This article is a collaboration between MedPage Today and:

BARCELONA -- An enormous prospective study of food intake in adults, reported here, challenges several staunchly held beliefs about dietary components and their association with health risks: finding, for example that diets rich in fats, including saturated fats, don't increase mortality risk, but high-carbohydrate diets do.

And the study, called PURE (Prospective Urban Rural Epidemiology), also found that the benefits of fruits, vegetables, and legumes top out at just three to four total servings per day.

In sum, the results suggest that nutritional guidelines and conventional wisdom regarding these basic dietary elements may be seriously mistaken.

PURE investigators recorded food intake using questionnaires in 135,000 people in 18 countries, including high-, medium- and low-income nations. The latest findings from the ongoing study, with median follow-up of 7.4 years, were outlined in two separate presentations at the European Society of Cardiology meeting here, which were accompanied by simultaneous publications in The Lancet and in Lancet: Diabetes & Endocrinology.

Carbohydrates and Fats: Unexpected Findings

One presentation and Lancet paper led by Mahshid Dehghan, PhD, of McMaster University in Hamilton, Ontario, focused on the association of fats and carbohydrate intake with cardiovascular disease and mortality.

Defying expectations, PURE found that high carbohydrate intake was associated with a significant increase in the risk of death, while both total fat and saturated and unsaturated fats were associated with a decreased risk of death. However, fat consumption was not associated with cardiovascular disease or cardiovascular mortality, though saturated fat had an inverse association with stroke.

"Global dietary guidelines should be reconsidered in light of these findings," Dehghan concluded.

These findings may be partly explained by the paper in Lancet: Diabetes & Endocrinology, which looked at the effect of dietary nutrients on lipids and blood pressure. The authors found that high intake of carbohydrates had "the most adverse impact on cardiovascular risk factors" while monounsaturated fats had a beneficial effect and saturated fat had a neutral effect.

"Reducing saturated fatty acids and replacing them with carbohydrates might have an adverse effect on cardiovascular disease risk," they concluded. "Current recommendations to reduce total fat and saturated fatty acids in all populations, which de facto increases carbohydrate intake, are not supported by our data."

Fruits, Vegetables, Legumes: Benefits Limited

The second presentation and Lancet paper, by Andrew Mente, PhD, also of McMaster University, challenges the widely held and nearly religious belief that more is always better when it comes to fruits, vegetables, and legumes.

The study did confirm that fruits and veggies (and legumes) in moderation are good for you, but it did not show that the benefits keep growing with increased consumption. Instead, the PURE researchers found that the maximum benefit was achieved with three to four serving per day. Current guidelines recommend that people consume five servings a day. The authors note that many people in lower income countries are unable to afford this high level of consumption.

"Optimal health benefits can be achieved with a more modest level of consumption, an approach that is likely to be much more affordable," write the PURE investigators.

"For the first time, our study provides a global look at the realities of people's diets in many countries and gives a clearer picture of people's fat and carbohydrate intake," said Dehghan, in a press release. "The current focus on promoting low-fat diets ignores the fact that most people's diets in low and middle income countries are very high in carbohydrates, which seem to be linked to worse health outcomes. In low- and middle-income countries, where diets sometimes consist of more than 65% of energy from carbohydrates, guidelines should refocus their attention towards reducing carbohydrate intake, instead of focusing on reducing fats. The best diets will include a balance of carbohydrates and fats – approximately 50-55% carbohydrates and around 35% total fat, including both saturated and unsaturated fats. "

Interpreting the Data

In an interview, Mente stressed both the strength and limitations of the PURE findings. As an observational study PURE is only capable of finding associations; causation is impossible to prove, though in their multivariate analysis the authors attempted to adjust for every known risk factor.

The PURE results are particularly relevant in poorer countries and in the poorer sections of richer countries, where carbs -- largely low quality -- comprise more than three-quarters of energy intake. "It's that population that needs to reduce carb intake to more moderate levels. Our data doesn't support low carb but certainly it supports a moderate carb intake of 55%," said Mente.

Similarly, he noted that existing guidelines have traditionally called for lower fat intake, below 30%, "but they haven't specified what that should be." The current papers don't give details on individual foods. Mente said that is the next stage of their research.

Mente also emphasized that the PURE results need to be put in the proper perspective. Although the associations have very large long-term population effects, at the individual level the effects are almost negligible, a fact which many people fail to grasp.

"The effects are modest effects, in the neighborhood of a 20% reduction in relative risk. So if the annual [absolute] risk of mortality is 1%, it would be reduced to 0.8%. At the individual level, it is tiny. And nowhere near what you find for smoking and lung cancer -- about 200 times smaller in fact," said Mente.

"Dietary exposures in general have modest effects on clinical outcomes. Even in the PREDIMED trial in 2013, where they evaluated an entire dietary pattern, and presumably an additive effect of multiple foods, they found a 30% reduction in risk. So you might imagine how modest the effect for individual foods would be. Typically most foods or nutrients are associated with about a 10% change in relative risk. Small."

"Having said all that, at a population level, if these small effects are true and not due to confounding, they would translate into thousands or even millions of fewer deaths annually, depending on the size of the population, if the exposure is common which is certainly true for diet. Therefore, from a public health perspective, which deals with policy and impact on populations, the findings are important."