PURE study
© Lancet
A new study of dietary habits in 135,000 people around the world is set to shake up the nutrition field, with results showing high fat intake-including saturated fat-was associated with a reduced risk of mortality.

The PURE study, which followed participants from 18 countries for 7 years, also found that high carbohydrate intake was associated with an increased risk of mortality, although the data do not discriminate between processed and unprocessed carbohydrates.

While the study found a beneficial effect of increasing consumption of fruit, vegetables, and legumes on mortality, the maximum benefit was seen at three to four servings a day (equivalent to 375-500 g/day), with no additional benefit with higher intakes. The benefit from fruit, vegetables, and legumes was greater if they were eaten raw rather than cooked.

There was no association of either fat (total or saturated) or carbohydrate intake or fruit/vegetable/legume intake with major cardiovascular-disease events.

Senior author of the PURE study, Dr Salim Yusuf (McMaster University, Hamilton, ON), commented to theheart.org / Medscape Cardiology: "My hope is that our results will stop the whole population from feeling guilty if they eat fat in moderation. While very high fat intake-when it accounts for 40% or more of your dietary intake-may be bad, the average fat intake is about 30% and that's okay. We're all afraid of saturated fat, but actually we shouldn't be. Saturated fat in moderation actually appears good for you.

"Also, you don't need to stress out trying to eat five or more portions of fruit and vegetables, when three or four will probably have the same benefits. We've had enough evangelism in dietary guidelines. We need more moderation."

He added: "My advice to the general population to lead a healthy lifestyle is don't smoke and take exercise-those two things are very clearly beneficial. And then I would say maintain a reasonable weight. You don't want to be too overweight but you also don't want to be too skinny. Eat a balanced diet-a bit of meat, fish, several portions of fruit and vegetables, but you don't have to be vegan or eat an excessive amount of plants to be healthy.

"This is good old-fashioned advice. When I showed these results to my mother, she said, 'Why did you bother doing this study? This is what our grandmothers and their grandmothers have been advocating for centuries.' And actually she is right."

The study was presented today at the European Society of Cardiology 2017 Congress. It was also published as two separate papers in the Lancet-one on the fat and carbohydrate outcome data[1] and one on fruit/vegetables/legumes outcome data[2]. A third paper in Lancet Diabetes and Endocrinology focuses on effects of the different dietary patterns on lipid levels and blood pressure[3].

The PURE trial documented 5796 deaths and 4784 major cardiovascular-disease events.

Directly Contradictory to Recent AHA Advisory

The saturated-fat findings will be particularly controversial, especially in the cardiology community, which has traditionally held the mantra that saturated fat is the number-one dietary enemy.

Indeed, just a few weeks ago, the American Heart Association issued a new "advisory" recommending minimizing intake of saturated fat and replacing it with polyunsaturated fat or carbohydrate. The PURE findings appear to be in direct contradiction to this advice.

Commenting on this at her hotline presentation, PURE co-lead author Dr Mahshid Dehghan (McMaster University) said: "The upper levels of saturated fat intake in our study (mean 10%-13% of dietary energy) was associated with a significantly reduced mortality compared with low levels of saturated fat, and very low saturated-fat intake appears harmful. Current guidelines that recommend total fat below 30% and saturated fat below 10% of energy intake are not supported by our data."

Yusuf commented further: "The AHA guidelines are not based on the best evidence-saturated fat was labeled as a villain years ago, and the traditional church has kept on preaching that message. They have been resistant to change."

The AHA issued a statement in response to the PURE data stating "a nutrition study of PURE's scale and scope is extremely challenging" and suggesting the PURE results "be interpreted with significant caution."

The AHA says the self-reported food frequency questionnaire used as the study tool "poses some limitations." Specifically, "Individuals tend to over- or underrecall food intake, in general. In addition, the tool may not fully account for cultural differences in food patterns and may underrepresent locally relevant foods."

But the AHA added: "While we feel it's important to pay attention to saturated fats and refined carbohydrates, they are just part of the puzzle. Consumers should focus on an overall balanced diet."

Co-chair of ESC hotline session, Dr Laura Mauri (Brigham and Women's Hospital, Boston, MA), congratulated the PURE investigators for "this incredible source of information" but asked how the data can be compared with the randomized trials such as PREDIMED with the Mediterranean diet.

Dehghan replied: "Randomized trials of nutrition are difficult to conduct, as people need to be followed for many years, which is not really feasible. Observational studies with biomarker data probably give better information as long as there is extensive adjustment for confounding."

Others questioned whether the PURE data were applicable to a US population, as the study included only three Western countries (Canada, Sweden, and Poland), which contributed just 12% of the study participants.

Dehghan responded on this to theheart.org / Medscape Cardiology "We believe our message is relevant to the US population. Our data included saturated-fat levels up to about 18% of dietary intake, and the average saturated-fat intake in the US is 14%. But more important, we found that low levels of saturated fat are harmful. The AHA is recommending saturated fat should be less than 6% of energy intake. Our study suggests that this is linked to higher mortality levels."

She added that an analysis of Asian vs non-Asian countries, which have very different dietary patterns, showed the same results, with higher mortality linked to lower fat and higher carbohydrate intake.

While she acknowledged that a low-fat/high-carbohydrate profile may be a proxy for poverty, she pointed out that the PURE results had been "extensively adjusted for many confounders, including household income-more so than in any previous study."

She reported a model in which which replacing 5% of energy from carbohydrate with polyunsaturated fat was associated with a statistically significant 11% reduction in mortality. Replacing 5% of carbohydrate with saturated fat, monounsaturated fat, or protein was associated with smaller nonsignificant reductions in mortality. All these substitutions had no effect on cardiovascular disease in the model.

Asked what the mechanism could be behind the mortality effects if it wasn't cardiovascular, Dehghan said: "We think it is a noncardiovascular mechanism-maybe cancer, infectious disease, or respiratory disease-but we don't have enough events as yet to make any statements on this. We hope to find more data on cause of deaths as we keep following the population in the future."

In a comment accompanying the PURE publication in the Lancet[4], Drs Christopher E Ramsden and Anthony F Domenichiello (National Institutes of Health, Bethesda, MD), suggest that one potential explanation for the better mortality with higher fat levels in PURE could be that nutrient-dense meats corrected one or more nutrient deficiencies that are common in many of the countries included in the study.

They also suggest that the processed foods, including added sugars and refined grains, are likely driving the adverse mortality effects with carbohydrates.

They conclude: "The PURE study is an impressive undertaking that will contribute to public health for years to come. Initial PURE findings challenge conventional diet-disease tenets that are largely based on observational associations in European and North American populations, adding to the uncertainty about what constitutes a healthy diet. This uncertainty is likely to prevail until well-designed randomized controlled trials are done. Until then, the best medicine for the nutrition field is a healthy dose of humility."

Biomarker Data

In the biomarker paper, the PURE investigators report that intake of total fat and each type of fat was associated with higher concentrations of total cholesterol and LDL cholesterol but also with higher HDL cholesterol and apolipoprotein A1 (apoA1), and lower triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and ratio of apolipoprotein B (apoB) to apoA1.

Higher carbohydrate intake was associated with lower total cholesterol, LDL cholesterol, and apoB, but also with lower HDL cholesterol and apoA1 and higher triglycerides, ratio of total cholesterol to HDL cholesterol, ratio of triglycerides to HDL cholesterol, and apoB-to-apoA1 ratio.

Higher intakes of total fat, saturated fatty acids, and carbohydrates were associated with higher blood pressure, whereas higher protein intake was associated with lower blood pressure.

Replacement of saturated fatty acids with carbohydrates was associated with the most adverse effects on lipids, whereas replacement of saturated fatty acids with unsaturated fats improved some risk markers (LDL cholesterol and blood pressure), but seemed to worsen others (HDL cholesterol and triglycerides).

The authors conclude: "Our data are at odds with current recommendations to reduce total fat and saturated fats. Reducing saturated-fatty-acid intake and replacing it with carbohydrate has an adverse effect on blood lipids. Substituting saturated fatty acids with unsaturated fats might improve some risk markers, but might worsen others. Simulations suggest that the apoB-to-apoA1 ratio probably provides the best overall indication of the effect of saturated fatty acids on cardiovascular disease risk among the markers tested. Focusing on a single lipid marker such as LDL cholesterol alone does not capture the net clinical effects of nutrients on cardiovascular risk."

In a comment accompanying the biomarker paper[5], Drs Nita G Forouhi and Fumiaki Imamura (University of Cambridge School of Clinical Medicine, UK) and Dr Naveed Sattar (Oxford Centre for Diabetes, Endocrinology and Metabolism, UK) point out that because diet varied substantially between world regions (eg, the estimated mean saturated fat intake in China is 5.6% of total energy vs about 11% in North America and Europe), pooling data across regions might be problematic. They also recommend that the cross-sectional evidence should be considered hypothesis generating and that the prospective findings need to be replicated.

But they conclude: "For now, despite some caveats, the PURE study's findings broadly support the notion that reducing total fat intake may be unwarranted and that replacing saturated fat intake with (refined) carbohydrates is not a good recipe for cardiovascular health."

The PURE study was funded from more than 50 sources including the Population Health Research Institute at McMaster University, the Heart and Stroke Foundation of Ontario and Canada, and the Canadian Institutes of Health Research. The researchers report no relevant financial relationships.