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Beneficial effects of soy supplementation on postmenopausal atherosclerosis are dependent on pretreatment stage of plaque progression

Meléndez, Giselle C. MD1; Register, Thomas C. PhD1; Appt, Susan E. DVM1; Clarkson, Thomas B. DVM1; Franke, Adrian A. PhD2; Kaplan, Jay R. PhD1

doi: 10.1097/GME.0000000000000307
Original Articles

Objective The objective of this study was to use a well-established monkey model of atherosclerosis to determine how life stage and preexisting atherosclerosis influence the effectiveness of high-isoflavone soy diet in inhibiting progression of atherosclerosis.

Methods For 34 months, premenopausal monkeys were fed an atherogenic diet, with protein derived primarily from either animal sources (casein-lactalbumin [CL], n = 37) or high-isoflavone soy beans (Soy, n = 34). Animals were ovariectomized and randomized to groups fed the same diet (CL-CL, n = 20; Soy-Soy, n = 17) or an alternate diet (CL-Soy, n = 17; Soy-CL, n = 17) for an additional 34 months. At ovariectomy, the left common iliac artery was removed to determine the amount of premenopausal atherosclerosis. At necropsy, the right common iliac artery and coronary arteries were collected, and atherosclerosis extent was quantified. CL-CL condition was considered “control.”

Results Modeling Asian women who remain in Asia, monkeys fed soy protein both premenopausally and postmenopausally had a markedly reduced extent of coronary artery atherosclerosis relative to CL controls (P = 0.008). The subset of animals that modeled Asian women who migrate to a Western country (consuming soy premenopausally and CL postmenopausally) had increased progression of postmenopausal iliac artery atherosclerosis (P = 0.003) and was not protected against the development of coronary artery atherosclerosis relative to controls. Relevant to the administration of soy diets to postmenopausal Western women, monkeys fed CL premenopausally and switched to soy postmenopausally derived atheroprotective benefits only if they began the postmenopausal treatment period with relatively small (below the median) plaques. Relative to controls, this group (with small plaques at ovariectomy) had reduced progression of iliac atherosclerosis (P = 0.038) and smaller coronary artery plaques (P = 0.0001) that were less complicated (P = 0.05) relative to controls.

Conclusions The results suggest that significant atheroprotective benefits of dietary soy are derived from treatment that begins premenopausally and continues postmenopausally or from treatment that is started during early postmenopause (when plaques are still small).

From the 1Department of Pathology/Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC; and 2University of Hawaii Cancer Center, Honolulu, HI.

Received March 25, 2014; revised and accepted June 17, 2014.

Funding/support: This project was supported by National Institutes of Health grants HL45666 and HL079421 (J.R.K.).

Financial disclosure/conflicts of interest: G.C.M. received support as a Wake-Merck Cardiovascular Research Fellow by an education grant from Merck Pharmaceuticals.

Address correspondence to: Giselle C. Meléndez, MD, Department of Pathology/Comparative Medicine, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040. E-mail:

© 2015 by The North American Menopause Society.