Gardner 2001.

Methods	Parallel randomised controlled clinical trial, randomisation ratio 1 : 1
Participants	Inclusion criteria: the fasting plasma LDL‐cholesterol concentration of 3.37‐4.92 mmol/L (130‐190 mg/dL) and a triacylglycerol concentration < 2.82 mmol/L (< 250 mg/dL); postmenopausal (≥ 1 year since their last menstrual cycle), age < 80 years, and a BMI of 20–31 kg/m2 Exclusion criteria: smokers, had been taking hormone replacements or lipid‐lowering medication during the previous 3 months, had a history of cardiovascular disease or diabetes, or had breast, endometrial or ovarian cancer in the previous 10 years Diagnostic criteria: not specified
Interventions	Number of study centres: 1 Treatment before study: no Titration period: 12 wks
Outcomes	Outcomes reported in abstract of publication: TC, LDL‐C, HDL‐C and triacylglycerol
Study details	Run‐in period: yes Study terminated before regular end (for benefit/because of adverse events): no
Publication details	Language of publication: English Commercial/non‐commercial/other funding: not reported Publication status: peer‐reviewed journal
Stated aim of study	Quote from publication: "to determine the effect of soy protein and isoflavones on plasma lipid concentrations in postmenopausal, moderately hypercholesterolemic women"
Notes	"LDL‐cholesterol was calculated according to the method of Friedewald unless the triacylglycerols were > 4.52 mmol/L (> 400 mg/dL), in which case the LDL‐C value was considered missing data (3 LDL‐cholesterol data points were excluded: 1 in the Milk group, 0 in the Soy– group, and 2 in the Soy+ group)" Abbreviations: HDL: high‐density‐lipoprotein; LDL: low‐density‐lipoprotein
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote from publication: "The subjects were randomly assigned to 12 wk of dietary protein supplementation (42 g/d) with either a milk protein (Milk group) or 1 of 2 soy proteins containing either trace amounts of isoflavones (Soy– group) or 80 mg aglycone isoflavones (Soy+ group)", "Randomization was performed in blocks of 30 participants" Comment: no details provided
Allocation concealment (selection bias)	Low risk	Quote from publication: "Dietary supplements containing a mixture of protein, carbohydrate, and calcium in powder form (Shaklee Corporation, Hayward, CA) were provided in sealed packets, each containing one‐half of the daily dose (21 g protein/packet 2 packets/d)", "All supplements were formulated to be identical in taste, color, and odor"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote from publication: "Participants, investigators, study staff, and laboratory technicians were blinded to treatment assignments until the conclusion of the trial"
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote from publication: "Participants, investigators, study staff, and laboratory technicians were blinded to treatment assignments until the conclusion of the trial"
Incomplete outcome data (attrition bias) All outcomes	High risk	Quote from publication: "These analyses showed a stable composition of isoflavone concentrations throughout the study (data not shown)", "Of the 115 women who entered the study, 21 withdrew before study completion", "Statistical analyses were performed on data" Comment: number of participants analyzed was less than number of participants randomized
Selective reporting (reporting bias)	Low risk	Comment: none detected
Other bias	High risk	Quote "At the onset of the study, the participants were instructed to take the full dose of the protein supplements. However, we had a higher than anticipated dropout rate early in the study because of adverse gastrointestinal responses to the acute dietary change. Therefore, gradual adaptation to the protein supplements was recommended for the latter four‐fifths of participants. These participants began the 4‐wk run‐in phase by consuming one‐half of the goal dose rather than the full dose. These participants were then encouraged to increase their intake to the full dose by week 3 of the run‐in phase". "Exceptions to group comparability at randomization included a higher average age and a higher number of years since menopause in the Soy+ group and a lower percentage of married women in the Soy– group than in the Soy+ group" Comment: not all participants performed the run‐in phase; several baseline characteristics of participants were not equally distributed between the intervention and placebo groups