Blueberries and raspberries as endocrine modulators: Mechanisms, clinical evidence, and translational guidance

Resumen

Endocrine pathways are increasingly recognized as important targets for preventive and adjunctive care. Blueberries (Vaccinium spp.) and raspberries (Rubus spp.) are particularly rich in anthocyanins, ellagitannins, and related flavonoids with hormone-modulating properties. Recent evidence from mechanistic and clinical studies, particularly in 2023–2024, suggests that berry-derived bioactives impact estrogen receptors, insulin signaling, and the hypothalamic–pituitary–adrenal (HPA) axis. Yet issues of bioavailability, microbiome conversion, and dosing remain insufficiently integrated.

Key findings highlight selective estrogen receptor modulator–like activity that improves estrogen metabolism and menopausal health; enhanced insulin sensitivity via AMPK activation, insulin receptor signaling, and α-amylase/α-glucosidase inhibition; and HPA axis modulation with reduced cortisol exposure and improved circadian rhythms. Clinical trials in peri- and postmenopausal women report better sleep, mood, and hot-flash outcomes, while pilot studies in polycystic ovary syndrome (PCOS) suggest improved insulin sensitivity and lower androgen levels. Preliminary data also indicate antioxidative and immune-modulatory effects on thyroid function.

Whole berries (≈150–200 g/day) or standardized freeze-dried equivalents consistently deliver endocrine-relevant benefits with excellent tolerability. Although plasma levels of parent anthocyanins are low, microbiome-derived metabolites such as urolithins and inter-individual variability in metabolism likely shape clinical responses.

Blueberries and raspberries act as multi-target endocrine modulators through receptor, enzyme, neuroendocrine, and microbiome-mediated mechanisms. Their routine dietary inclusion represents a practical, safe strategy to support hormonal balance across life stages. Large-scale trials remain essential to define effective dosing, compare whole fruits versus extracts, and explore personalized nutrition approaches.

Novelty: This study is among the first to integrate mechanistic, clinical, and translational evidence on blueberries and raspberries as endocrine modulators. Unlike prior research focusing on single pathways, we highlight their combined effects on estrogen receptors, insulin signaling, and the HPA axis, while also considering microbiome-derived metabolites such as urolithins. By synthesizing recent 2023–2024 findings, this work reframes these berries as clinically relevant functional foods with the potential to support menopausal health, PCOS, and broader hormonal balance.

Keywords: flavonoids; anthocyanins; ellagitannins; endocrine function; blueberries; raspberries; phytochemicals; insulin sensitivity; stress hormones