Skip to main content
Log in

Effect of soy on metabolic syndrome and cardiovascular risk factors: a randomized controlled trial

European Journal of Nutrition Aims and scope Submit manuscript

Cite this article



Cardiovascular diseases are currently the commonest cause of death worldwide. Different strategies for their primary prevention have been planned, taking into account the main known risk factors, which include an atherogenic lipid profile and visceral fat excess.


The study was designed as a randomized, parallel, single-center study with a nutritional intervention duration of 12 weeks. Whole soy foods corresponding to 30 g/day soy protein were given in substitution of animal foods containing the same protein amount.


Soy nutritional intervention resulted in a reduction in the number of MetS features in 13/26 subjects. Moreover, in the soy group we observed a significant improvement of median percentage changes for body weight (−1.5 %) and BMI (−1.5 %), as well as for atherogenic lipid markers, namely TC (−4.85 %), LDL-C (−5.25 %), non-HDL-C (−7.14 %) and apoB (−14.8 %). Since the majority of the studied variables were strongly correlated, three factors were identified which explained the majority (52 %) of the total variance in the whole data set. Among them, factor 1, which loaded lipid and adipose variables, explained the 22 % of total variance, showing a statistically significant difference between treatment arms (p = 0.002).


The inclusion of whole soy foods (corresponding to 30 g/day protein) in a lipid-lowering diet significantly improved a relevant set of biomarkers associated with cardiovascular risk.

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.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others



Apolipoprotein B


Apolipoprotein A-I


Body mass index


Bioelectrical impedance analysis


High-sensitivity C-reactive protein


Cardiovascular diseases


Diastolic blood pressure


Fasting plasma glucose


Hip circumference


High-density lipoprotein cholesterol


Homeostatic model assessment


Heart rate


Low-density lipoprotein cholesterol


Lipoprotein (a)




Proprotein convertase subtilisin/kexin 9


Systolic blood pressure


Soluble intercellular adhesion molecular 1


Total cholesterol




Visceral fat rating


Waist circumference


  1. Organization WH (2015) Obesity and overweight.

  2. Oliveros E, Somers VK, Sochor O, Goel K, Lopez-Jimenez F (2014) The concept of normal weight obesity. Prog Cardiovasc Dis 56(4):426–433. doi:10.1016/j.pcad.2013.10.003

    Article  Google Scholar 

  3. Ebbert JO, Jensen MD (2013) Fat depots, free fatty acids, and dyslipidemia. Nutrients 5(2):498–508. doi:10.3390/nu5020498

    Article  CAS  Google Scholar 

  4. Scaglione R, Di Chiara T, Cariello T, Licata G (2010) Visceral obesity and metabolic syndrome: two faces of the same medal? Intern Emerg Med 5(2):111–119. doi:10.1007/s11739-009-0332-6

    Article  Google Scholar 

  5. Mangge H, Almer G, Truschnig-Wilders M, Schmidt A, Gasser R, Fuchs D (2010) Inflammation, adiponectin, obesity and cardiovascular risk. Curr Med Chem 17(36):4511–4520

    Article  CAS  Google Scholar 

  6. Nicklas BJ, Ambrosius W, Messier SP, Miller GD, Penninx BW, Loeser RF, Palla S, Bleecker E, Pahor M (2004) Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial. Am J Clin Nutr 79(4):544–551

    Article  CAS  Google Scholar 

  7. Ferri N, Ruscica M (2016) Proprotein convertase subtilisin/kexin type 9 (PCSK9) and metabolic syndrome: insights on insulin resistance, inflammation, and atherogenic dyslipidemia. Endocrine. doi:10.1007/s12020-016-0939-0

    Google Scholar 

  8. Lagos KG, Filippatos TD, Tsimihodimos V, Gazi IF, Rizos C, Tselepis AD, Mikhailidis DP, Elisaf MS (2009) Alterations in the high density lipoprotein phenotype and HDL-associated enzymes in subjects with metabolic syndrome. Lipids 44(1):9–16. doi:10.1007/s11745-008-3251-9

    Article  CAS  Google Scholar 

  9. Brown L, Poudyal H, Panchal SK (2015) Functional foods as potential therapeutic options for metabolic syndrome. Obes Rev 16(11):914–941. doi:10.1111/obr.12313

    Article  CAS  Google Scholar 

  10. Ruscica M, Gomaraschi M, Mombelli G, Macchi C, Bosisio R, Pazzucconi F, Pavanello C, Calabresi L, Arnoldi A, Sirtori CR, Magni P (2014) Nutraceutical approach to moderate cardiometabolic risk: results of a randomized, double-blind and crossover study with Armolipid Plus. J Clin Lipidol 8(1):61–68. doi:10.1016/j.jacl.2013.11.003

    Article  Google Scholar 

  11. van Nielen M, Feskens EJ, Rietman A, Siebelink E, Mensink M (2014) Partly replacing meat protein with soy protein alters insulin resistance and blood lipids in postmenopausal women with abdominal obesity. J Nutr 144(9):1423–1429. doi:10.3945/jn.114.193706

    Article  Google Scholar 

  12. Rebello CJ, Greenway FL, Finley JW (2014) A review of the nutritional value of legumes and their effects on obesity and its related co-morbidities. Obes Rev 15(5):392–407. doi:10.1111/obr.12144

    Article  CAS  Google Scholar 

  13. Harland JI, Haffner TA (2008) Systematic review, meta-analysis and regression of randomised controlled trials reporting an association between an intake of circa 25 g soya protein per day and blood cholesterol. Atherosclerosis 200(1):13–27. doi:10.1016/j.atherosclerosis.2008.04.006

    Article  CAS  Google Scholar 

  14. Anderson JW, Bush HM (2011) Soy protein effects on serum lipoproteins: a quality assessment and meta-analysis of randomized, controlled studies. J Am Coll Nutr 30(2):79–91

    Article  CAS  Google Scholar 

  15. Sirtori CR, Agradi E, Conti F, Mantero O, Gatti E (1977) Soybean-protein diet in the treatment of type-II hyperlipoproteinaemia. Lancet 1(8006):275–277

    Article  CAS  Google Scholar 

  16. Sirtori CR, Eberini I, Arnoldi A (2007) Hypocholesterolaemic effects of soya proteins: results of recent studies are predictable from the Anderson meta-analysis data. Br J Nutr 97(5):816–822. doi:10.1017/S0007114507670810

    Article  CAS  Google Scholar 

  17. Jenkins DJ, Mirrahimi A, Srichaikul K, Berryman CE, Wang L, Carleton A, Abdulnour S, Sievenpiper JL, Kendall CW, Kris-Etherton PM (2010) Soy protein reduces serum cholesterol by both intrinsic and food displacement mechanisms. J Nutr 140(12):2302S–2311S. doi:10.3945/jn.110.124958

    Article  CAS  Google Scholar 

  18. Allison DB, Gadbury G, Schwartz LG, Murugesan R, Kraker JL, Heshka S, Fontaine KR, Heymsfield SB (2003) A novel soy-based meal replacement formula for weight loss among obese individuals: a randomized controlled clinical trial. Eur J Clin Nutr 57(4):514–522. doi:10.1038/sj.ejcn.1601587

    Article  CAS  Google Scholar 

  19. Velasquez MT, Bhathena SJ (2007) Role of dietary soy protein in obesity. Int J Med Sci 4(2):72–82

    Article  CAS  Google Scholar 

  20. Takahira M, Noda K, Fukushima M, Zhang B, Mitsutake R, Uehara Y, Ogawa M, Kakuma T, Saku K (2011) Randomized, double-blind, controlled, comparative trial of formula food containing soy protein vs. milk protein in visceral fat obesity-FLAVO study. Circ J 75(9):2235–2243

    Article  CAS  Google Scholar 

  21. 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. doi:10.1038/ejcn.2012.186

    Article  CAS  Google Scholar 

  22. Mozaffarian D (2016) Dietary and policy priorities for cardiovascular disease, diabetes, and obesity: a comprehensive review. Circulation 133(2):187–225. doi:10.1161/CIRCULATIONAHA.115.018585

    Article  CAS  Google Scholar 

  23. Reinwald S, Weaver CM (2010) Soy components vs. whole soy: are we betting our bones on a long shot? J Nutr 140(12):2312S–2317S. doi:10.3945/jn.110.124008

    Article  CAS  Google Scholar 

  24. Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr (2009) International Diabetes Federation Task Force on E, Prevention, Hational Heart L, Blood I, American Heart A, World Heart F, International Atherosclerosis S, International Association for the Study of O. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 120(16):1640–1645. doi:10.1161/CIRCULATIONAHA.109.192644

    Article  CAS  Google Scholar 

  25. Schutz Y, Sarafian D, Miles JL, Montani JP, Dulloo AG (2012) Non-contact assessment of waist circumference: will tape measurements become progressively obsolete? Eur J Clin Nutr 66(2):269–272. doi:10.1038/ejcn.2011.183

    Article  CAS  Google Scholar 

  26. Thomas EL, Collins AL, McCarthy J, Fitzpatrick J, Durighel G, Goldstone AP, Bell JD (2010) Estimation of abdominal fat compartments by bioelectrical impedance: the validity of the ViScan measurement system in comparison with MRI. Eur J Clin Nutr 64(5):525–533. doi:10.1038/ejcn.2010.18

    Article  CAS  Google Scholar 

  27. Manios Y, Kanellakis S, Moschonis G, Pipidis I, Skoufas E, Zafiropulos V (2013) Estimation of abdominal fat mass: validity of abdominal bioelectrical impedance analysis and a new model based on anthropometry compared with dual-energy x-ray absorptiometry. Menopause 20(12):1280–1283. doi:10.1097/GME.0b013e31828f5cd8

    Article  Google Scholar 

  28. Estruch R, Ros E, Martinez-Gonzalez MA (2013) Mediterranean diet for primary prevention of cardiovascular disease. N Engl J Med 369(7):676–677. doi:10.1056/NEJMc1306659

    CAS  Google Scholar 

  29. Sniderman A, Williams K, de Graaf J (2010) Non-HDL C equals apolipoprotein B: except when it does not! Curr Opin Lipidol 21(6):518–524. doi:10.1097/MOL.0b013e32833ee80c

    Article  CAS  Google Scholar 

  30. Ruscica M, Macchi C, Gandini S, Morlotti B, Erzegovesi S, Bellodi L, Magni P (2016) Free and bound plasma leptin in anorexia nervosa patients during a refeeding program. Endocrine 51(2):380–383. doi:10.1007/s12020-015-0598-6

    Article  CAS  Google Scholar 

  31. Ruscica M, Ferri N, Macchi C, Meroni M, Lanti C, Ricci C, Maggioni M, Fracanzani AL, Badiali S, Fargion S, Magni P, Valenti L, Dongiovanni P (2016) Liver fat accumulation is associated with circulating PCSK9. Ann Med 48(5):384–391. doi:10.1080/07853890.2016.1188328

    Article  CAS  Google Scholar 

  32. Franceschini G, Calabresi L, Colombo C, Favari E, Bernini F, Sirtori CR (2007) Effects of fenofibrate and simvastatin on HDL-related biomarkers in low-HDL patients. Atherosclerosis 195(2):385–391. doi:10.1016/j.atherosclerosis.2006.10.017

    Article  CAS  Google Scholar 

  33. Favari E, Gomaraschi M, Zanotti I, Bernini F, Lee-Rueckert M, Kovanen PT, Sirtori CR, Franceschini G, Calabresi L (2007) A unique protease-sensitive high density lipoprotein particle containing the apolipoprotein A-I(Milano) dimer effectively promotes ATP-binding cassette A1-mediated cell cholesterol efflux. J Biol Chem 282(8):5125–5132. doi:10.1074/jbc.M609336200

    Article  CAS  Google Scholar 

  34. Locati D, Morandi S, Cupisti A, Ghiadoni L, Arnoldi A (2005) Characterization and quantification of soy isoflavone metabolites in serum of renal transplanted patients by high-performance liquid chromatography/electrospray ionization mass spectrometry. Rapid Commun Mass Spectrom 19(23):3473–3481. doi:10.1002/rcm.2222

    Article  CAS  Google Scholar 

  35. Nakamura Y, Okuda N, Okamura T, Kadota A, Miyagawa N, Hayakawa T, Kita Y, Fujiyoshi A, Nagai M, Takashima N, Ohkubo T, Miura K, Okayama A, Ueshima H, Group NDR (2014) Low-carbohydrate diets and cardiovascular and total mortality in Japanese: a 29-year follow-up of NIPPON DATA80. Br J Nutr 112(6):916–924. doi:10.1017/S0007114514001627

    Article  CAS  Google Scholar 

  36. Assmann G, Buono P, Daniele A, Della Valle E, Farinaro E, Ferns G, Krogh V, Kromhout D, Masana L, Merino J, Misciagna G, Panico S, Riccardi G, Rivellese AA, Rozza F, Salvatore F, Salvatore V, Stranges S, Trevisan M, Trimarco B, Vetrani C (2014) Functional foods and cardiometabolic diseases* international task force for prevention of cardiometabolic diseases. Nutr Metab Cardiovasc Dis 24(12):1272–1300. doi:10.1016/j.numecd.2014.10.010

    Article  CAS  Google Scholar 

  37. Sirtori CR, Galli C, Anderson JW, Arnoldi A (2009) Nutritional and nutraceutical approaches to dyslipidemia and atherosclerosis prevention: focus on dietary proteins. Atherosclerosis 203(1):8–17. doi:10.1016/j.atherosclerosis.2008.06.019

    Article  CAS  Google Scholar 

  38. Stein K (2000) FDA approves health claim labeling for foods containing soy protein. J Am Diet Assoc 100(3):292. doi:10.1016/S0002-8223(00)00088-2

    Article  CAS  Google Scholar 

  39. Ioannidis JP (2016) We need more randomized trials in nutrition-preferably large, long-term, and with negative results. Am J Clin Nutr 103(6):1385–1386. doi:10.3945/ajcn.116.136085

    Article  CAS  Google Scholar 

  40. Lerman RH, Minich DM, Darland G, Lamb JJ, Chang JL, Hsi A, Bland JS, Tripp ML (2010) Subjects with elevated LDL cholesterol and metabolic syndrome benefit from supplementation with soy protein, phytosterols, hops rho iso-alpha acids, and Acacia nilotica proanthocyanidins. J Clin Lipidol 4(1):59–68. doi:10.1016/j.jacl.2009.11.002

    Article  Google Scholar 

  41. Pischon T, Boeing H, Hoffmann K, Bergmann M, Schulze MB, Overvad K, van der Schouw YT, Spencer E, Moons KG, Tjonneland A, Halkjaer J, Jensen MK, Stegger J, Clavel-Chapelon F, Boutron-Ruault MC, Chajes V, Linseisen J, Kaaks R, Trichopoulou A, Trichopoulos D, Bamia C, Sieri S, Palli D, Tumino R, Vineis P, Panico S, Peeters PH, May AM, Bueno-de-Mesquita HB, van Duijnhoven FJ, Hallmans G, Weinehall L, Manjer J, Hedblad B, Lund E, Agudo A, Arriola L, Barricarte A, Navarro C, Martinez C, Quiros JR, Key T, Bingham S, Khaw KT, Boffetta P, Jenab M, Ferrari P, Riboli E (2008) General and abdominal adiposity and risk of death in Europe. N Engl J Med 359(20):2105–2120. doi:10.1056/NEJMoa0801891

    Article  CAS  Google Scholar 

  42. Twig G, Yaniv G, Levine H, Leiba A, Goldberger N, Derazne E, Ben-Ami Shor D, Tzur D, Afek A, Shamiss A, Haklai Z, Kark JD (2016) Body-mass index in 2.3 Million adolescents and cardiovascular death in adulthood. N Engl J Med 374(25):2430–2440. doi:10.1056/NEJMoa1503840

    Article  Google Scholar 

  43. Meigs JB (2000) Invited commentary: insulin resistance syndrome? Syndrome X? Multiple metabolic syndrome? A syndrome at all? Factor analysis reveals patterns in the fabric of correlated metabolic risk factors. Am J Epidemiol 152(10):908–911 (discussion 912)

    Article  CAS  Google Scholar 

  44. Anderson JW, Hoie LH (2005) Weight loss and lipid changes with low-energy diets: comparator study of milk-based versus soy-based liquid meal replacement interventions. J Am Coll Nutr 24(3):210–216

    Article  CAS  Google Scholar 

  45. Hodge AM, Boyko EJ, de Courten M, Zimmet PZ, Chitson P, Tuomilehto J, Alberti KG (2001) Leptin and other components of the metabolic syndrome in mauritius—a factor analysis. Int J Obes Relat Metab Disord 25(1):126–131

    Article  CAS  Google Scholar 

  46. Moreno LA, Pineda I, Rodriguez G, Fleta J, Giner A, Juste MG, Sarria A, Bueno M (2002) Leptin and metabolic syndrome in obese and non-obese children. Horm Metab Res 34(7):394–399. doi:10.1055/s-2002-33472

    Article  CAS  Google Scholar 

  47. Park HS, Lee MS, Park JY (2004) Leptin and the metabolic syndrome in Korean adolescents: factor analysis. Pediatr Int 46(6):697–703. doi:10.1111/j.1442-200x.2004.01984.x

    Article  CAS  Google Scholar 

  48. Zhang XM, Zhang YB, Chi MH (2016) Soy protein supplementation reduces clinical indices in type 2 diabetes and metabolic syndrome. Yonsei Med J 57(3):681–689. doi:10.3349/ymj.2016.57.3.681

    Article  CAS  Google Scholar 

  49. Morandi S, Locati D, Ferrario F, Chiesa G, Arnoldi A (2005) A simple method for the characterization and quantification of soy isoflavone metabolites in the serum of MMTV-Neu mice using high-performance liquid chromatography/electrospray ionization mass spectrometry with multiple reaction monitoring. Rapid Commun Mass Spectrom 19(2):153–161. doi:10.1002/rcm.1760

    Article  CAS  Google Scholar 

  50. Richelle M, Pridmore-Merten S, Bodenstab S, Enslen M, Offord EA (2002) Hydrolysis of isoflavone glycosides to aglycones by beta-glycosidase does not alter plasma and urine isoflavone pharmacokinetics in postmenopausal women. J Nutr 132(9):2587–2592

    Article  CAS  Google Scholar 

  51. Zheng Y, Hu J, Murphy PA, Alekel DL, Franke WD, Hendrich S (2003) Rapid gut transit time and slow fecal isoflavone disappearance phenotype are associated with greater genistein bioavailability in women. J Nutr 133(10):3110–3116

    Article  CAS  Google Scholar 

Download references


This study has been supported by an unrestricted grant to Centro Dislipidemie (A.S.S.T. Grande Ospedale Metropolitano Niguarda, Milano, Italy) from the Alpro Foundation (Gent, Belgium). The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; and in the decision to publish the results.

Author contributions

MR wrote the paper and performed ELISA experiments; PM wrote the paper and coordinated the study; AA, LC and CS conceived the study and critically revised the manuscript; CP selected the patients and acted as clinical monitor; SG performed all the statistical analyses; BM and CM performed biochemical analysis; MG and CV performed analysis on HDL; GA performed isoflavones analysis; and RB was the dietician. All authors reviewed the results and approved the final version of the manuscript.

Author information

Authors and Affiliations


Corresponding authors

Correspondence to Massimiliano Ruscica or Paolo Magni.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 177 kb)

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ruscica, M., Pavanello, C., Gandini, S. et al. Effect of soy on metabolic syndrome and cardiovascular risk factors: a randomized controlled trial. Eur J Nutr 57, 499–511 (2018).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: