Outcomes	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No of Participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk	Corresponding risk
	Control	Homocysteine-lowering treatments
Myocardial infarction	Low risk population		RR 1.03 (0.94 to 1.13)	20561 (7 studies)	⊕⊕⊕○ moderate1
	50 per 1000	51 per 1000 (47 to 56)
	High risk population
	100 per 1000	103 per 1000 (94 to 113)
Stroke	Low risk population		RR 0.89 (0.73 to 1.08)	18086 (5 studies)	⊕⊕⊕○ moderate
	50 per 1000	44 per 1000 (37 to 54)
	High risk population
	100 per 1000	89 per 1000 (73 to 108)
Death by any cause	Low risk population		RR 1 (0.92 to 1.09)	18679 (6 studies)	⊕⊕⊕○ moderate
	50 per 1000	50 per 1000 (46 to 55)
	High risk population
	100 per 1000	100 per 1000 (92 to 109)
Serious adverse events (Cancer)	Low risk population		RR 1.06 (0.9 to 1.25)	12361 (3 studies)	⊕⊕⊕○ moderate
	10 per 1000	11 per 1000 (9 to 12)
	High risk population
	50 per 1000	53 per 1000 (45 to 62)

^*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).

CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence

High quality: Further research is very unlikely to change our confidence in the estimate of effect.

Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.

Very low quality: We are very uncertain about the estimate.

¹The interventions have different characteristis across studies