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Isoflavones, equol producing status, and atherosclerosis in Japanese men in Japan

Zhang, Xiao (2022) Isoflavones, equol producing status, and atherosclerosis in Japanese men in Japan. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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Abstract

Coronary heart disease (CHD) is the leading cause of morbidity and mortality worldwide. Soy is a potential nutritional source for preventing CHD and is a standard part of the traditional Asian diet. The main components of soy that may exert cardioprotective effects are soy isoflavones (ISFs). The predominant ISFs, daidzein, and genistein are structurally similar to estradiol and mimic some effects of estrogen. Estradiol exerts its biological action by binding both estrogen receptor α (ERα) expressed in reproductive, central nervous, cardiovascular and other systems and estrogen receptor β (ERβ) expressed in cardiovascular, central nervous and other systems. ISFs, however, preferentially bind to ERβ. ISFs may reduce CHD risk by reducing inflammation and oxidation; the latter may prevent the oxidative damage to low-density lipoprotein (LDL) that contributes to atherogenesis.

Although there are clear cardiovascular benefits of ISFs in preclinical studies, evidence in humans is conflicting. Furthermore, ISFs have very small or no effects on traditional CVD risk factors. A growing hypothesis is that the ability of humans to metabolize daidzein to equol may contribute to the cardioprotective effects of ISFs. Cell culture and preclinical studies show that equol has a greater affinity for ERβ than its precursor daidzein, a longer half-life, greater bioavailability than daidzein and genistein, and more potent antioxidant activity than any other ISFs. Therefore, equol may be more cardioprotective than ISFs.

The mechanistic model of action of equol on atherosclerosis is not completely understood. Investigation of the effects of equol has primarily been conducted in the in vitro assays and preclinical studies and lacks a sturdy conclusion. In addition, very few studies have explored the association between equol-producing status and atherosclerosis in humans. In this dissertation, I first conducted a systematic review summarizing the current knowledge about the mechanisms underlying the potential cardioprotective effect of equol on inflammation, oxidation, and endothelial function. I then performed two cross-sectional analyses to delineate the link between equol producing status and aortic calcification in Japanese, a population being widely acknowledged to have a high prevalence of equol-producers.


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Details

Item Type: University of Pittsburgh ETD
Status: Unpublished
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Zhang, Xiaoxiz186@pitt.eduxiz186
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairSekikawa, Akiraakira@pitt.eduakira
Committee MemberMagnani, Jaredmagnanij@pitt.edumagnanij
Committee MemberSonger, Thomastjs@pitt.edutjs
Committee MemberBoudreau, Robertboudreaur@edc.pitt.eduboudreaur
Committee MemberBarinas-Mitchell, Emmabarinas@edc.pitt.edubarinas
Date: 4 January 2022
Date Type: Publication
Defense Date: 2 December 2021
Approval Date: 4 January 2022
Submission Date: 10 December 2021
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Number of Pages: 168
Institution: University of Pittsburgh
Schools and Programs: Graduate School of Public Health > Epidemiology
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: Atherosclerosis, isoflavone, equol, Japan
Date Deposited: 04 Jan 2022 15:14
Last Modified: 04 Jan 2022 15:14
URI: http://d-scholarship.pitt.edu/id/eprint/42061

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