Acute or Short-term Effects of Whey Protein Alone or Along with Carbohydrate on Inflammation: A Systematic Review of Clinical Trials
AbstractBackground: Excessive inflammatory response is associated with several diseases. Recently, there has been an increasing trend for investigation of the acute or short-term effects of whey protein alone or in combination with carbohydrates on inflammatory status, especially in athletes. This systematic review aimed to clarify these effects. Materials and Methods: PubMed, Scopus, and Web of Science databases were searched from January 1990 to September 2021, without language restriction. Adult studies examining the effects of whey protein alone or together with carbohydrates on interleukin-6, tumor necrosis factor-α, and C-reactive protein levels with a maximum duration of 15 days and with at least one comparison group were included. The quality of studies was analyzed using the Cochrane risk of bias tool. Results: Twenty-five studies met the inclusion criteria. Significant reductions in inflammatory markers was observed in seven out of 25 studies (28%). However, one out of 25 studies (4%) reported a significant increase in inflammatory status. Among those studies comparing the effects of whey protein alone with non-protein or protein-containing groups, 18.18% (two out of 11) and 10% (one out of ten) of the trials revealed a significant decrease in the markers, respectively. Moreover, of those studies comparing whey protein plus carbohydrate with non-protein or protein-containing groups, 33.33% (two out of six) and 40% (two out of five) of them showed a significant reduction in the inflammatory response, respectively. The quality of the majority of studies (84%) was poor. Conclusion: It seems that whey protein alone or the combination of it with carbohydrates may not affect the inflammatory markers in the short run (PROSPERO registration number: CRD42021273915).[GMJ.2023;12:e2441]
Abdulkhaleq LA, Assi MA, Abdullah R, Zamri-Saad M, Taufiq-Yap YH, Hezmee MNM. The crucial roles of inflammatory mediators in inflammation: A review. Vet World. 2018;11(5):627-35.
Oke SL, Tracey KJ. The inflammatory reflex and the role of complementary and alternative medical therapies. Ann N Y Acad Sci. 2009;1172:172-80.
Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature. 2008;454(7203):455-62.
Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019;25(12):1822-32.
Kantor ED, Lampe JW, Kratz M White. Lifestyle factors and inflammation associations by body mass index. PLoS One. 2013;8(7):e67833.
Wirth MD, Hébert JR, Shivappa N, Hand GA, Hurley TG, Drenowatz C, et al. Anti-inflammatory Dietary Inflammatory Index scores are associated with healthier scores on other dietary indices. Nutr Res. 2016;36(3):214-9.
Davoodi SH, Shahbazi R, Esmaeili S, Sohrabvandi S, Mortazavian A, Jazayeri S, et al. Health-related aspects of milk proteins. Iran J Pharm Res. 2016;15(3):573-91.
Patel SJ. Functional food relevance of whey protein: A review of recent findings and scopes ahead. J Funct Foods. 2015;19:308-19.
León-López A, Pérez-Marroquín XA, Campos-Lozada G, Campos-Montiel RG, Aguirre-Álvarez GJF. Characterization of whey-based fermented beverages supplemented with hydrolyzed collagen: Antioxidant activity and bioavailability. Foods. 2020;9(8):1106.
Wirunsawanya K, Upala S, Jaruvongvanich V, Sanguankeo A. Whey protein supplementation improves body composition and cardiovascular risk factors in overweight and obese patients: A systematic review and meta-analysis. J Am Coll Nutr. 2018;37(1):60-70.
Zhang J, Tong X, Wan Z, Wang Y, Qin L, Szeto IMY. Effect of whey protein on blood lipid profiles: a meta-analysis of randomized controlled trials. Eur J Clin Nutr. 2016;70(8):879-85.
Hassan K. Does whey protein supplementation improve the nutritional status in hypoalbuminemic peritoneal dialysis patients? Ther Apher Dial. 2017;21(5):485-92.
Aghamohammadi V, Haidari F, Mohammadshahi M, Ahmadi-Angali K, Asghari-Jafarabadi M. Whey supplementation combined with energy-restricted diet alleviates 2-arachidonoylglycerol, adipocytokines, inflammatory factors and body composition in obese women with metabolic syndrome: a randomized controlled trial. Endocrinol Metab Syndr. 2018;7(295):2161-1017.
Sprong R, Schonewille A, Van der Meer R. Dietary cheese whey protein protects rats against mild dextran sulfate sodium-induced colitis: Role of mucin and microbiota. J Dairy Sci. 2010;93(4):1364-71.
Zhou L-M, Xu J-Y, Rao C-P, Han S, Wan Z, Qin L-Q. Effect of whey supplementation on circulating C-reactive protein: A meta-analysis of randomized controlled trials. Nutrients. 2015;7(2):1131-43.
Qin L, Sun F-H, Huang Y, Sheridan S, Sit CH-P, Wong SH-S. Effect of pre-exercise ingestion of α-lactalbumin on subsequent endurance exercise performance and mood states. Br J Nutr. 2019;121(1):22-9.
Qin L, Wong SHS, Sun F-H, Huang Y, Sheridan S, Sit CHP. Effects of alpha-lactalbumin or whey protein isolate on muscle damage, muscle pain, and mood states following prolonged strenuous endurance exercise. Front Physiol. 2017;8:754.
Dahlquist DT, Stellingwerff T, Dieter BP, McKenzie DC, Koehle MS. Effects of macro-and micronutrients on exercise-induced hepcidin response in highly trained endurance athletes. Appl Physiol Nutr Metab. 2017;42(10):1036-43.
Hansen M, Bangsbo J, Jensen J, Bibby BM, Madsen K. Effect of whey protein hydrolysate on performance and recovery of top-class orienteering runners. Int J Sport Nutr Exerc Metab. 2015;25(2):97-109.
Schroer AB, Saunders MJ, Baur DA, Womack CJ, Luden ND. Cycling time trial performance may be impaired by whey protein and L-alanine intake during prolonged exercise. Int J Sport Nutr Exerc Metab. 2014;24(5):507-15.
Snipe RM, Khoo A, Kitic CM, Gibson PR, Costa RJ. Carbohydrate and protein intake during exertional heat stress ameliorates intestinal epithelial injury and small intestine permeability. Appl Physiol Nutr Metab. 2017;42(12):1283-92.
Livesey G. Assessment of carbohydrate availability, fermentability, and food energy value in humans using measurements of breath hydrogen. J Am Coll Nutr. 2021;40(5):480-2.
Alghannam AF, Gonzalez JT, Betts JA. Restoration of muscle glycogen and functional capacity: role of post-exercise carbohydrate and protein co-ingestion. Nutrients. 2018;10(2):253.
de Aguilar-Nascimento JE, Prado Silveira BR, Dock-Nascimento DB. Early enteral nutrition with whey protein or casein in elderly patients with acute ischemic stroke: A double-blind randomized trial. Nutrition. 2011;27(4):440-4.
Kullisaar T, Punab M, Türk S, Veskioja A, Songisepp E, Zilmer M. A fermented whey product benefits male patients with lower urinary tract symptoms. Food technologists, biotechnologists and nutritionists. 2011:63-8.
Deng Y, Fang Y, Li H, Chen J, An J, Qiao S, et al. A preoperative whey protein and glucose drink before hip fracture surgery in the aged improves symptomatic and metabolic recovery. Asia Pac J Clin Nutr. 2020;29(2):234-8.
Yi HC, Ibrahim Z, Abu Zaid Z, Mat Daud ZA, Md Yusop NB, Omar J, et al. Impact of enhanced recovery after surgery with preoperative whey protein-infused carbohydrate loading and postoperative early oral feeding among surgical gynecologic cancer patients an open-labelled randomized controlled trial. Nutrients. 2020;12(1):264.
Mizubuti Y, Vieira E, Silva T, d'Alessandro M, Generoso S, Teixeira A, et al. Comparing the effects of whey and casein supplementation on nutritional status and immune parameters in patients with chronic liver disease: a randomised double-blind controlled trial. Br J Nutr. 2021;125(7):768-79.
Hilkens L, De Bock J, Kretzers J, Kardinaal AF, Floris-Vollenbroek EG, Scholtens PA, et al. Whey protein supplementation does not accelerate recovery from a single bout of eccentric exercise. J Sports Sci. 2021;39(3):322-31.
de Carvalho CS, Silva TH, André JCS, de Barros LAS, Ferreira AA, Murad LB, et al. Preoperative fasting abbreviation with whey protein reduces the occurrence of postoperative complications in patients with head and neck cancer: a randomized clinical trial. Nutr Clin Pract. 2021;36(3):665-72.
Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6(7):e1000097.
Moosavian SP, Rahimlou M, Saneei P, Esmaillzadeh A. Effects of dairy products consumption on inflammatory biomarkers among adults: A systematic review and meta-analysis of randomized controlled trials. Nutr Metab Cardiovasc Dis. 2020;30(6):872-88.
Nieman KM, Anderson BD, Cifelli CJ. The effects of dairy product and dairy protein intake on inflammation: A systematic review of the literature. J Am Coll Nutr. 2021;40(6):571-82.
Ticinesi A, Meschi T, Lauretani F, Felis G, Franchi F, Pedrolli C, et al. Nutrition and inflammation in older individuals: focus on vitamin D, n-3 polyunsaturated fatty acids and whey proteins. Nutrients. 2016;8(4):186.
Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.
Nieman DC, Zwetsloot KA, Simonson AJ, Hoyle AT, Wang X, Nelson HK, et al. Effects of whey and pea protein supplementation on post-eccentric exercise muscle damage: a randomized trial. Nutrients. 2020;12(8):2382.
Saracino PG, Saylor HE, Hanna BR, Hickner RC, Kim J-S, Ormsbee MJ. Effects of pre-sleep whey vs plant-based protein consumption on muscle recovery following damaging morning exercise. Nutrients. 2020;12(7):2049.
Celik R, Kaymakci MS, Akalin D, Karademir E, Tuncer B, Bicim G, et al. Effect of casein and whey proteins on examination stress. Marmara Med J. 2019:58-61.
Mariotti F, Valette M, Lopez C, Fouillet H, Famelart M-H, Mathé V, et al. Casein compared with whey proteins affects the organization of dietary fat during digestion and attenuates the postprandial triglyceride response to a mixed high-fat meal in healthy, overweight men. J Nutr. 2015;145(12):2657-64.
Kinsey AW, Eddy WR, Madzima TA, Panton LB, Arciero PJ, Kim J-S, et al. Influence of night-time protein and carbohydrate intake on appetite and cardiometabolic risk in sedentary overweight and obese women. Br J Nutr. 2014;112(3):320-7.
Baba S, Ebihara S, Sakano K, Natsume M. Whey protein-containing product reduces muscle damage induced by running in male adults. Sport Sci Health. 2014;10(2):85-95.
Singh N, Mishra SK, Sachdev V, Sharma H, Upadhyay AD, Arora I, et al. Effect of oral glutamine supplementation on gut permeability and endotoxemia in patients with severe acute pancreatitis: a randomized controlled trial. Pancreas. 2014;43(6):867-73.
Pal S, Ellis V. Acute effects of whey protein isolate on blood pressure, vascular function and inflammatory markers in overweight postmenopausal women. Br J Nutr. 2011;105(10):1512-9.
Buckley JD, Thomson RL, Coates AM, Howe PR, DeNichilo MO, Rowney MK. Supplementation with a whey protein hydrolysate enhances recovery of muscle force-generating capacity following eccentric exercise. J Sci Med Sport. 2010;13(1):178-81.
Isenmann E, Blume F, Bizjak D, Hundsdörfer V, Pagano S, Schibrowski S, et al. Comparison of pro-regenerative effects of carbohydrates and protein administrated by shake and non-macro-nutrient matched food items on the skeletal muscle after acute endurance exercise. Nutrients. 2019;11(4):744.
Kerasioti E, Stagos D, Jamurtas A, Kiskini A, Koutedakis Y, Goutzourelas N, et al. Anti-inflammatory effects of a special carbohydrate-whey protein cake after exhaustive cycling in humans. Food Chem Toxicol. 2013;61:42-6.
Betts JA, Toone RJ, Stokes KA, Thompson D. Systemic indices of skeletal muscle damage and recovery of muscle function after exercise: effect of combined carbohydrate-protein ingestion. Appl Physiol Nutr Metab. 2009;34(4):773-84.
Jamshidi S, Mohsenpour MA, Masoumi SJ, Fatahi S, Nasimi N, Zahabi ES, et al. Effect of whey protein consumption on IL-6 and TNF-α: A systematic review and meta-analysis of randomized controlled trials. Diabetes Metab Syndr. 2021;16(1):102372.
Fekete ÁA, Givens DI, Lovegrove JA. Can milk proteins be a useful tool in the management of cardiometabolic health An updated review of human intervention trials. Proc Nutr Soc. 2016;75(3):328-41.
Biswas SK. Does the interdependence between oxidative stress and inflammation explain the antioxidant paradox? Oxid Med Cell Longev. 2016;2016:5698931.
Veskoukis AS, Kerasioti E, Skaperda Z, Papapostolou PA, Nepka C, Spandidos DA, et al. Whey protein boosts the antioxidant profile of rats by enhancing the activities of crucial antioxidant enzymes in a tissue-specific manner. Food Chem Toxicol. 2020;142:111508.
Corrochano AR, Buckin V, Kelly PM, Giblin L. Invited review: Whey proteins as antioxidants and promoters of cellular antioxidant pathways. J Dairy Sci. 2018;101(6):4747-61.
Brimelow RE, West NP, Williams LT, Cripps AW, Cox AJ. A role for whey-derived lactoferrin and immunoglobulins in the attenuation of obesity-related inflammation and disease. Crit Rev Food Sci Nutr. 2017;57(8):1593-602.
Elovaris RA, Hajishafiee M, Ullrich SS, Fitzgerald PC, Lange K, Horowitz M, et al. Intragastric administration of leucine and isoleucine does not reduce the glycaemic response to, or slow gastric emptying of, a carbohydrate-containing drink in type 2 diabetes. Diabetes Res Clin Pract. 2021;171:108618.
Liberman K, Njemini R, Luiking Y, Forti LN, Verlaan S, Bauer JM, et al. Thirteen weeks of supplementation of vitamin D and leucine-enriched whey protein nutritional supplement attenuates chronic low-grade inflammation in sarcopenic older adults: the PROVIDE study. Aging Clin Exp Res. 2019;31(6):845-54.
Arazi H, Taati B, Suzuki K. A review of the effects of leucine metabolite (β-hydroxy-β-methylbutyrate) supplementation and resistance training on inflammatory markers: A new approach to oxidative stress and cardiovascular risk factors. Antioxidants (Basel). 2018;7(10):148.
Zhenyukh O, Civantos E, Ruiz-Ortega M, Sánchez MS, Vazquez C, Peiro C, et al. High concentration of branched-chain amino acids promotes oxidative stress, inflammation and migration of human peripheral blood mononuclear cells via mTORC1 activation. Free Radic Biol Med. 2017;104:165-77.
Athira S, Mann B, Saini P, Sharma R, Kumar R, Singh AK. Production and characterisation of whey protein hydrolysate having antioxidant activity from cheese whey. J Sci Food Agric. 2015;95(14):2908-15.
Da Silva MS, Bigo C, Barbier O, Rudkowska I. Whey protein hydrolysate and branched-chain amino acids downregulate inflammation-related genes in vascular endothelial cells. Nutr Res. 2017;38:43-51.
Kloby Nielsen LL, Tandrup Lambert MN, Jeppesen PB. The effect of ingesting carbohydrate and proteins on athletic performance: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2020;12(5):1483.
Lawler TP, Cialdella-Kam L. Non-carbohydrate dietary factors and their influence on post-exercise glycogen storage: a review. Curr Nutr Rep. 2020;9(4):394-404.
McCartney D, Desbrow B, Irwin C. Post-exercise ingestion of carbohydrate, protein and water: a systematic review and meta-analysis for effects on subsequent athletic performance. Sports Med. 2018;48(2):379-408.
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