Beigi 2014.

Study characteristics
Methods	Study design: RCT parallel group
Participants	Country: Iran Nº patients: 30 (14 in folic acid group and 16 in placebo group) Setting: community Mean age: 39; 42 years in folic acid group and 36 years in placebo group Gender: all male Inclusion criteria: negative history of hypertension, diabetes mellitus, ischaemic heart disease, cerebrovascular disease, collagen vascular disease or vasculitis Exclusion criteria: quote "surgical sympathectomy or any sort of vascular bypass; using aspirin, calcium channel blocker, B6 or B12; stop smoking during the study and have not compliance of being treated. Also, patients with hypercoagulative state due to inherited thrombophilia (factor V Leiden, A202120G prothrombin variant, acquired activated protein C resistance, protein C and S deficiency, antithrombin deficiency"
Interventions	Treatment: Folic acid group: oral 5 mg folic acid tablet (by Jallinus Pharmacy, Tehran, Iran) Placebo group: oral placebo with the same colour, size, weight and box (by Amin Pharmacy, Isfahan, Iran) Duration of treatment: 1 day ‐ a single dose of folic acid or placebo Follow‐up: 6 months
Outcomes	Primary: major and minor amputations
Notes	Conflict of Interest: none declared The study authors reported the following regarding a link between homocysteine levels and Buergers disease: quote "At the beginning of the study, homocysteine level was higher than normal in 19 patients (63%). There was a significant decrease in homocysteine level during 6 months in folic acid group (P < 0.001), but there was no change in the placebo group."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computerised randomisation
Allocation concealment (selection bias)	Low risk	There was a person responsible for allocation concealment; codified using computerised randomisation, only revealed at the end of the trial
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double blind
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Doctor responsible for outcome assessment assessed the patients at the start and at the end of treatment, but was not responsible for drug administration
Incomplete outcome data (attrition bias) All outcomes	Low risk	Study without losses to follow‐up
Selective reporting (reporting bias)	High risk	Did not describe the development of rest pain or ischaemic ulcers after the treatment
Other bias	High risk	Participants without critical ischaemia were eligible, resulting in low chance of amputation. Conflict of interest: none declared