We include 15 randomised controlled trials (RCTs) (17 comparisons, ˜59,000 participants), which used a variety of interventions from providing all food to advice on how to reduce saturated fat. The included long-term trials suggested that reducing dietary saturated fat reduced the risk of cardiovascular events by 17% (risk ratio (RR) 0.83; 95% confidence interval (CI) 0.72 to 0.96, 13 comparisons, 53,300 participants of whom 8% had a cardiovascular event, I² 65%, GRADE moderate quality of evidence), but effects on all-cause mortality (RR 0.97; 95% CI 0.90 to 1.05; 12 trials, 55,858 participants) and cardiovascular mortality (RR 0.95; 95% CI 0.80 to 1.12, 12 trials, 53,421 participants) were less clear (both GRADE moderate quality of evidence). There was some evidence that reducing saturated fats reduced the risk of myocardial infarction (fatal and non-fatal, RR 0.90; 95% CI 0.80 to 1.01; 11 trials, 53,167 participants), but evidence for non-fatal myocardial infarction (RR 0.95; 95% CI 0.80 to 1.13; 9 trials, 52,834 participants) was unclear and there were no clear effects on stroke (any stroke, RR 1.00; 95% CI 0.89 to 1.12; 8 trials, 50,952 participants). These relationships did not alter with sensitivity analysis. Subgrouping suggested that the reduction in cardiovascular events was seen in studies that primarily replaced saturated fat calories with polyunsaturated fat, and no effects were seen in studies replacing saturated fat with carbohydrate or protein, but effects in studies replacing with monounsaturated fats were unclear (as we located only one small trial). Subgrouping and meta-regression suggested that the degree of reduction in cardiovascular events was related to the degree of reduction of serum total cholesterol, and there were suggestions of greater protection with greater saturated fat reduction or greater increase in polyunsaturated and monounsaturated fats. There was no evidence of harmful effects of reducing saturated fat intakes on cancer mortality, cancer diagnoses or blood pressure, while there was some evidence of improvements in weight and BMI.
In other words, no benefit from reducing SFA per se (some non-significant trends towards small benefits) on mortality and hard endpoints such as heart attacks. Non-significant trends and even null associations have been written up here as if they are meaningful. The Cochrane Collaboration surely wouldn't allow this in a review of drug trials, so why is it okay here?
Beneficial association between reduced SFA and cardiovascular events (17% RR), which is dependent on what SFA is replaced with, i.e. only PUFA. Because there is no reduction in individual classes of serious events, it's possible that the symptomatic relief of angina is the main benefit being shown here, but those figures aren't presented. In any case, this is almost certainly an effect of higher PUFA intakes and not SFA reduction.
An interesting point here is that this is the opposite of the prospective cohort data. Jakobsen et al. and Farvid et al. state that replacing SFA with PUFA (5%E) is associated with a 13% lower rate of CHD mortality, yet has (in Farvid et al.) non-significant effects on cardiovascular events in the randomised model. Non-randomised results from Farvid et al.:
“When the highest category was compared with the lowest category, dietary LA was associated with a 15% lower risk of CHD events (pooled RR, 0.85; 95% confidence intervals, 0.78-0.92; I(2)=35.5%) and a 21% lower risk of CHD deaths (pooled RR, 0.79; 95% confidence intervals, 0.71-0.89; I(2)=0.0%). A 5% of energy increment in LA intake replacing energy from saturated fat intake was associated with a 9% lower risk of CHD events (RR, 0.91; 95% confidence intervals, 0.87-0.96) and a 13% lower risk of CHD deaths (RR, 0.87; 95% confidence intervals, 0.82-0.94).”
Results from Jakobsen et al.
“For a 5% lower energy intake from SFAs and a concomitant higher energy intake from PUFAs, there was a significant inverse association between PUFAs and risk of coronary events (hazard ratio: 0.87; 95% CI: 0.77, 0.97); the hazard ratio for coronary deaths was 0.74 (95% CI: 0.61, 0.89).”
Subgroup analysis reveals that this effect on cardiovascular events in Hooper et al. 2015 is specific to PUFA and, though it is related to LDL, it depends on PUFA, not CHO, being the LDL-lowering replacement for SFA.
"We found no important effects of reducing SFA compared to usual or control diets on mortality when we subgrouped studies by SFA replacement (with PUFA, MUFA, CHO, or protein), mean duration, baseline SFA intake, or difference in SFA between intervention and control arms, decade of publication, or degree of reduction of serum total cholesterol. "
"There was a reduction in LDL in participants with reduced SFA compared to usual diet (MD -0.19 mmol/L, 95% CI -0.33 to -0.05, I² 37%, 5 RCTs, 3291 participants, P 0.006). There was no clear differential effect on LDL depending on the replacement for SFA (PUFA, MUFA, CHO or a mixture). "
yet - " the subgroup of studies which achieved a reduction in serum total cholesterol of at least 0.2 mmol/L reduced cardiovascular events by 26%, while studies that did not achieve this cholesterol reduction showed no clear effect."
"When we subgrouped according to replacement for SFA, the PUFA replacement group suggested a 27% reduction in cardiovascular events, while there were no clear effects of other replacement groups."
By the same token, harmful effects of higher PUFA intakes may also take years to develop.
"One surprising element of this review is the lack of ongoing trials. In all previous reviews we have been aware of ongoing trials, the results of which were likely to inform the review, but for this review we have not noted any new trials on the horizon and so perhaps the current evidence set is as definitive as we will achieve during the 'statin era'."
I predict that towards the end of the "statin era" we will begin to see RCTs of LCHF and Paleo diets in the primary and secondary prevention of CVD/CHD. And I predict that, given the very low bar set by SFA restricted diets - which seem here to be not much better for you than the rubbish people normally eat before they end up in hospital, which was after all the composition of the control diets - LCHF and Paleo diets will do pretty well in this regard.
According to Hooper's 2010 editorial she thinks this back-dated evidence, from times when PUFA baselines were lower than today, justifies current PUFA intakes - it does not necessarily warrant an increase on the scale suggested by Mozaffarian.
"Mozaffarian and colleagues go further in presenting
their results as a 10% risk reduction for each additional
5% of PUFA consumption, although they present no evidence
of a dose-response relationship (not presenting
subgrouping or meta-regression by PUFA intake) and do
not explain how much of the PUFA consist of ω-3 fats
in each trial.
This review addresses an important question and
re-opening the debate on the effectiveness of replacing saturated
by polyunsaturated fats on coronary heart disease
is very welcome. However, dietary patterns have changed
over the 20–50 years since these studies ware carried out.
It would be useful to examine the full data set, including
more recent trials before concluding, as the abstract does,
that “a shift toward greater population PUFA consumption
in place of SFA would significantly reduce rates of CHD.”
Such a shift has already occurred since these trials were
carried out, and further shifts may be unhelpful."
Hooper L. Meta-analysis of RCTs finds that increasing consumption of polyunsaturated fat as a replacement for saturated fat reduces the risk of coronary heart disease. . doi:10.1136/ebm1093.
C-enzyme Q10 and tocopherols as confounders in PUFA oils