Kidney stones are a common, costly, and painful disease, affecting about 10% of adults worldwide, with the prevalence and incidence still increasing globally1,2. Kidney stones significantly increase the risk of metabolic syndrome, cardiovascular disease and kidney failure, resulting in a huge disease burden3, 4, 5. Recent evidence showed that inflammation6 and hyperlipidemia7,8 play an important role in the pathogenesis of kidney stones. Therefore, anti-inflammatory and lipid-lowering treatments or supplements may have potential benefits for primary prevention of kidney stones.

Fish oil is a supplement with potential health benefits, including lowering blood pressure and triglycerides as well as anti-inflammatory effects9. A recent review10 reported that n-3 polyunsaturated fatty acids (PUFAs), particularly those in fish oil- eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), could produce favorable changes in urinary calcium and citrate, suggesting that fish oil may have a protective effect on kidney stone formation. However, a prospective study based on 3 large US cohorts11 found that intake of n-3 PUFAs (including fish oil supplements) was not consistently associated with the development of kidney stones in different population, indicating that increased intake of n-3 PUFAs was unlikely to reduce the risk for kidney stone formation. The possible explanations for the null findings may include, first, the low frequency of fish oil supplementation in this study11 resulted in an insufficient statistical power to identify a benefit of fish oil supplementation. Second, although genetic factors play a major role in the development of kidney stones1, the genetic risk associated with kidney stones was not considered in this study11, thus affecting the accuracy of the results. As such, to date, the association between fish oil supplementation and new-onset kidney stones remains uncertain. Whether the genetic risk of kidney stones may modify the association between fish oil supplementation and the risk of kidney stones has not been examined.

To address the above gaps in knowledge, we aimed to assess the association between regular fish oil use and new-onset kidney stones in participants with different levels of genetic risks of kidney stones, using date from the UK Biobank study.