Abstract
Cholelithiasis affects 10–20% of adults globally, and while cheese consumption may influence risk, underlying biological pathways remain unclear. In this prospective cohort study of 399,467 UK Biobank participants without prior cholelithiasis, we examined cheese intake frequency (never to ≥1/day) via baseline food-frequency questionnaires and identified incident cholelithiasis through hospital records, primary care data, and self-reports. Multivariable COX regression and causal mediation analyses assessed risk associations and mediation by cholesterol subtypes. Over follow-up, 15,897 participants developed cholelithiasis. Higher cheese intake showed a dose-dependent inverse association, with daily consumers having 26.3% lower odds (adjusted OR = 0.737, 95% CI: 0.653–0.832) versus non-consumers. HDL-C significantly mediated this association (proportion mediated: 4.03–6.98%). Frequent cheese consumption was associated with significantly lower cholelithiasis risk, partially mediated by HDL-C, suggesting a potential dietary strategy for prevention, though residual confounding and mechanisms require further investigation.
Data availability
This research was conducted using the UK Biobank resource under Application Number [456996]. The data are available to approved researchers through the UK Biobank access process (https://www.ukbiobank.ac.uk/). Restrictions apply to the availability of these data, which were used under license for the current study.
Code availability
Code supporting this study is available from the corresponding author upon reasonable request.
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Acknowledgements
We are grateful to the UK Biobank participants and the UK Biobank team for their dedication and contribution to this research. This research was conducted using the UK Biobank resource under Application Number 456996. Funding was provided by the Central Incentive Fund for Regional S&T Development (grant no. 25ZYJA024).
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The study was designed by Wenwen Yang and Rui Ji. Statistical analyses were performed by Wenwen Yang and Rui Ji. The manuscript was written by Wenwen Yang, Zhixian Bao, Yuhua Chen, Jie Gao, and Rui Ji. All authors contributed to the interpretation of data and commented on the manuscript. All authors read and approved the manuscript.
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Yang, W., Bao, Z., Chen, Y. et al. Cheese consumption and lower cholelithiasis risk a prospective UK biobank study with HDL-C mediation. npj Sci Food (2026). https://doi.org/10.1038/s41538-025-00644-z
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DOI: https://doi.org/10.1038/s41538-025-00644-z
