deviation or median (inter quartile range) unless otherwise indicated.