Effects of whey and soy protein supplementation on inflammatory cytokines in older adults: a systematic review and meta-analysis

Konstantinos Prokopidis, Mohsen Mazidi, Rajiv Sankaranarayanan, Behnam Tajik, Anne McArdle, Masoud Isanejad, Konstantinos Prokopidis, Mohsen Mazidi, Rajiv Sankaranarayanan, Behnam Tajik, Anne McArdle, Masoud Isanejad

Abstract

Background and aims: Low-grade inflammation is a mediator of muscle proteostasis. This study aimed to investigate the effects of isolated whey and soy proteins on inflammatory markers.

Methods: We conducted a systematic literature search of randomised controlled trials (RCT) through MEDLINE, Web of Science, Scopus and Cochrane Library databases from inception until September 2021. To determine the effectiveness of isolated proteins on circulating levels of C-reactive protein (CRP), IL-6 and TNF-α, a meta-analysis using a random-effects model was used to calculate the pooled effects (CRD42021252603).

Results: Thirty-one RCT met the inclusion criteria and were included in the systematic review and meta-analysis. A significant reduction of circulating IL-6 levels following whey protein [Mean Difference (MD): -0·79, 95 % CI: -1·15, -0·42, I2 = 96 %] and TNF-α levels following soy protein supplementation (MD: -0·16, 95 % CI: -0·26, -0·05, I2 = 68 %) was observed. The addition of soy isoflavones exerted a further decline in circulating TNF-α levels (MD: -0·20, 95 % CI: -0·31, -0·08, I2 = 34 %). According to subgroup analysis, whey protein led to a statistically significant decrease in circulating IL-6 levels in individuals with sarcopenia and pre-frailty (MD: -0·98, 95 % CI: -1·56, -0·39, I2 = 0 %). These findings may be dependent on participant characteristics and treatment duration.

Conclusions: These data support that whey and soy protein supplementation elicit anti-inflammatory effects by reducing circulating IL-6 and TNF-α levels, respectively. This effect may be enhanced by soy isoflavones and may be more prominent in individuals with sarcopenia.

Keywords: IL-6; Inflammation; Sarcopenia; Soy protein; TNF-α; Whey protein.

Figures

Fig. 1.
Fig. 1.
PRISMA flowchart of literature search via databases and registers.
Fig. 2.
Fig. 2.
Effects of whey protein supplementation on (a) hs-CRP, (b) CRP, (c) TNF-α and (d) IL-6. CRP, C-reactive protein.
Fig. 3.
Fig. 3.
Effects of soy protein supplementation on (a) hs-CRP, (b) CRP, (c) TNF-α and (d) IL-6. CRP, C-reactive protein.

References

    1. Chung HY, Kim DH, Lee EK, et al. (2019) Redefining chronic inflammation in aging and age-related diseases: proposal of the senoinflammation concept. Aging Dis 10, 367.
    1. Londhe P & Guttridge DC (2015) Inflammation induced loss of skeletal muscle. Bone 80, 131–142.
    1. Shaw S, Dennison E & Cooper C (2017) Epidemiology of sarcopenia: determinants throughout the lifecourse. Calcified Tissue Int 101, 229–247.
    1. Cruz-Jentoft AJ, Bahat G, Bauer J, et al. (2019) Sarcopenia: revised European consensus on definition and diagnosis. Age Agine 48, 16–31.
    1. Mitchell WK, Atherton PJ, Williams J, et al. (2012) Sarcopenia, dynapenia, and the impact of advancing age on human skeletal muscle size and strength; a quantitative review. Front Physiol 3, 260.
    1. Venturelli M, Reggiani C, Richardson RS, et al. (2018) Skeletal muscle function in the oldest-old: the role of intrinsic and extrinsic factors. Exerc Sport Sci Rev 46, 188.
    1. Li CW, Yu K, Shyh-Chang N, et al. (2019) Circulating factors associated with sarcopenia during ageing and after intensive lifestyle intervention. J Cachexia, Sarcopenia Muscle 10, 586–600.
    1. Rong Y-D, Bian A-L, Hu H-Y, et al. (2018) Study on relationship between elderly sarcopenia and inflammatory cytokine IL-6, anti-inflammatory cytokine IL-10. BMC Geriatr 18, 1–6.
    1. da Cunha Nascimento D, da Cunha Oliveira S, Vieira DCL, et al. (2018) The impact of sarcopenic obesity on inflammation, lean body mass, and muscle strength in elderly women. Int J Gen Med 11, 443.
    1. Schrager MA, Metter EJ, Simonsick E, et al. (2007) Sarcopenic obesity and inflammation in the InCHIANTI study. J Appl Physiol 102, 919–925.
    1. Jackson MJ & McArdle A (2011) Age-related changes in skeletal muscle reactive oxygen species generation and adaptive responses to reactive oxygen species. J Physiol 589, 2139–2145.
    1. Vasilaki A, Richardson A, Van Remmen H, et al. (2017) Role of nerve–muscle interactions and reactive oxygen species in regulation of muscle proteostasis with ageing. J Physiol 595, 6409–6415.
    1. Venturelli M, Morgan GR, Donato AJ, et al. (2014) Cellular aging of skeletal muscle: telomeric and free radical evidence that physical inactivity is responsible and not age. Clin Sci 127, 415–421.
    1. Dalle S, Rossmeislova L & Koppo K (2017) The role of inflammation in age-related sarcopenia. Front Physiol 8, 1045.
    1. Powers SK (2014) Can antioxidants protect against disuse muscle atrophy? Sports Med 44, 155–165.
    1. Mose M, Brodersen K, Rittig N, et al. (2021) Anabolic effects of oral leucine-rich protein with and without β-hydroxybutyrate on muscle protein metabolism in a novel clinical model of systemic inflammation—a randomized crossover trial. Am J Clin Nutr 114, 1159–1172.
    1. Rittig N, Bach E, Thomsen H, et al. (2016) Amino acid supplementation is anabolic during the acute phase of endotoxin-induced inflammation: a human randomized crossover trial. Clin Nutr 35, 322–330.
    1. Draganidis D, Chondrogianni N, Chatzinikolaou A, et al. (2017) Protein ingestion preserves proteasome activity during intense aseptic inflammation and facilitates skeletal muscle recovery in humans. Br J Nutr 118, 189–200.
    1. Wu SH, Shu XO, Chow W-H, et al. (2012) Soy food intake and circulating levels of inflammatory markers in Chinese women. J Acad Nutr Diet 112, 996–1004.e1004.
    1. Aguilera JM (2019) The food matrix: Implications in processing, nutrition and health. Crit Rev Food Sci Nutr 59, 3612–3629.
    1. Asbaghi O, Sadeghian M, Nazarian B, et al. (2020) The effect of vitamin E supplementation on selected inflammatory biomarkers in adults: a systematic review and meta-analysis of randomized clinical trials. Sci Rep 10, 1–17.
    1. Zhou L-M, Xu J-Y, Rao C-P, et al. (2015) Effect of whey supplementation on circulating C-reactive protein: a meta-analysis of randomized controlled trials. Nutrients 7, 1131–1143.
    1. Gholami A, Baradaran HR & Hariri M (2021) Can soy isoflavones plus soy protein change serum levels of interlukin-6? A systematic review and meta-analysis of randomized controlled trials. Phytother Res 35, 1147–1162.
    1. Page MJ, McKenzie JE, Bossuyt PM, et al. (2021) The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Int J Surg 88, 105906.
    1. Farrah K, Young K, Tunis MC, et al. (2019) Risk of bias tools in systematic reviews of health interventions: an analysis of PROSPERO-registered protocols. Syst Rev 8, 1–9.
    1. Higgins JP, Altman DG, Gøtzsche PC, et al. (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343.
    1. Borenstein M, Hedges LV, Higgins JP, et al. (2010) A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Meth 1, 97–111.
    1. Higgins JP, Thompson SG, Deeks JJ, et al. (2003) Measuring inconsistency in meta-analyses. BMJ 327, 557–560.
    1. Egger M, Smith GD, Schneider M, et al. (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315, 629–634.
    1. Rondanelli M, Klersy C, Terracol G, et al. (2016) Whey protein, amino acids, and vitamin D supplementation with physical activity increases fat-free mass and strength, functionality, and quality of life and decreases inflammation in sarcopenic elderly. Am J Clin Nutr 103, 830–840.
    1. Ahmadi A, Eftekhari MH, Mazloom Z, et al. (2020) Fortified whey beverage for improving muscle mass in chronic obstructive pulmonary disease: a single-blind, randomized clinical trial. Respir Res 21, 1–11.
    1. Bo Y, Liu C, Ji Z, et al. (2019) A high whey protein, vitamin D and E supplement preserves muscle mass, strength, and quality of life in sarcopenic older adults: a double-blind randomized controlled trial. Clin Nutr 38, 159–164.
    1. Bumrungpert A, Pavadhgul P, Nunthanawanich P, et al. (2018) Whey protein supplementation improves nutritional status, glutathione levels, and immune function in cancer patients: a randomized, double-blind controlled trial. J Med Food 21, 612–616.
    1. Bohl M, Bjørnshave A, Gregersen S, et al. (2016) Whey and casein proteins and medium-chain saturated fatty acids from milk do not increase low-grade inflammation in abdominally obese adults. Review Diabet Stud: RDS 13, 148.
    1. Biesek S, Vojciechowski AS, Ferreira AC, et al. (2021) Effects of exergames and protein supplementation on body composition and musculoskeletal function of prefrail community-dwelling older women: a randomized, controlled clinical trial. Int J Environ Res Public Health 18, 9324.
    1. Charles C, Yuskavage J, Carlson O, et al. (2009) Effects of high-dose isoflavones on metabolic and inflammatory markers in healthy postmenopausal women. Menopause 16, 395.
    1. Christie DR, Grant J, Darnell BE, et al. (2010) Metabolic effects of soy supplementation in postmenopausal Caucasian and African American women: a randomized, placebo-controlled trial. Am J Obstet Gynecol 203, 153. e151–153. e159.
    1. Fanti P, Asmis R, Stephenson TJ, et al. (2006) Positive effect of dietary soy in ESRD patients with systemic inflammation—correlation between blood levels of the soy isoflavones and the acute-phase reactants. Nephrol Dialysis Transplant 21, 2239–2246.
    1. Greany K, Nettleton J, Wangen K, et al. (2008) Consumption of isoflavone-rich soy protein does not alter homocysteine or markers of inflammation in postmenopausal women. Eur J Clin Nutr 62, 1419–1425.
    1. Hermansen K, Hansen B, Jacobsen R, et al. (2005) Effects of soy supplementation on blood lipids and arterial function in hypercholesterolaemic subjects. Eur J Clin Nutr 59, 843–850.
    1. Liu Z-M, Ho S, Chen Y-M, et al. (2012) The effects of isoflavones combined with soy protein on lipid profiles, C-reactive protein and cardiovascular risk among postmenopausal Chinese women. Nutr Metab Cardiovasc Dis 22, 712–719.
    1. Napora JK, Short RG, Muller DC, et al. (2011) High-dose isoflavones do not improve metabolic and inflammatory parameters in androgen-deprived men with prostate cancer. J Androl 32, 40–48.
    1. Teede HJ, Dalais FS & McGrath BP (2004) Dietary soy containing phytoestrogens does not have detectable estrogenic effects on hepatic protein synthesis in postmenopausal women. Am J Clin Nutr 79, 396–401.
    1. Törmälä R, Appt S, Clarkson TB, et al. (2008) Impact of soy supplementation on sex steroids and vascular inflammation markers in postmenopausal women using tibolone: role of equol production capability. Climacteric 11, 409–415.
    1. Sathyapalan T, Manuchehri AM, Thatcher NJ, et al. (2011) The effect of soy phytoestrogen supplementation on thyroid status and cardiovascular risk markers in patients with subclinical hypothyroidism: a randomized, double-blind, crossover study. J Clin Endocrinol Metab 96, 1442–1449.
    1. Hanson LN, Engelman HM, Alekel DL, et al. (2006) Effects of soy isoflavones and phytate on homocysteine, C-reactive protein, and iron status in postmenopausal women. Am J Clin Nutr 84, 774–780.
    1. Derosa G, D’Angelo A & Maffioli P (2020) Change of some oxidative stress parameters after supplementation with whey protein isolate in patients with type 2 diabetes. Nutrition 73, 110700.
    1. Rakvaag E, Fuglsang-Nielsen R, Bach Knudsen KE, et al. (2019) The combination of whey protein and dietary fiber does not alter low-grade inflammation or adipose tissue gene expression in adults with abdominal obesity. Rev Diabetic Stud 15, 83–94.
    1. Sohrabi Z, Eftekhari MH, Eskandari MH, et al. (2016) Intradialytic oral protein supplementation and nutritional and inflammation outcomes in hemodialysis: a randomized controlled trial. Am J Kidney Dis 68, 122–130.
    1. Sathyapalan T, Rigby AS, Bhasin S, et al. (2017) Effect of soy in men with type 2 diabetes mellitus and subclinical hypogonadism: a randomized controlled study. J Clin Endocrinol Metab 102, 425–433.
    1. Fekete AA, Giromini C, Chatzidiakou Y, et al. (2016) 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 104, 1534–1544.
    1. Fernandes RR, Nabuco HC, Junior PS, et al. (2018) Effect of protein intake beyond habitual intakes following resistance training on cardiometabolic risk disease parameters in pre-conditioned older women. Exp Gerontol 110, 9–14.
    1. Kirk B, Mooney K, Vogrin S, et al. (2021) Leucine-enriched whey protein supplementation, resistance-based exercise, and cardiometabolic health in older adults: a randomized controlled trial. J Cachexia, Sarcopenia Muscle 12, 2022–2033.
    1. Ma L, Grann K, Li M, et al. (2011) A pilot study to evaluate the effect of soy isolate protein on the serum lipid profile and other potential cardiovascular risk markers in moderately hypercholesterolemic Chinese adults. Ecol Food Nutr 50, 473–485.
    1. Nabuco HC, Tomeleri CM, Fernandes RR, et al. (2019) Effect of whey protein supplementation combined with resistance training on body composition, muscular strength, functional capacity, and plasma-metabolism biomarkers in older women with sarcopenic obesity: A randomized, double-blind, placebo-controlled trial. Clin Nutr ESPEN 32, 88–95.
    1. Stojkovic V, Simpson CA, Sullivan RR, et al. (2017) The effect of dietary glycemic properties on markers of inflammation, insulin resistance, and body composition in postmenopausal American women: an ancillary study from a multicenter protein supplementation trial. Nutrients 9, 484.
    1. Duff WR, Chilibeck PD, Rooke JJ, et al. (2014) The effect of bovine colostrum supplementation in older adults during resistance training. Int J Sport Nutr Exerc Metab 24, 276–285.
    1. Laviolette L, Lands LC, Dauletbaev N, et al. (2010) Combined effect of dietary supplementation with pressurized whey and exercise training in chronic obstructive pulmonary disease: a randomized, controlled, double-blind pilot study. J Med Food 13, 589–598.
    1. Weinheimer EM, Conley TB, Kobza VM, et al. (2012) Whey protein supplementation does not affect exercise training-induced changes in body composition and indices of metabolic syndrome in middle-aged overweight and obese adults. J Nutr 142, 1532–1539.
    1. Mizubuti Y, Vieira E, Silva T, et al. (2021) 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 125, 768–779.
    1. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. (2010) Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in older people. Age Ageing 39, 412–423.
    1. Fried LP, Tangen CM, Walston J, et al. (2001) Frailty in older adults: evidence for a phenotype. J Gerontol Ser A: Biol Sci Med Sci 56, M146–M157.
    1. Niccoli S, Kolobov A, Bon T, et al. (2017) Whey protein supplementation improves rehabilitation outcomes in hospitalized geriatric patients: a double blinded, randomized controlled trial. J Nutr Gerontol Geriatr 36, 149–165.
    1. Kerasioti E, Stagos D, Priftis A, et al. (2014) Antioxidant effects of whey protein on muscle C2C12 cells. Food Chem 155, 271–278.
    1. Liberman K, Njemini R, Luiking Y, et al. (2019) 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 31, 845–854.
    1. Kaulmann A & Bohn T (2014) Carotenoids, inflammation, and oxidative stress—implications of cellular signaling pathways and relation to chronic disease prevention. Nutr Res 34, 907–929.
    1. Mehta AK, Singh BP, Arora N, et al. (2010) Choline attenuates immune inflammation and suppresses oxidative stress in patients with asthma. Immunobiology 215, 527–534.
    1. Elenkova M, Tipton DA, Karydis A, et al. (2019) Vitamin D attenuates human gingival fibroblast inflammatory cytokine production following advanced glycation end product interaction with receptors for AGE. J Periodontal Res 54, 154–163.
    1. Agbalalah T, Hughes SF, Freeborn EJ, et al. (2017) Impact of vitamin D supplementation on endothelial and inflammatory markers in adults: a systematic review. J Steroid Biochem Mol Biol 173, 292–300.
    1. Jamka M, Woźniewicz M, Walkowiak J, et al. (2016) The effect of vitamin D supplementation on selected inflammatory biomarkers in obese and overweight subjects: a systematic review with meta-analysis. Eur J Nutr 55, 2163–2176.
    1. Calder PC, Bosco N, Bourdet-Sicard R, et al. (2017) Health relevance of the modification of low grade inflammation in ageing (inflammageing) and the role of nutrition. Ageing Res Rev 40, 95–119.
    1. Hariri M, Ghasemi A, Baradaran HR, et al. (2021) Beneficial effect of soy isoflavones and soy isoflavones plus soy protein on serum concentration of C-reactive protein among postmenopausal women: an updated systematic review and meta-analysis of randomized controlled trials. Complementary Ther Med 59, 102715.
    1. Peluso I, Raguzzini A & Serafini M (2013) Effect of flavonoids on circulating levels of TNF-α and IL-6 in humans: a systematic review and meta-analysis. Mol Nutr Food Res 57, 784–801.
    1. Khodarahmi M, Jafarabadi MA, Moludi J, et al. (2019) A systematic review and meta-analysis of the effects of soy on serum hs-CRP. Clin Nutr 38, 996–1011.
    1. Cassidy A, Brown JE, Hawdon A, et al. (2006) Factors affecting the bioavailability of soy isoflavones in humans after ingestion of physiologically relevant levels from different soy foods. J Nutr 136, 45–51.
    1. Reinwald S, Akabas SR & Weaver CM (2010) Whole v. the piecemeal approach to evaluating soy. J Nutr 140, 2335S–2343S.
    1. Khodarahmi M, Foroumandi E & Asghari Jafarabadi M (2021) Effects of soy intake on circulating levels of TNF-α and interleukin-6: a systematic review and meta-analysis of randomized controlled trials. Eur J Nutr 60, 581–601.
    1. Rezazadegan M, Mirjalili F, Clark CC, et al. (2021) The effect of soya consumption on inflammatory biomarkers: a systematic review and meta-analysis of clinical trials. Br J Nutr 125, 780–791.
    1. Patel RP, Boersma BJ, Crawford JH, et al. (2001) Antioxidant mechanisms of isoflavones in lipid systems: paradoxical effects of peroxyl radical scavenging. Free Radical Biol Med 31, 1570–1581.
    1. Rodríguez-Roque MJ, Rojas-Graü MA, Elez-Martínez P, et al. (2013) Soymilk phenolic compounds, isoflavones and antioxidant activity as affected by in vitro gastrointestinal digestion. Food Chem 136, 206–212.
    1. Jin L, Zhao X, Qin Y, et al. (2015) Soy isoflavones protect against H2O2-induced injury in human umbilical vein endothelial cells. Mol Med Rep 12, 4476–4482.

Source: PubMed

3
Iratkozz fel