Elsevier

Clinical Nutrition

Volume 35, Issue 2, April 2016, Pages 496-506
Clinical Nutrition

Original article
High dietary protein intake is associated with an increased body weight and total death risk

https://doi.org/10.1016/j.clnu.2015.03.016Get rights and content

Highlights

  • Higher protein intake is related to a high risk of weight gain and death at long-term.

  • Higher animal protein intake is related to fatal and non-fatal cardiovascular outcomes.

  • No association was found between protein intake and abdominal obesity.

Summary

Background & aims

High dietary protein diets are widely used to manage overweight and obesity. However, there is a lack of consensus about their long-term efficacy and safety. Therefore, the aim of this study was to assess the effect of long-term high-protein consumption on body weight changes and death outcomes in subjects at high cardiovascular risk.

Methods

A secondary analysis of the PREDIMED trial was conducted. Dietary protein was assessed using a food-frequency questionnaire during the follow-up. Cox proportional hazard models were used to estimate the multivariate-adjusted hazard ratio (HR) and 95% confidence intervals (95%CI) for protein intake in relation to the risk of body weight and waist circumference changes, cardiovascular disease, cardiovascular death, cancer death and total death.

Results

Higher total protein intake, expressed as percentage of energy, was significantly associated with a greater risk of weight gain when protein replaced carbohydrates (HR: 1.90; 95%CI: 1.05, 3.46) but not when replaced fat (HR: 1.69; 95%CI: 0.94, 3.03). However, no association was found between protein intake and waist circumference. Contrary, higher total protein intake was associated with a greater risk of all-cause death in both carbohydrate and fat substitution models (HR: 1.59; 95%CI: 1.08, 2.35; and HR: 1.66; 95%CI: 1.13, 2.43, respectively). A higher consumption of animal protein was associated with an increased risk of fatal and non-fatal outcomes when protein substituted carbohydrates or fat.

Conclusions

Higher dietary protein intake is associated with long-term increased risk of body weight gain and overall death in a Mediterranean population at high cardiovascular risk.

Introduction

The alarming rise in overweight and obesity in developing countries has generated a plethora of dietary strategies for managing body weight. Moderate- or high-protein diets have gained in popularity and have been widely promoted for losing weight, preserving lean body mass, and maintaining weight loss [1]. Advocates of these diets often recommend protein intakes at or above 1.2 g protein/kg body weight/day (g prot/kg BW/d) or >25E% (percentage of energy) consumed. These amounts are substantially higher than usual recommendations for healthy adults which are set at 0.8 g prot/kg BW/d [2], [3], [4] or recent recommendations for healthy older subjects set at 1.0–1.2 g protein/kg BW/day [5].

Several randomized controlled trials (RCTs) have investigated the short-term effects of high-protein (HPD) versus low-protein (LPD) diets and reported that HPD have advantages in terms of adiposity and blood lipid profile [6], [7], [8]. Similarly, in a pooled analysis of 15 RCTs lasting between 28 days and 12 months, HPD showed favorable effects on obesity and cardiovascular risk markers [9]. In addition, a meta-analysis of weight-loss studies conducted in adults consuming either a HPD (>15E%) or a LPD (<15E%) with a follow-up of at least 12 months, demonstrated a greater body weight (BW) loss and an improvement of triglyceride and insulin levels in HPD. However, no differences were observed in concentrations of HDL and LDL-cholesterol or fasting glucose [10]. Despite the generalized use of HPD, there is no consensus about their long-term efficacy and safety. A meta-analysis of RCTs with a minimum 12-month follow-up demonstrated that high-protein diets (up to 25E%) had neither beneficial nor detrimental effects on weight, body composition and fat distribution, or cardiovascular risk [11]. Data from large-scale, long-term cohort studies have shown a positive association between protein intake and weight gain [12], [13], [14] and suggest that physiological mechanisms supporting the beneficial effect of high protein intake in weight control could depend on body mass index and waist circumference [14]. Additionally, in two recent systematic reviews conducted in healthy adults [15] and older adults [16], including prospective cohort, case–control and long-term intervention studies, the association between protein consumption and different clinical outcomes ranged from probable or suggestive to inconclusive. Safer intakes were between 15 and 20E% of total protein, and inconclusively harmful were above 20–23E%. Risk of all-cause death and type 2 diabetes (T2D) seemed to increase with long-term total protein intake of 20–23E%.

Since there is a lack of consensus about the long-term associations between the amount and type of dietary protein, weight control and death, the aim of the present study was to analyse, in the same population, both the long-term body weight changes and the incidence of several fatal clinical outcomes resulting from total, animal and vegetable protein consumption in a high cardiovascular risk cohort.

Section snippets

Study population

This prospective cohort analysis was based on the PREDIMED (PREvención con DIeta MEDiterránea) cohort, which is a large, parallel group, multicenter, controlled, randomized clinical trial conducted in 7447 older adults at high cardiovascular risk. The aim was to assess the effects of Mediterranean diet on the primary prevention of diseases with cardiovascular origin. The detailed study protocol was already published [17]. Eligible participants were men (55–80 years) and women (60–80 years),

Results

Of the 7447 subjects in the PREDIMED cohort, 7216 were included in this secondary analysis. Subjects with extremes of total energy intake (n = 153) and with incomplete dietary data at baseline were excluded (n = 78). The baseline characteristics of the study population according to the quintile of cumulative average E% from total protein are shown in Table 1. Participants in the highest quintile of dietary protein had a higher prevalence of diabetes and a family history of CV disease, but a

Discussion

The main findings of the present study indicate that long-term high protein intake seems to be associated with an increased risk of weight gain, and overall death in middle-aged subjects and older adults at high cardiovascular risk, compared with moderate consumption. Moreover, higher animal protein consumption was associated with an increased risk of cardiovascular event and cardiovascular, cancer and total death, compared with moderate consumption.

Conclusions

Taken together, the results of our study do not support the generalized use of high protein diets as a tool for better weight control in the long term and indicate that in middle-aged subjects or older adults these diets can have potentially adverse health consequences related to cardiovascular disease and cancer. There is a huge need for further molecular and clinical studies to elucidate the mechanisms by which the quantity and source of protein can differentially affect body composition and

Statement of authorship

The authors' responsibilities are as follows: MB and JS-S had full access to all the data in the study and take full responsibility for the integrity and accuracy of the data analysis. Study concept and design: MB and JS-S. Acquisition of data: MB, MR-C, DC, RE, MF, FA, EG-G, MF, JL, JB, LS-M, MAM, PB-C, CS and JS-S. Analysis and interpretation of data: PH-A, MB, JS-S. Drafting the manuscript: PH-A, MB, JS-S. Critical revision of the manuscript for important intellectual content: PH-A, MB,

Conflict of interest

JS-S serves on the board of the International Nut and Dried Fruit Council, and receives grant support through his institution from the International Nut and Dried Fruit Council. LS-M serves on the boards of the Mediterranean Diet Foundation. No other potential conflict of interest relevant to this article was reported.

Funding sources

We acknowledge Ciberobn and RTIC RD 06/0045 and FIS PI12/0153, PI05/2584 and PI07/1138, which are initiatives of ISCIII, Spain, and are grateful for the grants from the Centro Nacional de Investigaciones Cardiovasculares (CNIC 06/2007), Fondo de Investigación Sanitaria (PI07/0473; PI10/02658; PI12/0153), Ministerio de Ciencia e Innovación (AGL-2009-13906-C02, AGL2010-22319-C03), Ministerio de Sanidad-Plan Nacional de drogas (2010/087) and Fundación Mapfre 2010, the Government of the Basque

Acknowledgments

The authors thank the participants for their enthusiastic collaboration, the PREDIMED personnel for excellent assistance and the personnel of all affiliated primary care centers.

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