NDHS Open 1st 1968.

Methods	National Diet‐Heart Study (NDHS) – Open First phase RCT, several arms, parallel (n‐6 LA vs SFA + MUFA), 1 year Summary risk of bias: low
Participants	Free‐living men aged 45‐54 years CVD risk: low Control: randomised 382, analysed 341 Interventions B, C, X combined: randomised 829, analysed 726 Mean years in trial: control 0.95, intervention 0.93 % male: 100 Age: unclear Age range: all 45‐54 years Smokers: 39% to 40% current smokers in each arm Hypertension: unclear Medications taken by at least 50% of those in the control group: not reported 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: not reported Location: USA Ethnicty: white 98.2%, non‐white 1.8% (not reported by intervention arm)
Interventions	Type: diet provided (bought from a trial shop) Comparison: increased PUFA (n‐6) vs usual diet (replacement of SFA + MUFA) Control aims: total fat 40% E, dietary cholesterol 650‐750 mg/d, P/S 0.4 (assume PUFA 6.8% E as at Faribault) (foods bought from a trial shop – normal foods) Intervention aims: B (C, X) total fat 30% E (40% E, 30% E), SFA < 9% E (< 9% E, < 9% E), dietary cholesterol 350‐450 mg/d (350‐450 mg/d, 350‐450 mg/d), PUFA 15% E (18‐20% E, 15% E), P/S 1.5 (2.0, 1.5) (foods bought from a trial shop – saturated fats removed and replaced by polyunsaturated oils and fats) Dose aim:increase B 8.2% E, C 12.2% E, X 8.2% E n‐6 Baseline n‐6 (tables IX 1 and 3): 3.7% LA, 3.9% PUFA Compliance by biomarkers: good, serum total cholesterol significantly reduced in intervention compared to control (−0.45 mmol/L, 95% CI −0.55 to −0.35). Data on fatty acid composition of red blood cells provided in chapter 10 (table X6: LA rose by 1 in control, by 2 to 3 in other arms, at the expense of MUFA which did not alter in control, fell by 2 or 3 in other arms. Palmitic acid remained constant in control and remained constant or fell by 1 in intervention arms, stearic did not alter in control and remained constant or rose by 1 in intervention arms – no statistical significance or variance info provided, units unclear, probably % of LA + oleic + palmitic+stearic) Compliance by dietary intake: good. Nutritionists subjective adherence ratings of excellent or good (as compared to fair or poor) intervention B 58%, intervention C 60%, control D 55%. Dietary intake computed from 7‐day food records at 28 weeks (table IX3, no later data found): Energy intake: intervention B 2154 kcal/d (SD 432), intervention C 2262 kcal/d (SD 435), intervention X 2117 kcal/d (SD 447), control D 2228 kcal/d (SD 456) Total fat intake: intervention B 29.7% E, intervention C 34.4% E, intervention X 31.7% E, control D 34.9% E (decrease B 5.2% E, C 0.5% E, X 3.2 total fat) Saturated fat intake: intervention B 7.1% E, intervention C 7.4% E, intervention X 8.9% E, control D 11.6% E (decrease B 4.5% E, C 4.2% E, X 2.7% E SFA) PUFA intake: intervention B 9.9% E, intervention C 13.2% E, intervention X 6.5% E, control D 4.9% E (increase B 5.0% E, C 8.3% E, X 1.6 PUFA) PUFA n‐3 intake: not reported PUFA n‐6 intake: not reported, probably similar to PUFA Trans fat intake: not reported MUFA intake (by subtraction of SFA and PUFA from total fat): intervention B 12.7% E, intervention C 13.8% E, intervention X 16.3% E, control D 18.4% E (decrease B 5.7% E, C 4.6% E, X 2.1% E MUFA) CHO intake: intervention B 48.7% E, intervention C 45.3% E, intervention X 49.5% E, control D 44.7% E (increase B 4.0% E, C 0.6% E, X 4.8% E CHO) Sugars intake: not reported Protein intake: intervention B 18.6% E, intervention C 17.6% E, intervention X 17.1% E, control D 17.4% E (increase B 1.2% E, C 0.2% E, X −0.3% E protein, little change) Alcohol intake: intervention B 2.1% E, intervention C 2.1% E, intervention X 1.7% E, control D 2.2% E (minimal change) Duration of intervention: 1 year
Outcomes	Main study outcomes: lipid levels and dietary assessment Dropouts: intervention B 42, C 34, X 5, control D 36 Available outcomes: CVD events (MI and PAD events), cancer diagnoses, total cholesterol (weight, diastolic BP and TG data available but without SDs)
Notes	Study funding: National Heart Institute Response to contact: not attempted as study completed in 1967
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Stratified randomisation by the statistical centre
Allocation concealment (selection bias)	Low risk	Stratified randomisation by the statistical centre
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants and study personnel (aside from the store manager) were blinded to allocation. Blinding of participants was checked using a questionnaire which found no difference between intervention and control participants in guesses at dietary composition.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Outcome assessors were reported as blinded to treatment allocation
Incomplete outcome data (attrition bias) All outcomes	Low risk	12% dropouts, well described
Selective reporting (reporting bias)	Unclear risk	No protocol or trial registry entry found
Attention Bias	Low risk	Interventions and follow‐ups delivered in an equivalent way across arms
Compliance	Low risk	Good compliance by biomarkers
Other bias	Low risk	None noted