Highlights
- •Dietary proteins are an important part of a healthy diet.
- •Higher protein diets showed favourable effects on cardiometabolic risk factors.
- •The effects were small and more research on the long-term impacts is needed.
Abstract
Background and aims
Higher protein (HP) diets may lead to lower cardiometabolic risk, compared to lower
protein (LP) diets. This systematic review and meta-analysis aims to investigate the
effects of HP versus LP diets on cardiometabolic risk factors in adults, using the totality of the current
evidence from randomised controlled trials (RCTs).
Methods
Systematic searches were conducted in electronic databases, up to November 2020. Random
effects meta-analyses were conducted to pool the standardised mean differences (SMD)
and 95% confidence intervals (CI). The main outcomes were weight loss, body mass index
(BMI), waist circumference, fat mass, systolic and diastolic BP, total cholesterol,
HDL-and LDL-cholesterol, triacylglycerol, fasting glucose and insulin, and glycated
haemoglobin.
Results
Fifty-seven articles reporting on 54 RCTs were included, involving 4344 participants
(65% female, mean age: 46 (SD 10) years, mean BMI: 33 (SD 3) kg/m2), with a mean study duration of 18 weeks (range: 4 to 156 weeks). Compared to LP
diets (range protein (E%):10–23%), HP diets (range protein (E%): 20–45%) led to more
weight loss (SMD -0.13, 95% CI: -0.23, −0.03), greater reductions in fat mass (SMD
-0.14, 95% CI: -0.24, −0.04), systolic BP (SMD -0.12, 95% CI: -0.21, −0.02), total
cholesterol (SMD -0.11, 95% CI: -0.19, −0.02), triacylglycerol (SMD -0.22, 95% CI:
-0.30, −0.14) and insulin (SMD -0.12, 95% CI: -0.22, −0.03). No significant differences
were observed for the other outcomes.
Conclusions
Higher protein diets showed small, but favourable effects on weight loss, fat mass
loss, systolic blood pressure, some lipid outcomes and insulin, compared to lower
protein diets.
Graphical abstract

Graphical Abstract
Keywords
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References
- Dietary protein intake and human health.Food Funct. 2016; 7: 1251-1265https://doi.org/10.1039/c5fo01530h
- Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids.Institute of Medicine, Washington DC2005
- Scientific opinion on dietary reference values for protein: dietary reference value for protein.EFSA J. 2012; 10: 2557https://doi.org/10.2903/j.efsa.2012.2557
- Protein intake and exercise for optimal muscle function with aging: recommendations from the ESPEN Expert Group.Clin. Nutr. 2014; 33: 929-936https://doi.org/10.1016/j.clnu.2014.04.007
- Dietary protein intake is associated with lean mass change in older, community-dwelling adults: the Health, Aging, and Body Composition (Health ABC) Study.Am. J. Clin. Nutr. 2008; 87: 150-155https://doi.org/10.1093/ajcn/87.1.150
- A review of nutritional requirements of adults aged ≥65 Years in the UK.J. Nutr. 2020; 150: 2245-2256https://doi.org/10.1093/jn/nxaa153
- Nordic Nutrition Recommendations 2012-Integrating nutrition and physical activity.Nord Nutr. Recomm. 2014. 2014; 5
- Government Dietary Recommendations-Government recommendations for energy and nutrients for males and females aged 1-18 years and 19+ years.in: Public Health England. 2016 (London, United Kingdom)
- Protein-Background document of the Dutch dietary guidelines 2015.Health Council of the Netherlands, The Hague2015
- Revised reference values for the intake of protein.Ann. Nutr. Metab. 2019; 74: 242-250https://doi.org/10.1159/000499374
- Dietary protein intake and all-cause and cause-specific mortality: results from the Rotterdam Study and a meta-analysis of prospective cohort studies.Eur. J. Epidemiol. 2020; 35: 411-429https://doi.org/10.1007/s10654-020-00607-6
- Associations of processed meat, unprocessed red meat, poultry, or fish intake with incident cardiovascular disease and all-cause mortality.JAMA Intern. Med. 2020; 180: 503-512https://doi.org/10.1001/jamainternmed.2019.6969
- Dietary protein consumption and the risk of type 2 diabetes: a systematic review and meta-analysis of cohort studies.Nutrients. 2017; 9https://doi.org/10.3390/nu9090982
- High-protein diets increase cardiovascular risk by activating macrophage mTOR to suppress mitophagy.Nat. Metab. 2020; 2: 110-125https://doi.org/10.1038/s42255-019-0162-4
- A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution.J. Clin. Invest. 2016; 126: 3263-3278https://doi.org/10.1172/JCI85946
- Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population.Cell Metabol. 2014; 19 ([pii]): 407-417https://doi.org/10.1016/j.cmet.2014.02.006S1550-4131(14)00062-X
- A word of caution against excessive protein intake.Nat. Rev. Endocrinol. 2020; 16: 59-66https://doi.org/10.1038/s41574-019-0274-7
- Effects of energy-restricted high-protein, low-fat compared with standard-protein, low-fat diets: a meta-analysis of randomized controlled trials.Am. J. Clin. Nutr. 2012; 96: 1281-1298https://doi.org/10.3945/ajcn.112.044321
- Effects of higher- versus lower-protein diets on health outcomes: a systematic review and meta-analysis.Eur. J. Clin. Nutr. 2012; 66: 780-788https://doi.org/10.1038/ejcn.2012.37
- Low-carbohydrate diets differing in carbohydrate restriction improve cardiometabolic and anthropometric markers in healthy adults: a randomised clinical trial.PeerJ. 2019; 7e6273https://doi.org/10.7717/peerj.6273
- Effect of a high protein weight loss diet on weight, high-sensitivity C-reactive protein, and cardiovascular risk among overweight and obese women: a parallel clinical trial.Int. J. Endocrinol. 2013. 2013; 971724https://doi.org/10.1155/2013/971724
- Influence of protein intake, race, and age on responses to a weight-reduction intervention in obese women.Curr. Dev. Nutr. 2017; 1https://doi.org/10.3945/cdn.117.000703
- Effect of dietary protein content on weight gain, energy expenditure, and body composition during overeating.J. Am. Med. Assoc. 2012; 307: 47-55
- Effect of the intake of dietary protein on insulin resistance in subjects with obesity: a randomized controlled clinical trial.Eur. J. Nutr. 2020; https://doi.org/10.1007/s00394-020-02428-5
- Higher protein diet for weight management in young overweight women: a 12-month randomized controlled trial.Diabetes Obes. Metabol. 2013; 15: 572-575
- Effect of a 6-month vegan low-carbohydrate ('Eco-Atkins') diet on cardiovascular risk factors and body weight in hyperlipidaemic adults: a randomised controlled trial.BMJ Open. 2014; 4e003505https://doi.org/10.1136/bmjopen-2013-003505
- Short term elevation in dietary protein intake does not worsen insulin resistance or lipids in older adults with metabolic syndrome: a randomized-controlled trial.BMC Nutr. 2017; 3https://doi.org/10.1186/s40795-017-0152-4
- Energy-restricted, high-protein diets more effectively impact cardiometabolic profile in overweight and obese women than lower-protein diets.Clin. Nutr. 2017; 36: 371-379https://doi.org/10.1016/j.clnu.2016.01.018
- Improved function with enhanced protein intake per meal: a pilot study of weight reduction in frail, obese older adults.J. Gerontol. A Biol. Sci. Med. Sci. 2016; 71: 1369-1375https://doi.org/10.1093/gerona/glv210
- The PREVIEW intervention study: results from a 3-year randomized 2 x 2 factorial multinational trial investigating the role of protein, glycaemic index and physical activity for prevention of type 2 diabetes.Diabetes Obes. Metabol. 2020; https://doi.org/10.1111/dom.14219
- Normal vs. high-protein weight loss diets in men: effects on body composition and indices of metabolic syndrome.Obesity. 2013; 21: E204-E210https://doi.org/10.1002/oby.20078
- Comparison of low calorie high protein and low calorie standard protein diet on waist circumference of adults with visceral obesity and weight cycling.BMC Res. Notes. 2018; 11 (674-674)https://doi.org/10.1186/s13104-018-3781-z
- Effects of a high-protein diet including whole eggs on muscle composition and indices of cardiometabolic health and systemic inflammation in older adults with overweight or obesity: a randomized controlled trial.Nutrients. 2018; 10 (946-946)https://doi.org/10.3390/nu10070946
- Comparison of the effects of 52 weeks weight loss with either a high-protein or high-carbohydrate diet on body composition and cardiometabolic risk factors in overweight and obese males.Nutr. Diabetes. 2012; 2: e40https://doi.org/10.1038/nutd.2012.11
- Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.PLoS Med. 2009; 6e1000097https://doi.org/10.1371/journal.pmed.1000097
- Long-term effects of low-fat diets either low or high in protein on cardiovascular and metabolic risk factors: a systematic review and meta-analysis.Nutr. J. 2013; 12: 48https://doi.org/10.1186/1475-2891-12-48
- Long term weight maintenance after advice to consume low carbohydrate, higher protein diets--a systematic review and meta analysis.Nutr. Metabol. Cardiovasc. Dis. 2014; 24: 224-235https://doi.org/10.1016/j.numecd.2013.11.006
- Covidence systematic review software.(Covidence. Available from:)https://www.covidence.org/Date: 2020
- WebPlotDigitalizer version 4.4.(Available from:)
- High-protein diets in hyperlipidemia: effect of wheat gluten on serum lipids, uric acid, and renal function.Am. J. Clin. Nutr. 2001; 74: 57-63https://doi.org/10.1093/ajcn/74.1.57
- Insulin sensitivity and secretion in young, healthy subjects are not changed by Zone and Mediterranean diets.Mediterr. J. Nutr. Metabol. 2010; 3: 233-237
- Varying protein source and quantity do not significantly improve weight loss, fat loss, or satiety in reduced energy diets among midlife adults.Nutr. Res. 2011; 31: 104-112
- Effect of normal-fat diets, either medium or high in protein, on body weight in overweight subjects: a randomised 1-year trial.Int. J. Obes. Relat. Metab. Disord. 2004; 28: 1283-1290https://doi.org/10.1038/sj.ijo.0802767
- RoB 2: a revised tool for assessing risk of bias in randomised trials.BMJ. 2019; 366: l4898https://doi.org/10.1136/bmj.l4898
- Cochrane handbook for systematic reviews of interventions version 5.1.0.in: The Cochrane Collaboration. 2011
- Meta-analysis in clinical trials.Contr. Clin. Trials. 1986; 7: 177-188https://doi.org/10.1016/0197-2456(86)90046-2
- Measuring inconsistency in meta-analyses.BMJ. 2003; 327: 557-560https://doi.org/10.1136/bmj.327.7414.557
- Bias in meta-analysis detected by a simple, graphical test.BMJ. 1997; 315: 629-634https://doi.org/10.1136/bmj.315.7109.629
- Trim and fill: a simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis.Biometrics. 2000; 56: 455-463https://doi.org/10.1111/j.0006-341x.2000.00455.x
- Effects of weight loss on a low-carbohydrate diet on flow-mediated dilatation, adhesion molecules and adiponectin.Br. J. Nutr. 2007; 98: 852-859https://doi.org/10.1017/s0007114507747815
- Dietary protein and blood pressure: a systematic review.PloS One. 2010; 5e12102https://doi.org/10.1371/journal.pone.0012102
- Effects of variation in protein and carbohydrate intake on body mass and composition during energy restriction: a meta-regression 1.Am. J. Clin. Nutr. 2006; 83: 260-274https://doi.org/10.1093/ajcn/83.2.260
- Effects of dietary protein intake on body composition changes after weight loss in older adults: a systematic review and meta-analysis.Nutr. Rev. 2016; 74: 210-224https://doi.org/10.1093/nutrit/nuv065
- Diets with high or low protein content and glycemic index for weight-loss maintenance.N. Engl. J. Med. 2010; 363: 2102-2113https://doi.org/10.1056/NEJMoa1007137
- Dietary protein and energy balance in relation to obesity and Co-morbidities.Front. Endocrinol. 2018; 9: 443https://doi.org/10.3389/fendo.2018.00443
- Intake of total protein, plant protein and animal protein in relation to blood pressure: a meta-analysis of observational and intervention studies.J. Hum. Hypertens. 2013; 27: 564-571https://doi.org/10.1038/jhh.2013.16
- Whey protein lowers blood pressure and improves endothelial function and lipid biomarkers in adults with prehypertension and mild hypertension: results from the chronic Whey2Go randomized controlled trial.Am. J. Clin. Nutr. 2016; 104: 1534-1544https://doi.org/10.3945/ajcn.116.137919
- Plasma concentrations and ACE-inhibitory effects of tryptophan-containing peptides from whey protein hydrolysate in healthy volunteers.Eur. J. Nutr. 2020; 59: 1135-1147https://doi.org/10.1007/s00394-019-01974-x
- Activity and bioavailability of food protein-derived angiotensin-I-converting enzyme-inhibitory peptides.Compr. Rev. Food Sci. Food Saf. 2021; https://doi.org/10.1111/1541-4337.12711
- Increasing protein intake modulates lipid metabolism in healthy young men and women consuming a high-fat hypercaloric diet.J. Nutr. 2014; 144: 1174-1180https://doi.org/10.3945/jn.114.191072
- Weight loss and total lipid profile changes in overweight women consuming beef or chicken as the primary protein source.Nutrition. 2003; 19: 409-414https://doi.org/10.1016/s0899-9007(02)01080-8
- Effects of beef and chicken consumption on plasma lipid levels in hypercholesterolemic men.Arch. Intern. Med. 1994; 154: 1261-1267
- Comparison of the effects of lean red meat vs lean white meat on serum lipid levels among free-living persons with hypercholesterolemia: a long-term, randomized clinical trial.Arch. Intern. Med. 1999; 159: 1331-1338https://doi.org/10.1001/archinte.159.12.1331
- A systematic review of the effects of plant compared with animal protein sources on features of metabolic syndrome.J. Nutr. 2017; 147: 281-292https://doi.org/10.3945/jn.116.239574
- Effect of plant protein on blood lipids: a systematic review and meta-analysis of randomized controlled trials.J. Am. Heart Assoc. 2017; 6https://doi.org/10.1161/jaha.117.006659
- Primary prevention of cardiovascular disease with a mediterranean diet supplemented with extra-virgin olive oil or nuts.N. Engl. J. Med. 2018; 378: e34https://doi.org/10.1056/NEJMoa1800389
- Reduction in the incidence of type 2 diabetes with the Mediterranean diet: results of the PREDIMED-Reus nutrition intervention randomized trial.Diabetes Care. 2011; 34: 14-19https://doi.org/10.2337/dc10-1288
- The PREVIEW intervention study: results from a 3-year randomized 2 x 2 factorial multinational trial investigating the role of protein, glycaemic index and physical activity for prevention of type 2 diabetes.Diabetes Obes. Metabol. 2021; 23: 324-337https://doi.org/10.1111/dom.14219
- High-protein vs. standard-protein diets in overweight and obese patients with heart failure and diabetes mellitus: findings of the Pro-HEART trial.ESC Heart Fail. 2021; https://doi.org/10.1002/ehf2.13213
- Dietary intake of protein from different sources and weight regain, changes in body composition and cardiometabolic risk factors after weight loss: the DIOGenes study.Nutrients. 2017; 9https://doi.org/10.3390/nu9121326
- High protein vs high carbohydrate hypoenergetic diet for the treatment of obese hyperinsulinemic subjects.Int. J. Obes. Relat. Metab. Disord. 1999; 23: 1202-1206https://doi.org/10.1038/sj.ijo.0801064
Article Info
Publication History
Published online: May 25, 2021
Accepted:
May 19,
2021
Received in revised form:
April 25,
2021
Received:
March 4,
2021
Identification
Copyright
© 2021 Elsevier B.V. All rights reserved.