Comparison 1. Quinine versus placebo.

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Difference in number of cramps over 2 weeks (GIV) ‐ fixed‐effect	14		Cramp number (Fixed, 95% CI)	‐1.81 [‐2.20, ‐1.42]
2 Difference in number of cramps over 2 weeks ‐ random‐effects (minus Connolly 1992)	13		Cramp Number (Random, 95% CI)	‐2.45 [‐3.54, ‐1.36]
3 Difference in number of cramps according to quinine dose (GIV) ‐ fixed‐effect	14		Cramp Number (Fixed, 95% CI)	‐1.81 [‐2.20, ‐1.42]
3.1 500 mg quinine	1		Cramp Number (Fixed, 95% CI)	‐8.7 [‐10.30, ‐7.10]
3.2 400 mg quinine	2		Cramp Number (Fixed, 95% CI)	‐3.36 [‐4.83, ‐1.89]
3.3 300 to 325 mg quinine	5		Cramp Number (Fixed, 95% CI)	‐0.79 [‐1.31, ‐0.26]
3.4 260 mg quinine	3		Cramp Number (Fixed, 95% CI)	‐1.29 [‐2.15, ‐0.42]
3.5 200 mg quinine	3		Cramp Number (Fixed, 95% CI)	‐3.22 [‐4.40, ‐2.04]
4 Difference in cramp intensity (GIV) ‐ fixed‐effect	7		Cramp intensity (Fixed, 95% CI)	‐0.12 [‐0.20, ‐0.05]
5 Change in cramp duration (min) ‐ random‐effects	2		Change in duration (Random, 95% CI)	‐1.35 [‐4.00, 1.30]
6 Difference in number of cramp days over 2 weeks (GIV) ‐ random‐effects (minus Connolly 1992	7		Cramp days (Random, 95% CI)	‐1.15 [‐1.93, ‐0.38]
7 Participants suffering minor adverse events	16	1447	Risk Difference (M‐H, Fixed, 95% CI)	0.03 [0.00, 0.06]
8 Participants suffering specific minor adverse events	18		Risk Difference (M‐H, Fixed, 95% CI)	Subtotals only
8.1 Gastrointestinal	18	1581	Risk Difference (M‐H, Fixed, 95% CI)	0.03 [0.01, 0.05]
8.2 Headache	18	1581	Risk Difference (M‐H, Fixed, 95% CI)	0.00 [‐0.02, 0.02]
8.3 Tinnitus	18	1581	Risk Difference (M‐H, Fixed, 95% CI)	0.01 [‐0.00, 0.02]
9 Participants suffering major adverse events	18	1613	Risk Difference (M‐H, Fixed, 95% CI)	0.00 [‐0.01, 0.02]
10 Participants suffering specific major adverse events (gastrointestinal)	18	1613	Risk Difference (M‐H, Fixed, 95% CI)	0.01 [‐0.00, 0.02]