Abstract
Background/obejctive
Although the high-protein diets (HPDs) on weight control and body composition management are well investigated, mix results have been reported across studies and this variability may be attributed to differences in the composition of other macronutrients within HPDs. The aim of this study was to evaluate the impacts of HPDs with varied macronutrient compositions on body composition and cardiometabolic health outcomes through a systematic review, pairwise, and network meta-analysis.
Methods
A comprehensive search of four databases (PubMed, Embase, CINAHL, and Web of Science) was conducted to identify relevant randomized controlled trials. A total of 83 articles were selected for systematic review and both meta-analyses.
Results
Significant reduction in body mass (BM) (standardized mean difference [SMD] = −0.25; 95% CI: −0.40, −0.11), body mass index (BMI) (SMD = −0.26; 95% CI: −0.38, −0.15), waist circumference (WC) (SMD = −0.19; 95% CI: −0.33, −0.04), fat mass (FM) (mean difference [MD] = −0.64 kg; 95% CI: −0.98, −0.29), along with increase in lean body mass (LBM) (MD = 0.34 kg; 95% CI: 0.11, 0.57) were observed with HPDs regiments compared to normal-protein diets. Specifically, the high-protein, moderate-carbohydrate and high-fat diet ranked the best in reducing BM, BMI, WC, FM, systolic blood pressure, diastolic blood pressure and increasing LBM; while the high-protein, low-carbohydrate and high-fat diet obtained the highest score in reducing triglyceride and increasing high-density lipoprotein cholesterol.
Conclusion
HPDs effectively reduce FM and increase LBM, and offers potential cardiometabolic benefits. Additionally, the manipulation of carbohydrate content in HPDs may further influence these outcomes.
Registration
PROSPERO (CRD42023483907).
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to the full article PDF.
USD 39.95
Prices may be subject to local taxes which are calculated during checkout



Similar content being viewed by others
Data availability
Data described in the manuscript, code book, and analytic code will be made available upon request.
References
World Health Organization. Obesity and overweight. 2021.
Boutari C, Mantzoros CS A. 2022 update on the epidemiology of obesity and a call to action: as its twin COVID-19 pandemic appears to be receding, the obesity and dysmetabolism pandemic continues to rage on. Metabolism. 2022;133:155217.
Najafi F, Pasdar Y, Nazar MM, Darbandi M. Association between obesity phenotypes and non-alcoholic fatty liver: a large population-based study. BMC Endocr Disord. 2024;24:96.
Dang K, Wang X, Hu J, Zhang Y, Cheng L, Qi X, et al. The association between triglyceride-glucose index and its combination with obesity indicators and cardiovascular disease: NHANES 2003–2018. Cardiovasc Diabetol 2024;23:8.
Pakhare M, Anjankar A. Critical correlation between obesity and cardiovascular diseases and recent advancements in obesity. Cureus 2024;16.
Sassano M, Castagna C, Villani L, Quaranta G, Pastorino R, Ricciardi W, et al. National taxation on sugar-sweetened beverages and its association with overweight, obesity, and diabetes. Am J Clin Nutr. 2024;119:990–1006.
Blüher M. Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019;15:288–98.
Müller MJ, Lagerpusch M, Enderle J, Schautz B, Heller M, Bosy-Westphal A. Beyond the body mass index: tracking body composition in the pathogenesis of obesity and the metabolic syndrome. Obes Rev 2012;13:6–13.
Kushner RF. Medical management of obesity. Clinical nutrition in gastrointestinal disease. CRC Press; 2024. p. 585–94.
Chao AM, Quigley KM, Wadden TA. Dietary interventions for obesity: clinical and mechanistic findings. J Clin Investig. 2021;131.
Halton TL, Hu FB. The effects of high protein diets on thermogenesis, satiety and weight loss: a critical review. J Am Coll Nutr. 2004;23:373–85.
Leidy HJ, Clifton PM, Astrup A, Wycherley TP, Westerterp-Plantenga MS, Luscombe-Marsh ND, et al. The role of protein in weight loss and maintenance. Am J Clin Nutr. 2015;101:1320S–1329S.
Wycherley TP, Moran LJ, Clifton PM, Noakes M, Brinkworth GD. 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;96:1281–98.
Schwingshackl L, Hoffmann G. 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;12:1–9.
Astrup A, Larsen TM, Harper A. Atkins and other low-carbohydrate diets: hoax or an effective tool for weight loss? Lancet. 2004;364:897–9.
Nordmann AJ, Nordmann A, Briel M, Keller U, Yancy WS, Brehm BJ, et al. Effects of low-carbohydrate vs low-fat diets on weight loss and cardiovascular risk factors: a meta-analysis of randomized controlled trials. Arch Intern Med 2006;166:285–93.
Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. N. Engl J Med. 2008;359:229–41.
Hall KD, Guo J. Obesity energetics: body weight regulation and the effects of diet composition. Gastroenterology. 2017;152:1718–27.e3.
Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg 2010;8:336–41.
Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med 2015;162:777–84.
Schwingshackl L, Chaimani A, Hoffmann G, Schwedhelm C, Boeing H. Impact of different dietary approaches on blood pressure in hypertensive and prehypertensive patients: protocol for a systematic review and network meta-analysis. BMJ open. 2017;7:e014736.
Haarbo J, Gotfredsen A, Hassager C, Christiansen C. Validation of body composition by dual energy X-ray absorptiometry (DEXA). Clin Physiol 1991;11:331–41.
Teunissen-Beekman KF, Dopheide J, Geleijnse JM, Bakker SJ, Brink EJ, de Leeuw PW, et al. Protein supplementation lowers blood pressure in overweight adults: effect of dietary proteins on blood pressure (PROPRES), a randomized trial. Am J Clin Nutr. 2012;95:966–71.
Chaimani A, Salanti G. Visualizing assumptions and results in network meta-analysis: the network graphs package. Stata J. 2015;15:905–50.
White IR. Network meta-analysis. Stata J. 2015;15:951–85.
Ndanuko RN, Tapsell LC, Charlton KE, Neale EP, Batterham MJ. Dietary patterns and blood pressure in adults: a systematic review and meta-analysis of randomized controlled trials. Adv Nutr. 2016;7:76–89.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group* t. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009;151:264–9.
Liu K, Hui S, Wang B, Kaliannan K, Guo X, Liang L. Comparative effects of different types of tree nut consumption on blood lipids: a network meta-analysis of clinical trials. Am J Clin Nutr. 2020;111:219–27.
Chaimani A, Higgins JP, Mavridis D, Spyridonos P, Salanti G. Graphical tools for network meta-analysis in STATA. PLoS One. 2013;8:e76654.
Higgins JPTT J, Chandler J, Cumpston M, Li T, Page MJ, Welch VA. Cochrane handbook for systematic reviews of interventions version 6.3 (updated February 2022), Chichester: Wiley-Blackwell, 2022.
Hc B. The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 1997;50:683–91.
Dias S, Welton NJ, Caldwell DM, Ades AE. Checking consistency in mixed treatment comparison meta-analysis. Stat Med. 2010;29:932–44.
Jackson D, Barrett JK, Rice S, White IR, Higgins JP. A design-by-treatment interaction model for network meta-analysis with random inconsistency effects. Stat Med. 2014;33:3639–54.
Chaimani A, Salanti G. Using network meta-analysis to evaluate the existence of small-study effects in a network of interventions. Res Synth Methods. 2012;3:161–76.
Shim S, Yoon B-H, Shin I-S, Bae J-M. Network meta-analysis: application and practice using Stata. Epidemiol Health 2017;39.
Salanti G, Del Giovane C, Chaimani A, Caldwell DM, Higgins JP. Evaluating the quality of evidence from a network meta-analysis. PLoS One. 2014;9:e99682.
Brignardello-Petersen R, Bonner A, Alexander PE, Siemieniuk RA, Furukawa TA, Rochwerg B, et al. Advances in the GRADE approach to rate the certainty in estimates from a network meta-analysis. J Clin Epidemiol. 2018;93:36–44.
Jonasson L, Guldbrand H, Lundberg AK, Nystrom FH. Advice to follow a low-carbohydrate diet has a favourable impact on low-grade inflammation in type 2 diabetes compared with advice to follow a low-fat diet. Ann Med. 2014;46:182–7.
Volek JS, Phinney SD, Forsythe CE, Quann EE, Wood RJ, Puglisi MJ, et al. Carbohydrate restriction has a more favorable impact on the metabolic syndrome than a low fat diet. Lipids. 2009;44:297–309.
Glynn EL, Fleming SA, Edwards CG, Wilson MJ, Evans M, Leidy HJ. Consuming a protein and fiber-based supplement preload promotes weight loss and alters metabolic markers in overweight adults in a 12-week, randomized, double-blind, placebo-controlled trial. J Nutr. 2022;152:1415–25.
Thomsen MN, Skytte MJ, Samkani A, Carl MH, Weber P, Astrup A, et al. Dietary carbohydrate restriction augments weight loss-induced improvements in glycaemic control and liver fat in individuals with type 2 diabetes: a randomised controlled trial. Diabetologia. 2022;65:506–17.
Toscani MK, Mario FM, Radavelli-Bagatini S, Wiltgen D, Matos MC, Spritzer PM. Effect of high-protein or normal-protein diet on weight loss, body composition, hormone, and metabolic profile in southern Brazilian women with polycystic ovary syndrome: a randomized study. Gynecol Endocrinol 2011;27:925–30.
Due A, Toubro S, Skov AR, Astrup A. 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;28:1283–90.
Dorans KS, Bazzano LA, Qi L, He H, Chen J, Appel LJ, et al. Effects of a low-carbohydrate dietary intervention on hemoglobin A1c: a randomized clinical trial. JAMA Netw Open. 2022;5:e2238645.
Kleiner RE, Hutchins AM, Johnston CS, Swan PD. Effects of an 8-week high-protein or high-carbohydrate diet in adults with hyperinsulinemia. MedGenMed. 2006;8:39.
Silva TR, Lago SC, Yavorivski A, Ferreira LL, Fighera TM, Spritzer PM. Effects of high protein, low-glycemic index diet on lean body mass, strength, and physical performance in late postmenopausal women: a randomized controlled trial. Menopause. 2020;28:307–17.
Pasiakos SM, Cao JJ, Margolis LM, Sauter ER, Whigham LD, McClung JP, et al. Effects of high-protein diets on fat-free mass and muscle protein synthesis following weight loss: a randomized controlled trial. FASEB J. 2013;27:3837–47.
Sørensen LB, Søe M, Halkier KH, Stigsby B, Astrup A. Effects of increased dietary protein-to-carbohydrate ratios in women with polycystic ovary syndrome. Am J Clin Nutr 2012;95:39–48.
Abete I, Parra D, De Morentin BM, Alfredo Martinez J. Effects of two energy-restricted diets differing in the carbohydrate/protein ratio on weight loss and oxidative changes of obese men. Int J Food Sci Nutr. 2009;60:1–13.
Clifton PM, Bastiaans K, Keogh JB. High protein diets decrease total and abdominal fat and improve CVD risk profile in overweight and obese men and women with elevated triacylglycerol. Nutr Metab Cardiovasc Dis 2009;19:548–54.
Leidy HJ, Carnell NS, Mattes RD, Campbell WW. Higher protein intake preserves lean mass and satiety with weight loss in pre-obese and obese women. Obesity. 2007;15:421–9.
Varady KA, Bhutani S, Klempel MC, Phillips SA. Improvements in vascular health by a low-fat diet, but not a high-fat diet, are mediated by changes in adipocyte biology. Nutr J 2011;10:8.
Heggen E, Svendsen M, Klemsdal TO, Tonstad S. Low carbohydrate and moderately fat-reduced diets similarly affected early weight gain in varenicline-treated overweight or obese smokers. Nicotine Tob Res. 2016;18:1440–8.
Martens EA, Gonnissen HK, Gatta-Cherifi B, Janssens PL, MS Westerterp-Plantenga. Maintenance of energy expenditure on high-protein vs. high-carbohydrate diets at a constant body weight may prevent a positive energy balance. Clin Nutr 2015;34:968–75.
Haghighat N, Ashtary-Larky D, Bagheri R, Mahmoodi M, Rajaei M, Alipour M, et al. The effect of 12 weeks of euenergetic high-protein diet in regulating appetite and body composition of women with normal-weight obesity: a randomised controlled trial. Br J Nutr 2020;124:1044–51.
Claessens M, van Baak MA, Monsheimer S, Saris WH. The effect of a low-fat, high-protein or high-carbohydrate ad libitum diet on weight loss maintenance and metabolic risk factors. Int J Obes. 2009;33:296–304.
Sun J, Ruan Y, Xu N, Wu P, Lin N, Yuan K, et al. The effect of dietary carbohydrate and calorie restriction on weight and metabolic health in overweight/obese individuals: a multi-center randomized controlled trial. BMC Med. 2023;21:192.
Martens EA, Gatta-Cherifi B, Gonnissen HK, Westerterp-Plantenga MS. The potential of a high protein-low carbohydrate diet to preserve intrahepatic triglyceride content in healthy humans. PLoS One. 2014;9:e109617.
Aldrich ND, Reicks MM, Sibley SD, Redmon JB, Thomas W, Raatz SK. 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;31:104–12.
Soenen S, Martens EA, Hochstenbach-Waelen A, Lemmens SG, MS Westerterp-Plantenga. Normal protein intake is required for body weight loss and weight maintenance, and elevated protein intake for additional preservation of resting energy expenditure and fat free mass. J Nutr 2013;143:591–6.
Papakonstantinou E, Triantafillidou D, Panagiotakos D, Koutsovasilis A, Saliaris M, Manolis A, et al. A high-protein low-fat diet is more effective in improving blood pressure and triglycerides in calorie-restricted obese individuals with newly diagnosed type 2 diabetes. Eur J Clin Nutr. 2010;64:595–602.
Petrisko M, Kloss R, Bradley P, Birrenkott E, Spindler A, Clayton ZS, et al. Biochemical, anthropometric, and physiological responses to carbohydrate-restricted diets versus a low-fat diet in obese adults: a randomized crossover trial. J Med Food. 2020;23:206–14.
Winn NC, Pettit-Mee R, Walsh LK, Restaino RM, Ready ST, Padilla J, et al. Metabolic implications of diet and energy intake during physical inactivity. Med Sci Sports Exerc 2019;51:995.
Dyson P, Beatty S, Matthews D. A low-carbohydrate diet is more effective in reducing body weight than healthy eating in both diabetic and non-diabetic subjects. Diabet Med 2007;24:1430–5.
Seshadri P, Iqbal N, Stern L, Williams M, Chicano KL, Daily DA, et al. A randomized study comparing the effects of a low-carbohydrate diet and a conventional diet on lipoprotein subfractions and C-reactive protein levels in patients with severe obesity. Am J Med. 2004;117:398–405.
Dalle Grave R, Calugi S, Gavasso I, El Ghoch M, Marchesini G. A randomized trial of energy-restricted high-protein versus high-carbohydrate, low-fat diet in morbid obesity. Obesity. 2013;21:1774–81.
Al-Sarraj T, Saadi H, Calle MC, Volek JS, Fernandez ML. Carbohydrate restriction, as a first-line dietary intervention, effectively reduces biomarkers of metabolic syndrome in Emirati adults. J Nutr. 2009;139:1667–76.
Thomson CA, Stopeck AT, Bea JW, Cussler E, Nardi E, Frey G, et al. Changes in body weight and metabolic indexes in overweight breast cancer survivors enrolled in a randomized trial of low-fat vs. reduced carbohydrate diets. Nutr Cancer. 2010;62:1142–52.
Meckling KA, O’Sullivan C, Saari D. Comparison of a low-fat diet to a low-carbohydrate diet on weight loss, body composition, and risk factors for diabetes and cardiovascular disease in free-living, overweight men and women. J Clin Endocrinol Metab. 2004;89:2717–23.
Raeini-Sarjaz M, Vanstone CA, Papamandjaris AA, Wykes LJ, Jones PJ. Comparison of the effect of dietary fat restriction with that of energy restriction on human lipid metabolism. Am J Clin Nutr. 2001;73:262–7.
Ogilvie A, Watford M, Wu G, Sukumar D, Kwon J, Shapses S. Decreased fasting serum glucogenic amino acids with a higher compared to normal protein diet during energy restriction in women: a randomized controlled trial. Amino Acids. 2021;53:1467–72.
Jenkins DJ, Wong JM, Kendall CW, Esfahani A, Ng VW, Leong TC, et al. 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;4:e003505.
Engberink M, Geleijnse J, Bakker S, Larsen T, Handjieva-Darlesnka T, Kafatos A, et al. Effect of a high-protein diet on maintenance of blood pressure levels achieved after initial weight loss: the DiOGenes randomized study. J Hum Hypertens. 2015;29:58–63.
Noakes M, Keogh JB, Foster PR, Clifton PM. Effect of an energy-restricted, high-protein, low-fat diet relative to a conventional high-carbohydrate, low-fat diet on weight loss, body composition, nutritional status, and markers of cardiovascular health in obese women. Am J Clin Nutr. 2005;81:1298–306.
Yılmaz SK, Eskici G, Mertoǧlu C, Ayaz A. Effect of different protein diets on weight loss, inflammatory markers, and cardiometabolic risk factors in obese women. J Res Med Sci 2021;26:28.
Bray GA, Redman LM, Rood J, de Jonge L, Smith SR. Effect of overeating dietary protein at different levels on circulating lipids and liver lipid: the PROOF study. Nutrients. 2020;12:3801.
McAdam JS, McGinnis KD, Beck DT, Haun CT, Romero MA, Mumford PW, et al. Effect of whey protein supplementation on physical performance and body composition in army initial entry training soldiers. Nutrients. 2018;10:1248.
Ballesteros-Pomar MD, Calleja-Fernández AR, Vidal-Casariego A, Urioste-Fondo AM, Cano-Rodríguez I. Effectiveness of energy-restricted diets with different protein:carbohydrate ratios: the relationship to insulin sensitivity. Public Health Nutr. 2010;13:2119–26.
de Luis DA, Izaola O, Aller R, de la Fuente B, Bachiller R, Romero E. Effects of a high-protein/low carbohydrate versus a standard hypocaloric diet on adipocytokine levels and insulin resistance in obese patients along 9 months. J Diabetes Complic. 2015;29:950–4.
Li J, Gower B, McLain A, Yarar-Fisher C. Effects of a low-carbohydrate/high-protein diet on metabolic health in individuals with chronic spinal cord injury: An exploratory analysis of results from a randomized controlled trial. Physiol Rep. 2022;10:e15501.
Ebbeling CB, Leidig MM, Sinclair KB, Seger-Shippee LG, Feldman HA, Ludwig DS. Effects of an ad libitum low-glycemic load diet on cardiovascular disease risk factors in obese young adults. Am J Clin Nutr 2005;81:976–82.
Gordon MM, Bopp MJ, Easter L, Miller GD, Lyles MF, Houston DK, et al. Effects of dietary protein on the composition of weight loss in post-menopausal women. J Nutr Health Aging. 2008;12:505–9.
Bazzano LA, Hu T, Reynolds K, Yao L, Bunol C, Liu Y, et al. Effects of low-carbohydrate and low-fat diets: a randomized trial. Ann Intern Med 2014;161:309–18.
Pedersen E, Jesudason DR, Clifton PM. High protein weight loss diets in obese subjects with type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis 2014;24:554–62.
Johnston CS, Tjonn SL, Swan PD. High-protein, low-fat diets are effective for weight loss and favorably alter biomarkers in healthy adults. J Nutr 2004;134:586–91.
Malaguti M, Baldini M, Angeloni C, Biagi P, Hrelia S. High-protein-PUFA supplementation, red blood cell membranes, and plasma antioxidant activity in volleyball athletes. Int J Sport Nutr Exerc Metab 2008;18:301–12.
Papadaki A, Linardakis M, Plada M, Larsen TM, Damsgaard CT, van Baak MA, et al. Impact of weight loss and maintenance with ad libitum diets varying in protein and glycemic index content on metabolic syndrome. Nutrition. 2014;30:410–7.
Guldbrand H, Dizdar B, Bunjaku B, Lindström T, Bachrach-Lindström M, Fredrikson M, et al. In type 2 diabetes, randomisation to advice to follow a low-carbohydrate diet transiently improves glycaemic control compared with advice to follow a low-fat diet producing a similar weight loss. Diabetologia. 2012;55:2118–27.
Clifton PM, Keogh JB, Noakes M. Long-term effects of a high-protein weight-loss diet. Am J Clin Nutr 2008;87:23–9.
Lim SS, Noakes M, Keogh JB, Clifton PM. Long-term effects of a low carbohydrate, low fat or high unsaturated fat diet compared to a no-intervention control. Nutr Metab Cardiovasc Dis 2010;20:599–607.
Brinkworth GD, Noakes M, Parker B, Foster P, Clifton PM. Long-term effects of advice to consume a high-protein, low-fat diet, rather than a conventional weight-loss diet, in obese adults with type 2 diabetes: one-year follow-up of a randomised trial. Diabetologia. 2004;47:1677–86.
Verboeket-van de Venne WP, Westerterp KR, Hermans-Limpens TJ, de Graaf C, van het Hof KH, Weststrate JA. Long-term effects of consumption of full-fat or reduced-fat products in healthy non-obese volunteers: assessment of energy expenditure and substrate oxidation. Metabolism. 1996;45:1004–10.
Tang M, Armstrong CL, Leidy HJ, Campbell WW. Normal vs. high-protein weight loss diets in men: effects on body composition and indices of metabolic syndrome. Obesity. 2013;21:E204–10.
Calleja Fernández A, Vidal Casariego A, Cano Rodríguez I, Ballesteros Pomar MD. One-year effectiveness of two hypocaloric diets with different protein/carbohydrate ratios in weight loss and insulin resistance. Nutr Hosp 2012;27:2093–101.
Nickols-Richardson SM, Coleman MD, Volpe JJ, Hosig KW. Perceived hunger is lower and weight loss is greater in overweight premenopausal women consuming a low-carbohydrate/high-protein vs high-carbohydrate/low-fat diet. J Am Diet Assoc. 2005;105:1433–7.
Soenen S, Bonomi AG, Lemmens SG, Scholte J, Thijssen MA, van Berkum F, et al. Relatively high-protein or ‘low-carb’ energy-restricted diets for body weight loss and body weight maintenance? Physiol Behav 2012;107:374–80.
Michalczyk MM, Maszczyk A, Stastny P. The effects of low-energy moDERATE-Carbohydrate (MCD) and mixed (MixD) diets on serum lipid profiles and body composition in middle-aged men: a randomized controlled parallel-group clinical trial. Int J Environ Res Public Health. 2020;17.
Brehm BJ, Spang SE, Lattin BL, Seeley RJ, Daniels SR, D’Alessio DA. The role of energy expenditure in the differential weight loss in obese women on low-fat and low-carbohydrate diets. J Clin Endocrinol Metab. 2005;90:1475–82.
Jesudason DR, Pedersen E, Clifton PM. Weight-loss diets in people with type 2 diabetes and renal disease: a randomized controlled trial of the effect of different dietary protein amounts. Am J Clin Nutr 2013;98:494–501.
Phuong NM, Giang NH, Linh NT, Hien VTT, Huong LT, Yamamoto S. Effects of high-protein and high-carbohydrate diets on body weight were similar in healthy young Vietnamese women with normal body weight. Nutr. Today 2019; 54.
Wekesa AL, Doyle LM, Fitzmaurice D, O’Donovan O, Phelan JP, Ross MD, et al. Influence of a low-carbohydrate diet on endothelial microvesicles in overweight women. Appl Physiol Nutr Metab 2016;41:522–7.
Treyzon L, Chen S, Hong K, Yan E, Carpenter CL, Thames G, et al. A controlled trial of protein enrichment of meal replacements for weight reduction with retention of lean body mass. Nutr J. 2008;7:1–6.
Brehm BJ, Seeley RJ, Daniels SR, D’Alessio DA. A randomized trial comparing a very low carbohydrate diet and a calorie-restricted low fat diet on body weight and cardiovascular risk factors in healthy women. J Clin Endocrinol Metab. 2003;88:1617–23.
Drummen M, Dorenbos E, Vreugdenhil AC, Stratton G, Raben A, Westerterp-Plantenga MS, et al. Associations of brain reactivity to food cues with weight loss, protein intake and dietary restraint during the PREVIEW intervention. Nutrients. 2018;10:1771.
Summer SS, Brehm BJ, Benoit SC, D’alessio DA. Adiponectin changes in relation to the macronutrient composition of a weight-loss diet. Obesity. 2011;19:2198–204.
De la Iglesia R, Lopez-Legarrea P, Celada P, Sánchez-Muniz FJ, Martinez JA, Zulet MA. Beneficial effects of the RESMENA dietary pattern on oxidative stress in patients suffering from metabolic syndrome with hyperglycemia are associated to dietary TAC and fruit consumption. Int J Mol Sci. 2013;14:6903–19.
Davis NJ, Tomuta N, Schechter C, Isasi CR, Segal-Isaacson C, Stein D, et al. Comparative study of the effects of a 1-year dietary intervention of a low-carbohydrate diet versus a low-fat diet on weight and glycemic control in type 2 diabetes. Diabetes Care. 2009;32:1147–52.
McMillan-Price J, Petocz P, Atkinson F, O’Neill K, Samman S, Steinbeck K, et al. Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults: a randomized controlled trial. Arch Intern Med 2006;166:1466–75.
Witjaksono F, Jutamulia J, Annisa NG, Prasetya SI, Nurwidya F. 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;11:1–5.
Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA. 2007;297:969–77.
Mateo-Gallego R, Lamiquiz-Moneo I, Perez-Calahorra S, Marco-Benedí V, Bea A, Baila-Rueda L, et al. Different protein composition of low-calorie diet differently impacts adipokine profile irrespective of weight loss in overweight and obese women. Nutr, Metab Cardiovasc Dis. 2018;28:133–42.
Farnsworth E, Luscombe ND, Noakes M, Wittert G, Argyiou E, Clifton PM. Effect of a high-protein, energy-restricted diet on body composition, glycemic control, and lipid concentrations in overweight and obese hyperinsulinemic men and women. Am J Clin Nutr. 2003;78:31–39.
De Jonge L, Bray GA, Smith SR, Ryan DH, De Souza RJ, Loria CM, et al. Effect of diet composition and weight loss on resting energy expenditure in the POUNDS LOST study. Obesity. 2012;20:2384–9.
Bray GA, Smith SR, De Jonge L, Xie H, Rood J, Martin CK, et al. Effect of dietary protein content on weight gain, energy expenditure, and body composition during overeating: a randomized controlled trial. JAMA. 2012;307:47–55.
Sargrad KR, Homko C, Mozzoli M, Boden G. Effect of high protein vs high carbohydrate intake on insulin sensitivity, body weight, hemoglobin A1c, and blood pressure in patients with type 2 diabetes mellitus. J Am Diet Assoc 2005;105:573–80.
Liu X, Zhang G, Ye X, Li H, Chen X, Tang L, et al. Effects of a low-carbohydrate diet on weight loss and cardiometabolic profile in Chinese women: a randomised controlled feeding trial. Br J Nutr. 2013;110:1444–53.
De Luis D, Aller R, Izaola O, Gonzalez Sagrado M, Bellioo D, Conde R. Effects of a low-fat versus a low-carbohydrate diet on adipocytokines in obese adults. Horm Res. 2007;67:296–300.
Kitabchi AE, McDaniel KA, Wan JY, Tylavsky FA, Jacovino CA, Sands CW, et al. Effects of high-protein versus high-carbohydrate diets on markers of β-cell function, oxidative stress, lipid peroxidation, proinflammatory cytokines, and adipokines in obese, premenopausal women without diabetes: a randomized controlled trial. Diabetes Care. 2013;36:1919–25.
Griffin H, Cheng H, O’Connor H, Rooney K, Petocz P, Steinbeck K. Higher protein diet for weight management in young overweight women: a 12-month randomized controlled trial. Diabetes, Obes Metab. 2013;15:572–5.
Luis D, Aller R, Izaola O, Sagrado MG, Conde R. Modulation of insulin concentrations and metabolic parameters in obese patients by− 55CT polymorphism of the UCP3 gene secondary to two hypocaloric diets. Horm Metab Res. 2009;41:62–66.
Paddon-Jones D, Westman E, Mattes RD, Wolfe RR, Astrup A, Westerterp-Plantenga M. Protein, weight management, and satiety. Am J Clin Nutr 2008;87:1558s–1561s.
Kim JE, O’Connor LE, Sands LP, Slebodnik MB, Campbell WW. Effects of dietary protein intake on body composition changes after weight loss in older adults: a systematic review and meta-analysis. Nutr Rev. 2016;74:210–24.
Ankarfeldt MZ, Larsen SC, Ängquist L, Husemoen LLN, Roswall N, Overvad K, et al. Interaction between genetic predisposition to adiposity and dietary protein in relation to subsequent change in body weight and waist circumference. PLoS One. 2014;9:e110890.
Bopp MJ, Houston DK, Lenchik L, Easter L, Kritchevsky SB, Nicklas BJ. Lean mass loss is associated with low protein intake during dietary-induced weight loss in postmenopausal women. J Am Diet Assoc 2008;108:1216–20.
Geirsdottir OG, Arnarson A, Ramel A, Jonsson PV, Thorsdottir I. Dietary protein intake is associated with lean body mass in community-dwelling older adults. Nutr Res. 2013;33:608–12.
McNeel RL, Mersmann HJ. Low-and high-carbohydrate diets: body composition differences in rats. Obes Res. 2005;13:1651–60.
Lobley GE, Bremner DM, Holtrop G, Johnstone AM, Maloney C. Impact of high-protein diets with either moderate or low carbohydrate on weight loss, body composition, blood pressure and glucose tolerance in rats. Br J Nutr. 2007;97:1099–108.
Børsheim E, Cree MG, Tipton KD, Elliott TA, Aarsland A, Wolfe RR. Effect of carbohydrate intake on net muscle protein synthesis during recovery from resistance exercise. J Appl Physiol. 2004;96:674–8.
Figueiredo VC, Cameron-Smith D. Is carbohydrate needed to further stimulate muscle protein synthesis/hypertrophy following resistance exercise? J Int Soc Sports Nutr. 2013;10:42.
Fujita S, Rasmussen BB, Cadenas JG, Grady JJ, Volpi E. Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability. Am J Physiol-Endocrinol Metab. 2006;291:E745–E754.
Koopman R, Wagenmakers AJ, Manders RJ, Zorenc AH, Senden JM, Gorselink M, et al. Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects. Am J Physiol Endocrinol Metab 2005;288:E645–53.
Howarth KR, Moreau NA, Phillips SM, Gibala MJ. Coingestion of protein with carbohydrate during recovery from endurance exercise stimulates skeletal muscle protein synthesis in humans. J Appl Physiol. 2009;106:1394–402.
Veldhorst MA, Westerterp-Plantenga MS, Westerterp KR. Gluconeogenesis and energy expenditure after a high-protein, carbohydrate-free diet. Am J Clin Nutr. 2009;90:519–26.
Yao Y, Huang V, Seah V, Kim JE. Impact of quantity and type of dietary protein on cardiovascular disease risk factors using standard and network meta-analyses of randomized controlled trials. Nutr Rev. 2024: nuae086.
Ichikawa R, Takano K, Fujimoto K, Kobayashi M, Kitamura T, Shichiri M, et al. Robust increase in glucagon secretion after oral protein intake, but not after glucose or lipid intake in Japanese people without diabetes. J Diabetes Investig. 2023;14:1172–4.
Pereira MJ, Thombare K, Sarsenbayeva A, Kamble PG, Almby K, Lundqvist M, et al. Direct effects of glucagon on glucose uptake and lipolysis in human adipocytes. Mol Cell Endocrinol. 2020;503:110696.
Mohammadi F, Yadegar A, Rabizadeh S, Ayati A, Seyedi SA, Nabipoorashrafi SA, et al. Correlates of normal and decreased HDL cholesterol levels in type 2 diabetes: a cohort-based cross-sectional study. Lipids Health Dis. 2024;23:18.
Pasanisi F, Contaldo F, de Simone G, Mancini M. Benefits of sustained moderate weight loss in obesity. Nutr Metab Cardiovasc Dis 2001;11:401–6.
Lafontan M, Langin D. Lipolysis and lipid mobilization in human adipose tissue. Prog Lipid Res. 2009;48:275–97.
Lundsgaard A-M, Bojsen-Møller KN, Kiens B. Dietary regulation of hepatic triacylglycerol content—the role of eucaloric carbohydrate restriction with fat or protein replacement. Adv Nutr. 2023.
Galvão R, Plavnik FL, Ribeiro FF, Ajzen SA, Christofalo DMSJ, Kohlmann O Jr. Effects of different degrees of insulin sensitivity on endothelial function in obese patients. Arq Bras Cardiol 2012;98:45–51.
Paoli A, Rubini A, Volek J, Grimaldi K. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr. 2013;67:789–96.
Schwingshackl L, Hoffmann G. Comparison of the long-term effects of high-fat v. low-fat diet consumption on cardiometabolic risk factors in subjects with abnormal glucose metabolism: a systematic review and meta-analysis. Br J Nutr. 2014;111:2047–58.
Funding
This research was funded by National University of Singapore.
Author information
Authors and Affiliations
Contributions
The authors’ responsibilities were as follows—JEK and YY: conceived and designed the study; YY, SL, and ZH: screened and collected the data; YY: analyzed the data and wrote the manuscript; JEK: supervised and revised the manuscript; JEK and YY: had primary responsibility for final content; all authors: read and approved the final manuscript.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary information
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Yao, Y., Lin, S., He, Z. et al. Impact of other macronutrient composition within high-protein diet on body composition and cardiometabolic health: a systematic review, pairwise, and network meta-analysis of randomized controlled trials. Int J Obes 49, 1480–1489 (2025). https://doi.org/10.1038/s41366-025-01806-5
Received:
Revised:
Accepted:
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41366-025-01806-5


