Effect of S-equol and Soy Isoflavones on Heart and Brain

Author(s): Akira Sekikawa*, Masafumi Ihara, Oscar Lopez, Chikage Kakuta, Brian Lopresti, Aya Higashiyama, Howard Aizenstein, Yue-Fang Chang, Chester Mathis, Yoshihiro Miyamoto, Lewis Kuller, Chendi Cui.

Journal Name: Current Cardiology Reviews

Volume 15 , Issue 2 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Observational studies in Asia show that dietary intake of soy isoflavones had a significant inverse association with coronary heart disease (CHD). A recent randomized controlled trial (RCT) of soy isoflavones on atherosclerosis in the US, however, failed to show their benefit. The discrepancy may be due to the much lower prevalence of S-equol producers in Westerners: Only 20-30% of Westerners produce S-equol in contrast to 50-70% in Asians. S-equol is a metabolite of dietary soy isoflavone daidzein by gut microbiome and possesses the most antiatherogenic properties among all isoflavones. Several short-duration RCTs documented that soy isoflavones improves arterial stiffness. Accumulating evidence shows that both atherosclerosis and arterial stiffness are positively associated with cognitive decline/dementia. Therefore, potentially, soy isoflavones, especially S-equol, are protective against cognitive decline/dementia.

Methods/Results: This narrative review of clinical and epidemiological studies provides an overview of the health benefits of soy isoflavones and introduces S-equol. Second, we review recent evidence on the association of soy isoflavones and S-equol with CHD, atherosclerosis, and arterial stiffness as well as the association of atherosclerosis and arterial stiffness with cognitive decline/ dementia. Third, we highlight recent studies that report the association of soy isoflavones and S-equol with cognitive decline/dementia. Lastly, we discuss the future directions of clinical and epidemiological research on the relationship of S-equol and CHD and dementia.

Conclusions: Evidence from observational studies and short-term RCTs suggests that S-equol is anti-atherogenic and improves arterial stiffness and may prevent CHD and cognitive impairment/ dementia. Well-designed long-term (≥ 2years) RCTs should be pursued.

Keywords: S-equol, soy isoflavones, atherosclerosis, arterial stiffness, coronary heart disease, cognitive decline, cognitive impairment, dementia.

[1]
Messina M. Insights gained from 20 years of soy research. J Nutr 2010; 140(12): 2289S-95S.
[2]
Anthony MS, Clarkson TB, Bullock BC, Wagner JD. Soy protein versus soy phytoestrogens in the prevention of diet-induced coronary artery atherosclerosis of male cynomolgus monkeys. Arterioscler Thromb Vasc Biol 1997; 17(11): 2524-31.
[3]
Clarkson TB. Soy, Soy phytoestrogens and cardiovascular disease. J Nutr 2002; 132(3): 566S-9.
[4]
Kokubo Y, Iso H, Ishihara J, et al. Association of dietary intake of soy, beans, and isoflavones with risk of cerebral and myocardial infarctions in Japanese populations: The Japan Public Health Center Based (JPHC) study cohort I. Circulation 2007; 116(22): 2553-62.
[5]
Zhang X, Shu XO, Gao Y-T, et al. Soy food consumption is associated with lower risk of coronary heart disease in Chinese women. J Nutr 2003; 133(9): 2874-8.
[6]
Hodis HN, Mack WJ, Kono N, et al. Isoflavone soy protein supplementation and atherosclerosis progression in healthy postmenopausal women. Stroke 2011; 42(11): 3168-75.
[7]
Zhang X, Gao YT, Yang G, et al. Urinary isoflavonoids and risk of coronary heart disease. Int J Epidemiol 2012; 41(5): 1367-75.
[8]
Ahuja V, Miura K, Vishnu A, et al. Significant inverse association of equol-producer status with coronary artery calcification but not dietary isoflavones in healthy Japanese men. Br J Nutr 2017; 117(2): 260-6.
[9]
Curtis PJ, Potter J, Kroon PA, et al. Vascular function and atherosclerosis progression after 1 y of flavonoid intake in statin-treated postmenopausal women with type 2 diabetes: A double-blind randomized controlled trial. Am J Clin Nutr 2013; 97(5): 936-42.
[10]
Hazim S, Curtis PJ, Schar MY, et al. 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 2016; 103(3): 694-702.
[11]
Nestel P, Fujii A, Zhang L. An isoflavone metabolite reduces arterial stiffness and blood pressure in overweight men and postmenopausal women. Atherosclerosis 2007; 192(1): 184-9.
[12]
Teede HJ, McGrath BP, DeSilva L, Cehun M, Fassoulakis A, Nestel PJ. Isoflavones reduce arterial stiffness: A placebo-controlled study in men and postmenopausal women. Arterioscler Thromb Vasc Biol 2003; 23(6): 1066-71.
[13]
Palombo C, Kozakova M. Arterial stiffness, atherosclerosis and cardiovascular risk: Pathophysiologic mechanisms and emerging clinical indications. Vascul Pharmacol 2016; 77: 1-7.
[14]
Qiu C, Fratiglioni L. A major role for cardiovascular burden in age-related cognitive decline. Natl Rev 2015; 12(5): 267-77.
[15]
Cheng PF, Chen JJ, Zhou XY, et al. Do soy isoflavones improve cognitive function in postmenopausal women? A meta-analysis. Menopause 2015; 22: 198-206.
[16]
Wilkins HM, Mahnken JD, Welch P, et al. A mitochondrial biomarker-based study of S-equol in Alzheimer’s disease subjects: Results of a single-arm, pilot trial. J Alzheimers Dis 2017; 59(1): 291-300.
[17]
Messina M. Soy and health update: Evaluation of the clinical and epidemiologic literature. Nutrients 2016; 8(12): E754.
[18]
Jia M, Dahlman-Wright K, Gustafsson JA. Estrogen receptor alpha and beta in health and disease. Best Pract Res Clin Endocrinol Metab 2015; 29(4): 557-68.
[19]
Wei P, Liu M, Chen Y, Chen DC. Systematic review of soy isoflavone supplements on osteoporosis in women. Asian Pac J Trop Med 2012; 5(3): 243-8.
[20]
Fritz H, Seely D, Flower G, et al. Soy, red clover, and isoflavones and breast cancer: A systematic review. PLoS One 2013; 8(11): e81968.
[21]
van Die MD, Bone KM, Williams SG, Pirotta MV. Soy and soy isoflavones in prostate cancer: A systematic review and meta-analysis of randomized controlled trials. BJU Int 2014; 113(5b): E119-30.
[22]
Thomas AJ, Ismail R, Taylor-Swanson L, et al. Effects of isoflavones and amino acid therapies for hot flashes and co-occurring symptoms during the menopausal transition and early postmenopause: A systematic review. Maturitas 2014; 78(4): 263-76.
[23]
Balk E, Chung M, Chew P, et al. Effects of Soy on Health Outcomes Evidence Report/Technology Assessment No 126. Rockville, MD: Agency for Healthcare Research and Quality 2005.
[24]
Klein MA, Nahin RL, Messina MJ, et al. Guidance from an NIH workshop on designing, implementing, and reporting clinical studies of soy interventions. J Nutr 2010; 140(6): 1192S-204.
[25]
Valentin-Blasini L, Sadowski MA, Walden D, Caltabiano L, Needham LL, Barr DB. Urinary phytoestrogen concentrations in the U.S. population (1999-2000). J Expo Anal Environ Epidemiol 2005; 15(6): 509-23.
[26]
Liu W, Tanabe M, Harada KH, Koizumi A. Levels of urinary isoflavones and lignan polyphenols in Japanese women. Environ Health Prev Med 2013; 18(5): 394-400.
[27]
Kim Y, Yoo KY, Goodman MT. Differences in incidence, mortality and survival of breast cancer by regions and countries in Asia and contributing factors. Asian Pac J Cancer Prev 2015; 16(7): 2857-70.
[28]
Kimura T. East meets West: ethnic differences in prostate cancer epidemiology between East Asians and Caucasians. Chin J Cancer 2012; 31(9): 421-9.
[29]
Baber RJ. East is east and West is west: Perspectives on the menopause in Asia and The West. Climacteric 2014; 17(1): 23-8.
[30]
Cauley JA, Chalhoub D, Kassem AM, Fuleihan Gel H. Geographic and ethnic disparities in osteoporotic fractures. Nat Rev Endocrinol 2014; 10(6): 338-51.
[31]
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(5): 276-82.
[32]
Food and Drug Administration Food labeling, health claims, soy protein, and coronary heart disease. Fed Regist 1999; 57: 699-733.
[33]
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.
[34]
Tokede OA, Onabanjo TA, Yansane A, Gaziano JM, Djousse L. Soya products and serum lipids: A meta-analysis of randomised controlled trials. Br J Nutr 2015; 114(6): 831-43.
[35]
Messina M, Nagata C, Wu AH. Estimated Asian adult soy protein and isoflavone intakes. Nutr Cancer 2006; 55(1): 1-12.
[36]
Setchell KD. Phytoestrogens: The biochemistry, physiology, and implications for human health of soy isoflavones. Am J Clin Nutr 1998; 68(6)(Suppl.): 1333s-46s.
[37]
Clarkson TB, Anthony MS, Morgan TM. Inhibition of postmenopausal atherosclerosis progression: A comparison of the effects of conjugated equine estrogens and soy phytoestrogens. J Clin Endocrinol Metab 2001; 86(1): 41-7.
[38]
Ruiz-Larrea MB, Mohan AR, Paganga G, Miller NJ, Bolwell GP, Rice-Evans CA. Antioxidant activity of phytoestrogenic isoflavones. Free Radic Res 1997; 26(1): 63-70.
[39]
Jenkins DJ, Kendall CW, Vidgen E, et al. Effect of soy-based breakfast cereal on blood lipids and oxidized low-density lipoprotein. Metabolism 2000; 49(11): 1496-500.
[40]
Wiseman H, O’Reilly JD, Adlercreutz H, et al. Isoflavone phytoestrogens consumed in soy decrease F2-isoprostane concentrations and increase resistance of low-density lipoprotein to oxidation in humans. Am J Clin Nutr 2000; 72(2): 395-400.
[41]
Jenkins DJ, Kendall CW, Jackson C-JC, et al. Effects of high- and low-isoflavone soyfoods on blood lipids, oxidized LDL, homocysteine, and blood pressure in hyperlipidemic men and women. Am J Clin Nutr 2002; 76(2): 365-72.
[42]
Beavers KM, Jonnalagadda SS, Messina MJ. Soy consumption, adhesion molecules, and pro-inflammatory cytokines: A brief review of the literature. Nutr Rev 2009; 67(4): 213-21.
[43]
Steinberg D. The LDL modification hypothesis of atherogenesis: An update. J Lipid Res 2009; 50(Suppl.): S376-81.
[44]
Vega-Lopez S, Yeum KJ, Lecker JL, et al. Plasma antioxidant capacity in response to diets high in soy or animal protein with or without isoflavones. Am J Clin Nutr 2005; 81(1): 43-9.
[45]
Sen C, Morimoto Y, Heak S, Cooney RV, Franke AA, Maskarinec G. Soy foods and urinary isoprostanes: Results from a randomized study in premenopausal women. Food Funct 2012; 3(5): 517-21.
[46]
Hodgson JM, Puddey IB, Croft KD, Mori TA, Rivera J, Beilin LJ. Isoflavonoids do not inhibit in vivo lipid peroxidation in subjects with high-normal blood pressure. Atherosclerosis 1999; 145(1): 167-72.
[47]
Davies SS, Roberts LJ 2nd.. F2-isoprostanes as an indicator and risk factor for coronary heart disease. Free Radic Biol Med 2011; 50(5): 559-66.
[48]
Roberts LJ, Morrow JD. Measurement of F(2)-isoprostanes as an index of oxidative stress in vivo. Free Radic Biol Med 2000; 28(4): 505-13.
[49]
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.
[50]
Taku K, Umegaki K, Sato Y, Taki Y, Endoh K, Watanabe S. Soy isoflavones lower serum total and LDL cholesterol in humans: a meta-analysis of 11 randomized controlled trials. Am J Clin Nutr 2007; 85(4): 1148-56.
[51]
Setchell KD, Cole SJ. Method of defining equol-producer status and its frequency among vegetarians. J Nutr 2006; 136(8): 2188-93.
[52]
Marrian GF, Haslewood GA. Equol, a new inactive phenol isolated from the ketohydroxyoestrin fraction of mares’ urine. Biochem J 1932; 26(4): 1227-32.
[53]
Setchell KD, Clerici C. Equol: History, chemistry, and formation. J Nutr 2010; 140(7): 1355S-62S.
[54]
Axelson M, Kirk DN, Farrant RD, Cooley G, Lawson AM, Setchell KD. The identification of the weak oestrogen equol [7-hydroxy-3-(4′-hydroxyphenyl)chroman] in human urine. Biochem J 1982; 201(2): 353-7.
[55]
Hwang J, Wang J, Morazzoni P, Hodis HN, Sevanian A. The phytoestrogen equol increases nitric oxide availability by inhibiting superoxide production: an antioxidant mechanism for cell-mediated LDL modification. Free Radic Biol Med 2003; 34(10): 1271-82.
[56]
Setchell KD, Brown NM, Lydeking-Olsen E. The clinical importance of the metabolite sequel-a clue to the effectiveness of soy and its isoflavones. J Nutr 2002; 132(12): 3577-84.
[57]
Joy S, Siow RC, Rowlands DJ, et al. The isoflavone Equol mediates rapid vascular relaxation: Ca2+-independent activation of endothelial nitric-oxide synthase/Hsp90 involving ERK1/2 and Akt phosphorylation in human endothelial cells. J Biol Chem 2006; 281(37): 27335-45.
[58]
Jackman KA, Woodman OL, Chrissobolis S, Sobey CG. Vasorelaxant and antioxidant activity of the isoflavone metabolite equol in carotid and cerebral arteries. Brain Res 2007; 1141: 99-107.
[59]
Cheng C, Wang X, Weakley SM, et al. The soybean isoflavonoid equol blocks ritonavir-induced endothelial dysfunction in porcine pulmonary arteries and human pulmonary artery endothelial cells. J Nutr 2010; 140(1): 12-7.
[60]
Mitchell JH, Gardner PT, McPhail DB, Morrice PC, Collins AR, Duthie GG. Antioxidant efficacy of phytoestrogens in chemical and biological model systems. Arch Biochem Biophys 1998; 360(1): 142-8.
[61]
Arora A, Nair MG, Strasburg GM. Antioxidant activities of isoflavones and their biological metabolites in a liposomal system. Arch Biochem Biophys 1998; 356(2): 133-41.
[62]
Muthyala RS, Ju YH, Sheng S, et al. Equol, a natural estrogenic metabolite from soy isoflavones: convenient preparation and resolution of R- and S-equols and their differing binding and biological activity through estrogen receptors alpha and beta. Bioorg Med Chem 2004; 12(6): 1559-67.
[63]
Setchell KD, Zhao X, Shoaf SE, Ragland K. The pharmacokinetics of S-(-)equol administered as SE5-OH tablets to healthy postmenopausal women. J Nutr 2009; 139(11): 2037-43.
[64]
Setchell KD, Clerici C. Equol: Pharmacokinetics and biological actions. J Nutr 2010; 140(7): 1363S-8S.
[65]
Lund TD, Munson DJ, Haldy ME, Setchell KD, Lephart ED, Handa RJ. Equol is a novel anti-androgen that inhibits prostate growth and hormone feedback. Biol Reprod 2004; 70(4): 1188-95.
[66]
Yuan JP, Wang JH, Liu X. Metabolism of dietary soy isoflavones to equol by human intestinal microflora--implications for health. Mol Nutr Food Res 2007; 51(7): 765-81.
[67]
Rafii F. The role of colonic bacteria in the metabolism of the natural isoflavone daidzin to equol. Metabolites 2015; 5(1): 56-73.
[68]
Jackson RL, Greiwe JS, Schwen RJ. Emerging evidence of the health benefits of S-equol, an estrogen receptor beta agonist. Nutr Rev 2011; 69(8): 432-48.
[69]
Uchiyama S, Ueno T, Suzuki T. Identification of a newly isolated equol-producing lactic acid bacterium from the human feces (in Japanese: abstract in English). J Intestinal Microbiol 2007; 21: 217-20.
[70]
Nagata C, Ueno T, Uchiyama S, et al. Dietary and lifestyle correlates of urinary excretion status of equol in Japanese women. Nutr Cancer 2008; 60(1): 49-54.
[71]
Usui T, Tochiya M, Sasaki Y, et al. 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) 2013; 78: 365-72.
[72]
Maskarinec G, Yamakawa R, Hebshi S, Franke AA. Urinary isoflavonoid excretion and soy consumption in three generations of Japanese women in Hawaii. Eur J Clin Nutr 2007; 61(2): 255-61.
[73]
Franke AA, Lai JF, Pagano I, Morimoto Y, Maskarinec G. Equol production changes over time in pre-menopausal women. Br J Nutr 2012; 107(8): 1201-6.
[74]
Frankenfeld CL, Atkinson C, Thomas WK, et al. High concordance of daidzein-metabolizing phenotypes in individuals measured 1 to 3 years apart. Br J Nutr 2005; 94(6): 873-6.
[75]
Setchell KD, Brown NM, Summer S, et al. Dietary factors influence production of the soy isoflavone metabolite s-(-)equol in healthy adults. J Nutr 2013; 143(12): 1950-8.
[76]
Hong KW, Ko KP, Ahn Y, et al. Epidemiological profiles between equol producers and nonproducers: A genomewide association study of the equol-producing phenotype. Genes Nutr 2012; 7(4): 567-74.
[77]
Song KB, Atkinson C, Frankenfeld CL, et al. Prevalence of daidzein-metabolizing phenotypes differs between Caucasian and Korean American women and girls. J Nutr 2006; 136(5): 1347-51.
[78]
Atkinson C, Newton KM, Stanczyk FZ, Westerlind KC, Li L, Lampe JW. Daidzein-metabolizing phenotypes in relation to serum hormones and sex hormone binding globulin, and urinary estrogen metabolites in premenopausal women in the United States. Cancer Causes Control 2008; 19(10): 1085-93.
[79]
Tseng M, Byrne C, Kurzer MS, Fang CY. Equol-producing status, isoflavone intake, and breast density in a sample of U.S. Chinese women. Cancer Epidemiol Biomarkers Prev 2013; 22(11): 1975-83.
[80]
Arai Y, Uehara M, Sato Y, et al. Comparison of isoflavones among dietary intake, plasma concentration and urinary excretion for accurate estimation of phytoestrogen intake. J Epidemiol 2000; 10(2): 127-35.
[81]
Morton MS, Arisaka O, Miyake N, Morgan LD, Evans BA. Phytoestrogen concentrations in serum from Japanese men and women over forty years of age. J Nutr 2002; 132(10): 3168-71.
[82]
Fujimoto K, Tanaka M, Hirao Y, et al. Age-stratified serum levels of isoflavones and proportion of equol producers in Japanese and Korean healthy men. Prostate Cancer Prostatic Dis 2008; 11(3): 252-7.
[83]
Cai Y, Guo K, Chen C, et al. Soya isoflavone consumption in relation to carotid intima-media thickness in Chinese equol excretors aged 40-65 years. Br J Nutr 2012; 108(9): 1698-704.
[84]
Pusparini Y, Hidayat A. Effect of soy isoflavone supplementation on endothelial dysfunction and oxidative stress in equol-producing postmenopausal women. Endocr Metab Immune Disord Drug Targets 2015; 15(1): 71-9.
[85]
Liu B, Qin L, Liu A, et al. Prevalence of the equol-producer phenotype and its relationship with dietary isoflavone and serum lipids in healthy Chinese adults. J Epidemiol 2010; 20(5): 377-84.
[86]
Guo K, Zhang B, Chen C, et al. Daidzein-metabolising phenotypes in relation to serum lipids and uric acid in adults in Guangzhou, China. Br J Nutr 2010; 104(1): 118-24.
[87]
Akaza H, Miyanaga N, Takashima N, et al. Comparisons of percent equol producers between prostate cancer patients and controls: Case-controlled studies of isoflavones in Japanese, Korean and American residents. Jpn J Clin Oncol 2004; 34(2): 86-9.
[88]
Wu AH, Yu MC, Tseng CC, Twaddle NC, Doerge DR. Plasma isoflavone levels versus self-reported soy isoflavone levels in Asian-American women in Los Angeles County. Carcinogenesis 2004; 25(1): 77-81.
[89]
Miyanaga N, Akaza H, Takashima N, et al. Higher consumption of green tea may enhance equol production. Asian Pac J Cancer Prev 2003; 4(4): 297-301.
[90]
Atkinson C, Newton KM, Bowles EJ, Yong M, Lampe JW. Demographic, anthropometric, and lifestyle factors and dietary intakes in relation to daidzein-metabolizing phenotypes among premenopausal women in the United States. Am J Clin Nutr 2008; 87(3): 679-87.
[91]
Hedlund TE, Maroni PD, Ferucci PG, et al. Long-term dietary habits affect soy isoflavone metabolism and accumulation in prostatic fluid in caucasian men. J Nutr 2005; 135(6): 1400-6.
[92]
Lampe JW, Skor HE, Li S, Wahala K, Howald WN, Chen C. Wheat bran and soy protein feeding do not alter urinary excretion of the isoflavan equol in premenopausal women. J Nutr 2001; 131(3): 740-4.
[93]
Rowland IR, Wiseman H, Sanders TA, Adlercreutz H, Bowey EA. Interindividual variation in metabolism of soy isoflavones and lignans: Influence of habitual diet on equol production by the gut microflora. Nutr Cancer 2000; 36(1): 27-32.
[94]
Frankenfeld CL, McTiernan A, Tworoger SS, et al. Serum steroid hormones, sex hormone-binding globulin concentrations, and urinary hydroxylated estrogen metabolites in post-menopausal women in relation to daidzein-metabolizing phenotypes. J Steroid Biochem Mol Biol 2004; 88(4-5): 399-408.
[95]
Lampe JW, Karr SC, Hutchins AM, Slavin JL. Urinary equol excretion with a soy challenge: Influence of habitual diet. Proc Soc Exp Biol Med 1998; 217(3): 335-9.
[96]
Lampe JW, Gustafson DR, Hutchins AM, et al. Urinary isoflavonoid and lignan excretion on a Western diet: relation to soy, vegetable, and fruit intake. Cancer Epidemiol Biomarkers Prev 1999; 8(8): 699-707.
[97]
Wiseman H, Casey K, Bowey EA, et al. Influence of 10 wk of soy consumption on plasma concentrations and excretion of isoflavonoids and on gut microflora metabolism in healthy adults. Am J Clin Nutr 2004; 80(3): 692-9.
[98]
Tanaka M, Fujimoto K, Chihara Y, et al. Isoflavone supplements stimulated the production of serum equol and decreased the serum dihydrotestosterone levels in healthy male volunteers. Prostate Cancer Prostatic Dis 2009; 12(3): 247-52.
[99]
Nettleton JA, Greany KA, Thomas W, Wangen KE, Adlercreutz H, Kurzer MS. Plasma phytoestrogens are not altered by probiotic consumption in postmenopausal women with and without a history of breast cancer. J Nutr 2004; 134(8): 1998-2003.
[100]
Bonorden MJ, Greany KA, Wangen KE, et al. Consumption of Lactobacillus acidophilus and Bifidobacterium longum do not alter urinary equol excretion and plasma reproductive hormones in premenopausal women. Eur J Clin Nutr 2004; 58(12): 1635-42.
[101]
Teas J, Hurley TG, Hebert JR, Franke AA, Sepkovic DW, Kurzer MS. Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women. J Nutr 2009; 139(5): 939-44.
[102]
Finegold JA, Asaria P, Francis DP. Mortality from ischaemic heart disease by country, region, and age: Statistics from World Health Organisation and United Nations. Int J Cardiol 2013; 168(2): 934-45.
[103]
Benjamin EJ, Blaha MJ, Chiuve SE, et al. Heart disease and stroke statistics-2017 update: A report from the American Heart Association. Circulation 2017; 135(10): e146-603.
[104]
Yamori Y, Liu L, Ikeda K, Mizushima S, Nara Y, Simpson FO. Different associations of blood pressure with 24-hour urinary sodium excretion among pre- and post-menopausal women. WHO Cardiovascular Diseases and Alimentary Comparison (WHO-CARDIAC) Study. J Hypertens 2001; 19(3 Pt 2): 535-8.
[105]
Yamori Y. Food factors for atherosclerosis prevention: Asian perspective derived from analyses of worldwide dietary biomarkers. Exp Clin Cardiol 2006; 11(2): 94-8.
[106]
Ho SY, Schooling M, Hui LL, McGhee SM, Mak KH, Lam TH. Soy consumption and mortality in Hong Kong: Proxy-reported case-control study of all older adult deaths in 1998. Prev Med 2006; 43(1): 20-6.
[107]
van der Schouw YT, Kreijkamp-Kaspers S, Peeters PHM, Keinan-Boker L, Rimm EB, Grobbee DE. Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in western women. Circulation 2005; 111(4): 465-71.
[108]
Yu D, Zhang X, Xiang YB, et al. Association of soy food intake with risk and biomarkers of coronary heart disease in Chinese men. Int J Cardiol 2014; 172(2): e285-7.
[109]
Talaei M, Koh WP, van Dam RM, Yuan JM, Pan A. Dietary soy intake is not associated with risk of cardiovascular disease mortality in Singapore Chinese adults. J Nutr 2014; 144(6): 921-8.
[110]
Greenland P, Bonow RO, Brundage BH, et al. ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: A report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography. J Am Coll Cardiol 2007; 49(3): 378-402.
[111]
Bots ML, Sutton-Tyrrell K. Lessons from the past and promises for the future for carotid intima-media thickness. J Am Coll Cardiol 2012; 60(17): 1599-604.
[112]
Naqvi TZ, Lee MS. Carotid intima-media thickness and plaque in cardiovascular risk assessment. JACC Cardiovasc Imaging 2014; 7(10): 1025-38.
[113]
Peters SA, Bakker M, den Ruijter HM, Bots ML. Added value of CAC in risk stratification for cardiovascular events: A systematic review. Eur J Clin Invest 2012; 42(1): 110-6.
[114]
Goldberger ZD, Valle JA, Dandekar VK, Chan PS, Ko DT, Nallamothu BK. Are changes in carotid intima-media thickness related to risk of nonfatal myocardial infarction? A critical review and meta-regression analysis. Am Heart J 2010; 160(4): 701-14.
[115]
Nambi V, Chambless L, Folsom AR, et al. Carotid intima-media thickness and presence or absence of plaque improves prediction of coronary heart disease risk: The ARIC (Atherosclerosis Risk In Communities) study. J Am Coll Cardiol 2010; 55(15): 1600-7.
[116]
Costanzo P, Perrone-Filardi P, Vassallo E, et al. Does carotid intima-media thickness regression predict reduction of cardiovascular events?: A meta-analysis of 41 randomized trials. J Am Coll Cardiol 2010; 56(24): 2006-20.
[117]
Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: A systematic review and meta-analysis. Circulation 2007; 115(4): 459-67.
[118]
Touboul PJ, Hennerici MG, Meairs S, et al. Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011. Cerebrovasc Dis (Basel, Switzerland) 2012; 34(4): 290-6
[119]
Rumberger JA, Simons DB, Fitzpatrick LA, Sheedy PF, Schwartz RS. Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area: A histopathologic correlative study. Circulation 1995; 92(8): 2157-62.
[120]
Gepner AD, Young R, Delaney JA, et al. Comparison of coronary artery calcium presence, carotid plaque presence, and carotid intima-media thickness for cardiovascular disease prediction in the multi-ethnic study of atherosclerosis. Circ Cardiovasc Imaging 2015; 8(1): e002262.
[121]
Folsom AR, Kronmal RA, Detrano RC, et al. Coronary artery calcification compared with carotid intima-media thickness in the prediction of cardiovascular disease incidence: The Multi-Ethnic Study of Atherosclerosis (MESA). Arch Intern Med 2008; 168(12): 1333-9.
[122]
Gepner AD, Young R, Delaney JA, et al. Comparison of carotid plaque score and coronary artery calcium score for predicting cardiovascular disease events: The multi-ethnic study of atherosclerosis. J Am Heart Assoc 2017; 6(2): e005179.
[123]
Arad Y, Spadaro LA, Roth M, Newstein D, Guerci AD. Treatment of asymptomatic adults with elevated coronary calcium scores with atorvastatin, vitamin C, and vitamin E: the St. Francis Heart Study randomized clinical trial. J Am Coll Cardiol 2005; 46(1): 166-72.
[124]
Houslay ES, Cowell SJ, Prescott RJ, et al. Progressive coronary calcification despite intensive lipid-lowering treatment: A randomised controlled trial. Heart 2006; 92(9): 1207-12.
[125]
Raggi P, Davidson M, Callister TQ, et al. Aggressive versus moderate lipid-lowering therapy in hypercholesterolemic postmenopausal women: Beyond Endorsed Lipid Lowering With EBT Scanning (BELLES). Circulation 2005; 112(4): 563-71.
[126]
Ohkuma T, Ninomiya T, Tomiyama H, et al. Brachial-ankle pulse wave velocity and the risk prediction of cardiovascular disease: An individual participant data meta-analysis. Hypertension 2017; 69(6): 1045-52.
[127]
Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: A systematic review and meta-analysis. J Am Coll Cardiol 2010; 55(13): 1318-27.
[128]
Ben-Shlomo Y, Spears M, Boustred C, et al. Aortic pulse wave velocity improves cardiovascular event prediction: An individual participant meta-analysis of prospective observational data from 17,635 subjects. J Am Coll Cardiol 2014; 63(7): 636-46.
[129]
Cecelja M, Chowienczyk P. Dissociation of aortic pulse wave velocity with risk factors for cardiovascular disease other than hypertension: A systematic review. Hypertension 2009; 54(6): 1328-36.
[130]
Zieman SJ, Melenovsky V, Kass DA. Mechanisms, pathophysiology, and therapy of arterial stiffness. Arterioscler Thromb Vasc Biol 2005; 25(5): 932-43.
[131]
Townsend RR, Wilkinson IB, Schiffrin EL, et al. Recommendations for improving and standardizing vascular research on arterial stiffness: A scientific statement from the American Heart Association. Hypertension 2015; 66(3): 698-722.
[132]
Chan YH, Lau KK, Yiu KH, et al. Isoflavone intake in persons at high risk of cardiovascular events: implications for vascular endothelial function and the carotid atherosclerotic burden. Am J Clin Nutr 2007; 86(4): 938-45.
[133]
Zhang B, Chen YM, Huang LL, et al. Greater habitual soyfood consumption is associated with decreased carotid intima-media thickness and better plasma lipids in Chinese middle-aged adults. Atherosclerosis 2008; 198(2): 403-11.
[134]
Hodis HN, Mack WJ. The timing hypothesis and hormone replacement therapy: A paradigm shift in the primary prevention of coronary heart disease in women. Part 2: Comparative risks. J Am Geriatr Soc 2013; 61(6): 1011-8.
[135]
Liu ZM, Ho SC, Chen YM, et al. 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(4): 709-17.
[136]
Bots ML, Evans GW, Riley WA, Grobbee DE. Carotid intima-media thickness measurements in intervention studies: Design options, progression rates, and sample size considerations: A point of view. Stroke 2003; 34(12): 2985-94.
[137]
Uemura H, Katsuura-Kamano S, Nakamoto M, et al. Inverse association between soy food consumption, especially fermented soy products intake and soy isoflavone, and arterial stiffness in Japanese men. Sci Rep 2018; 8(1): 9667.
[138]
Yoshikata R, Myint KZ, Ohta H. Relationship between equol producer status and metabolic parameters in 743 Japanese women: Equol producer status is associated with antiatherosclerotic conditions in women around menopause and early postmenopause. Menopause 2017; 24(2): 216-24.
[139]
Hoshida S, Miki T, Nakagawa T, et al. Different effects of isoflavones on vascular function in premenopausal and postmenopausal smokers and nonsmokers: NYMPH study. Heart Vessels 2011; 26(6): 590-5.
[140]
Yoshikata R, Myint KZY, Ohta H. Effects of equol supplement on bone and cardiovascular parameters in middle-aged japanese women: A prospective observational study. J Altern Complement Med 2018; 24(7): 701-8.
[141]
Teede HJ, Dalais FS, Kotsopoulos D, Liang Y-L, Davis S, McGrath BP. Dietary soy has both beneficial and potentially adverse cardiovascular effects: A placebo-controlled study in men and postmenopausal women. J Clin Endocrinol Metab 2001; 86(7): 3053-60.
[142]
Nestel PJ, Yamashita T, Sasahara T, et al. Soy isoflavones improve systemic arterial compliance but not plasma lipids in menopausal and perimenopausal women. Arterioscler Thromb Vasc Biol 1997; 17(12): 3392-8.
[143]
Richter CK, Skulas-Ray AC, Fleming JA, et al. Effects of isoflavone-containing soya protein on ex vivo cholesterol efflux, vascular function and blood markers of CVD risk in adults with moderately elevated blood pressure: A dose-response randomised controlled trial. Br J Nutr 2017; 117(10): 1403-13.
[144]
Liu XX, Li SH, Chen JZ, et al. Effect of soy isoflavones on blood pressure: A meta-analysis of randomized controlled trials. Nutr Metab Cardiovas 2012; 22(6): 463-70.
[145]
Kou T, Wang Q, Cai J, et al. Effect of soybean protein on blood pressure in postmenopausal women: A meta-analysis of randomized controlled trials. Food Funct 2017; 8(8): 2663-71.
[146]
He FJ, Li J, Macgregor GA. Effect of longer term modest salt reduction on blood pressure: Cochrane systematic review and meta-analysis of randomised trials. BMJ 2013; 346: 1325.
[147]
Yang B, Chen Y, Xu T, et al. Systematic review and meta-analysis of soy products consumption in patients with type 2 diabetes mellitus. Asia Pac J Clin Nutr 2011; 20(4): 593-602.
[148]
Ding M, Pan A, Manson JE, et al. Consumption of soy foods and isoflavones and risk of type 2 diabetes: a pooled analysis of three US cohorts. Eur J Clin Nutr 2016; 70(12): 1381-7.
[149]
Li W, Ruan W, Peng Y, Wang D. Soy and the risk of type 2 diabetes mellitus: A systematic review and meta-analysis of observational studies. Diabetes Res Clin Pract 2018; 137: 190-9.
[150]
Ko KP, Kim CS, Ahn Y, et al. Plasma isoflavone concentration is associated with decreased risk of type 2 diabetes in Korean women but not men: Results from the Korean Genome and Epidemiology Study. Diabetologia 2015; 58(4): 726-35.
[151]
Ricci E, Cipriani S, Chiaffarino F, Malvezzi M, Parazzini F. Effects of soy isoflavones and genistein on glucose metabolism in perimenopausal and postmenopausal non-Asian women: A meta-analysis of randomized controlled trials. Menopause 2010; 17(5): 1080-6.
[152]
Birru RL, Ahuja V, Vishnu A, et al. The impact of equol-producing status in modifying the effect of soya isoflavones on risk factors for CHD: A systematic review of randomised controlled trials. J Nutr Sci 2016; 5: e30.
[153]
Badeau R, Jauhiainen M, Metso J, et al. Effect of isolated isoflavone supplementation on ABCA1-dependent cholesterol efflux potential in postmenopausal women. Menopause 2007; 14(2): 293-9.
[154]
Clerici C, Setchell KDR, Battezzati PM, et al. Pasta naturally enriched with isoflavone aglycons from soy germ reduces serum lipids and improves markers of cardiovascular risk. J Nutr 2007; 137(10): 2270-8.
[155]
Gallagher JC, Satpathy R, Rafferty K, Haynatzka V. The effect of soy protein isolate on bone metabolism. Menopause 2004; 11(3): 290-8.
[156]
Greany KA, Nettleton JA, Wangen KE, Thomas W, Kurzer MS. Probiotic consumption does not enhance the cholesterol-lowering effect of soy in postmenopausal women. J Nutr 2004; 134(12): 3277-83.
[157]
Greany KA, Nettleton JA, Wangen KE, Thomas W, Kurzer MS. Consumption of isoflavone-rich soy protein does not alter homocysteine or markers of inflammation in postmenopausal women. Eur J Clin Nutr 2008; 62(12): 1419-25.
[158]
Hall WL, Vafeiadou K, Hallund J, et al. Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: Interactions with genotype and equol production. Am J Clin Nutr 2005; 82(6): 1260-1268 quiz 365-6..
[159]
Hallund J, Bugel S, Tholstrup T, et al. Soya isoflavone-enriched cereal bars affect markers of endothelial function in postmenopausal women. Br J Nutr 2006; 95(6): 1120-6.
[160]
Kreijkamp-Kaspers S, Kok L, Bots ML, Grobbee DE, Lampe JW, van der Schouw YT. Randomized controlled trial of the effects of soy protein containing isoflavones on vascular function in postmenopausal women. Am J Clin Nutr 2005; 81(1): 189-95.
[161]
Kreijkamp-Kaspers S, Kok L, Grobbee DE, et al. Effect of soy protein containing isoflavones on cognitive function, bone mineral density, and plasma lipids in postmenopausal women: A randomized controlled trial. JAMA 2004; 292(1): 65-74.
[162]
Ma Y, Chiriboga D, Olendzki BC, Nicolosi R, Merriam PA, Ockene IS. Effect of soy protein containing isoflavones on blood lipids in moderately hypercholesterolemic adults: A randomized controlled trial. J Am Coll Nutr 2005; 24(4): 275-85.
[163]
Mangano KM, Hutchins-Wiese HL, Kenny AM, et al. Soy proteins and isoflavones reduce interleukin-6 but not serum lipids in older women: A randomized controlled trial. Nutr Res 2013; 33(12): 1026-33.
[164]
McVeigh BL, Dillingham BL, Lampe JW, Duncan AM. Effect of soy protein varying in isoflavone content on serum lipids in healthy young men. Am J Clin Nutr 2006; 83(2): 244-51.
[165]
Meyer BJ, Larkin TA, Owen AJ, Astheimer LB, Tapsell LC, Howe PR. Limited lipid-lowering effects of regular consumption of whole soybean foods. Ann Nutr Metab 2004; 48(2): 67-78.
[166]
Nikander E, Tiitinen A, Laitinen K, Tikkanen M, Ylikorkala O. Effects of isolated isoflavonoids on lipids, lipoproteins, insulin sensitivity, and ghrelin in postmenopausal women. J Clin Endocrinol Metab 2004; 89(7): 3567-72.
[167]
Pipe EA, Gobert CP, Capes SE, Darlington GA, Lampe JW, Duncan AM. Soy protein reduces serum LDL cholesterol and the LDL cholesterol: HDL cholesterol and apolipoprotein B: Apolipoprotein A-I ratios in adults with type 2 diabetes. J Nutr 2009; 139(9): 1700-6.
[168]
Qin Y, Shu F, Zeng Y, et al. Daidzein supplementation decreases serum triglyceride and uric acid concentrations in hypercholesterolemic adults with the effect on triglycerides being greater in those with the GA compared with the GG genotype of ESR-beta RsaI. J Nutr 2014; 144(1): 49-54.
[169]
Reimann M, Dierkes J, Carlsohn A, et al. Consumption of soy isoflavones does not affect plasma total homocysteine or asymmetric dimethylarginine concentrations in healthy postmenopausal women. J Nutr 2006; 136(1): 100-5.
[170]
Steinberg FM, Guthrie NL, Villablanca AC, Kumar K, Murray MJ. Soy protein with isoflavones has favorable effects on endothelial function that are independent of lipid and antioxidant effects in healthy postmenopausal women. Am J Clin Nutr 2003; 78(1): 123-30.
[171]
Thorp AA, Howe PR, Mori TA, et al. Soy food consumption does not lower LDL cholesterol in either equol or nonequol producers. Am J Clin Nutr 2008; 88(2): 298-304.
[172]
Tormala R, Appt S, Clarkson TB, et al. Equol production capability is associated with favorable vascular function in postmenopausal women using tibolone; no effect with soy supplementation. Atherosclerosis 2008; 198(1): 174-8.
[173]
Tormala R, Appt S, Clarkson TB, et al. Impact of soy supplementation on sex steroids and vascular inflammation markers in postmenopausal women using tibolone: Role of equol production capability. Climacteric 2008; 11(5): 409-15.
[174]
Tormala RM, Nikander E, Tiitinen A, Vaisanen-Tommiska M, Ylikorkala O, Mikkola TS. Serum cholesterol efflux potential in postmenopausal women treated with isolated isoflavones. Menopause 2006; 13(1): 96-101.
[175]
Welty FK, Lee KS, Lew NS, Zhou J. 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.
[176]
West SG, Hilpert KF, Juturu V, et al. 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 Women's Health (2002) 2005; 14(3): 253-62.
[177]
Hall WL, Vafeiadou K, Hallund J, et al. Soy-isoflavone-enriched foods and markers of lipid and glucose metabolism in postmenopausal women: Interactions with genotype and equol production. Am J Clin Nutr 2006; 83(3): 592-600.
[178]
Wong WW, Taylor AA, Smith EO, Barnes S, Hachey DL. Effect of soy isoflavone supplementation on nitric oxide metabolism and blood pressure in menopausal women. Am J Clin Nutr 2012; 95(6): 1487-94.
[179]
Wolters FJ, Ikram M. Epidemiology of dementia: the burden on society, the challenges for research.In: Perneczky R, editor Biomarkers for Alzheimer’s Disease Drug Development. New York, NY: Springer New York 2018; pp. 3-14.
[180]
Zissimopoulos J, Crimmins E, St Clair P. The value of delaying Alzheimer’s disease onset. Forum Health Econ Policy 2014; 18(1): 25-39.
[181]
Chui HC, Zheng L, Reed BR, Vinters HV, Mack WJ. Vascular risk factors and Alzheimer’s disease: Are these risk factors for plaques and tangles or for concomitant vascular pathology that increases the likelihood of dementia? An evidence-based review. Alzheimers Res Ther 2012; 4(1): 1.
[182]
Tan ZS, Seshadri S, Beiser A, et al. Plasma total cholesterol level as a risk factor for Alzheimer disease: The Framingham Study. Arch Intern Med 2003; 163(9): 1053-7.
[183]
Kuller LH, Lopez OL, Mackey RH, et al. Subclinical cardiovascular disease and death, dementia, and coronary heart disease in patients 80+ years. J Am Coll Cardiol 2016; 67(9): 1013-22.
[184]
Handy CE, Desai CS, Dardari ZA, et al. The association of coronary artery calcium with noncardiovascular disease: The multi-ethnic study of atherosclerosis. JACC Cardiovasc Imaging 2016; 9(5): 568-76.
[185]
van Sloten TT, Protogerou AD, Henry RM, Schram MT, Launer LJ, Stehouwer CD. Association between arterial stiffness, cerebral small vessel disease and cognitive impairment: A systematic review and meta-analysis. Neurosci Biobehav Rev 2015; 53: 121-30.
[186]
Mirahmadi SM, Shahmohammadi A, Rousta AM, et al. Soy isoflavone genistein attenuates lipopolysaccharide-induced cognitive impairments in the rat via exerting anti-oxidative and anti-inflammatory effects. Cytokine 2018; 104: 151-9.
[187]
Bonet-Costa V, Herranz-Perez V, Blanco-Gandia M, et al. Clearing amyloid-beta through ppargamma/apoe activation by genistein is a treatment of experimental Alzheimer’s disease. J Alzheimers Dis 2016; 51(3): 701-11.
[188]
Ye S, Wang TT, Cai B, et al. Genistein protects hippocampal neurons against injury by regulating calcium/calmodulin dependent protein kinase IV protein levels in Alzheimer’s disease model rats. Neural Regen Res 2017; 12(9): 1479-84.
[189]
Wang Y, Cai B, Shao J, et al. Genistein suppresses the mitochondrial apoptotic pathway in hippocampal neurons in rats with Alzheimer’s disease. Neural Regen Res 2016; 11(7): 1153-8.
[190]
Newman AB, Fitzpatrick AL, Lopez O, et al. Dementia and Alzheimer’s disease incidence in relationship to cardiovascular disease in the cardiovascular health study cohort. J Am Geriatr Soc 2005; 53(7): 1101-7.
[191]
van Oijen M, de Jong FJ, Witteman JC, Hofman A, Koudstaal PJ, Breteler MM. Atherosclerosis and risk for dementia. Ann Neurol 2007; 61(5): 403-10.
[192]
Wendell CR, Zonderman AB, Metter EJ, Najjar SS, Waldstein SR. Carotid intimal medial thickness predicts cognitive decline among adults without clinical vascular disease. Stroke 2009; 40(10): 3180-5.
[193]
Romero JR, Beiser A, Seshadri S, et al. Carotid artery atherosclerosis, MRI indices of brain ischemia, aging, and cognitive impairment: The Framingham study. Stroke 2009; 40(5): 1590-6.
[194]
Sander K, Bickel H, Forstl H, et al. Carotid- intima media thickness is independently associated with cognitive decline. The INVADE study. Int J Geriatr Psychiatry 2010; 25(4): 389-94.
[195]
Arntzen KA, Schirmer H, Johnsen SH, Wilsgaard T, Mathiesen EB. Carotid atherosclerosis predicts lower cognitive test results: A 7-year follow-up study of 4,371 stroke-free subjects - the Tromso study. Cerebrovasc Dis (Basel, Switzerland) 2012; 33(2): 159-65.
[196]
Zhong W, Cruickshanks KJ, Schubert CR, et al. Carotid atherosclerosis and 10-year changes in cognitive function. Atherosclerosis 2012; 224(2): 506-10.
[197]
Moon JH, Lim S, Han JW, et al. Carotid intima-media thickness is associated with the progression of cognitive impairment in older adults. Stroke 2015; 46(4): 1024-30.
[198]
Zeki Al Hazzouri A, Vittinghoff E, Sidney S, Reis JP, Jacobs DR Jr, Yaffe K. Intima-media thickness and cognitive function in stroke-free middle-aged adults: findings from the coronary artery risk development in young adults study. Stroke 2015; 46(8): 2190-6.
[199]
Cardiovacular Epidemiology Site - epi-c.jp (in Japanese): LIfe Science Publishing Co., Ltd.; [Available from: http://www.epi-c.jp/
[200]
Knopman D, Boland LL, Mosley T, et al. Cardiovascular risk factors and cognitive decline in middle-aged adults. Neurology 2001; 56(1): 42-8.
[201]
Knopman DS, Mosley TH, Catellier DJ, Coker LH. Fourteen-year longitudinal study of vascular risk factors, APOE genotype, and cognition: The ARIC MRI Study. Alzheimers Dement 2009; 5(3): 207-14.
[202]
Schott LL, Wildman RP, Brockwell S, Simkin-Silverman LR, Kuller LH, Sutton-Tyrrell K. Segment-specific effects of cardiovascular risk factors on carotid artery intima-medial thickness in women at midlife. Arterioscler Thromb Vasc Biol 2004; 24(10): 1951-6.
[203]
O’Leary DH, Polak JF, Kronmal RA, et al. Distribution and correlates of sonographically detected carotid artery disease in the Cardiovascular Health Study. The CHS Collaborative Research Group. Stroke 1992; 23(12): 1752-60.
[204]
Fujiyoshi A, Jacobs DR Jr, Fitzpatrick AL, et al. Coronary artery calcium and risk of dementia in MESA (Multi-Ethnic Study of Atherosclerosis). Circ Cardiovasc Imaging 2017; 10(5): e005349.
[205]
Vidal JS, Sigurdsson S, Jonsdottir MK, et al. Coronary artery calcium, brain function and structure: The AGES-Reykjavik Study. Stroke 2010; 41(5): 891-7.
[206]
Cui C, Sekikawa A, Kuller L, et al. Aortic stiffness is associated with increased risk of incident dementia in older adults. J Alzheimers Dis 2018; 66(1): 297-306.
[207]
Pase MP, Beiser A, Himali JJ, et al. Aortic stiffness and the risk of incident mild cognitive impairment and dementia. Stroke 2016; 47(9): 2256-61.
[208]
Poels MM, van Oijen M, Mattace-Raso FU, et al. Arterial stiffness, cognitive decline, and risk of dementia: The Rotterdam study. Stroke 2007; 38(3): 888-92.
[209]
Waldstein SR, Rice SC, Thayer JF, Najjar SS, Scuteri A, Zonderman AB. Pulse pressure and pulse wave velocity are related to cognitive decline in the Baltimore Longitudinal Study of Aging. Hypertension 2008; 51(1): 99-104.
[210]
Zeki Al Hazzouri A, Newman AB, Simonsick E, et al. Pulse wave velocity and cognitive decline in elders: The Health, Aging, and Body Composition study. Stroke 2013; 44(2): 388-93.
[211]
Taniguchi Y, Fujiwara Y, Nofuji Y, et al. Prospective study of arterial stiffness and subsequent cognitive decline among community-dwelling older Japanese. J Epidemiol 2015; 25(9): 592-9.
[212]
Scuteri A, Nilsson PM, Tzourio C, Redon J, Laurent S. Microvascular brain damage with aging and hypertension: pathophysiological consideration and clinical implications. J Hypertens 2011; 29(8): 1469-77.
[213]
O’Rourke MF, Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: Cause and logic of therapy. Hypertension 2005; 46(1): 200-4.
[214]
Tsao CW, Himali JJ, Beiser AS, et al. Association of arterial stiffness with progression of subclinical brain and cognitive disease. Neurology 2016; 86(7): 619-26.
[215]
Hughes TM, Kuller LH, Barinas-Mitchell EJ, et al. Pulse wave velocity is associated with beta-amyloid deposition in the brains of very elderly adults. Neurology 2013; 81(19): 1711-8.
[216]
Nation DA, Edland SD, Bondi MW, et al. Pulse pressure is associated with Alzheimer biomarkers in cognitively normal older adults. Neurology 2013; 81(23): 2024-7.
[217]
Nakamoto M, Otsuka R, Nishita Y, et al. Soy food and isoflavone intake reduces the risk of cognitive impairment in elderly Japanese women. Eur J Clin Nutr 2018; 72(10): 1458-62.
[218]
Ozawa M, Ninomiya T, Ohara T, et al. Dietary patterns and risk of dementia in an elderly Japanese population: The Hisayama Study. Am J Clin Nutr 2013; 97(5): 1076-82.
[219]
Chan R, Chan D, Woo J. A cross sectional study to examine the association between dietary patterns and cognitive impairment in older Chinese people in Hong Kong. J Nutr Health Aging 2013; 17(9): 757-65.
[220]
Okubo H, Inagaki H, Gondo Y, et al. Association between dietary patterns and cognitive function among 70-year-old Japanese elderly: A cross-sectional analysis of the SONIC study. Nutr J 2017; 16(1): 56.
[221]
Thorp AA, Sinn N, Buckley JD, Coates AM, Howe PR. Soya isoflavone supplementation enhances spatial working memory in men. Br J Nutr 2009; 102(9): 1348-54.
[222]
File S, Jarrett N, Fluck E, Duffy R, Casey K, Wiseman H. Eating soya improves human memory. Psychopharmacology 2001; 157(4): 430-6.
[223]
Kelly GE, Joannou GE, Reeder AY, Nelson C, Waring MA. The variable metabolic response to dietary isoflavones in humans Proc Soc Exp Biol Med (New York, NY) 1995; 208(1): 40-3
[224]
Igase M, Igase K, Tabara Y, Ohyagi Y, Kohara K. Cross-sectional study of equol producer status and cognitive impairment in older adults. Geriatr Gerontol Int 2017; 17(11): 2103-8.
[225]
Henderson VW, St John JA, Hodis HN, et al. Long-term soy isoflavone supplementation and cognition in women: A randomized, controlled trial. Neurology 2012; 78(23): 1841-8.
[226]
Gleason CE, Carlsson CM, Barnet JH, et al. A preliminary study of the safety, feasibility and cognitive efficacy of soy isoflavone supplements in older men and women. Age Ageing 2009; 38(1): 86-93.
[227]
Gleason CE, Fischer BL, Dowling NM, et al. Cognitive Effects of Soy Isoflavones in Patients with Alzheimer’s Disease. J Alzheimers Dis 2015; 47(4): 1009-19.
[228]
Vazquez L, Guadamuro L, Giganto F, Mayo B, Florez AB. Development and use of a real-time quantitative pcr method for detecting and quantifying equol-producing bacteria in human faecal samples and slurry cultures. Front Microbiol 2017; 8: 1155.
[229]
Akaza H, Miyanaga N, Takashima N, et al. Is daidzein non-metabolizer a high risk for prostate cancer? A case-controlled study of serum soybean isoflavone concentration. Jpn J Clin Oncol 2002; 32(8): 296-300.
[230]
Ozasa K, Nakao M, Watanabe Y, et al. Serum phytoestrogens and prostate cancer risk in a nested case-control study among Japanese men. Cancer Sci 2004; 95(1): 65-71.
[231]
Kurahashi N, Iwasaki M, Inoue M, Sasazuki S, Tsugane S. Plasma isoflavones and subsequent risk of prostate cancer in a nested case-control study: The Japan Public Health Center. J Clin Oncol 2008; 26(36): 5923-9.
[232]
Kunisue T, Tanabe S, Isobe T, Aldous KM, Kannan K. Profiles of phytoestrogens in human urine from several Asian countries. J Agric Food Chem 2010; 58(17): 9838-46.
[233]
Shimazu T, Inoue M, Sasazuki S, et al. Plasma isoflavones and the risk of lung cancer in women: a nested case-control study in Japan. Cancer Epidemiol Biomarkers Prev 2011; 20(3): 419-27.
[234]
Miyanaga N, Akaza H, Hinotsu S, et al. Prostate cancer chemoprevention study: An investigative randomized control study using purified isoflavones in men with rising prostate-specific antigen. Cancer Sci 2012; 103(1): 125-30.
[235]
Hozawa A, Sugawara Y, Tomata Y, et al. Relationship between serum isoflavone levels and disability-free survival among community-dwelling elderly individuals: Nested case-control study of the Tsurugaya project. J Gerontol A Biol Sci Med Sci 2013; 68(4): 465-72.
[236]
Michikawa T, Inoue M, Sawada N, et al. Plasma isoflavones and risk of primary liver cancer in Japanese women and men with hepatitis virus infection: A nested case-control study. Cancer Epidemiol Biomarkers Prev 2015; 24(3): 532-7.
[237]
Takeda T, Ueno T, Uchiyama S, Hiramatsu K, Shiina M. Relation between premenstrual syndrome and equol-production status. J Obstet Gynaecol Res 2016; 42(11): 1575-80.
[238]
Liu ZM, Ho SC, Chen YM, Liu J, Woo J. Cardiovascular risks in relation to daidzein metabolizing phenotypes among Chinese postmenopausal women. PLoS One 2014; 9(2): e87861.
[239]
Nagata Y, Sugiyama Y, Fukuta F, et al. Relationship of serum levels and dietary intake of isoflavone, and the novel bacterium Slackia sp. strain NATTS with the risk of prostate cancer: A case-control study among Japanese men. Int Urol Nephrol 2016; 48(9): 1453-60.
[240]
Grace PB, Taylor JI, Low YL, et al. Phytoestrogen concentrations in serum and spot urine as biomarkers for dietary phytoestrogen intake and their relation to breast cancer risk in European prospective investigation of cancer and nutrition-norfolk. Cancer Epidemiol Biomarkers Prev 2004; 13(5): 698-708.
[241]
Peeters PH, Slimani N, van der Schouw YT, et al. Variations in plasma phytoestrogen concentrations in European adults. J Nutr 2007; 137(5): 1294-300.
[242]
Newton KM, Reed SD, Uchiyama S, et al. A cross-sectional study of equol producer status and self-reported vasomotor symptoms. Menopause 2015; 22(5): 489-95.
[243]
Reverri EJ, LaSalle CD, Franke AA, Steinberg FM. Soy provides modest benefits on endothelial function without affecting inflammatory biomarkers in adults at cardiometabolic risk. Mol Nutr Food Res 2015; 59(2): 323-33.


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 15
ISSUE: 2
Year: 2019
Page: [114 - 135]
Pages: 22
DOI: 10.2174/1573403X15666181205104717

Article Metrics

PDF: 62
HTML: 12
EPUB: 1
PRC: 1