Table 1

Randomised controlled trials of diet with mortality and/or cardiovascular event outcomes

StudyPopulationDietary InterventionDurationCholesterol reductionMortality benefit?CVE benefit?Comments
Ball, 1965 Research Committee264 men<65 years s/p MIReduce total fat to 40 g/d3 yearsTC −7%*No (RR 0.87, 95% CI 0.51 to 1.50)No (RR 1.01, 95% CI 0.73 to 1.38)CVE=CHD death or mi
Rose, 196554 subjects<70 years, CHDCorn oil 80 g/d2 yearsTC −0.58 mmol/LNo (RR 5.31, 95% CI 0.32 to 89.44)No (RR 1.16, 95% CI 0.59 to 2.29)Small population
Cholesterol reduction NS
Rose, 196552 subjects<70 years, CHDOlive oil 80 g/d2 yearsTC unchangedNo (RR 1.50, 95% CI 0.17 to 13.05)No (RR 1.10, 95% CI 0.48 to 2.50)Small population
Leren, 1966
Oslo Diet Heart
412 men s/p MIReduced animal fat and cholesterol, replaced with vegetable oil4.3 yearsTC −1.07 mmol/L*No (RR 0.82, 95% CI 0.54 to 1.26) Yes (RR 0.71, 95% CI 0.55 to 0.92)
Morris, 1968
Medical Research Council
393 men s/p MIReplace saturated fat with three ounces soy bean oil/d4 yearsTC −0.64 mmol/L*No (RR 0.88, 95% CI 0.55 to 1.41)No (RR 0.82, 95% CI 0.62 to 1.07)
Dayton, 1969
Los Angeles VA
883 menReplace SFA with mainly PUFA8 yearsTC −0.37 mmol/LNo (RR 0.98, 95% CI 0.83 to 1.15)No (RR 0.79, 95% CI 0.94 to 1.0)Cholesterol reduction NS
Miettinen, et al, 6 1972
Finnish Mental Hospital
10 612 patients with psychological illnessReplace SFA with PUFA6–12 yearsTC −14%* Yes (RR 0.71, 95% CI 0.64 to 0.79)Not reportedNot truly randomised (cluster randomised)
Houtsmuller, 1979102 DM retinopathyReplace SFA with mainly PUFA6 yearsTC –0.47 mmol/L*Not reported Yes (RR 0.27, 95% CI 0.14 to 0.52)Small population
Hjermann, 1981
Oslo Cardiovascular Study
1232 high-risk menSmoking cessation+replace SFA with PUFA5 yearsNot reportedNo (RR 0.69, 95% CI 0.37 to 1.29) Yes (RR 0.57, 95% CI 0.35 to 0.93)Multiple simultaneous interventions
Cholesterol not reported
Burr et al, 11 1989
DART
2033 men <70 years s/p MIReplace SFA with PUFA, carbohydrate and protein2 yearsTC −0.26 mmol/L*No (RR 1.0, 95% CI 0.77 to 1.30)No (RR 0.91, 95% CI 0.72 to 1.16)
Burr et al, 11 1989
DART-fish
2033 men <70 years s/p MIFish two times/week2 yearsTC unchanged Yes (RR 0.71, 95% CI 0.54 to 0.93)No (RR 0.84, 95% CI 0.66 to 1.07)
Burr et al, 11 1989
DART-fibre
2033 men <70 years s/p MIFibre 18 g/day2 yearsTC unchangedNo (RR 1.27, 95% CI 0.99 to 1.65)No (RR 1.23, 95% CI 0.97 to 1.57)
Watts, 1992
STARS
50 men s/p MIReduced fat, replaced with PUFA, high fibre2 yearsTC −14%*
LDL −16%*
No (RR 0.35, 95% CI 0.04 to 3.12)No (RR 0.31, 95% CI 0.10 to 1.01)Small population
Watts, 1992
STARS
48 men s/p MIReduced fat, replaced with PUFA, high fibre+cholestyramine2 yearsTC −25%*
LDL −36%*
No (RR 0.15, 95% CI 0.01 to 2.83)* Yes (RR 0.11, 95% CI 0.01 to 0.78)*Small population
Drug+diet used to lower cholesterol
Black, 1994133 non-melanoma skin cancerReplace SFA with carbohydrate and protein2 yearsNot reportedNo (RR 0.51, 95% CI 0.05 to 5.46)No (RR 0.20, 95% CI 0.01 to 4.15)Small population
Cholesterol not reported
de Lorgeril et al, 10 1999
Lyon Diet Heart Study
605 s/p MIMediterranean diet5 yearsTC unchanged Yes (RR 0.44, 95% CI 0.21 to 0.94) Yes (RR 0.28, 95% CI 0.15 to 0.53)
Moy, 2001327 siblings of patients with CHDNurse supervised reduced total fat, replacement unclear2 yearsLDL −0.29 mmol/L*Not reportedNo (RR 1.68, 95% CI 0.41 to 6.87)
Burr et al, 8 2003
DART-2-fish
1528 men angina <70 years≥2 fish portions/week and/or fish oil 3 g/d3–9 yearsNot reportedNo (RR 1.29, 95% CI 1.03 to 1.63)Not reportedCholesterol not reported
Increased mortality among fish oil users
Trial interrupted for 1 year
Burr et al, 8 2003
DART-2-vegetable
1543 men angina <70 years4–5 portions fruits+vegetables/d+OJ + >8 g/d of soluble fibre3–9 yearsNot reportedNo (RR 1.20, 95% CI 0.95 to 1.51)Not reportedCholesterol not reported
Trial interrupted for 1 year
Burr et al, 8 2003
DART-2-fish+vegetable
1571 men angina <70 yearsBoth fish and fruits/vegetables as above3–9 yearsNot reportedNo (RR 1.23, 95% CI 0.98 to 1.55)Not reportedCholesterol not reported
Trial interrupted for 1 year
Ley, 2004176 glucose intolerantReplace SFA with carbohydrate and protein5 yearsTC −0.05 mmol/LNo (RR 0.33, 95% CI 0.67 to 1.61)No (RR 0.69, 95% CI 0.34 to 1.40)Cholesterol reduction NS
Howard, 2006
WHI
48 835 post-menopausal women, 50–79 yearsReduced total fat, replaced with increased fruits, vegetables, grains8.1 yearsTC −3.26 mg/dL*
LDL –3.55 mg/dL*
No (HR 1.02, 95% CI 0.84 to 1.25)No (HR 0.98, 95% CI 0.88 to 1.09)
Chlebowski, 2006
WINS
2437 women with breast cancerReduced SFA replaced with carbohydrate and protein5 yearsTC –0.14 mmol/LNo (RR 1.18, 95% CI 0.60 to 2.32)Not reportedCholesterol reduction NS
Tuttle, 2008
THIS-DIET
101 s/p first MILow fat Mediterranean diet (>0.75% of calories from omega-3) versus low fat2 yearsLDL −3 mg/dLNo (RR 0.98, 95% CI 0.02 to 48.50)No (RR 0.98, 95% CI 0.40 to 2.41)Small population
Both groups counselled low fat+low cholesterol
Cholesterol reduction NS
Ramsden, 2013
Sydney Diet Heart Study
458 men recent coronary event, 30–59 yearsReplace SFA with omega-6 linoleic acid (safflower oil)3.25 yearsTC −8%*No (HR 1.62, 95% CI 1.0 to 2.64)No (HR 1.7, 95% CI 1.03 to 2.8) Increased CVE and mortality with intervention
Brancati, 2013
Look-AHEAD
5145 obese T2DMReduced calories and increased exercise versus DM support+education9.6 yearsLDL –1.2 mg/dL in control group*No (HR 0.85, 95% CI 0.69 to 1.04)No (HR 0.95, 95% CI 0.83 to 1.09)Multiple simultaneous interventions
Ramsden, 2016
Minnesota Coronary Experiment
9423 institutionalisedReplace SFA with linoleic acid (corn oil)>1 year (2355 subjects)TC −13%*No (HR 1.22, 95% CI 1.14 to 1.32)Not reportedMany patients lost to follow-up
Increased mortality with intervention
Estruch et al, 9 2018
PREDIMED
7447 subjectsMediterranean diet4.8 yearsNot reportedNo (RR 0.89, 95% CI 0.71 to 1.12) Yes (RR 0.70, 95% CI 0.55 to 0.89)Article retracted and republished
Cholesterol not reported
  • *Statistically significant p<0.05.

  • CHD, coronary heart disease; CVE, cardiovascular event; DM, diabetes mellitus; LDL, low-density lipoprotein-cholesterol; MI, myocardial infarction; NS, not significant; OJ, orange juice; PUFA, polyunsaturated fatty acid; RR, risk ratio; s/p, status post; SFA, saturated fatty acid; T2DM, type 2 diabetes mellitus; TC, total cholesterol; VA, Veterans Administration.