Whole Soy Flour Incorporated into a Muffin and Consumed at 2 Doses of Soy Protein Does Not Lower LDL Cholesterol in a Randomized, Double-Blind Controlled Trial of Hypercholesterolemic Adults

Emily Mt Padhi, Heather J Blewett, Alison M Duncan, Randolph P Guzman, Aileen Hawke, Koushik Seetharaman, Rong Tsao, Thomas Ms Wolever, D Dan Ramdath, Emily Mt Padhi, Heather J Blewett, Alison M Duncan, Randolph P Guzman, Aileen Hawke, Koushik Seetharaman, Rong Tsao, Thomas Ms Wolever, D Dan Ramdath

Abstract

Background: Soy protein may reduce coronary heart disease (CHD) risk by lowering LDL cholesterol, but few studies have assessed whether whole soy flour displays a similar effect.

Objective: The aim of this study was to assess the dose effect of whole soy flour incorporated into muffins on plasma LDL cholesterol in hypercholesterolemic adults.

Methods: Adults aged 30-70 y (n = 243) with elevated LDL cholesterol (≥3.0 and ≤5.0 mmol/L) were stratified by LDL cholesterol and randomly assigned to consume 2 soy muffins containing 25 g soy protein [high-dose soy (HDS)], 1 soy and 1 wheat muffin containing 12.5 g soy protein and 12.5 g whey protein [low-dose soy (LDS)], or 2 wheat muffins containing 25 g whey protein (control) daily for 6 wk while consuming a self-selected diet. Fasting blood samples were collected at weeks 0, 3, and 6 for analysis of plasma lipids [total, LDL, and HDL cholesterol and triglycerides (TGs)], glucose, insulin, C-reactive protein (CRP), and isoflavones. Blood pressures also were measured. Dietary intake was assessed at weeks 0 and 4 with the use of 3 d food records. Treatment effects were assessed with the use of intention-to-treat analysis with multiple imputation and LDL cholesterol as the primary outcome.

Results: In total, 213 (87.6%) participants completed the trial. Participants were primarily Caucasian (83%) and mostly female (63%), with a mean ± SD body mass index (in kg/m2) of 28.0 ± 4.6 and systolic and diastolic blood pressures of 122 ± 16 and 77 ± 11 mm Hg, respectively. Despite a dose-dependent increase in plasma isoflavones (P < 0.001), neither HDS nor LDS had a significant effect on LDL cholesterol compared with control (mean ± SEM changes: control, -0.04 ± 0.05 mmol/L; HDS, 0.01 ± 0.05 mmol/L; and LDS, -0.04 ± 0.06 mmol/L). There were no significant treatment effects on total or HDL cholesterol, TGs, CRP, homeostatic model assessment of insulin resistance, blood pressure, or the Framingham 10-y CHD risk score.

Conclusion: Consuming 12.5 or 25 g protein from defatted soy flour incorporated into muffins does not reduce LDL cholesterol or other CHD risk factors in hypercholesterolemic adults. This trial was registered at clinicaltrials.gov as NCT01547585.

Keywords: LDL cholesterol; cardiovascular disease; dose-response; isoflavones; randomized clinical trial; soy flour.

Conflict of interest statement

Author disclosures: TMS Wolever and his wife (Judy Wolever) are employees and part owners of Glycemic Index Laboratories, Inc., a contract research organization. EMT Padhi, HJ Blewett, AM Duncan, RP Guzman, A Hawke, K Seetharaman, R Tsao, and DD Ramdath, no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Consolidated Standards of Reporting Trials diagram showing flow of participants through trial. The HDS group received 25 g/d soy protein; the LDS group received 12.5 g/d soy protein and 12.5 g/d whey protein; and the control group received 25 g/d whey protein. ALT, alanine transaminase; AST, aspartate transaminase; HDS, high-dose soy; LDL-C, LDL cholesterol; LDS, low-dose soy.

References

    1. World Health Organization [Internet]. Geneva: World Health Organization; 2015. World health statistics 2012. 2012. [cited 2014 Oct 5]. Available from: .
    1. Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, Abraham J, Adair T, Aggarwal R, Ahn SY, et al. . Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012;380:2095–128. Corrected and republished from: Lancet 2013;391:628.
    1. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirbsy A, Sourjina T, Peto R, Collins R, et al. . Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90 056 participants in 14 randomised trials of statins. Lancet 2005;366:1267–78.
    1. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn L, Greenlund K, Daniels S, Nichol G, Tomaselli GF, et al. . Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic Impact Goal through 2020 and beyond. Circulation 2010;121:586–613.
    1. Rao V, Al-Weshahy. Plant-based diets and control of lipids and coronary heart disease risk. Curr Atheroscler Rep 2008;10:478–85.
    1. Tuso PJ, Ismail MH, Ha BP, Bartolotto C. Nutritional update for physicians: Plant-based diets. Perm J 2013;17:61–6.
    1. Ferdowsian HR, Barnard ND. Effects of plant-based diets on plasma lipids. Am J Cardiol 2009;104:947–56.
    1. Anderson JW, Johnstone BM, Cook-Newell ME. Meta-analysis of the effects of soy-protein intake on serum lipids. N Engl J Med 1995;333:276–82.
    1. Cederroth CR, Nef S. Soy, phytoestrogens and metabolism: a review. Mol Cell Endocrinol 2009;304:30–42.
    1. Reinwald S, Akabas SR, Weaver CM. Whole versus the piecemeal approach to evaluating soy. J Nutr 2010;140:2335S–43S.
    1. U.S. Food and Drug Administration [Internet]. Silver Spring (MD): U.S. Food and Drug Administration; 2014. Code of Federal Regulations Title 21, Volume 2, Sec. 101.82 Health Claims: Soy protein and risk of coronary heart disease (CHD). 2014. [cited 2014 Oct 28]. Available from: .
    1. Zhan S, Ho SC. Meta-analysis of the effects of soy-protein containing isoflavones on the lipid profile. Am J Clin Nutr 2005;81:397–408.
    1. Harland JI, Haffner TA. 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 2008;200:13–27.
    1. Weggemans RM, Trautwein EA. Relation between soy-associated isoflavones and LDL and HDL cholesterol concentrations in humans: a meta-analysis. Eur J Clin Nutr 2003;57:940–6.
    1. Zhuo X-G, Melby MK, Watanabe S. Soy isoflavones intake lowers serum LDL cholesterol: a meta-analysis of 8 randomized controlled trials in humans. J Nutr 2004;134:2395–400.
    1. Reynolds K, Chin A, Lees KA, Kguyen A, Bujnowski D, He J. A meta-analysis of the effect of soy protein supplementation on serum lipids. Am J Cardiol 2006;98:633–40.
    1. Taku K, Umegaki K, Sato Y. Soy isoflavones lower serum total and LDL cholesterol in humans: a meta-analysis of 11 randomized controlled trials. Am J Clin Nutr 2007;85:1148–56.
    1. Jenkins DJA, Mirrahimi A, Srichaikul K, Berryman CE, Wang L, Carleton A, Abdulnour S, Sievenpiper JL, Kendall CWC, Kris-Etherton PM. Soy protein reduces serum cholesterol by both intrinsic and food displacement mechanisms. J Nutr 2010;140:2302S–11S.
    1. Anderson JW, Bush HM. Soy protein effects on serum lipoproteins: a quality assessment and meta-analysis of randomized, controlled studies. J Am Coll Nutr. 2011;30:79–91.
    1. Sacks FM, Lichtenstein A, Van Horn L, Harris W, Kris-Etherton P, Winston M. Soy-protein, isoflavones, and cardiovascular health: An American Heart Association advisory panel for professionals from the Nutrition Committee. Circulation 2006;113:1034–44.
    1. Girgih AT, Myrie SB, Aluko RE, Jones PJH. Is category ‘A’ status assigned to soy-protein and coronary heart disease risk reduction health claim by the United States Food and Drug Administration still justifiable? Trends Food Sci Technol 2013;30:121–32.
    1. European Food Safety Authority. Scientific opinion on the substantiation of a health claim related to soy-protein and reduction of blood cholesterol concentrations pursuant to Article 14 of the Regulation (EC) No 1924/2006. EFSA J 2010;8:1688–702.
    1. Benkhedda K, Boudrault C, Sinclair SE, Marles RJ, Xiao CW, Underhill L. Health Canada’s proposal to accept a health claim about soy products and cholesterol lowering. Int Food Risk Anal J 2014;4:1–12.
    1. Health Canada [Internet]. Ottawa (ON): Health Canada; 2015. Summary of Health Canada's assessment of a health claim about soy protein and cholesterol lowering. 2015. [cited 2015 Apr 16]. Available from: .
    1. World Health Organization [Internet]. Geneva. World Health Organization; 2015. Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia. Report of a WHO/IDF consultation. 2006. [cited 2014 Jul 9]. Available from: .
    1. Health Canada [Internet]. Ottawa. Health Canada; 2015. Canadian guidelines for body weight classification in adults – quick reference tool for professionals. 2003. [cited 2014 Jul 15]. Available from: .
    1. World Health Organization [Internet]. Geneva. World Health Organization; 2015. Waist circumference and waist-hip ratio: report of a WHO expert consultation, Geneva, 8–11, December 2008. 2011. [cited 2014 Jul 9]. Available from: .
    1. University of Oxford [Internet]. Oxford (United Kingdom). University of Oxford; 2015. HOMA calculator. 2015. [cited 2014 Sep 13]. Available from: .
    1. National Institutes of Health [Internet]. Bethseda (MD). US Department of Health & Human Services; 2015. Risk assessment tool for estimating your 10-year risk of having a heart attack. 2014 [cited 2014 Nov 28]. Available from: .
    1. Taylor JI, Grace PB, Bingham SA. Optimization of conditions for the enzymatic hydrolysis of phytoestrogen conjugates in urine and plasma. Anal Biochem 2005;341:220–9.
    1. Valentín-Blasini L, Blount BC, Schurz Rogers H, Needham LL. HPLC-MS/MS method for the measurement of seven phytoestrogens in human serum and urine. J Expo Anal Environ Epidemiol 2000;10:799–807.
    1. Shao S, Duncan AM, Yang R, Marcone MF, Rajcan I, Tsao R. Systematic evaluation of pre-HPLC sample processing methods on total and individual isoflavones in soybeans and soy products. Food Res Int 2011;44:2425–34.
    1. Setchell KDR, Cole SJ. Method of defining equol-producer status and its frequency among vegetarians. J Nutr 2006;136:2188–93.
    1. Wolever TMS, Tosh SM, Gibbs AL, Brand-Miller J, Duncan AM, Hart V, Lamarche B, Thomson BA, Duss R, Wood PJ. Physicochemical properties of oat β-glucan influence its ability to reduce serum LDL-C in humans: a randomized clinical trial. Am J Clin Nutr 2010;92:723–32.
    1. Schafer JL. Analysis of incomplete multivariate data. London (United Kingdom): Chapman & Hall; 1997.
    1. Yuan Y. Multiple imputation using SAS software. J Stat Softw 2011;45:1–25.
    1. Liu ZM, Ho SC, Chen Y, Ho S, To K, Tomlinson B. Whole soy, but not purified daidzein, had a favorable effect on improvement of cardiovascular risks: A 6-month randomized, double-blind, and placebo-controlled trial in equol-producing postmenopausal women. Mol Nutr Food Res 2014;58:709–17.
    1. Consonni A, Lovati MR, Parolari A, Manzoni C, Morazzoni P, Magni C, Duranti M. Heterologous expression and purification of the soybean 7S globulin α′ subunit extension region: In vitro evidence of its involvement in cell cholesterol homeostasis. Protein Expr Purif 2011;80:125–9.
    1. Arellano-Martínez GL, Granados O, Palacios-González B, Torres N, Medina-Vera I, Tovar AR. Soya protein stimulates bile acid excretion by the liver and intestine through direct and indirect pathways influenced by the presence of dietary cholesterol. Br J Nutr 2014;111:2059–66.
    1. Torres N, Torre-Villalvazo I, Tovar AR. Regulation of lipid metabolism by soy protein and its implication in diseases mediated by lipid disorders. J Nutr Biochem 2006;17:365–73.
    1. Amigo-Benavent M, Clemente A, Caira S, Stiuso P, Ferranti P, del Castillo MD. Use of phytochemomics to evaluate the bioavailability and bioactivity of antioxidant peptides of soybean β-conglycinin. Electrophoresis 2014;35:1582–9.
    1. Ma D, Taku K, Zhang Y, Jia M, Wang Y, Wang P. Serum lipid-improving effect of soybean β-conglycinin in hyperlipidaemic menopausal women. Br J Nutr 2013;110:1680–4.
    1. Kohno M, Hirotsuka M, Kito M, Matsuzawa Y. Decreases in serum triacylglycerol and visceral fat mediated by dietary soybean β-conglycinin. J Atheroscler Thromb 2006;13:247–55.
    1. West SG, Hilpert KF, Juturu V, Bordi PL, Lampe JW, Mousa SA, Kris-Etherton PM. Effects of including soy protein in a blood cholesterol-lowering diet on markers of cardiac risk in men and in postmenopausal women with and without hormone replacement therapy. J Womens Health (Larchmt) 2005;14:253–62.
    1. Dent SB, Peterson CT, Brace LD, Swain JH, Reddy MB, Hanson KB, Robinson JG, Alekel DL. Soy protein intake by perimenopausal women does not affect circulating lipids and lipoproteins or coagulation and fibrinolytic factors. J Nutr 2001;131:2280–7.
    1. Ridges L, Sunderland R, Moerman K, Meyer B, Astheimer L, Howe P. Cholesterol lowering benefits of soy and linseed enriched foods. Asia Pac J Clin Nutr 2001;10:204–11.
    1. Jenkins DJA, Kendall CWC, Vidgen E, Vuksan V, Jackson C-J, Augustin LSA, Lee B, Garsetti M, Agarwal S, Rao AV, et al. . Effect of soy-based breakfast cereal on blood lipids and oxidized low-density lipoprotein. Metabolism 2000;49:1496–500.
    1. Ahn-Jarvis J, Clinton SK, Riedl KM, Vodovotz Y, Schwartz SJ. Impact of food matrix on isoflavones metabolism and cardiovascular biomarkers in adults with hypercholesterolemia. Food Funct 2012;3:1051–8.
    1. Moghaddam AS, Entezari MH, Iraj B, Askari GR, Maracy MR. The effects of consumption of bread fortified with soy bean flour on metabolic profile in type 2 diabetic women: a cross-over randomized controlled clinical trial. Int J Prev Med 2014;5:1529–36.
    1. Lan-Pidhainy X, Brummer Y, Tosh SM, Wolever TM, Wood PJ. Reducing beta-glucan solubility in oat bran muffins by freeze-thaw treatment attenuates its hypoglycemic effect. Cereal Chem 2007;84:512–7.
    1. Matthan NR, Jalbert SM, Ausman LM, Kuvin JT, Kara RH, Lichtenstein AH. Effect of soy-protein from differently processed products on cardiovascular disease risk factors and vascular endothelial function in hypercholesterolemic subjects. Am J Clin Nutr 2007;85:960–6.
    1. Jackson RL, Greiwe JS, Schwen RJ. Emerging evidence of the health benefits of S-equol, an estrogen receptor β-agonist. Nutr Rev 2011;69:432–48.
    1. Thorp AA, Howe PRC, Mori TA, Coates AM, Buckley JD, Hodgson J, Mansour J, Meyer BJ. Soy food consumption does not lower LDL-C in either equol or nonequol producers. Am J Clin Nutr 2008;88:298–304.
    1. Wong JMW, Kendall CWC, de Souza R, Emam A, Marchi A, Vidgen E, Holmes C, Jenkins DJA. The effect on the blood lipid profile of soy foods combined with a prebiotic: A randomized controlled trial. Metabolism 2010;59:1331–40.
    1. Virk-Baker MK, Barnes S. Krontiras, Nagy TR. S-(−)equol producing status not associated with breast cancer risk among low isoflavone consuming US postmenopausal women undergoing a physician recommended breast biopsy. Nutr Res 2014;34:116–25.

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