Reduction in saturated fat intake for cardiovascular disease

Abstract

Background: Reducing saturated fat reduces serum cholesterol, but effects on other intermediate outcomes may be less clear. Additionally, it is unclear whether the energy from saturated fats eliminated from the diet are more helpfully replaced by polyunsaturated fats, monounsaturated fats, carbohydrate or protein.

Objectives: To assess the effect of reducing saturated fat intake and replacing it with carbohydrate (CHO), polyunsaturated (PUFA), monounsaturated fat (MUFA) and/or protein on mortality and cardiovascular morbidity, using all available randomised clinical trials.

Search methods: We updated our searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid) and Embase (Ovid) on 15 October 2019, and searched Clinicaltrials.gov and WHO International Clinical Trials Registry Platform (ICTRP) on 17 October 2019.

Selection criteria: Included trials fulfilled the following criteria: 1) randomised; 2) intention to reduce saturated fat intake OR intention to alter dietary fats and achieving a reduction in saturated fat; 3) compared with higher saturated fat intake or usual diet; 4) not multifactorial; 5) in adult humans with or without cardiovascular disease (but not acutely ill, pregnant or breastfeeding); 6) intervention duration at least 24 months; 7) mortality or cardiovascular morbidity data available.

Data collection and analysis: Two review authors independently assessed inclusion, extracted study data and assessed risk of bias. We performed random-effects meta-analyses, meta-regression, subgrouping, sensitivity analyses, funnel plots and GRADE assessment.

Main results: We included 15 randomised controlled trials (RCTs) (16 comparisons, ~59,000 participants), that used a variety of interventions from providing all food to advice on reducing saturated fat. The included long-term trials suggested that reducing dietary saturated fat reduced the risk of combined cardiovascular events by 21% (risk ratio (RR) 0.79; 95% confidence interval (CI) 0.66 to 0.93, 11 trials, 53,300 participants of whom 8% had a cardiovascular event, I² = 65%, GRADE moderate-quality evidence). Meta-regression suggested that greater reductions in saturated fat (reflected in greater reductions in serum cholesterol) resulted in greater reductions in risk of CVD events, explaining most heterogeneity between trials. The number needed to treat for an additional beneficial outcome (NNTB) was 56 in primary prevention trials, so 56 people need to reduce their saturated fat intake for ~four years for one person to avoid experiencing a CVD event. In secondary prevention trials, the NNTB was 32. Subgrouping did not suggest significant differences between replacement of saturated fat calories with polyunsaturated fat or carbohydrate, and data on replacement with monounsaturated fat and protein was very limited. We found little or no effect of reducing saturated fat on all-cause mortality (RR 0.96; 95% CI 0.90 to 1.03; 11 trials, 55,858 participants) or cardiovascular mortality (RR 0.95; 95% CI 0.80 to 1.12, 10 trials, 53,421 participants), both with GRADE moderate-quality evidence. There was little or no effect of reducing saturated fats on non-fatal myocardial infarction (RR 0.97, 95% CI 0.87 to 1.07) or CHD mortality (RR 0.97, 95% CI 0.82 to 1.16, both low-quality evidence), but effects on total (fatal or non-fatal) myocardial infarction, stroke and CHD events (fatal or non-fatal) were all unclear as the evidence was of very low quality. There was little or no effect on cancer mortality, cancer diagnoses, diabetes diagnosis, HDL cholesterol, serum triglycerides or blood pressure, and small reductions in weight, serum total cholesterol, LDL cholesterol and BMI. There was no evidence of harmful effects of reducing saturated fat intakes.

Authors' conclusions: The findings of this updated review suggest that reducing saturated fat intake for at least two years causes a potentially important reduction in combined cardiovascular events. Replacing the energy from saturated fat with polyunsaturated fat or carbohydrate appear to be useful strategies, while effects of replacement with monounsaturated fat are unclear. The reduction in combined cardiovascular events resulting from reducing saturated fat did not alter by study duration, sex or baseline level of cardiovascular risk, but greater reduction in saturated fat caused greater reductions in cardiovascular events.

Trial registration: ClinicalTrials.gov NCT00000611 NCT02062424 NCT00692536 NCT01954472 NCT01005498 NCT01634841 NCT03354377.

Conflict of interest statement

Lee Hooper: LH is a member of the World Health Organization Nutrition Guidance Expert Advisory Group (NUGAG). WHO paid for her travel, accommodation and expenses to attend NUGAG meetings in Geneva, China and South Korea where the evidence of effects of dietary fats on health was discussed and guidance developed. LH's institution was given grant funding from WHO to carry out the 2019 update of this systematic review, to update a systematic review on the relationship between total fat intake and body weight and a series of systematic reviews on the health effects of polyunsaturated fatty acids.

Nicole Martin: None known

Asmaa Abdelhamid: None known

Oluseyi Florence Jimoh: This review was funded by a grant from the World Health Organization.

Eve Foster: None known

Christian Kirk: None known

Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

Figures

1

Study flow diagram for this systematic review (update searches run October 2019).

2

Methodological quality summary: review authors' judgements about each methodological quality item for each included study. Please note that while Rose 1965 (Rose corn oil 1965; Rose olive 1965) appears twice in this summary, it is a single trial. Rose 1965 was a 3‐arm trial and we have used the two intervention arms separately in the review.

3

Funnel plot of comparison: fat modification or reduction vs usual diet ‐ total mortality.

4

Funnel plot of comparison: fat modification or reduction vs usual diet ‐ cardiovascular mortality

5

Funnel plot of comparison: fat modification or reduction vs usual diet ‐ combined cardiovascular events.

6

Exploration of saturated fat cut‐offs

1.1. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 1: ALL‐CAUSE MORTALITY

1.2. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 2: All‐cause mortality, SA low summary risk of bias

1.3. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 3: All‐cause mortality, SA aim to reduce SFA

1.4. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 4: All‐cause mortality, SA statistically significant SFA reduction

1.5. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 5: All‐cause mortality, SA TC reduction

1.6. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 6: All‐cause mortality, SA excluding WHI

1.7. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 7: All‐cause mortality, SA Mantel‐Haenszel fixed‐effect

1.8. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 8: All‐cause mortality, SA Peto fixed‐effect

1.9. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 9: All‐cause mortality, subgroup by any substitution

1.10. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 10: All‐cause mortality, subgroup by main substitution

1.11. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 11: All‐cause mortality, subgroup by duration

1.12. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 12: All‐cause mortality, subgroup by baseline SFA

1.13. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 13: All‐cause mortality, subgroup by SFA change

1.14. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 14: All‐cause mortality, subgroup by sex

1.15. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 15: All‐cause mortality, subgroup by CVD risk

1.16. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 16: All‐cause mortality, subgroup by TC reduction

1.17. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 17: All‐cause mortality, subgroup decade of publication

1.18. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 18: CARDIOVASCULAR MORTALITY

1.19. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 19: CVD mortality, SA low summary risk of bias

1.20. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 20: CVD mortality, SA aim to reduce SFA

1.21. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 21: CVD mortality, SA statistically significant SFA reduction

1.22. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 22: CVD mortality, SA TC reduction

1.23. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 23: CVD mortality, SA excluding WHI

1.24. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 24: CVD mortality, SA Mantel‐Haenszel fixed‐effect

1.25. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 25: CVD mortality, SA Peto fixed‐effect

1.26. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 26: CVD mortality, subgroup by any substitution

1.27. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 27: CVD mortality, subgroup by main substitution

1.28. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 28: CVD mortality, subgroup by duration

1.29. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 29: CVD mortality, subgroup by baseline SFA

1.30. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 30: CVD mortality, subgroup by SFA change

1.31. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 31: CVD mortality, subgroup by sex

1.32. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 32: CVD mortality, subgroup by CVD risk

1.33. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 33: CVD mortality, subgroup by TC reduction

1.34. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 34: CVD mortality, subgroup decade of publication

1.35. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 35: COMBINED CARDIOVASCULAR EVENTS

1.36. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 36: CVD events, SA low summary risk of bias

1.37. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 37: CVD events, SA aim to reduce SFA

1.38. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 38: CVD events, SA statistically significant SFA reduction

1.39. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 39: CVD events, SA TC reduction

1.40. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 40: CVD events, SA excluding WHI

1.41. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 41: CVD events, SA Mantel‐Haenszel fixed‐effect

1.42. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 42: CVD events, SA Peto fixed‐effect

1.43. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 43: CVD events, SA excluding trials with additional interventions

1.44. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 44: CVD events, subgroup by any substitution

1.45. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 45: CVD events, subgroup by main substitution

1.46. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 46: CVD events, subgroup by duration

1.47. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 47: CVD events, subgroup by baseline SFA

1.48. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 48: CVD events, subgroup by SFA change

1.49. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 49: CVD events, subgroup by sex

1.50. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 50: CVD events, subgroup by CVD risk

1.51. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 51: CVD events, subgroup by TC reduction

1.52. Analysis

Comparison 1: SFA reduction vs usual diet ‐ primary outcomes, Outcome 52: CVD events, subgroup decade of publication

2.1. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 1: MYOCARDIAL INFARCTION

2.2. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 2: MI, SA by low summary risk of bias

2.3. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 3: MI, SA aim to reduce SFA

2.4. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 4: MI, SA statistically significant SFA reduction

2.5. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 5: MI, SA by TC reduction

2.6. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 6: MI, SA excluding WHI

2.7. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 7: MI, SA Mantel‐Haenszel fixed‐effect

2.8. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 8: MI, SA Peto fixed‐effect

2.9. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 9: MI, subgroup by any substitution

2.10. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 10: MI, subgroup by main substitution

2.11. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 11: MI, subgroup by duration

2.12. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 12: MI, subgroup by baseline SFA

2.13. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 13: MI, subgroup by SFA change

2.14. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 14: MI, subgroup by sex

2.15. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 15: MI, subgroup by CVD risk

2.16. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 16: MI, subgroup by TC reduction

2.17. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 17: MI, subgroup decade of publication

2.18. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 18: NON‐FATAL MYOCARDIAL INFARCTION

2.19. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 19: Non‐fatal MI, SA by low summary risk of bias

2.20. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 20: Non‐fatal MI, SA aim to reduce SFA

2.21. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 21: Non‐fatal MI, SA statistically significant SFA reduction

2.22. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 22: Non‐fatal MI, SA by TC reduction

2.23. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 23: Non‐fatal MI, SA excluding WHI

2.24. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 24: Non‐fatal MI, SA Mantel‐Haenszel fixed‐effect

2.25. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 25: Non‐fatal MI, SA Peto fixed‐effect

2.26. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 26: Non‐fatal MI, subgroup by any substitution

2.27. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 27: Non‐fatal MI, subgroup by main substitution

2.28. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 28: Non‐fatal MI, subgroup by duration

2.29. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 29: Non‐fatal MI, subgroup by baseline SFA

2.30. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 30: Non‐fatal MI, subgroup by SFA change

2.31. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 31: Non‐fatal MI, subgroup by sex

2.32. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 32: Non‐fatal MI, subgroup by CVD risk

2.33. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 33: Non‐fatal MI, subgroup by TC reduction

2.34. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 34: Non‐fatal MI, subgroup decade of publication

2.35. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 35: STROKE

2.36. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 36: Stroke, SA by low summary risk of bias

2.37. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 37: Stroke, SA aim to reduce SFA

2.38. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 38: Stroke, SA statistically significant SFA reduction

2.39. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 39: Stroke, SA by TC reduction

2.40. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 40: Stroke, SA excluding WHI

2.41. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 41: Stroke, SA Mantel‐Haenszel fixed‐effect

2.42. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 42: Stroke, SA Peto fixed‐effect

2.43. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 43: Stroke, subgroup by any substitution

2.44. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 44: Stroke, subgroup by main substitution

2.45. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 45: Stroke, subgroup by duration

2.46. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 46: Stroke, subgroup by baseline SFA

2.47. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 47: Stroke, subgroup by SFA change

2.48. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 48: Stroke, subgroup by sex

2.49. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 49: Stroke, subgroup by CVD risk

2.50. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 50: Stroke, subgroup by TC reduction

2.51. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 51: Stroke, subgroup decade of publication

2.52. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 52: CORONARY HEART DISEASE MORTALITY

2.53. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 53: CHD mortality, SA by low summary risk of bias

2.54. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 54: CHD mortality, SA aim to reduce SFA

2.55. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 55: CHD mortality, SA statistically significant SFA reduction

2.56. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 56: CHD mortality, SA by TC reduction

2.57. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 57: CHD mortality, SA excluding WHI

2.58. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 58: CHD mortality, SA Mantel‐Haenszel fixed‐effect

2.59. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 59: CHD mortality, SA Peto fixed‐effect

2.60. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 60: CHD mortality, subgroup by any substitution

2.61. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 61: CHD mortality, subgroup by main substitution

2.62. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 62: CHD mortality, subgroup by duration

2.63. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 63: CHD mortality, subgroup by baseline SFA

2.64. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 64: CHD mortality, subgroup by SFA change

2.65. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 65: CHD mortality, subgroup by sex

2.66. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 66: CHD mortality, subgroup by CVD risk

2.67. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 67: CHD mortality, subgroup by TC reduction

2.68. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 68: CHD mortality, subgroup decade of publication

2.69. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 69: CORONARY HEART DISEASE EVENTS

2.70. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 70: CHD events, SA by low summary risk of bias

2.71. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 71: CHD events, SA excluding WHI

2.72. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 72: CHD events, SA statistically significant SFA reduction

2.73. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 73: CHD events, SA by TC reduction

2.74. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 74: CHD events, SA aim to reduce SFA

2.75. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 75: CHD events, SA Mantel‐Haenszel fixed‐effect

2.76. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 76: CHD events, SA Peto fixed‐effect

2.77. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 77: CHD events, subgroup by any substitution

2.78. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 78: CHD events, subgroup by main substitution

2.79. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 79: CHD events, subgroup by duration

2.80. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 80: CHD events, subgroup by baseline SFA

2.81. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 81: CHD events, subgroup by SFA change

2.82. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 82: CHD events, subgroup by sex

2.83. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 83: CHD events, subgroup by CVD risk

2.84. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 84: CHD events, subgroup by TC reduction

2.85. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 85: CHD events, subgroup decade of publication

2.86. Analysis

Comparison 2: SFA reduction vs usual diet ‐ secondary health events, Outcome 86: DIABETES DIAGNOSES

3.1. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 1: Total cholesterol, mmol/L

3.2. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 2: TC, mmol/L, subgroup by any replacement

3.3. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 3: TC, mmol/L, subgroup by main replacement

3.4. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 4: LDL cholesterol, mmol/L

3.5. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 5: LDL, mmol/L, subgroup by any replacement

3.6. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 6: LDL, mmol/L, subgroup by main replacement

3.7. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 7: HDL cholesterol, mmol/L

3.8. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 8: HDL, mmol/L, subgroup by any replacement

3.9. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 9: HDL, mmol/L, subgroup by main replacement

3.10. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 10: Triglycerides, mmol/L

3.11. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 11: TG, mmol/L, subgroup by any replacement

3.12. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 12: TG, mmol/L, subgroup by main replacement

3.13. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 13: total cholesterol /HDL ratio

3.14. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 14: TC /HDL ratio, subgroup by any replacement

3.15. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 15: TC /HDL ratio, subgroup by main replacement

3.16. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 16: LDL /HDL ratio

3.17. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 17: Lp(a), mmol/L

3.18. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 18: Lp(a), mmol/L, subgroup by any replacement

3.19. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 19: Lp(a), mmol/L, subgroup by main replacement

3.20. Analysis

Comparison 3: SFA reduction vs usual diet ‐ secondary blood outcomes, Outcome 20: Insulin sensitivity

4.1. Analysis

Comparison 4: SFA reduction vs usual diet ‐ secondary outcomes including potential adverse effects, Outcome 1: Cancer diagnoses

4.2. Analysis

Comparison 4: SFA reduction vs usual diet ‐ secondary outcomes including potential adverse effects, Outcome 2: Cancer deaths

4.3. Analysis

Comparison 4: SFA reduction vs usual diet ‐ secondary outcomes including potential adverse effects, Outcome 3: Weight, kg

4.4. Analysis

Comparison 4: SFA reduction vs usual diet ‐ secondary outcomes including potential adverse effects, Outcome 4: BMI, kg/m2

4.5. Analysis

Comparison 4: SFA reduction vs usual diet ‐ secondary outcomes including potential adverse effects, Outcome 5: Systolic Blood Pressure, mmHg

4.6. Analysis

Comparison 4: SFA reduction vs usual diet ‐ secondary outcomes including potential adverse effects, Outcome 6: Diastolic Blood Pressure, mmHg

4.7. Analysis

Comparison 4: SFA reduction vs usual diet ‐ secondary outcomes including potential adverse effects, Outcome 7: Quality of Life