NDHS Open 1st 1968.

Methods	National Diet‐Heart Study (NDHS) ‐ open first phase RCT, several arms, parallel (n6 LA vs SFA), 1 year Summary risk of bias: low
Participants	Free‐living men aged 45‐54 years CVD risk: low Interventions B, C, X combined: randomised 829, analysed 726 Control: randomised 382, analysed 341 Mean years in trial: control 0.95, Interventions 0.93 % male: 100 Age: unclear Age range: all 45‐54 years Smokers: 39%‐40% current smokers in each arm Hypertension: unclear Medications taken by ≥ 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 < 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: ↑ PUFA (n‐6) vs usual diet (replacement of SFA and 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% E‐20% E, 15% E), P/S 1.5 (2.0, 1.5) (foods bought from a trial shop ‐ SFAs 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&3): 3.7% LA, 3.9% PUFA Compliance by biomarkers: serum TC 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 2‐3 in other arms, at the expense of MUFA which did not alter in control, fell by 2‐3 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, kcal/d: intervention B 2154 (SD432), intervention C 2262 (SD435), intervention X 2117 (SD447), control D 2228 (SD456) Total fat intake, % E: intervention B 29.7, intervention C 34.4, intervention X 31.7, control D 34.9 (decrease B 5.2% E, C 0.5% E, X 3.2 total fat) SFA intake, % E: intervention B 7.1, intervention C 7.4, intervention X 8.9, control D 11.6 (decrease B 4.5% E, C 4.2% E, X 2.7% E SFA) PUFA intake, % E: intervention B 9.9, intervention C 13.2, intervention X 6.5, control D 4.9 (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, % E (by subtraction of SFA and PUFA from total fat): intervention B 12.7, intervention C 13.8, intervention X 16.3, control D 18.4 (decrease B 5.7% E, C 4.6% E, X 2.1% E MUFA) CHO intake, % E: intervention B 48.7, intervention C 45.3, intervention X 49.5, control D 44.7 (increase B 4.0% E, C 0.6% E, X 4.8% E CHO) Sugars intake: not reported Protein intake, % E: intervention B 18.6, intervention C 17.6, intervention X 17.1, control D 17.4 (increase B 1.2% E, C 0.2% E, X ‐0.3% E protein, little change) Alcohol intake, % E: intervention B 2.1, intervention C 2.1, intervention X 1.7, control D 2.2 (minimal change) Compliance, other methods: also assessed adherence ratings by nutritionists, subjectively, by recall and by food records. Poor adherence by 17%‐29%, others were fair, good or excellent. Inclusion basis: aimed to increase PUFA intake as well as increase PUFA/SFA, reduce SFA slightly and reduce dietary cholesterol. PUFA dose: achieved B 5.0% E, C 8.3% E, X 1.6 PUFA Duration of intervention: 1 year
Outcomes	Main trial outcomes: lipid levels and dietary assessment Dropouts: intervention B 42, C 34, X 5, control D 36 Available outcomes: CV events (MI and PAD events), cancer diagnoses, TC (weight, diastolic BP and TG data available but without SDs) Response to contact: not attempted as trial completed in 1967
Notes	All intervention arms combined for data analysis Aim was to replace saturates with polyunsaturates, but oils used were omega‐6 fats Dose calculations Control: assume from Faribault 17% E SFA, P/S 0.4 so PUFA 6.8% E Interventions: B PUFA 15% E, ↑8.2% E C PUFA 19% E, ↑12.2% E X PUFA 15% E, ↑8.2% E Mean for all interventions ↑10% E Trial funding: National Heart Institute
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 trial 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	Equivalent, both groups bought special foods from trial shop
Compliance	Low risk	TC 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 shows LA rose by 1 in control, by 2‐3 in other arms, at the expense of MUFA, which did not alter in control, fell by 2 or 3 in other arms.
Other bias	Low risk	None noted