Dietary (poly)phenols as modulators of natural killer cell function and immunosenescence: From molecular pathways to clinical evidence

Acharya et al., 2026 | Phytomedicine | Systematic Review

Citation

Acharya Asmita, Mazzola Giuseppe, ... Perna Simone. Dietary (poly)phenols as modulators of natural killer cell function and immunosenescence: From molecular pathways to clinical evidence. Phytomedicine. 2026-Feb;151:157814. doi:10.1016/j.phymed.2026.157814

Abstract

BACKGROUND: Aging is characterized by immunosenescence, involving the decline of Natural Killer (NK) cell function and persistent low-grade inflammation, increasing susceptibility to age-related diseases. Dietary polyphenols have emerged as potential agents to mitigate this decline and enhance immune responses. OBJECTIVE: This systematic review aims to synthesize current evidence on the capacity of dietary polyphenols to modulate Natural Killer (NK) cell plasticity and counteract immunosenescence, offering insights into their potential as therapeutic interventions for healthy aging. METHODS: Adhering to PRISMA guidelines, studies investigating NK cells in human, animal, or in vitro aging models, with interventions involving polyphenols or plant extracts, and reporting outcomes such as NK cytotoxicity, cytokine production, senescence markers, or inflammation, were included. Non-English, non-primary research, or studies lacking data on polyphenol-NK interactions were excluded. A comprehensive search was conducted across PubMed, Embase, Web of Science, Scopus, and Cochrane Library from 2010 to June 2025. Risk of bias was assessed using SYRCLE's tool for preclinical studies, Cochrane RoB 2 for clinical trials, and standardized protocols for in vitro studies. RESULTS: 19 studies were included for qualitative and quantitative synthesis. Findings consistently demonstrate that various polyphenols (e.g., resveratrol, verbenalin, catechins, quercetin, polyphenol-rich blueberry extracts) enhance NK cell activation and cytotoxicity, modulate T cell subsets, and improve innate immune functions like phagocytosis and chemotaxis across in vitro, animal, and human models. While in vitro studies generally exhibited a low risk of bias, most in vivo studies were classified with "some concerns" due to reporting limitations in their methodology. CONCLUSION: Polyphenols exhibit significant dose- and context-dependent immunomodulatory roles, particularly in enhancing NK cell function and mitigating immunosenescence. While preclinical data are promising, further clinical trials addressing bioavailability challenges and interindividual variability are crucial to translating these findings into effective and personalized dietary and therapeutic strategies for promoting immune health in aging populations.

Key Findings

19 studies were included for qualitative and quantitative synthesis. Findings consistently demonstrate that various polyphenols (e.g., resveratrol, verbenalin, catechins, quercetin, polyphenol-rich blueberry extracts) enhance NK cell activation and cytotoxicity, modulate T cell subsets, and improve innate immune functions like phagocytosis and chemotaxis across in vitro, animal, and human models. While in vitro studies generally exhibited a low risk of bias, most in vivo studies were classified

Outcomes Measured

• Requires manual extraction

Population

MeSH Terms

• Killer Cells, Natural
• Humans
• Polyphenols
• Immunosenescence
• Animals
• Plant Extracts
• Aging
• Diet

Evidence Classification

• Level: Systematic Review
• Publication Types: Journal Article, Systematic Review
• Vertical: quercetin

Provenance

• PMID: 41544470
• DOI: 10.1016/j.phymed.2026.157814
• PMCID: Not in PMC
• Verified: 2026-04-09 via PubMed E-utilities API

Source extracted via PubMed E-utilities API on 2026-04-09