Sport Physiology

Sport Physiology

Differential Effects of Whey Protein Supplementation on Strength Across Various Muscle Groups in Adults: A Systematic Review and Meta-Analysis

Document Type : Review Article

Authors
1 Department of Physical Education and Sports Science, Faculty of Humanities, University of Kashan, Kashan, Iran.
2 Dpartment of Sports Physiology, Faculty of Sports Science, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran
3 Department of Sports Physiology, Faculty of Sports Sciences, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan, Iran.
4 Dpartment of Physical Education and Sports Science, Faculty of Humanities, University of Kashan, Kashan, Iran
5 Dpartment of Physical Education and Sports Science, Faculty of Human Sciences, Yasouj University, Yasouj, Iran
Abstract
Background and Purpuse
Skeletal muscle function is essential for performing daily tasks, maintaining independence, and preserving quality of life. Age-related neuromuscular decline, inactivity, and metabolic disorders contribute significantly to muscle atrophy and strength loss, increasing dependence and healthcare costs. Resistance training remains a fundamental strategy to counteract these effects, while nutritional supplementation, especially protein, has emerged as a synergistic aid. Among protein sources, whey protein—a rapidly absorbed dairy derivative rich in leucine—exerts potent stimulation of muscle protein synthesis through activation of the mTORC1 pathway. Its bioactive constituents, including lactoferrin and immunoglobulins, further support its widespread clinical and athletic use aimed at enhancing recovery and adaptive responses. Despite broad adoption, evidence on whey protein's efficacy in improving muscular strength across diverse adult populations is inconsistent. Some trials report marked gains, others minimal, confounding interpretation. This variance is linked to heterogeneity in training protocols (intensity, duration, exercise selection), participant factors (age, baseline strength, nutrition), and methodologies (dosing, strength assessments).Addressing these discrepancies, our systematic review and meta-analysis comprehensively evaluated whey protein's effects on adult muscle strength. It aimed to delineate strength response variances across movement patterns (e.g., compound lower-body exercises like squats versus isolated upper-body movements) while considering moderators including training intensity, supplementation protocol, and participant age. Synthesizing controlled trial data clarifies whey protein’s mechanistic action and practical efficacy. Findings indicate maximal benefits for lower-body compound movements combined with adequate resistance training, notably in older or protein-deficient individuals. These outcomes endorse whey supplementation as a strategic intervention against sarcopenia and functional decline, contingent on individualized application and movement specificity.
Methods
Adhering strictly to Cochrane and PRISMA guidelines, we executed exhaustive literature searches up to November 29, 2024, across PubMed, Scopus, and Web of Science, using curated search terms encompassing whey protein and various performance metrics. Supplementing electronic searches, manual Google Scholar and reference mining ensured comprehensive inclusion. Eligible studies were RCTs or non-randomized trials involving adults, reporting pre- and post-intervention muscle strength for targeted movements: biceps curl, chest press, knee and leg extension, squat, and isokinetic knee extension, with experimental arms receiving whey protein against controls. Exclusions involved animal studies, non-primary reports, crossover designs, and studies lacking relevant strength data.Extracted data detailed study design, demographics, training modalities, supplementation regimes (type, dose, timing), and strength outcomes (mean ± SD). Where necessary, numeric data were retrieved from graphical content using GetData software or through author correspondence. Methodological quality was assessed via a modified 9-item PEDro scale, excluding participant/instructor blinding criteria specific to exercise interventions. Scores ranged 0-9, with higher indicating superior quality.Random-effects statistical models generated weighted mean differences (WMDs) and 95% confidence intervals (CI). Heterogeneity was quantified by I² statistics, categorized as mild (<25%), low (25–50%), moderate (50–75%), or high (>75%). Publication bias assessment employed funnel plots and Egger’s regression, with p<0.10 indicating bias. Analyses utilized Comprehensive Meta-Analysis (CMA) software version 2.
Results
Whey protein supplementation significantly enhanced muscle strength in chest press (WMD = 3.914 kg; 95% CI: 0.784 to 7.045; P = 0.014), leg press (WMD = 9.118 kg; 95% CI: 2.187 to 16.048; P = 0.010), and squat (WMD = 7.657 kg; 95% CI: 5.324 to 9.990; P = 0.001) compared to controls. Conversely, no significant strength changes emerged for biceps curl (WMD = -0.992 kg; 95% CI: -2.538 to 4.521; P = 0.582), knee extension (WMD = 1.926 kg; 95% CI: -0.156 to 4.008; P = 0.070), or isokinetic knee extension (WMD = 3.786 kg; 95% CI: -1.748 to 9.319; P = 0.180).
Conclusion
Synthesizing findings from 20 studies, this meta-analysis confirms whey protein’s capacity to enhance muscular strength predominantly in multi-joint lower-body exercises, encompassing leg press, squat, with a trend toward knee extension improvement. A modest yet significant chest press strength increment was observed, while isolated upper-body strength measured by biceps curl showed no enhancement. Isokinetic strength gains were likewise non-significant. These outcomes suggest whey supplementation, particularly paired with resistance training, preferentially augments strength in complex lower-body movements. Its influence on upper-body musculature appears inconsistent and movement-specific. Hence, whey protein’s application should target lower-body strength optimization, notably for older individuals or those with inadequate protein intake. Further investigations are needed to elucidate molecular mechanisms underpinning these differential responses and refine protocols enhancing upper-body adaptation. Longitudinal, rigorously designed trials are imperative to establish comprehensive guidelines maximizing whey protein's ergogenic potential.

Article Message
This comprehensive analysis indicates whey protein effectively augments muscular strength in adults during lower-body multi-joint exercises like squats and leg presses, while evidence remains inconclusive regarding upper-body and isokinetic muscle performance. Variable responsiveness across muscle groups underscores the necessity for tailored supplementation strategies combined with targeted resistance training. Whey protein supplementation thus emerges as a valuable nutritional adjunct for enhancing muscular performance, with consideration for dosage, intervention duration, and individual training modalities.
Ethical Considerations
This systematic review is registered with the international Prospero database under code CRD420251157160.
Authors’ Contributions
All authors participated in all study phases including design, implementation, analysis, and manuscript preparation.
Conflict of Interest
The authors declare no conflict of interest.
Acknowledgments
Gratitude is extended to primary study authors who provided raw data contributing to this synthesis.


Keywords

Subjects


1. Mitchell WK, Williams J, Atherton P, Larvin M, Lund J, Narici M. Sarcopenia, dynapenia, and the impact of advancing age on human skeletal muscle size and strength; a quantitative review. Front Physiol. 2012;3:260. https://doi.org/10.3389/fphys.2012.00260
2. Ojanen T, Rauhala T, Häkkinen K. Strength and power profiles of the lower and upper extremities in master throwers at different ages. J Strength Cond Res. 2007;21(1):216-22. https://doi.org/10.1519/00124278-200702000-00039
3. Narici MV, Maffulli N. Sarcopenia: characteristics, mechanisms and functional significance. Br Med Bull. 2010;95:139-59. https://doi.org/10.1093/bmb/ldq008
4. Gault ML, Willems ME. Aging, functional capacity and eccentric exercise training. Aging Dis. 2013;4(6):351-63. http://doi.org/10.14336/AD.2013.0400351
5. Terjung RL, Clarkson P, Eichner ER, Greenhaff PL, Hespel PJ, Israel RG, et al. American College of Sports Medicine roundtable. The physiological and health effects of oral creatine supplementation. Med Sci Sports Exerc. 2000;32(3):706-17. http://doi.org/10.1097/00005768-200003000-00024.
6. Morton RW, Murphy KT, McKellar SR, Schoenfeld BJ, Henselmans M, Helms E, et al. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. British Journal of Sports Medicine. 2018;52(6):376-84. https://doi.org/10.1136/bjsports-2017-097608
7. Bloomer RJ. The role of nutritional supplements in the prevention and treatment of resistance exercise-induced skeletal muscle injury. Sports Med. 2007;37(6):519-32. http://doi.org/10.2165/00007256-200737060-00005.
8. Marshall K. Therapeutic applications of whey protein. Altern Med Rev. 2004;9(2):136-56.
9. Ha E, Zemel MB. Functional properties of whey, whey components, and essential amino acids: mechanisms underlying health benefits for active people (review). J Nutr Biochem. 2003;14(5):251-8. https://doi.org/10.1016/S0955-2863(03)00030-5
10. Sinnott R, Maddela R, Nelson E, Singh K, Anderson J. The modifying effects of a calcium-rich whey protein supplement (OsoLean™ Powder) on weight loss and waist circumference in overweight subjects: a preliminary study. The Open Nutraceuticals Journal. 2009;2:36-41. http://doi.org/10.2174/1876396000902010036
11. Hamarsland H, Nordengen AL, Nyvik Aas S, Holte K, Garthe I, Paulsen G, et al. Native whey protein with high levels of leucine results in similar post-exercise muscular anabolic responses as regular whey protein: a randomized controlled trial. J Int Soc Sports Nutr. 2017;14:43. http://doi.org/10.1186/s12970-017-0202-y
12. Jakubowski JS, Wong EPT, Nunes EA, Noguchi KS, Vandeweerd JK, Murphy KT, et al. Equivalent hypertrophy and strength gains in β-Hydroxy-β-Methylbutyrate- or leucine-supplemented men. Med Sci Sports Exerc. 2019;51(1):65-74. http://doi.org/10.1249/MSS.0000000000001752
13. Bemben MG, Witten MS, Carter JM, Eliot KA, Knehans AW, Bemben DA. The effects of supplementation with creatine and protein on muscle strength following a traditional resistance training program in middle-aged and older men. J Nutr Health Aging. 2010;14(2):155-9. https://doi.org/10.1007/s12603-009-0124-8
14. Boutry-Regard C, Vinyes-Parés G, Breuillé D, Moritani T. Supplementation with whey protein, Omega-3 fatty acids and polyphenols combined with electrical muscle stimulation increases muscle strength in elderly adults with limited mobility: a randomized controlled trial. Nutrients. 2020;12(6). https://doi.org/10.3390/nu12061866
15. Obradović J, Vukadinović Jurišić M, Rakonjac D. The effects of leucine and whey protein supplementation with eight weeks of resistance training on strength and body composition. J Sports Med Phys Fitness. 2020;60(6):864-9. https://doi.org/10.23736/s0022-4707.20.09742-x 
16. Sharp MH, Lowery RP, Shields KA, Lane JR, Gray JL, Partl JM, et al. The effects of beef, chicken, or whey protein after workout on body composition and muscle performance. J Strength Cond Res. 2018;32(8):2233-42. http://doi.org/10.1519/JSC.0000000000001936
17. Holwerda AM, Overkamp M, Paulussen KJM, Smeets JSJ, van Kranenburg J, Backx EMP, et al. Protein supplementation after exercise and before sleep does not further augment muscle mass and strength gains during resistance exercise training in active older men. J Nutr. 2018;148(11):1723-32. https://doi.org/10.1093/jn/nxy169
18. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015;4(1):1. http://doi.org/10.1186/2046-4053-4-1
19. Tarsilla M. Cochrane handbook for systematic reviews of interventions. Journal of Multidisciplinary Evaluation. 2008;6:142-8. https://doi.org/10.56645/jmde.v6i14.284
20. Kazeminasab F, Bagheri Z, Tajabadi F. The effect of whey protein supplementation on muscle soreness and factors of muscle damage after exercise training in healthy adults: a systematic review and meta-analysis of clinical trial studies. Journal of Isfahan Medical School. 2024;42(772):526-44. http://doi.org/10.48305/jims.v42.i772.0526
21. Khalafi M, Malandish A, Rosenkranz SK, Ravasi AA. Effect of resistance training with and without caloric restriction on visceral fat: a systemic review and meta-analysis. Obes Rev. 2021;22(9):e13275. http://doi.org/10.1111/obr.13275
22. Kazeminasab F, Sharafifard F, Miraghajani M, Behzadnejad N, Rosenkranz SK. The effects of exercise training on insulin resistance in children and adolescents with overweight or obesity: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2023;14:1178376. https://doi.org/10.3389/fendo.2023.1178376
23. Kazeminasab F, Baharlooie M, Khalafi M. The Impact of exercise on serum levels of leptin and adiponectin in obese children and adolescents: a systematic review and meta-analysis. Iranian Journal of Endocrinology and Metabolism. 2022;23(6):409-25. https://dor.isc.ac/dor/20.1001.1.16834844.1400.23.6.5.9
24. Khalafi M, Sakhaei MH, Kazeminasab F, Symonds ME, Rosenkranz SK. The impact of high-intensity interval training on vascular function in adults: A systematic review and meta-analysis. Frontiers in Cardiovascular Medicine. 2022;9:1046560. https://doi.org/10.3389/fcvm.2022.1046560
25. Wen H, Wang L. Reducing effect of aerobic exercise on blood pressure of essential hypertensive patients: a meta-analysis. Medicine. 2017;96(11). http://doi.org/10.1097/MD.0000000000006150
26. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997;315(7109):629-34. https://doi.org/10.1136/bmj.315.7109.629 
27. Taylor LW, Wilborn C, Roberts MD, White A, Dugan K. Eight weeks of pre- and postexercise whey protein supplementation increases lean body mass and improves performance in Division III collegiate female basketball players. Appl Physiol Nutr Metab. 2016;41(3):249-54. http://doi.org/10.1139/apnm-2015-0463
28. Herda AA, Herda TJ, Costa PB, Ryan ED, Stout JR, Cramer JT. Muscle performance, size, and safety responses after eight weeks of resistance training and protein supplementation: a randomized, double-blinded, placebo-controlled clinical trial. The Journal of Strength & Conditioning Research. 2013;27(11). http://doi.org/10.1519/JSC.0b013e31828c289f
29. Kim CB, Park JH, Park HS, Kim HJ, Park JJ. Effects of whey protein supplement on 4-week resistance exercise-induced improvements in muscle mass and isokinetic muscular function under dietary control. Nutrients. 2023;15(4). https://doi.org/10.3390/nu15041003
30. Chalé A, Cloutier GJ, Hau C, Phillips EM, Dallal GE, Fielding RA. Efficacy of whey protein supplementation on resistance exercise-induced changes in lean mass, muscle strength, and physical function in mobility-limited older adults. J Gerontol A Biol Sci Med Sci. 2013;68(6):682-90. https://doi.org/10.1093/gerona/gls221
31. Candow DG, Burke NC, Smith-Palmer T, Burke DG. Effect of whey and soy protein supplementation combined with resistance training in young adults. International Journal of Sport Nutrition and Exercise Metabolism. 2006;16(3):233-44. http://doi.org/10.1123/ijsnem.16.3.233
32. Dudgeon WD, Kelley EP, Scheett TP. Effect of Whey protein in conjunction with a caloric-restricted diet and resistance training. J Strength Cond Res. 2017;31(5):1353-61. http://doi.org/10.1519/JSC.0000000000001196
33. Hulmi JJ, Laakso M, Mero AA, Häkkinen K, Ahtiainen JP, Peltonen H. The effects of whey protein with or without carbohydrates on resistance training adaptations. J Int Soc Sports Nutr. 2015;12:48. http://doi.org/10.1186/s12970-015-0109-4
34. Hwang PS, Andre TL, McKinley-Barnard SK, Morales Marroquín FE, Gann JJ, Song JJ, et al. Resistance training-induced elevations in muscular strength in trained men are maintained after 2 weeks of detraining and not differentially affected by whey protein supplementation. J Strength Cond Res. 2017;31(4):869-81. http://doi.org/10.1519/JSC.0000000000001807
35. Mori H, Tokuda Y. Effect of whey protein supplementation after resistance exercise on the muscle mass and physical function of healthy older women: a randomized controlled trial. Geriatr Gerontol Int. 2018;18(9):1398-404. http://doi.org/10.1111/ggi.13499
36. Nabuco HCG, Tomeleri CM, Fernandes RR, Sugihara Junior P, Cavalcante EF, Venturini D, et al. Effects of protein intake beyond habitual intakes associated with resistance training on metabolic syndrome-related parameters, isokinetic strength, and body composition in older women. J Aging Phys Act. 2019;27(4):545–52. http://doi.org/10.1123/japa.2018-0370
37. Nabuco HCG, Tomeleri CM, Sugihara Junior P, Fernandes RR, Cavalcante EF, Antunes M, et al. Effects of whey protein supplementation pre- or post-resistance training on muscle mass, muscular strength, and functional capacity in pre-conditioned older women: a randomized clinical trial. Nutrients. 2018;10(5). https://doi.org/10.3390/nu10050563
38. Reidy PT, Borack MS, Markofski MM, Dickinson JM, Deer RR, Husaini SH, et al. Protein supplementation has minimal effects on muscle adaptations during resistance exercise training in young men: a double-blind randomized clinical trial. J Nutr. 2016;146(9):1660-9. https://doi.org/10.3945/jn.116.231803
39. Weisgarber KD, Candow DG, Farthing JP. Whey protein and high-volume resistance training in postmenopausal women. The Journal of Nutrition, Health and Aging. 2015;19(5):511-7. https://doi.org/10.1007/s12603-015-0454-7
40. Weisgarber KD, Candow DG, Vogt ES. Whey protein before and during resistance exercise has no effect on muscle mass and strength in untrained young adults. Int J Sport Nutr Exerc Metab. 2012;22(6):463-9. http://doi.org/10.1123/ijsnem.22.6.463
41. Sugihara Junior P, Ribeiro AS, Nabuco HCG, Fernandes RR, Tomeleri CM, Cunha PM, et al. Effects of whey protein supplementation associated with resistance training on muscular strength, hypertrophy, and muscle quality in preconditioned older women. Int J Sport Nutr Exerc Metab. 2018;28(5):528-35. http://doi.org/10.1123/ijsnem.2017-0253
42. Hulmi JJ, Lockwood CM, Stout JR. Effect of protein/essential amino acids and resistance training on skeletal muscle hypertrophy: a case for whey protein. Nutrition & Metabolism. 2010;7:1-11. http://doi.org/10.1186/1743-7075-7-51
43. Witard OC, Wardle SL, Macnaughton LS, Hodgson AB, Tipton KD. Protein considerations for optimising skeletal muscle mass in healthy young and older adults. Nutrients. 2016;8(4):181. https://doi.org/10.3390/nu8040181
44. Churchward-Venne TA, Burd NA, Phillips SM. Nutritional regulation of muscle protein synthesis with resistance exercise: strategies to enhance anabolism. Nutrition & metabolism. 2012;9:1-8. http://doi.org/10.1186/1743-7075-9-40
45. Phillips SM. A brief review of critical processes in exercise-induced muscular hypertrophy. Sports Medicine. 2014;44:71-7. http://doi.org/10.1007/s40279-014-0152-3
46. Holwerda AM, Paulussen KJ, Overkamp M, Smeets JS, Gijsen AP, Goessens JP, et al. Daily resistance-type exercise stimulates muscle protein synthesis in vivo in young men. Journal of Applied Physiology. 2018;124(1):66-75. https://doi.org/10.1152/japplphysiol.00610.2017
47. Breen L, Phillips SM. Skeletal muscle protein metabolism in the elderly: interventions to counteract the'anabolic resistance'of ageing. Nutrition & metabolism. 2011;8:1-11. http://doi.org/10.1186/1743-7075-8-68
48. Li M, Liu F. Effect of whey protein supplementation during resistance training sessions on body mass and muscular strength: a meta-analysis. Food & Function. 2019;10(5):2766-73. https://doi.org/10.1039/C9FO00182D
49. Snijders T, Verdijk LB, Smeets JS, McKay BR, Senden JM, Hartgens F, et al. The skeletal muscle satellite cell response to a single bout of resistance-type exercise is delayed with aging in men. Age. 2014;36:1-15. http://doi.org/10.1007/s11357-014-9699-z
50. Hartman JW, Tang JE, Wilkinson SB, Tarnopolsky MA, Lawrence RL, Fullerton AV, et al. Consumption of fat-free fluid milk after resistance exercise promotes greater lean mass accretion than does consumption of soy or carbohydrate in young, novice, male weightlifters. The American Journal of Clinical Nutrition. 2007;86(2):373-81. https://doi.org/10.1093/ajcn/86.2.373
51. Erskine RM, Fletcher G, Hanson B, Folland JP. Whey protein does not enhance the adaptations to elbow flexor resistance training. Medicine and Science in Sports and Exercise. 2012;44(9):1791-800. http://doi.org/10.1249/MSS.0b013e318256c48d
52. Phillips SM, Van Loon LJ. Dietary protein for athletes: from requirements to optimum adaptation. Food, Nutrition and Sports Performance III. 2013:29-38. http://doi.org/10.1080/02640414.2011.619204
53. Candow DG, Burke NC, Smith-Palmer T, Burke DG. Effect of whey and soy protein supplementation combined with resistance training in young adults. Int J Sport Nutr Exerc Metab. 2006;16(3):233-44. http://doi.org/10.1123/ijsnem.16.3.233
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Volume 17, Issue 67
Summer 2025
Pages 79-102

  • Receive Date 14 July 2025
  • Revise Date 07 October 2025
  • Accept Date 19 October 2025