Connect with us through our social channels
High blood pressure (BP) is an important risk factor for cardiovascular disease (CVD) worldwide.1,2Current guidelines classify adults with an average systolic blood pressure (SBP) of 130 to 139 mmHg and/or diastolic blood pressure (DBP) of 80 to 89 mmHg as having stage 1 hypertension (previously, these numbers would have qualified as only prehypertension).3 Adults with stage 1 hypertension have about a 2-fold increase in CVD risk compared with their counterparts with a normal BP (SBP < 120 mm Hg and DBP < 80 mm Hg).3 Furthermore, evidence suggests that lowering SPB to below 130 mmHg further reduces CVD risk.4
Sodium is undoubtedly the dietary constituent that is most linked with BP. Warnings about the hypertensive effects of salt actually date back centuries, although in 1904 Ambard and Beaujard are credited with first suggesting salt increases blood pressure.5Close behind in recognition, is potassium, which in contrast to sodium, is hypotensive.6 Besides these two minerals, there are almost certainly many other dietary factors, including alcohol and fiber, that affect BP as well. Although soy has received relatively little attention in this regard, there is intriguing evidence that one or more soy components lower blood pressure.
Not surprisingly, health authorities emphasize the benefit of adopting an overall dietary pattern that lowers disease risk rather than focusing on making single dietary changes. That sentiment certainly applies to elevated BP because there is ample evidence that overall dietary pattern impacts this condition. For example, clinical and population studies show that vegetarian diets can have BP-lowering effects,7 likely as a result of multiple dietary factors common to these diets.8 Vegetarians do typically consume greater amounts of soyfoods than their nonvegetarian counterparts, but even vegetarian diets lacking in soy are associated with lower BP.9
Perhaps the diet best known for its hypotensive effects is the DASH (Dietary Approaches to Stop Hypertension) diet.10,11This diet is rich in fruits and vegetables and low-fat dairy products and is low in total and saturated fat. Much less well recognized, however, is that the portfolio diet, which was first shown to markedly lower circulating cholesterol levels in 2002,12also lowers blood pressure. In fact, this diet was shown to lower SBP and DBP in comparison to the DASH diet.13The portfolio diet contains 22 g soy protein per 1,000 calories.
The potential hypotensive effects of soy began to receive serious attention with the publication of a 2002 study conducted by Spanish investigators. For this 3-month trial, 40 men and women with mild-to-moderate hypertension were randomly assigned to consume either 500 ml of soymilk (made from whole soybeans) twice per day or equal amounts of cow’s milk.14At the study’s conclusion, SBP decreased (mean ± SD) in the soy group by 18.4 ± 10.7 mmHg compared with a 1.4 ± 7.2 mmHg reduction in the cow's milk group (P < 0.0001). DBP decreased in the soy group by 15.9 ± 9.8 mmHg vs. a 3.7 ± 5.0 mmHg reduction in the cow's milk group (P < 0.0001). Urinary genistein, the primary soybean isoflavone, was strongly and significantly (p=0.002) correlated with the decrease in BP.
Three years later, similar results were reported by Chinese investigators, although in this case the intervention product was an isoflavone-rich isolated soy protein (ISP).15Participants (N=302) were 35 to 64 years of age with an initial untreated SBP between 130 and 159 mmHg and/or a DBP of 80 to 99 mmHg. Study participants were randomly assigned to receive 40 g of ISP or complex carbohydrate for 12 weeks. Compared with the control group, SBP and DPB decreased by 4.31 mmHg (P < 0.001) and 2.76 mmHg (P < 0.001), respectively. It is notable that this study led to an article in the Canadian Medical Association Journal entitled “Soy protein: the next antihypertensive agent?”.16
Interest in the hypotensive effects of soy protein gained further momentum in 2007 when a U.S. trial from Beth Israel Deaconess Medical Center showed soynuts dramatically lowered BP in both normo- and hypertensives, although the effect was especially pronounced in the latter.17In this study, 60 healthy postmenopausal women were randomized in a crossover design to a Therapeutic Lifestyle Changes (TLC) diet alone or a TLC diet of similar energy, fat, and protein content in which soynuts (containing 25 g of soy protein and 101 mg of aglycone isoflavones) replaced 25 g of non-soy protein. Each diet was followed for 8 weeks. Compared with the TLC diet alone, the TLC diet plus soynuts lowered SBP and DBP 9.9% and 6.8%, respectively, in hypertensive women and 5.2% and 2.9%, respectively, in normotensive women.
Each of the three aforementioned clinical trials show very robust hypotensive effects of soy although their experimental designs do not allow insight to be gained about the soy component(s) responsible for these effects. More importantly, as discussed next, most studies show much more modest reductions in BP in response to soy.
The first meta-analysis of the clinical data to examine the effects of soy on BP was published in 2008. Hooper et al.18found that soyfoods (5 studies, n=299), ISP (9 studies, n=962) and isoflavone extracts (7 studies, n=401) lowered SPB (mean, 95% confidence interval) by 5.76 mmHg (-12.29, 0.77), 1.60 mmHg (-3.62, 0.42) and 2.60 mmHg (-5.20, 0.00), respectively. For DPB, these values were -4.04 mmHg (8.30, 0.22), -1.99 mmHg (-2.86, -1.12) and 0.05 mmHg (-1.66, 1.76), respectively. Although 5 of the 6 measures were in the direction of a hypotensive effect, only the effect of ISP on DBP was statistically significant.18The fact that only the effect of ISP was significant suggests that the protein in soy is the primary hypotensive agent. However, this speculation directly contrasts with the results of a meta-analysis published one year later.
In 2010, a meta-analysis by Taku et al.19involving 14 randomized controlled trials (N=789) found that in normotensive and prehypertensive participants, in comparison to the placebo, isoflavone supplements lowered SBP by 1.92 mmHg (p = 0.01) whereas there were no effects on DBP. The duration of the trials ranged from 2 to 24 weeks and the isoflavone intervention dose from 25 to 375 mg/d (aglycone equivalents). Although Hooper et al.19didn’t find a significant effect of isoflavone supplements, the non-significant decrease in this meta-analysis was actually larger (-2.60 vs -1.92 mmHg) than the significant effect found by Taku et al.19
The largest meta-analysis conducted to date, which was published in 2011 and involved 27 studies, found that relative to the control, soy lowered SBP by 2.21 mmHg (p= 0.021) and DBP by 1.44 mmHg (p=0.012).20Soy lowered BP in both normo- and hypertensives, although the decrease was much larger in the latter. More importantly, significant reductions were found only in trials using carbohydrate as the control, not in trials that used milk products as the control.
That latter finding is particularly interesting because of research suggesting dairy/milk reduces blood pressure21(although the evidence is rather inconsistent22) and a subsequently published meta-analysis that reported a similar finding. More specifically, when all 12 trials were included in the analysis, soy lowered SBP and DBP in postmenopausal women by 3.03 (p=0.003) and 0.71 (p=0.012) mmHg, respectively. However, in the five trials in which the control was a non-dairy, non-soy protein, the reduction in SBP and DBP was 6.45 and 0.85 mmHg, respectively, whereas in the five trials in which the control was milk or caseinate, there was no effect of soy. Sub-analysis also showed that trials that intervened with ≥25 g/d soy protein and ≥100 mg/d isoflavones, produced significantly greater decreases in BP than trials intervening with lesser amounts of each of these soy components.
In summary, despite the encouraging evidence, the data do not allow definitive conclusions to be made about the impact of soy on BP. Much of the data are derived from studies in which BP was not the primary outcome of interest, so considerable caution is warranted. Furthermore, because the trials intervened with a variety of soy products, including whole soyfoods, soy isoflavones and soy protein, it is difficult to make generalizations. It may be that each of these products is comprised of hypotensive components. Soy protein could lower BP as a result of hypotensive peptides formed upon digestion.23Isoflavones could lower BP by lowering vascular resistance, potentiating vasodilator mechanisms and reducing the activity of vasoconstriction inhibitors.24
Finally, although it is premature to conclude that soy lowers BP, it is not too early to recommend that those individuals concerned about BP incorporate soyfoods into their diet. As noted, elevated BP is a major risk factor for CVD. Meta-analyses indicate that soy protein lowers LDL-cholesterol levels25-27and whole soyfoods are sources of heart-healthy polyunsaturated fat.28-30Isoflavones may also possess coronary benefits.31-33When these attributes are considered along with the preliminary evidence in support of the hypotensive effects of soy, soyfoods seem like obvious choices for those with elevated BP.
1. Forouzanfar MH, Alexander L, Anderson HR, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386(10010):2287-323.
2. Lim SS, Vos T, Flaxman AD, et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet. 2012;380(9859):2224-60.
3. Whelton PK, Carey RM. The 2017 Clinical Practice Guideline for High Blood Pressure. JAMA. 2017;318(21):2073-4.
4. Ettehad D, Emdin CA, Kiran A, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016;387(10022):957-67.
5. Ha SK. Dietary salt intake and hypertension. Electrolyte & blood pressure : E & BP. 2014;12(1):7-18.
6. Hajjar IM, Grim CE, George V, et al. Impact of diet on blood pressure and age-related changes in blood pressure in the US population: analysis of NHANES III. Arch Intern Med. 2001;161(4):589-93.
7. Yokoyama Y, Nishimura K, Barnard ND, et al. Vegetarian diets and blood pressure: a meta-analysis. JAMA Internal Medicine. 2014;174(4):577-87.
8. Yokoyama Y, Levin SM, Barnard ND. Association between plant-based diets and plasma lipids: a systematic review and meta-analysis. Nutr Rev. 2017;75(9):683-98.
9. Rizzo NS, Jaceldo-Siegl K, Sabate J, et al. Nutrient profiles of vegetarian and nonvegetarian dietary patterns. Journal of the Academy of Nutrition and Dietetics. 2013;113(12):1610-9.
10. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med. 1997;336(16):1117-24.
11. Gay HC, Rao SG, Vaccarino V, et al. Effects of different dietary interventions on blood pressure: Systematic review and meta-analysis of randomized controlled trials. Hypertension. 2016;67(4):733-9.
12. Jenkins DJ, Kendall CW, Faulkner D, et al. A dietary portfolio approach to cholesterol reduction: combined effects of plant sterols, vegetable proteins, and viscous fibers in hypercholesterolemia. Metabolism. 2002;51(12):1596-604.
13. Jenkins DJ, Jones PJ, Frohlich J, et al. The effect of a dietary portfolio compared to a DASH-type diet on blood pressure. Nutrition, metabolism, and cardiovascular diseases : NMCD. 2015;25(12):1132-9.
14. Rivas M, Garay RP, Escanero JF, et al. Soy milk lowers blood pressure in men and women with mild to moderate essential hypertension. J Nutr. 2002;132(7):1900-2.
15. He J, Gu D, Wu X, et al. Effect of soybean protein on blood pressure: a randomized, controlled trial. Ann Intern Med. 2005;143(1):1-9.
16. Cartagena AM. Soy protein: the next antihypertensive agent? CMAJ. 2005;173(5):486.
17. Welty FK, Lee KS, Lew NS, et al. Effect of soy nuts on blood pressure and lipid levels in hypertensive, prehypertensive, and normotensive postmenopausal women. Arch Intern Med. 2007;167(10):1060-7.
18. Hooper L, Kroon PA, Rimm EB, et al. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2008;88(1):38-50.
19. Taku K, Lin N, Cai D, et al. Effects of soy isoflavone extract supplements on blood pressure in adult humans: systematic review and meta-analysis of randomized placebo-controlled trials. J Hypertens. 2010;28(10):1971-82.
20. Dong JY, Tong X, Wu ZW, et al. Effect of soya protein on blood pressure: a meta-analysis of randomised controlled trials. Br J Nutr. 2011;106(3):317-26.
21. Machin DR, Park W, Alkatan M, et al. Hypotensive effects of solitary addition of conventional nonfat dairy products to the routine diet: a randomized controlled trial. Am J Clin Nutr. 2014;100(1):80-7.
22. Ding M, Huang T, Bergholdt HK, et al. Dairy consumption, systolic blood pressure, and risk of hypertension: Mendelian randomization study. BMJ. 2017;356j1000.
23. Coscueta ER, Amorim MM, Voss GB, et al. Bioactive properties of peptides obtained from Argentinian defatted soy flour protein by Corolase PP hydrolysis. Food Chem. 2016;19836-44.
24. Sureda A, Sanches Silva A, Sanchez-Machado DI, et al. Hypotensive effects of genistein: From chemistry to medicine. Chem Biol Interact. 2017;26837-46.
25. Zhan S, Ho SC. Meta-analysis of the effects of soy protein containing isoflavones on the lipid profile. Am J Clin Nutr. 2005;81(2):397-408.
26. 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(2):79-91.
27. Jenkins DJ, Mirrahimi A, Srichaikul K, et al. Soy protein reduces serum cholesterol by both intrinsic and food displacement mechanisms. J Nutr. 2010;140(12):2302S-11S.
28. Slavin M, Kenworthy W, Yu LL. Antioxidant properties, phytochemical composition, and antiproliferative activity of Maryland-grown soybeans with colored seed coats. J Agric Food Chem. 2009;57(23):11174-85.
29. Sacks FM, Lichtenstein A, Van Horn L, et al. Soy protein, isoflavones, and cardiovascular health: an American Heart Association Science Advisory for professionals from the Nutrition Committee. Circulation. 2006;113(7):1034-44.
30. Sacks FM, Lichtenstein AH, Wu JHY, et al. Dietary fats and cardiovascular disease: A presidential advisory from the American Heart Association. Circulation. 2017;136(3):e1-e23.
31. Sobenin IA, Myasoedova VA, Orekhov AN. Phytoestrogen-rich dietary supplements in anti-atherosclerotic therapy in postmenopausal women. Curr Pharm Des. 2016;22(2):152-63.
32. Pase MP, Grima NA, Sarris J. The effects of dietary and nutrient interventions on arterial stiffness: a systematic review. Am J Clin Nutr. 2011;93(2):446-54.
33. Li SH, Liu XX, Bai YY, et al. Effect of oral isoflavone supplementation on vascular endothelial function in postmenopausal women: a meta-analysis of randomized placebo-controlled trials. Am J Clin Nutr. 2010;91(2):480-6.
Mark Messina, PhD, MS is the executive director of the Soy Nutrition Institute, president of Nutrition Matters, Inc., a nutrition consulting company, and an adjunct professor in the School of Public Health at Loma Linda University. He has published more than 100 peer-reviewed articles on soyfoods and soybean components. Messina is the editorial chairperson for The Soy Connection newsletter and has been since its inception.
#  #  #
for the Soy Connection Health Professional Newsletter for the latest news on soy and opportunities to earn free CE credits.
All fields are required