On 2017 Jul 13, David Nunan commented:

On the day this editorial was released we contacted the Editor for consideration of the following commentary. We have yet to hear back from the Editor. To avoid further delay via formal submission, we present here a truncated version of our commentary.

Response to “Saturated fat does not clog the arteries: coronary heart disease is a chronic inflammatory condition, the risk of which can be effectively reduced from healthy lifestyle interventions”

Implausible discussions in saturated fat “research”

Definitive solutions won’t come from another million editorials (or a million views of one).

The British Journal of Sports Medicine again acts as the unusual home to an opinion editorial advocating for public health guidance on saturated fat to be revised based on selected “evidence”. As an editorial it was always going to struggle to avoid calls of “cherry picking”. More worrying was the failure to apply even the basic of evidence-based principles. Here, we do the job of authors (and editor[s]) in addressing the quality of the evidence presented and highlighting some of the contradictory evidence, the complexity and uncertainty of the evidence-base whilst being mindful of our own cognitive biases.

Effects of reducing saturated fat intake for cardiovascular disease

The authors refer to evidence from a “landmark” meta-analysis of observational studies to show a lack of an association between saturated fat consumption and all-cause mortality, coronary artery disease incidence and mortality, ischaemic stroke, and type 2 diabetes [1]. According to best practice evidence-based methods, the types of studies included here provide low quality evidence (unless specific criterion are met) [2]. Indeed, the review authors actually reported the certainty of reported associations (or lack there of) was “very low”, indicating any estimates of the effect are very uncertain [1].

Conversely, a high-quality meta-analysis of available RCTs (n= 17 with ~59,000 participants) from the Cochrane Collaboration, found moderate quality evidence from long-term trials that reducing dietary saturated fat lowered the risk of cardiovascular events (number needed to treat [NNT]=14), but no effect on all-cause and cardiovascular mortality, risk of myocardial infarction, and stroke, compared to usual diet [3]. The Cochrane review also found in subgroup analyses, the reduction in cardiovascular events was observed in the studies replacing saturated fat with polyunsaturated fat (but not with carbohydrates, protein, or monounsaturated fat).

Thus the consensus viewpoint of a beneficial effect of reduced dietary saturated fat and replacement with polyunsaturated fat in the general population appears to be underpinned by a higher quality evidence base.

Benefits of a Mediterranean diet on primary and secondary cardiovascular disease

In the section “dietary RCTs with outcome benefit in primary and secondary prevention”, the authors switch from saturated fat to low fat diets and cite two trials, namely the PREDIMED study [5] and the Lyon Diet Heart study [6].

The PREDIMED study investigated the effects of a Mediterranean diet including fish, whole grain cereals, fruits and supplemented with extra-virgin olive oil versus the same Mediterranean diet supplemented with mixed nuts, versus advice to reduce dietary fat on primary prevention of cardiovascular disease. The dietary interventions in PREDIMED were designed to increase intakes of mono- and poly-unsaturated fat and reduce intake of saturated fat.

The Lyon Diet Heart study examined the impact of a Mediterranean alpha-linolenic acid-rich (with significantly less lipids, saturated fat, cholesterol, and linoleic acid) compared to no dietary advice. This study also aimed to assess the effect of increase dietary intake of unsaturated (polyunsaturated) fats.

Both these studies support the current consensus to increase intakes of polyunsaturated dietary fats in replacement of saturated fat. These findings also suggest placing a limit on the percentage of calories from unsaturated fats may be unwarranted which has now been acknowledged in a recent consensus [7].

Furthermore, a meta-analysis reviewing the effects of the Mediterranean diet on vascular disease and mortality [8], found that using the best available data the Mediterranean diet reduced vascular events and incidence of stroke, but did not result in improvements in all-cause mortality, cardiovascular mortality, coronary events, or heart failure compared to controls. The review authors highlighted the limited quantity and quality of evidence and the uncertainty of the effects of a Mediterranean diet on cardiovascular outcomes, and the non-existence of data about adverse outcomes.

LDL-Cholesterol and Cardiovascular mortality

The authors support their view that the cardiovascular risk of LDL-cholesterol has been exaggerated with 45 year-old data from the Minnesota Coronary Experiment (MCE) [9] and a systematic review of observational studies [10]. However, the authors do not address observed limitations of the MCE study including discrepant event rate and selective outcome reporting, over 80% attrition (with lack of intention-to-treat analysis and a small event rate difference (n=21) plausibly driven by a higher unexplained drop out in the control group [11].

The review cited found that LDL-cholesterol is not associated with cardiovascular disease and is inversely associated with all-cause mortality in elderly populations [10]. However, the methodological quality of this review has been judged to be poor for, among other problems, non-uniform application of inclusion/exclusion criteria, a lack of critical appraisal of the methods used in the eligible studies (low quality observational studies), failure to account for multifactorial analysis (i.e., lack of control for confounders), and not considering statin use (see Eatz letter in response to [12] and [13]).

The authors fail to discuss large-scale RCT evidence showing that LDL-cholesterol reducing statin therapy reduces the risk of coronary deaths, myocardial infarction, strokes, coronary revascularisation procedures by ~25% for each mmol/L reduction in LDL-cholesterol during each year, following the first, it is taken [14]. We are aware of the on-going debate around the integrity of the data in relation to statins, particularly around associated harms, and their potential mechanisms. However, there appears general consensus on their effectiveness in reducing hard endpoints regardless of their underlying mechanism.

Therefore, given the flaws of the referenced trial and systematic review of observational studies and evidence in support of benefits of LDL-cholesterol lowering therapy, it is too early to dismiss LDL-cholesterol as a risk factor for cardiovascular disease and mortality.

We note with interest the authors’ statement “There is no business model or market to help spread this simple yet powerful intervention.” It’s not beyond comprehension that journals present a credible business model based on attracting controversy in areas of public health importance where clarity, not confusion, is needed. Notable conflicts of interest include income from a low budget film purporting the benefits of a high saturated fat diet.

The latest opinion editorial overlooks a large contradictory evidence-base and the inherent uncertainty with nutritional epidemiological studies and trials [15]. Arguably what is needed is a balanced discussion of dietary patterns over and above individual macronutrients that considers collaborative efforts for improving the evidence-base and our understanding of the complex relationship between dietary fat and health.

References available from corresponding author.

David Nunan^1*, Ian Lahart^2. ^1Senior Researcher, University of Oxford, UK. david.nunan@phc.ox.ac.uk *Corresponding author ^2Senior Lecturer in Exercise Physiology, University of Wolverhampton, UK

On 2017 Jul 13, David Nunan commented:

On the day this editorial was released we contacted the Editor for consideration of the following commentary. We have yet to hear back from the Editor. To avoid further delay via formal submission, we present here a truncated version of our commentary.

Response to “Saturated fat does not clog the arteries: coronary heart disease is a chronic inflammatory condition, the risk of which can be effectively reduced from healthy lifestyle interventions”

Implausible discussions in saturated fat “research”

Definitive solutions won’t come from another million editorials (or a million views of one).

The British Journal of Sports Medicine again acts as the unusual home to an opinion editorial advocating for public health guidance on saturated fat to be revised based on selected “evidence”. As an editorial it was always going to struggle to avoid calls of “cherry picking”. More worrying was the failure to apply even the basic of evidence-based principles. Here, we do the job of authors (and editor[s]) in addressing the quality of the evidence presented and highlighting some of the contradictory evidence, the complexity and uncertainty of the evidence-base whilst being mindful of our own cognitive biases.

Effects of reducing saturated fat intake for cardiovascular disease

The authors refer to evidence from a “landmark” meta-analysis of observational studies to show a lack of an association between saturated fat consumption and all-cause mortality, coronary artery disease incidence and mortality, ischaemic stroke, and type 2 diabetes [1]. According to best practice evidence-based methods, the types of studies included here provide low quality evidence (unless specific criterion are met) [2]. Indeed, the review authors actually reported the certainty of reported associations (or lack there of) was “very low”, indicating any estimates of the effect are very uncertain [1].

Conversely, a high-quality meta-analysis of available RCTs (n= 17 with ~59,000 participants) from the Cochrane Collaboration, found moderate quality evidence from long-term trials that reducing dietary saturated fat lowered the risk of cardiovascular events (number needed to treat [NNT]=14), but no effect on all-cause and cardiovascular mortality, risk of myocardial infarction, and stroke, compared to usual diet [3]. The Cochrane review also found in subgroup analyses, the reduction in cardiovascular events was observed in the studies replacing saturated fat with polyunsaturated fat (but not with carbohydrates, protein, or monounsaturated fat).

Thus the consensus viewpoint of a beneficial effect of reduced dietary saturated fat and replacement with polyunsaturated fat in the general population appears to be underpinned by a higher quality evidence base.

Benefits of a Mediterranean diet on primary and secondary cardiovascular disease

In the section “dietary RCTs with outcome benefit in primary and secondary prevention”, the authors switch from saturated fat to low fat diets and cite two trials, namely the PREDIMED study [5] and the Lyon Diet Heart study [6].

The PREDIMED study investigated the effects of a Mediterranean diet including fish, whole grain cereals, fruits and supplemented with extra-virgin olive oil versus the same Mediterranean diet supplemented with mixed nuts, versus advice to reduce dietary fat on primary prevention of cardiovascular disease. The dietary interventions in PREDIMED were designed to increase intakes of mono- and poly-unsaturated fat and reduce intake of saturated fat.

The Lyon Diet Heart study examined the impact of a Mediterranean alpha-linolenic acid-rich (with significantly less lipids, saturated fat, cholesterol, and linoleic acid) compared to no dietary advice. This study also aimed to assess the effect of increase dietary intake of unsaturated (polyunsaturated) fats.

Both these studies support the current consensus to increase intakes of polyunsaturated dietary fats in replacement of saturated fat. These findings also suggest placing a limit on the percentage of calories from unsaturated fats may be unwarranted which has now been acknowledged in a recent consensus [7].

Furthermore, a meta-analysis reviewing the effects of the Mediterranean diet on vascular disease and mortality [8], found that using the best available data the Mediterranean diet reduced vascular events and incidence of stroke, but did not result in improvements in all-cause mortality, cardiovascular mortality, coronary events, or heart failure compared to controls. The review authors highlighted the limited quantity and quality of evidence and the uncertainty of the effects of a Mediterranean diet on cardiovascular outcomes, and the non-existence of data about adverse outcomes.

LDL-Cholesterol and Cardiovascular mortality

The authors support their view that the cardiovascular risk of LDL-cholesterol has been exaggerated with 45 year-old data from the Minnesota Coronary Experiment (MCE) [9] and a systematic review of observational studies [10]. However, the authors do not address observed limitations of the MCE study including discrepant event rate and selective outcome reporting, over 80% attrition (with lack of intention-to-treat analysis and a small event rate difference (n=21) plausibly driven by a higher unexplained drop out in the control group [11].

The review cited found that LDL-cholesterol is not associated with cardiovascular disease and is inversely associated with all-cause mortality in elderly populations [10]. However, the methodological quality of this review has been judged to be poor for, among other problems, non-uniform application of inclusion/exclusion criteria, a lack of critical appraisal of the methods used in the eligible studies (low quality observational studies), failure to account for multifactorial analysis (i.e., lack of control for confounders), and not considering statin use (see Eatz letter in response to [12] and [13]).

The authors fail to discuss large-scale RCT evidence showing that LDL-cholesterol reducing statin therapy reduces the risk of coronary deaths, myocardial infarction, strokes, coronary revascularisation procedures by ~25% for each mmol/L reduction in LDL-cholesterol during each year, following the first, it is taken [14]. We are aware of the on-going debate around the integrity of the data in relation to statins, particularly around associated harms, and their potential mechanisms. However, there appears general consensus on their effectiveness in reducing hard endpoints regardless of their underlying mechanism.

Therefore, given the flaws of the referenced trial and systematic review of observational studies and evidence in support of benefits of LDL-cholesterol lowering therapy, it is too early to dismiss LDL-cholesterol as a risk factor for cardiovascular disease and mortality.

We note with interest the authors’ statement “There is no business model or market to help spread this simple yet powerful intervention.” It’s not beyond comprehension that journals present a credible business model based on attracting controversy in areas of public health importance where clarity, not confusion, is needed. Notable conflicts of interest include income from a low budget film purporting the benefits of a high saturated fat diet.

The latest opinion editorial overlooks a large contradictory evidence-base and the inherent uncertainty with nutritional epidemiological studies and trials [15]. Arguably what is needed is a balanced discussion of dietary patterns over and above individual macronutrients that considers collaborative efforts for improving the evidence-base and our understanding of the complex relationship between dietary fat and health.

References available from corresponding author.

David Nunan^1*, Ian Lahart^2. ^1Senior Researcher, University of Oxford, UK. david.nunan@phc.ox.ac.uk *Corresponding author ^2Senior Lecturer in Exercise Physiology, University of Wolverhampton, UK