Association of dairy intake with cardiovascular disease and mortality in 21 countries from five continents (PURE): a prospective cohort study

Summary

Background

Dietary guidelines recommend minimising consumption of whole-fat dairy products, as they are a source of saturated fats and presumed to adversely affect blood lipids and increase cardiovascular disease and mortality. Evidence for this contention is sparse and few data for the effects of dairy consumption on health are available from low-income and middle-income countries. Therefore, we aimed to assess the associations between total dairy and specific types of dairy products with mortality and major cardiovascular disease.

Methods

The Prospective Urban Rural Epidemiology (PURE) study is a large multinational cohort study of individuals aged 35–70 years enrolled from 21 countries in five continents. Dietary intakes of dairy products for 136 384 individuals were recorded using country-specific validated food frequency questionnaires. Dairy products comprised milk, yoghurt, and cheese. We further grouped these foods into whole-fat and low-fat dairy. The primary outcome was the composite of mortality or major cardiovascular events (defined as death from cardiovascular causes, non-fatal myocardial infarction, stroke, or heart failure). Hazard ratios (HRs) were calculated using multivariable Cox frailty models with random intercepts to account for clustering of participants by centre.

Findings

Between Jan 1, 2003, and July 14, 2018, we recorded 10 567 composite events (deaths [n=6796] or major cardiovascular events [n=5855]) during the 9·1 years of follow-up. Higher intake of total dairy (>2 servings per day compared with no intake) was associated with a lower risk of the composite outcome (HR 0·84, 95% CI 0·75–0·94; p_trend=0·0004), total mortality (0·83, 0·72–0·96; p_trend=0·0052), non-cardiovascular mortality (0·86, 0·72–1·02; p_trend=0·046), cardiovascular mortality (0·77, 0·58–1·01; p_trend=0·029), major cardiovascular disease (0·78, 0·67–0·90; p_trend=0·0001), and stroke (0·66, 0·53–0·82; p_trend=0·0003). No significant association with myocardial infarction was observed (HR 0·89, 95% CI 0·71–1·11; p_trend=0·163). Higher intake (>1 serving vs no intake) of milk (HR 0·90, 95% CI 0·82–0·99; p_trend=0·0529) and yogurt (0·86, 0·75–0·99; p_trend=0·0051) was associated with lower risk of the composite outcome, whereas cheese intake was not significantly associated with the composite outcome (0·88, 0·76–1·02; p_trend=0·1399). Butter intake was low and was not significantly associated with clinical outcomes (HR 1·09, 95% CI 0·90–1·33; p_trend=0·4113).

Interpretation

Dairy consumption was associated with lower risk of mortality and major cardiovascular disease events in a diverse multinational cohort.

Funding

Full funding sources are listed at the end of the paper (see Acknowledgments).

Introduction

Cardiovascular disease is the leading cause of mortality worldwide,¹ with 80% of the burden in low-income and middle-income countries. Dairy products are a major source of saturated fats, which have been presumed to adversely affect blood lipids and increase cardiovascular disease and mortality. Using this framework, dietary guidelines recommend minimising consumption of whole-fat dairy products for cardiovascular disease prevention in populations.² However, dairy products and dairy fat also contain potentially beneficial compounds—including specific aminoacids, medium-chain and odd-chain saturated fats, milk fat globule phospholipids, unsaturated and branched-chain fats, natural trans fats, vitamin K1 and K2, and calcium—and can contain probiotics, many of which might also affect health outcomes.³ Therefore, the net effect of dairy intake on health outcomes might not be reliably informed solely from its effect on a single risk marker (ie, LDL cholesterol) or fatty acids.

Research in context

Evidence before this study

Dietary guidelines recommend restricting the consumption of whole-fat dairy products based on concerns about an adverse effect on blood lipids. We systematically searched PubMed for relevant articles on dairy consumption published between Jan 1, 1970, and April 1, 2018, restricted to the English language using the search terms “total dairy”, “milk”, “yoghurt”, “yogurt”, “cheese”, “cream”, “butter”, “low fat dairy”, “whole fat dairy”, “high fat dairy”, “mortality”, and “cardiovascular disease”. Studies that evaluated association of dairy or dairy products and mortality and cardiovascular disease were considered. Most data are from Europe and North America and have yielded conflicting results, perhaps because of their relatively small sizes and few events.

Added value of this study

We studied 136 384 individuals from 21 countries in whom 10 567 events were recorded. Consistent with the meta-analysis of observational studies and randomised trials, but in contrast to current dietary guidelines, we found that greater dairy consumption was associated with lower risk of mortality and cardiovascular disease.

Implications of all the available evidence

In the context of all other related studies, findings from the Prospective Urban Rural Epidemiology (PURE) study indicate that consumption of dairy products should not be discouraged and perhaps even be encouraged in low-income and middle-income countries where dairy consumption is low.

Dairy products are a diverse food group, some are non-fermented (eg, milk) and others are fermented (eg, yoghurt and cheese), and these different foods could have varying effect on cardiovascular diseases and mortality. For example, a meta-analysis of cohort studies suggested a lower risk of hypertension with increasing milk consumption,⁴ with a neutral effect on cardiovascular disease.⁵ Mendelian randomisation studies did not show that dairy may be associated with hypertension, although a reduction in blood pressure was associated with dairy intake in the Dietary Approaches to Stop Hypertension (DASH) trial.5, 6 Meta-analysis of 20 randomised trials showed a non-significant increase in LDL cholesterol with either higher intake of whole-fat dairy or low-fat dairy.⁷ Another meta-analysis of small randomised trials showed that compared with tofu or fat-modified cheeses, cheese consumption increased LDL cholesterol concentration by a modest amount.⁸ Butter is also weakly associated with total mortality but is not associated with cardiovascular disease.⁹ However, other cohort studies have reported inconsistent results.¹⁰ Furthermore, most studies have been done in North America and Europe, where dairy consumption and saturated fatty acids intake are much higher than in other regions of the world (eg, China, India, and Africa). In North America and Europe, coronary heart disease is more common than strokes, whereas strokes are more common than coronary heart disease in other regions such as east Asia and Africa. Therefore, data from all world regions are essential to making global policy recommendations.

The Prospective Urban Rural Epidemiology (PURE) study provides a unique opportunity to study the associations of dairy intake and types of dairy products with cardiovascular disease events and mortality in diverse settings. Our aim was to assess the associations between total dairy and specific types of dairy products with mortality and major cardiovascular disease.