What does this research mean for the field?

Polyphenol supplementation in postmenopausal women increases circulating lipids but improves LDL particle quality and reduces LDL oxidation, with the extent of the benefit depending on age and gut microbiota metabotypes. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

The aim was to investigate how polyphenols affect lipid profiles and LDL oxidation in postmenopausal women.

July 1, 2026European Journal of Nutrition0 citationsOpen Access

Polyphenols increase circulating lipids but improve LDL particle quality and reduce LDL oxidation in postmenopausal women: metabotype- and age-dependent effects in a randomised, placebo-controlled crossover trial

MGMaría García-NicolásCentro de Edafología y Biología Aplicada del Segura MJMaría Paula Jarrín‐OrozcoCentro de Edafología y Biología Aplicada del Segura MRMaría Romo‐VaqueroCentro de Edafología y Biología Aplicada del Segura

Key Points

The aim was to investigate how polyphenols affect lipid profiles and LDL oxidation in postmenopausal women.
Randomized, placebo-controlled, crossover design with 90 mildly hypercholesterolemic postmenopausal women.
Participants received polyphenol supplementation or placebo for 8 weeks followed by a washout and 8-week placebo period.
Lipid profiles, inflammatory markers, and gut microbiota metabotypes were analyzed.
Total cholesterol, LDL cholesterol, and triglycerides increased by 7%, 9.5%, and 16% respectively (p < 0.001).
Oxidised LDL decreased significantly (p < 0.001), and ratios indicating LDL oxidation quality improved.
The strongest reduction in oxidised LDL was observed in equol producers (65%, p < 0.001).

Abstract

PURPOSE: Menopause increases cardiometabolic risk via dyslipidaemia, oxidative stress, and low-grade inflammation. Polyphenols may modulate these processes, but human evidence is inconsistent. We investigated the effects of polyphenol supplementation on lipid profile, LDL oxidation, and polyphenol-related gut microbiota metabotypes in postmenopausal women. METHODS: In the PolyPAUSE randomised, placebo-controlled, crossover trial, 90 mildly hypercholesterolemic, non-medicated postmenopausal women received a daily polyphenol mixture providing ellagitannins+ellagic acid (312.0 ± 30.9 mg), resveratrol (133.2 ± 10.1 mg), and isoflavones (166.3 ± 27.3 mg) for 8 weeks, followed by a 4-week washout and an 8-week placebo period. Serobiochemical and bone-related markers were analysed at hospital laboratories. Apolipoprotein B (ApoB), oxidised LDL (oxLDL), and lipopolysaccharide-binding protein (LBP) were measured by ELISA, and myeloperoxidase activity by spectrophotometry. Gut microbiota metabotypes were classified as urolithin A/B (UMA/UMB), equol producers/non‑producers (EP/ENP), and lunularin producers/non‑producers (LP/LNP) using UPLC‑ESI‑QTOF‑MS. RESULTS: Polyphenol supplementation did not affect LBP or bone markers. Total cholesterol (Tchol), LDL-cholesterol (LDLc), and triglycerides (TGs) increased by 7%, 9.5%, and 16%, respectively (p < 0.001) in ~ 80% of completers (n = 78), with age‑related increases. ApoB showed a borderline reduction (p = 0.056), and oxLDL decreased (p < 0.001). Ratios indicating LDL particle quality and oxidative burden (LDLc/ApoB, oxLDL/LDLc, oxLDL/ApoB) improved (p < 0.001) despite higher circulating lipid concentrations. Myeloperoxidase activity showed marginal decreases in the full cohort (p = 0.08) and in LNP (p = 0.06). Metabotyping showed that the strongest oxLDL reduction occurred in EP (65%, p < 0.001) and the UMA + EP+LNP cluster (60%, p < 0.001). CONCLUSION: Polyphenol supplementation increased Tchol, LDLc, and TGs age-dependently, yet improved LDL oxidative quality. The extent of oxLDL reduction depended on metabotypes, supporting precision health approaches to better characterise cardiometabolic responses to polyphenol intake in postmenopausal women.

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