Summary of findings 1. Effect of reducing saturated fat compared to usual saturated fat on CVD risk in adults (note: for the full set of GRADE tables see additional tables 24 to 28).

Low saturated fat compared with usual saturated fat for CVD risk
Patient or population: people at any baseline risk of CVD Intervention: lower saturated fat intake Comparison: higher saturated fat intake Settings: Any, including community‐dwelling and institutions. Included RCTs were conducted in North America, Europe and Australia/New Zealand, no studies were carried out in industrialising or developing countries.
Outcomes	Relative effect (95% CI)	Anticipated absolute effects (95% CI)		No of Participants (studies)	Quality of the evidence (GRADE)	Comments
		Risk with higher SFA intake	Risk with lower SFA intake
All‐cause mortality follow‐up mean duration 56 months1	RR 0.96 (0.90 to 1.03)	62 per 1000	60 per 1000 (56 to 64)	55,858 (12)	⊕⊕⊕⊝ Moderate2,3,4,5,6	Critical importance. Reducing saturated fat intake probably makes little or no difference to all‐cause mortality.
Cardiovascular mortality follow‐up mean duration 53 months1	RR 0.94 (0.78 to 1.13)	19 per 1000	18 per 1000 (15 to 22)	53,421 (11)	⊕⊕⊕⊝ Moderate2,3,4,6,7	Critical importance. Reducing saturated fat intake probably makes little or no difference to cardiovascular mortality.
Combined cardiovascular events follow‐up mean duration 52 months1	RR 0.83 (0.70 to 0.98)	85 per 1000	70 per 1000 (59 to 83)	53,758 (13)	⊕⊕⊕⊝ Moderate4,8,9,10,11	Critical importance. Reducing saturated fat intake probably reduces cardiovascular events (to a greater extent with greater cholesterol reduction).
Myocardial infarctions follow‐up mean duration 55 months	RR 0.90 (0.80 to 1.01)	32 per 1000	29 per 1000 (25 to 32)	53,167 (11)	⊕⊝⊝⊝ VeryLow 3,4,5,11,12	Critical importance. The effect of reducing saturated fat intake on risk of myocardial infarction is unclear as the evidence is of very low quality.
Non‐fatal MI follow‐up mean duration 55 months1	RR 0.97 (0.87 to 1.07)	26 per 1000	25 per 1000 (23 to 28)	52,834 (8)	⊕⊕⊝⊝ Low3,4,5,6,13	Critical importance. Reducing saturated fat may have little or no effect on risk of non‐fatal myocardial infarction.
Stroke follow‐up mean duration 59 months1	RR 0.92 (0.68 to 1.25)	22 per 1000	20 per 1000 (15 to 27)	50,952 (7)	⊕⊝⊝⊝ VeryLow 3,4,6,13,14	Critical importance. The effect of reducing saturated fat on the risk of stroke is unclear as the evidence was of very low quality.
CHD mortality follow‐up mean duration 65 months1	RR 0.97 (0.82 to 1.16)	16 per 1000	16 per 1000 (13 to 19)	53,159 (9)	⊕⊕⊝⊝ Low2,3,4,6,14	Critical importance. Reducing saturated fat intake may have little or no effect on CHD mortality.
CHD events follow‐up mean duration 59 months1	RR 0.83 (0.68 to 1.01)	42 per 1000	35 per 1000 (29 to 43)	53,199 (11)	⊕⊝⊝⊝ Verylow 4,5,6,12,15	Critical importance. The effect of reducing saturated fat on risk of CHD events is unclear as the evidence is of very low quality.
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; RR: Risk Ratio; CHD: coronary heart disease.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

¹Minimum study duration was 24 months.

²Risk of bias. Limiting trials to those at low summary risk of bias also suggested little or no effect. Not downgraded.

³Inconsistency. We found no important heterogeneity; I² ≤ 30%. Not downgraded.

⁴Indirectness. These RCTs directly assessed the effect of lower vs higher saturated fat intake on health outcomes of interest. Participants included men and women with and without CVD at baseline (also some participants with CVD risk factors like diabetes, or at risk of cancers). However, no trials included participants from developing countries. Not downgraded.

⁵Imprecision. The 95% CI includes both no effect and a benefit. Downgraded once.

⁶Publication bias. The funnel plot, and comparison of fixed‐ and random‐effects meta‐analyses did not suggest major small‐study (publication) bias. Not downgraded.

⁷Imprecision. The 95% CI includes both harm and benefit. Downgraded once.

⁸Risk of bias. Limiting trials to those at low summary risk of bias suggested a smaller and non‐statistically significant effect (RR 0.96, 95% CI 0.76 to 1.20) suggesting little or no effect on risk of CVD events. Downgraded once (along with publication bias).

⁹Inconsistency. Although heterogeneity was high, I² = 65%, this was mostly explained by the degree of cholesterol‐lowering (a dose effect). Not downgraded.

¹⁰Imprecision. The 95% CI includes only benefit or minimal effect. Not downgraded.

¹¹Publication bias. The funnel plot did not suggest publication bias, but comparison of fixed‐ and random‐effects meta‐analyses suggested possible small‐study (publication) bias. Downgraded once (along with risk of bias, downgraded once in total).

¹²Risk of bias. Limiting trials to those at low summary risk of bias moved the RR slightly towards 1.0, suggesting little or no effect on total MI. Downgraded once.

¹³Risk of bias. Limiting trials to those at low summary risk of bias moved the RR slightly away from 1.0, suggesting that reducing SFA reduces the risk of non‐fatal MI. This was also seen in several other sensitivity analyses. Downgraded once.

¹⁴Imprecision. The 95% CI includes both important benefits and important harms. Downgraded twice.

¹⁵Inconsistency. Heterogeneity was high, I² = 65%. Downgraded once.