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We investigated the associations of urinary phytoestrogens with serum uric acid concentrations and hyperuricemia risk in a nationally representative U.S. population and explored the potential effect modification by smoking status. This study included 8,160 participants aged 20 years and older from the 1999\u20132010 National Health and Nutrition Examination Survey (NHANES). Urinary concentrations of phytoestrogens were determined using high-performance liquid chromatography\u2013tandem mass spectrometry and adjusted for urinary creatinine. Multivariable linear and logistic regression models were employed to evaluate associations with serum uric acid levels and hyperuricemia risk, while restricted cubic splines were applied to examine nonlinear dose-response relationships. Following multivariable adjustment, higher urinary concentrations of total phytoestrogens, isoflavones, lignans, and several specific compounds were linked to a lower risk of hyperuricemia. The strongest associations were exhibited for microbial metabolites, including equol [OR (95% CI) for quartile 4 vs. 1: 0.46 (0.35, 0.59)], enterolactone [0.60 (0.49, 0.74)], and O-desmethylangolensin (O-DMA) [0.64 (0.51, 0.79)]. These inverse associations were more pronounced among current smokers (p-interaction for total phytoestrogens and isoflavones\u2009=\u20090.019) and largely followed L-shaped dose\u2013response patterns. This study suggested that elevated urinary phytoestrogen levels were associated with a reduced risk of hyperuricemia in U.S. adults, particularly among current smokers. If confirmed by prospective studies, phytoestrogen-rich diets may represent a promising strategy for hyperuricemia prevention.<\/jats:p>","DOI":"10.1038\/s41598-026-45911-5","type":"journal-article","created":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T12:46:06Z","timestamp":1778071566000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Urinary phytoestrogens and hyperuricemia risk in a nationally representative population: an effect modified by smoking status"],"prefix":"10.1038","volume":"16","author":[{"given":"Chunliang","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huizhi","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengrou","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaying","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinliang","family":"Niu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"45911_CR1","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1038\/s41392-024-01916-y","volume":"9","author":"L Du","year":"2024","unstructured":"Du, L. et al. 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