Isoflavone Soy Protein Supplementation and Atherosclerosis Progression in Healthy Postmenopausal Women: A Randomized Controlled Trial

Randomized, placebo-controlled trial in healthy postmenopausal women without diabetes or cardiovascular disease. The ISP arm randomized 175 participants; 162 were analyzed for CIMT progression and 144 completed the initial 2.5-year trial. Participants were recruited from the general population in the Greater Los Angeles area, with mean baseline age 60.8 (7.2) years.

Isoflavone soy protein was administered orally as 25 g twice daily for a total of 50 g/day for 2.7 years, delivered in beverage powder-food packs or food bars versus placebo. The active regimen provided 91 mg aglycon equivalents of isoflavones per day (154 mg total isoflavone conjugates plus aglycons), including genistein 52 mg, daidzein 36 mg, and glycitein 3 mg aglycon equivalents.

Isoflavone soy protein did not significantly slow carotid intima-media thickness progression overall. CIMT progression rates were 4.77 (3.39-6.16) mm/year in the ISP group and 5.68 (4.30-7.06) mm/year in placebo, for a between-group difference of -0.91 (-2.86 to 1.05; P = 0.36). A predefined subgroup randomized within 5 years of menopause showed a possible benefit: difference -4.62 (-9.21 to -0.04; P = 0.05), with a similar trend in Asian participants. The intervention was reported as safe and well tolerated, with no major adverse events attributable to ISP, although respiratory symptoms were more frequent and 1 stroke occurred in an ISP participant.

The overall effect was null, and the apparent benefit was limited to subgroup analyses that are vulnerable to chance findings and reduced power. Follow-up and completion were imperfect, with 162 analyzed for CIMT progression and 144 completing the initial trial, and the population was restricted to healthy postmenopausal women from one U.S. region, limiting generalizability. The optional extended visit and multiple subgroup comparisons further complicate interpretation.