Skip to main content

Advertisement

Log in

Effects of soy intake on circulating levels of TNF-α and interleukin-6: a systematic review and meta-analysis of randomized controlled trials

  • Review
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

Purpose

Pro-inflammatory mediators, including serum tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), can be used as biomarkers to indicate or monitor disease. This study was designed to ascertain the effects of soy products on TNF-α and IL-6 levels.

Methods

PubMed, EMBASE, Science Direct, Web of Science, Google Scholar and the Cochrane Central Register of Controlled Trials were searched to November 2019 for RCTs around the effects of soy-based products on TNF-α and IL-6. A random effects model was used to calculate overall effect size.

Results

In total, 29 eligible publications were considered in the present systematic review, of which 25 were included in this meta-analysis. The overall effect of soy products on TNF-α and IL-6 levels failed to reach statistical significance (MD = − 0.07; 95% CI − 0.22–0.09; I2 50.9; MD = 0.03; 95% CI − 0.07–0.14; I2 42.1, respectively). According to a subgroup analysis, natural soy products led to a reduction in TNF-α concentration compared with processed soy products (MD = − 0.32; 95% CI − 0.45 to − 0.19; I2 0.0). Moreover, IL-6 reduction was stronger in participants who were affected by different diseases (MD = − 0.04; 95% CI − 0.07 to − 0.02; I2 0.0).

Conclusions

A review of RCTs published to November 2019 found that natural soy products are effective in lowering TNF-α levels. While the beneficial effects on reduction of IL-6 appeared stronger in individuals affected by different diseases, this finding cannot be generalized to all individuals affected by different diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

  1. Guarner V, Rubio-Ruiz ME (2015) Low-grade systemic inflammation connects aging, metabolic syndrome and cardiovascular disease. Interdiscip Top Gerontol 40:99–106. https://doi.org/10.1159/000364934

    Article  PubMed  Google Scholar 

  2. Minihane AM, Vinoy S, Russell WR, Baka A, Roche HM, Tuohy KM, Teeling JL, Blaak EE, Fenech M, Vauzour D, McArdle HJ, Kremer BH, Sterkman L, Vafeiadou K, Benedetti MM, Williams CM, Calder PC (2015) Low-grade inflammation, diet composition and health: current research evidence and its translation. Br J Nutr 114(7):999–1012. https://doi.org/10.1017/s0007114515002093

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Graves DT, Kayal RA (2008) Diabetic complications and dysregulated innate immunity. Front Biosci 13:1227–1239. https://doi.org/10.2741/2757

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Ramdath DD, Padhi EM, Sarfaraz S, Renwick S, Duncan AM (2017) Beyond the cholesterol-lowering effect of soy protein: a review of the effects of dietary soy and its constituents on risk factors for cardiovascular disease. Nutrients. https://doi.org/10.3390/nu9040324

    Article  PubMed  PubMed Central  Google Scholar 

  5. Beavers KM, Jonnalagadda SS, Messina MJ (2009) Soy consumption, adhesion molecules, and pro-inflammatory cytokines: a brief review of the literature. Nutr Rev 67(4):213–221. https://doi.org/10.1111/j.1753-4887.2009.00191.x

    Article  PubMed  Google Scholar 

  6. Sacks FM, Lichtenstein A, Van Horn L, Harris W, Kris-Etherton P, Winston M (2006) Soy protein, isoflavones, and cardiovascular health: an American Heart Association Science Advisory for professionals from the Nutrition Committee. Circulation 113(7):1034–1044. https://doi.org/10.1161/circulationaha.106.171052

    Article  CAS  PubMed  Google Scholar 

  7. Cederroth CR, Zimmermann C, Nef S (2012) Soy, phytoestrogens and their impact on reproductive health. Mol Cell Endocrinol 355(2):192–200. https://doi.org/10.1016/j.mce.2011.05.049

    Article  CAS  PubMed  Google Scholar 

  8. Cederroth CR, Nef S (2009) Soy, phytoestrogens and metabolism: a review. Mol Cell Endocrinol 304(1–2):30–42. https://doi.org/10.1016/j.mce.2009.02.027

    Article  CAS  PubMed  Google Scholar 

  9. Ito A, Bebo BF Jr, Matejuk A, Zamora A, Silverman M, Fyfe-Johnson A, Offner H (2001) Estrogen treatment down-regulates TNF-alpha production and reduces the severity of experimental autoimmune encephalomyelitis in cytokine knockout mice. J Immunol 167(1):542–552. https://doi.org/10.4049/jimmunol.167.1.542

    Article  CAS  PubMed  Google Scholar 

  10. Register TC, Cann JA, Kaplan JR, Williams JK, Adams MR, Morgan TM, Anthony MS, Blair RM, Wagner JD, Clarkson TB (2005) Effects of soy isoflavones and conjugated equine estrogens on inflammatory markers in atherosclerotic, ovariectomized monkeys. J Clin Endocrinol Metab 90(3):1734–1740. https://doi.org/10.1210/jc.2004-0939

    Article  CAS  PubMed  Google Scholar 

  11. Conklin CM, Bechberger JF, MacFabe D, Guthrie N, Kurowska EM, Naus CC (2007) Genistein and quercetin increase connexin43 and suppress growth of breast cancer cells. Carcinogenesis 28(1):93–100. https://doi.org/10.1093/carcin/bgl106

    Article  CAS  PubMed  Google Scholar 

  12. Dhayakaran RPA, Neethirajan S, Xue J, Shi J (2015) Characterization of antimicrobial efficacy of soy isoflavones against pathogenic biofilms. LWT-Food Sci Technol 63(2):859–865

    Article  Google Scholar 

  13. Messina M (2014) Soy foods, isoflavones, and the health of postmenopausal women. Am J Clin Nutr 100(Suppl 1):423s–430s. https://doi.org/10.3945/ajcn.113.071464

    Article  CAS  PubMed  Google Scholar 

  14. Yu J, Bi X, Yu B, Chen D (2016) Isoflavones: anti-inflammatory benefit and possible caveats. Nutrients. https://doi.org/10.3390/nu8060361

    Article  PubMed  PubMed Central  Google Scholar 

  15. Nagata C (2000) Ecological study of the association between soy product intake and mortality from cancer and heart disease in Japan. Int J Epidemiol 29(5):832–836. https://doi.org/10.1093/ije/29.5.832

    Article  CAS  PubMed  Google Scholar 

  16. Faraj A, Vasanthan T (2004) Soybean isoflavones: effects of processing and health benefits. Food Rev Int 20:51–75. https://doi.org/10.1081/FRI-120028830

    Article  CAS  Google Scholar 

  17. Setchell KD, Brown NM, Lydeking-Olsen E (2002) The clinical importance of the metabolite equol-a clue to the effectiveness of soy and its isoflavones. J Nutr 132(12):3577–3584. https://doi.org/10.1093/jn/132.12.3577

    Article  CAS  PubMed  Google Scholar 

  18. Setchell KD, Clerici C (2010) Equol: history, chemistry, and formation. J Nutr 140(7):1355s–1362s. https://doi.org/10.3945/jn.109.119776

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Acharjee S, Zhou JR, Elajami TK, Welty FK (2015) Effect of soy nuts and equol status on blood pressure, lipids and inflammation in postmenopausal women stratified by metabolic syndrome status. Metabolism 64(2):236–243. https://doi.org/10.1016/j.metabol.2014.09.005

    Article  CAS  PubMed  Google Scholar 

  20. Moher D, Liberati A, Tetzlaff J, Altman DG (2009) Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 151(4):264–269

    Article  Google Scholar 

  21. Khodarahmi M, Jafarabadi MA, Moludi J, Abbasalizad Farhangi M (2019) A systematic review and meta-analysis of the effects of soy on serum hs-CRP. Clin Nutr 38(3):996–1011. https://doi.org/10.1016/j.clnu.2018.09.007

    Article  CAS  PubMed  Google Scholar 

  22. Miller A, Chen Y-F, Xing D, Feng W, Oparil S (2003) Hormone replacement therapy and inflammation—interactions in cardiovascular disease. Hypertension 42:657–663. https://doi.org/10.1161/01.HYP.0000085560.02979.0C

    Article  CAS  PubMed  Google Scholar 

  23. Jain MK, Ridker PM (2005) Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discovery 4(12):977–987. https://doi.org/10.1038/nrd1901

    Article  CAS  PubMed  Google Scholar 

  24. Higgins J, Green S (2008) Cochrane handbook for systematic reviews of interventions (Vol. 5): Wiley Online Library

  25. Follmann D, Elliott P, Suh I, Cutler J (1992) Variance imputation for overviews of clinical trials with continuous response. J Clin Epidemiol 45(7):769–773. https://doi.org/10.1016/0895-4356(92)90054-q

    Article  CAS  PubMed  Google Scholar 

  26. Mazidi M, Rezaie P, Ferns GA, Gao HK (2016) Impact of different types of tree nut, peanut, and soy nut consumption on serum C-reactive protein (CRP): a systematic review and meta-analysis of randomized controlled clinical trials. Medicine (Baltimore) 95(44):e5165. https://doi.org/10.1097/md.0000000000005165

    Article  CAS  Google Scholar 

  27. Hozo SP, Djulbegovic B, Hozo I (2005) Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol 5:13. https://doi.org/10.1186/1471-2288-5-13

    Article  PubMed  PubMed Central  Google Scholar 

  28. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    Article  CAS  Google Scholar 

  29. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21(11):1539–1558

    Article  Google Scholar 

  30. Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315(7109):629–634

    Article  CAS  Google Scholar 

  31. Egger M, Davey-Smith G, Altman D (2008) Systematic reviews in health care: meta-analysis in context. John Wiley & Sons

  32. Jenkins DJ, Kendall CW, Connelly PW, Jackson CJ, Parker T, Faulkner D, Vidgen E (2002) Effects of high- and low-isoflavone (phytoestrogen) soy foods on inflammatory biomarkers and proinflammatory cytokines in middle-aged men and women. Metabolism 51(7):919–924. https://doi.org/10.1053/meta.2002.33352

    Article  CAS  PubMed  Google Scholar 

  33. Fanti P, Asmis R, Stephenson TJ, Sawaya BP, Franke AA (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 Dial Transplant 21(8):2239–2246. https://doi.org/10.1093/ndt/gfl169

    Article  CAS  PubMed  Google Scholar 

  34. Li Y, Zhang H (2017) Soybean isoflavones ameliorate ischemic cardiomyopathy by activating Nrf2-mediated antioxidant responses. Food Funct 8(8):2935–2944. https://doi.org/10.1039/c7fo00342k

    Article  CAS  PubMed  Google Scholar 

  35. Hilpert KF, Kris-Etherton PM, West SG (2005) Lipid response to a low-fat diet with or without soy is modified by C-reactive protein status in moderately hypercholesterolemic adults. J Nutr 135(5):1075–1079. https://doi.org/10.1093/jn/135.5.1075

    Article  CAS  PubMed  Google Scholar 

  36. Campbell CG, Brown BD, Dufner D, Thorland WG (2006) Effects of soy or milk protein during a high-fat feeding challenge on oxidative stress, inflammation, and lipids in healthy men. Lipids 41(3):257–265. https://doi.org/10.1007/s11745-006-5095-5

    Article  CAS  PubMed  Google Scholar 

  37. Gonzales GF, Tello J, Zevallos-Concha A, Baquerizo L, Caballero L (2018) Nitrogen balance after a single oral consumption of sacha inchi (Plukenetia volubilis L.) protein compared to soy protein: a randomized study in humans. Toxicol Mech Methods 28(2):140–147. https://doi.org/10.1080/15376516.2017.1373880

    Article  CAS  PubMed  Google Scholar 

  38. Serrano JC, Martin-Gari M, Cassanye A, Granado-Serrano AB, Portero-Otin M (2017) Characterization of the post-prandial insulinemic response and low glycaemic index of a soy beverage. PLoS ONE 12(8):e0182762. https://doi.org/10.1371/journal.pone.0182762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ramezani N, Moafi A, Nadjarzadeh A, Yousefian S, Reisi N, Salehi-Abargouei A (2018) The effect of soy nut compared to cowpea nut on body weight, blood cells, inflammatory markers and chemotherapy complications in children with acute lymphoblastic leukemia: a randomized controlled clinical. Trial 70(7):1017–1025. https://doi.org/10.1080/01635581.2018.1495240

    Article  CAS  Google Scholar 

  40. Faghih S, Hedayati M, Abadi A, Kimiagar SM (2010) Comparison of the effects of cows milk, fortified soy milk, and calcium supplement on plasma adipocytokines in overweight or obese women. Int J Endocrinol Metab 8(4):188–193

    CAS  Google Scholar 

  41. Moghadam AS, Entezari MH, Iraj B, Askari GR, Merati MR (2017) The effects of soybean-flour-enriched bread intake on inflammatory markers among type 2 diabetic women: a cross-over randomized controlled clinical trial. J Kermanshah Univ Med Sci (J Kermanshah Univ Med Sci) 21(1):1–6

    Google Scholar 

  42. Hermansen K, Hansen B, Jacobsen R, Clausen P, Dalgaard M, Dinesen B, Holst JJ, Pedersen E, Astrup A (2005) Effects of soy supplementation on blood lipids and arterial function in hypercholesterolaemic subjects. Eur J Clin Nutr 59(7):843–850. https://doi.org/10.1038/sj.ejcn.1602151

    Article  CAS  PubMed  Google Scholar 

  43. Chi XX, Zhang T (2013) The effects of soy isoflavone on bone density in north region of climacteric Chinese women. J Clin Biochem Nutr 53(2):102–107. https://doi.org/10.3164/jcbn.13-37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Berg A, Schaffner D, Pohlmann Y, Baumstark MW, Deibert P, Konig D, Gollhofer A (2012) A soy-based supplement alters energy metabolism but not the exercise-induced stress response. Exerc Immunol Rev 18:128–141

    PubMed  Google Scholar 

  45. Christie DR, Grant J, Darnell BE, Chapman VR, Gastaldelli A, Sites CK (2010) Metabolic effects of soy supplementation in postmenopausal Caucasian and African American women: a randomized, placebo-controlled trial. Am J Obstet Gynecol 203(2):153.e151-159. https://doi.org/10.1016/j.ajog.2010.02.058

    Article  CAS  Google Scholar 

  46. Beavers KM, Serra MC, Beavers DP, Cooke MB, Willoughby DS (2010) Soy and the exercise-induced inflammatory response in postmenopausal women. Appl Physiol Nutr Metab 35(3):261–269. https://doi.org/10.1139/h10-015

    Article  CAS  PubMed  Google Scholar 

  47. Charles C, Yuskavage J, Carlson O, John M, Tagalicud AS, Maggio M, Muller DC, Egan J, Basaria S (2009) Effects of high-dose isoflavones on metabolic and inflammatory markers in healthy postmenopausal women. Menopause 16(2):395–400. https://doi.org/10.1097/gme.0b013e3181857979

    Article  PubMed  PubMed Central  Google Scholar 

  48. Azadbakht L, Kimiagar M, Mehrabi Y, Esmaillzadeh A, Hu FB, Willett WC (2007) Soy consumption, markers of inflammation, and endothelial function: a cross-over study in postmenopausal women with the metabolic syndrome. Diabetes Care 30(4):967–973. https://doi.org/10.2337/dc06-2126

    Article  CAS  PubMed  Google Scholar 

  49. Nadadur M, Stanczyk FZ, Tseng CC, Kim L, Wu AH (2016) The effect of reduced dietary fat and soy supplementation on circulating adipocytokines in postmenopausal women: a randomized controlled 2-month trial. Nutr Cancer 68(4):554–559. https://doi.org/10.1080/01635581.2016.1158294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Tomayko EJ, Kistler BM, Fitschen PJ, Wilund KR (2015) Intradialytic protein supplementation reduces inflammation and improves physical function in maintenance hemodialysis patients. J Ren Nutr 25(3):276–283. https://doi.org/10.1053/j.jrn.2014.10.005

    Article  CAS  PubMed  Google Scholar 

  51. Reverri EJ, LaSalle CD, Franke AA, Steinberg FM (2015) Soy provides modest benefits on endothelial function without affecting inflammatory biomarkers in adults at cardiometabolic risk. Mol Nutr Food Res 59(2):323–333. https://doi.org/10.1002/mnfr.201400270

    Article  CAS  PubMed  Google Scholar 

  52. Rebholz CM, Reynolds K, Wofford MR, Chen J, Kelly TN, Mei H, Whelton PK, He J (2013) Effect of soybean protein on novel cardiovascular disease risk factors: a randomized controlled trial. Eur J Clin Nutr 67(1):58–63. https://doi.org/10.1038/ejcn.2012.186

    Article  CAS  PubMed  Google Scholar 

  53. Napora JK, Short RG, Muller DC, Carlson OD, Odetunde JO, Xu X, Carducci M, Travison TG, Maggio M, Egan JM, Basaria S (2011) High-dose isoflavones do not improve metabolic and inflammatory parameters in androgen-deprived men with prostate cancer. J Androl 32(1):40–48. https://doi.org/10.2164/jandrol.110.010983

    Article  CAS  PubMed  Google Scholar 

  54. Miraghajani MS, Esmaillzadeh A, Najafabadi MM, Mirlohi M, Azadbakht L (2012) Soy milk consumption, inflammation, coagulation, and oxidative stress among type 2 diabetic patients with nephropathy. Diabetes Care 35(10):1981–1985. https://doi.org/10.2337/dc12-0250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Zemel MB, Sun X, Sobhani T, Wilson B (2010) Effects of dairy compared with soy on oxidative and inflammatory stress in overweight and obese subjects. Am J Clin Nutr 91(1):16–22. https://doi.org/10.3945/ajcn.2009.28468

    Article  CAS  PubMed  Google Scholar 

  56. Nasca MM, Zhou JR, Welty FK (2008) Effect of soy nuts on adhesion molecules and markers of inflammation in hypertensive and normotensive postmenopausal women. Am J Cardiol 102(1):84–86. https://doi.org/10.1016/j.amjcard.2008.02.100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ryan-Borchers TA, Park JS, Chew BP, McGuire MK, Fournier LR, Beerman KA (2006) Soy isoflavones modulate immune function in healthy postmenopausal women. Am J Clin Nutr 83(5):1118–1125. https://doi.org/10.1093/ajcn/83.5.1118

    Article  CAS  PubMed  Google Scholar 

  58. Deibert P, Solleder F, Konig D, Vitolins MZ, Dickhuth HH, Gollhofer A, Berg A (2011) Soy protein based supplementation supports metabolic effects of resistance training in previously untrained middle aged males. Aging Male 14(4):273–279. https://doi.org/10.3109/13685538.2011.565091

    Article  CAS  PubMed  Google Scholar 

  59. Siefker K, DiSilvestro RA (2006) Safety and antioxidant effects of a modest soy protein intervention in hemodialysis patients. J Med Food 9(3):368–372. https://doi.org/10.1089/jmf.2006.9.368

    Article  CAS  PubMed  Google Scholar 

  60. Kwak JH, Ahn CW, Park SH, Jung SU, Min BJ, Kim OY, Lee JH (2012) Weight reduction effects of a black soy peptide supplement in overweight and obese subjects: double blind, randomized, controlled study. Food Funct 3(10):1019–1024. https://doi.org/10.1039/c2fo10244g

    Article  CAS  PubMed  Google Scholar 

  61. Lebon J, Riesco E, Tessier D, Dionne IJ (2014) Additive effects of isoflavones and exercise training on inflammatory cytokines and body composition in overweight and obese postmenopausal women: a randomized controlled trial. Menopause 21(8):869–875. https://doi.org/10.1097/gme.0000000000000177

    Article  PubMed  Google Scholar 

  62. Lenn J, Uhl T, Mattacola C, Boissonneault G, Yates J, Ibrahim W, Bruckner G (2002) The effects of fish oil and isoflavones on delayed onset muscle soreness. Med Sci Sports Exerc 34(10):1605–1613. https://doi.org/10.1097/00005768-200210000-00012

    Article  CAS  PubMed  Google Scholar 

  63. Llaneza P, Gonzalez C, Fernandez-Inarrea J, Alonso A, Diaz F, Perez-Lopez FR (2012) Soy isoflavones improve insulin sensitivity without changing serum leptin among postmenopausal women. Climacteric 15(6):611–620. https://doi.org/10.3109/13697137.2011.631062

    Article  CAS  PubMed  Google Scholar 

  64. Llaneza P, Gonzalez C, Fernandez-Inarrea J, Alonso A, Diaz F, Arnott I, Ferrer-Barriendos J (2011) Soy isoflavones, diet and physical exercise modify serum cytokines in healthy obese postmenopausal women. Phytomedicine 18(4):245–250. https://doi.org/10.1016/j.phymed.2010.07.011

    Article  CAS  PubMed  Google Scholar 

  65. Mangano KM, Hutchins-Wiese HL, Kenny AM, Walsh SJ, Abourizk RH, Bruno RS, Lipcius R, Fall P, Kleppinger A, Kenyon-Pesce L, Prestwood KM, Kerstetter JE (2013) Soy proteins and isoflavones reduce interleukin-6 but not serum lipids in older women: a randomized controlled trial. Nutr Res 33(12):1026–1033. https://doi.org/10.1016/j.nutres.2013.08.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Maskarinec G, Oum R, Chaptman AK, Ognjanovic S (2009) Inflammatory markers in a randomised soya intervention among men. Br J Nutr 101(12):1740–1744. https://doi.org/10.1017/s0007114508147389

    Article  CAS  PubMed  Google Scholar 

  67. Kani AH, Alavian SM, Esmaillzadeh A, Adibi P, Haghighatdoost F, Azadbakht L (2017) Effects of a low-calorie, low-carbohydrate soy containing diet on systemic inflammation among patients with nonalcoholic fatty liver disease: a parallel randomized clinical trial. Horm Metab Res 49(9):687–692. https://doi.org/10.1055/s-0042-118707

    Article  CAS  PubMed  Google Scholar 

  68. Maskarinec G, Steude JS, Franke AA, Cooney RV (2009) Inflammatory markers in a 2-year soy intervention among premenopausal women. J Inflamm (Lond) 6:9. https://doi.org/10.1186/1476-9255-6-9

    Article  Google Scholar 

  69. Simao AN, Lozovoy MA, Bahls LD, Morimoto HK, Simao TN, Matsuo T, Dichi I (2012) Blood pressure decrease with ingestion of a soya product (kinako) or fish oil in women with the metabolic syndrome: role of adiponectin and nitric oxide. Br J Nutr 108(8):1435–1442. https://doi.org/10.1017/s0007114511006921

    Article  CAS  PubMed  Google Scholar 

  70. Peluso I, Raguzzini A, Serafini M (2013) Effect of flavonoids on circulating levels of TNF-alpha and IL-6 in humans: a systematic review and meta-analysis. Mol Nutr Food Res 57(5):784–801. https://doi.org/10.1002/mnfr.201200721

    Article  CAS  PubMed  Google Scholar 

  71. Tokede OA, Onabanjo TA, Yansane A, Gaziano JM, Djousse L (2015) Soya products and serum lipids: a meta-analysis of randomised controlled trials. Br J Nutr 114(6):831–843. https://doi.org/10.1017/s0007114515002603

    Article  CAS  PubMed  Google Scholar 

  72. Reinwald S, Akabas SR, Weaver CM (2010) Whole versus the piecemeal approach to evaluating soy. J Nutr 140(12):2335s–2343s. https://doi.org/10.3945/jn.110.124925

    Article  CAS  PubMed  Google Scholar 

  73. Zhang W, Teng SP, Popovich DG (2009) Generation of group B soyasaponins I and III by hydrolysis. J Agric Food Chem 57(9):3620–3625. https://doi.org/10.1021/jf803663j

    Article  CAS  PubMed  Google Scholar 

  74. Azadbakht L, Esmaillzadeh A (2012) Soy intake and metabolic health: beyond isoflavones. Arch Iran Med 15(8):460–461

    CAS  PubMed  Google Scholar 

  75. Azadbakht L, Esmaeilzadeh A (2008) Soy and cardio-metabolic abnormalities: an update. J Res Med Sci 13(2):88–96

    Google Scholar 

  76. Duan W, Kuo IC, Selvarajan S, Chua KY, Bay BH, Wong WS (2003) Antiinflammatory effects of genistein, a tyrosine kinase inhibitor, on a guinea pig model of asthma. Am J Respir Crit Care Med 167(2):185–192. https://doi.org/10.1164/rccm.200205-420OC

    Article  PubMed  Google Scholar 

  77. Han S, Wu H, Li W, Gao P (2015) Protective effects of genistein in homocysteine-induced endothelial cell inflammatory injury. Mol Cell Biochem 403(1–2):43–49. https://doi.org/10.1007/s11010-015-2335-0

    Article  CAS  PubMed  Google Scholar 

  78. Patel RP, Boersma BJ, Crawford JH, Hogg N, Kirk M, Kalyanaraman B, Parks DA, Barnes S, Darley-Usmar V (2001) Antioxidant mechanisms of isoflavones in lipid systems: paradoxical effects of peroxyl radical scavenging. Free Radic Biol Med 31(12):1570–1581. https://doi.org/10.1016/s0891-5849(01)00737-7

    Article  CAS  PubMed  Google Scholar 

  79. Rodriguez-Roque MJ, Rojas-Grau MA, Elez-Martinez P, Martin-Belloso O (2013) Soymilk phenolic compounds, isoflavones and antioxidant activity as affected by in vitro gastrointestinal digestion. Food Chem 136(1):206–212. https://doi.org/10.1016/j.foodchem.2012.07.115

    Article  CAS  PubMed  Google Scholar 

  80. Davis JN, Kucuk O, Djuric Z, Sarkar FH (2001) Soy isoflavone supplementation in healthy men prevents NF-kappa B activation by TNF-alpha in blood lymphocytes. Free Radic Biol Med 30(11):1293–1302. https://doi.org/10.1016/s0891-5849(01)00535-4

    Article  CAS  PubMed  Google Scholar 

  81. Draganidis D, Karagounis LG, Athanailidis I, Chatzinikolaou A, Jamurtas AZ, Fatouros IG (2016) Inflammaging and skeletal muscle: can protein intake make a difference? J Nutr 146(10):1940–1952. https://doi.org/10.3945/jn.116.230912

    Article  CAS  PubMed  Google Scholar 

  82. Jin L, Zhao X, Qin Y, Zhu W, Zhang W, Liu A, Luo Z (2015) Soy isoflavones protect against H2O2-induced injury in human umbilical vein endothelial cells. Mol Med Rep 12(3):4476–4482. https://doi.org/10.3892/mmr.2015.3949

    Article  CAS  PubMed  Google Scholar 

  83. Ma X, Jiang Z, Zhang J, Hu Y, Gao K, Wang L, Yang X (2015) Isoflavone ameliorates H2O2 induced injury by activating the antioxidant system of sow mammary gland cell. Nat Sci 07:571–580. https://doi.org/10.4236/ns.2015.712057

    Article  CAS  Google Scholar 

  84. Rallidis LS, Paschos G, Liakos GK, Velissaridou AH, Anastasiadis G, Zampelas A (2003) Dietary alpha-linolenic acid decreases C-reactive protein, serum amyloid A and interleukin-6 in dyslipidaemic patients. Atherosclerosis 167(2):237–242. https://doi.org/10.1016/s0021-9150(02)00427-6

    Article  CAS  PubMed  Google Scholar 

  85. Stenvinkel P, Ketteler M, Johnson RJ, Lindholm B, Pecoits-Filho R, Riella M, Heimburger O, Cederholm T, Girndt M (2005) IL-10, IL-6, and TNF-alpha: central factors in the altered cytokine network of uremia–the good, the bad, and the ugly. Kidney Int 67(4):1216–1233. https://doi.org/10.1111/j.1523-1755.2005.00200.x

    Article  CAS  PubMed  Google Scholar 

  86. Di Raimondo D, Tuttolomondo A, Butta C, Miceli S, Licata G, Pinto A (2012) Effects of ACE-inhibitors and angiotensin receptor blockers on inflammation. Curr Pharm Des 18(28):4385–4413. https://doi.org/10.2174/138161212802481282

    Article  PubMed  Google Scholar 

  87. Franke AA, Lai JF, Halm BM, Pagano I, Kono N, Mack WJ, Hodis HN (2012) Equol production changes over time in postmenopausal women. J Nutr Biochem 23(6):573–579. https://doi.org/10.1016/j.jnutbio.2011.03.002

    Article  CAS  PubMed  Google Scholar 

  88. Bolca S, Possemiers S, Herregat A, Huybrechts I, Heyerick A, De Vriese S, Verbruggen M, Depypere H, De Keukeleire D, Bracke M, De Henauw S, Verstraete W, Van de Wiele T (2007) Microbial and dietary factors are associated with the equol producer phenotype in healthy postmenopausal women. J Nutr 137(10):2242–2246. https://doi.org/10.1093/jn/137.10.2242

    Article  CAS  PubMed  Google Scholar 

  89. Hazim S, Curtis PJ, Schar MY, Ostertag LM, Kay CD, Minihane AM, Cassidy A (2016) Acute benefits of the microbial-derived isoflavone metabolite equol on arterial stiffness in men prospectively recruited according to equol producer phenotype: a double-blind randomized controlled trial. Am J Clin Nutr 103(3):694–702. https://doi.org/10.3945/ajcn.115.125690

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Usui T, Tochiya M, Sasaki Y, Muranaka K, Yamakage H, Himeno A, Shimatsu A, Inaguma A, Ueno T, Uchiyama S, Satoh-Asahara N (2013) Effects of natural S-equol supplements on overweight or obesity and metabolic syndrome in the Japanese, based on sex and equol status. Clin Endocrinol (Oxf) 78(3):365–372. https://doi.org/10.1111/j.1365-2265.2012.04400.x

    Article  CAS  Google Scholar 

Download references

Funding

There are no support from any organization for the submitted work; no financial relationships with any organizations that might have an interest in the submitted; and no other relationships or activities that could appear to have influenced the submitted work.

Author information

Authors and Affiliations

Authors

Contributions

MK designed this study. MK and EF searched the literature and extracted data. MK and MAJ analyzed data. MK and EF wrote the first draft of the manuscript and revised it. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Mahdieh Khodarahmi.

Ethics declarations

Conflict of interest

None.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Khodarahmi, M., Foroumandi, E. & Asghari Jafarabadi, M. 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 (2021). https://doi.org/10.1007/s00394-020-02458-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-020-02458-z

Keywords

Navigation