FLAX‐PAD 2013

Methods	Effects of Dietary Flaxseed on Symptoms of Cardiovascular Disease in Patients With Peripheral Arterial Disease (FLAX PAD) RCT, parallel, (n‐3 ALA vs mixed fat), 12 months Summary risk of bias: low
Participants	Patients with peripheral artery disease, over 40 years old N: 58 intervention, 52 control Level of risk for CVD: high (all had peripheral artery disease, 80% had hyperlipidaemia) Men: 74.1% intervention, 73.1% control Mean age in years (SD): 67.4 (8.06) intervention, 65.3 (9.4) control Age range: unclear Smokers: 19.2% intervention, 34.6% control Hypertension: 81% intervention, 69.2% control Medications taken by at least 50% of those in the control group: lipid lowering medication, antihypertensives, antithrombotics Medications taken by 20%‐49% of those in the control group: not reported Medications taken by some, but less than 20% of the control group: insulin or blood sugar‐lowering drugs Location: Canada Ethnicity: unclear
Interventions	Type: food supplement (milled flaxseed) Comparison: ALA vs unclear (mix of wheat, wheat germ and mixed dietary oils) Intervention: food products (i.e. bagels, muffins, bars, pasta, buns, and milled seeds) containing 30 g of milled flaxseed daily. Dose: ˜6.8 g/d ALA (calculated based on 30 g milled flaxseed/d) Control: placebo food products (i.e. bagels, muffins, bars, pasta, buns, and milled seeds) containing a mixture of wheat, wheat bran, and mixed dietary oils to replace the flaxseed daily Compliance: plasma levels of enterolignans and the n‐3 fatty acid ALA were used as markers of dietary compliancy Length of intervention: 12 months
Outcomes	Main study outcome: all‐cause mortality, cardiovascular mortality, stroke, and myocardial infarctions Dropouts: 15 intervention, 11 control Available outcomes: blood pressure, lipids, adverse events, plasma ALA Response to contact: yes (but no data provided)
Notes	Different intervention dropout figures reported in two publications (13 or 15) Study funding: funded by government organisations but foods created and provided by a company
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomly selected by a computer programme
Allocation concealment (selection bias)	Low risk	Allocation was concealed. The person who determined if a participant was eligible for inclusion in the trial was unaware, when this decision was made, of which group the subject would be allocated
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Product colour and texture were similar to disguise the composition of the product. Participants, personnel administering the intervention and those assessing the outcomes were blinded to group assignment
Blinding of outcome assessment (detection bias) All outcomes	Low risk	All personnel that collected or analysed data were blinded to the intervention
Incomplete outcome data (attrition bias) All outcomes	Low risk	All randomised accounted for in main outcomes
Selective reporting (reporting bias)	High risk	Prospectively registered October 2008, study start October 2008, primary outcome data completed March 2011, end date December 2017. Cardiovascular mortality and measures of adiposity not reported in a useable way
Attention	Low risk	Both groups had the same care
Compliance	Unclear risk	12 in intervention group and 8 in placebo group unwilling to comply with diet
Other bias	Low risk	None noted