Data Sheet 1_A systematic review of prospective evidence linking non-alcoholic fermented food consumption with lower mortality risk.docx

Fermented foods are consumed worldwide and are increasingly being studied for their potential health benefits. Although their consumption is widespread, their association with long-term health outcomes such as mortality risk remains unclear. The aim of this systematic review was to assess the association between the consumption of fermented foods and risk of all-cause, cardiovascular, and cancer-related mortality in generally healthy adult populations in accordance with the European Food Safety Authority (EFSA) framework for the substantiation of health claims. A comprehensive literature search identified prospective cohort studies from 1970 to 2025 that investigated the association between fermented food consumption and mortality outcomes. Risk of bias was assessed using the Newcastle-Ottawa Scale, and strength of evidence was evaluated based on study quality, sample size, and precision within a structured narrative framework that also classified the direction of association across categories. A complementary non-systematic review examined the compositional characteristics, mechanisms of action, and potential health risks associated with fermented foods. Fifty-two cohort studies were included. Fermented milk products (including yogurt), chocolate, and fermented soy products (particularly natto) suggested a modest inverse association with all-cause and cardiovascular mortality. Cheese was associated with reduced all-cause mortality in some studies, but it showed inconsistent effect on cardiovascular mortality. The evidence for cancer-related mortality was weaker, although yogurt and fermented milk displayed some protective trends. Evidence from a single cohort suggested a potential reduction in all-cause mortality with fermented vegetable consumption, whereas fermented meat suggested no clear association with mortality. Biological plausibility was supported by fermentation-derived compounds such as bioactive peptides, polyphenols, isoflavones, natto-kinase, and vitamin K2. Habitual consumption of certain fermented foods may be associated with modest reductions in mortality risk, but the current evidence remains insufficient to support EFSA-approved health claims. Randomized controlled trials are essential to demonstrate causality. While long-term trials with mortality endpoints are not feasible, studies targeting intermediate outcomes linked to mortality offer a practical alternative. These should be complemented by observational studies to capture long-term, real-world associations. Together, such efforts support the objectives of the COST Action PIMENTO (CA20128) in building a more robust evidence base on fermented foods and health.
Systematic review registrationThe protocol for this systematic review was registered with the Open Science Framework (OSF; registration ID: vg7f6; https://osf.io/vg7f6).