BioDesign 1984.

Methods	Double‐blind RCT of cross‐over design, based in Germany
Participants	24 participants (aged 51 to 64 years) who experienced at least 3 nocturnal leg muscle cramps per week
Interventions	A quinine‐vitamin E combination (4 tablets taken daily, each containing 64.8 mg quinine sulphate and 400 IU vitamin E) or quinine sulphate 64.8 mg (4 tablets taken daily) alone taken for 1 week each. 7‐day placebo washout periods before, between and after treatments
Outcomes	Cramp number, cramp duration, cramp intensity after treatment (graded 0 = better to 3 = much worse), adverse events
Notes	Unpublished study conducted by BioDesign (Germany)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "After randomization..." Comment: participants were allocated a number from 1 to14 and "randomized" to a specific group but no details of the randomization process are provided
Allocation concealment (selection bias)	Unclear risk	No details were given on how the allocation may have been concealed
Blinding (performance bias and detection bias) All outcomes	Low risk	Quote: "The study was designed as a double blind..."; "...5 containers with 30 capsules labelled with the number of the treatment week were provided." Comment: probably done as quinine‐vitamin E combination and quinine capsules are similar by description
Incomplete outcome data (attrition bias) All outcomes	Low risk	No drop‐outs from the trial
Selective reporting (reporting bias)	Low risk	All intended outcome measures were addressed in the results and analysis
Other bias	Unclear risk	Conducted by manufacturer of quinine tablets