Bioactive compounds for mitigating dietary methylmercury exposure: A review of bioaccessibility, toxicokinetics, and cellular damage

Methylmercury (MeHg) is a potent neurotoxicant that biomagnifies through aquatic food webs and accumulates at particularly high concentrations in large, long-lived predatory fish. As such, fish is the primary source of MeHg exposure in most people’s diets. However, seafood is culturally significant in many diets and provides high-quality protein, omega-3 fatty acids, and essential micro- and macronutrients. Identifying functional foods or bioactive compounds that reduce MeHg bioaccessibility or absorption, promote its elimination, or mitigate its toxicity could ameliorate MeHg-induced damage while preserving the nutritional and cultural benefits of seafood consumption. This review aims to identify a series of promising functional foods and bioactive compounds with the potential to reduce MeHg absorption, body burden, or toxicity. It examines interventions that reduce MeHg bioaccessibility or absorption, alter MeHg metabolism or excretion, or possess cytoprotective properties that decrease the risk of MeHg-induced damage. PubMed was searched in August 2026 using combinations of methylmercury, mercury, probiotics, selenium, sulfur, antioxidants, polyphenols, bioaccessibility, and toxicity. The search returned 1,482 results from the preceding ten years. Recent studies were prioritized, with foundational papers and additional studies identified through reference lists also considered. Evidence included reviews, in vitro experiments, animal studies, human observational studies, and clinical trials. Selected inorganic mercury studies were retained when they provided mechanistic evidence relevant to MeHg mitigation. Probiotics, tea polyphenols, sulfur-containing compounds, and certain dietary fibers demonstrated mercury binding, reduced concentrations of soluble MeHg, decreased epithelial transport, or increased fecal excretion. Probiotic interventions were found to alter MeHg accumulation or excretion in animal models, while selenium supplementation was shown to increase urinary mercury excretion in humans primarily exposed to inorganic mercury. Antioxidant and anti-inflammatory bioactives, including sulforaphane, curcumin, quercetin, selenium, and tea polyphenols, reduced mercury-induced oxidative stress, inflammation, mitochondrial dysfunction, and tissue injury in preclinical models involving either MeHg or inorganic mercury. The available evidence identifies probiotic approaches, co-ingested tea polyphenols, and carefully dosed selenium as leading candidates for mitigating MeHg absorption or toxicity. However, much of the research remains limited to in vitro and preclinical studies. Additional in vivo and human research using realistic dietary MeHg exposure is therefore required before these interventions can be incorporated into evidence-based functional foods for MeHg risk reduction. Novelty of study: This review compares bioactive compounds from three categories: those that reduce MeHg bioaccessibility, those that alter mercury kinetics and metabolism, and those that protect against tissue damage. By distinguishing reductions in mercury body burden from protection against mercury-induced injury, the review identifies the most promising candidates for preventive use alongside seafood consumption and highlights the evidence needed to translate them into human dietary strategies, including potential future functional food applications. Although previous papers have examined these mechanisms individually, this review unites these approaches by explaining the importance of each of them for reducing MeHg toxicity and how they can be applied together. This review evaluates how the available evidence can support dietary interventions in humans, and where further research is required. Keywords: Methylmercury; functional foods; bioactive compounds; mercury bioaccessibility; gastrointestinal absorption; mercury toxicokinetics; gut microbiome; oxidative stress