ORIGINAL RESEARCH article

Front. Nutr.

Sec. Clinical Nutrition

Volume 12 - 2025 | doi: 10.3389/fnut.2025.1601010

Association Between Serum Carotenoid Levels and Gallstones in Adults: A Cross-Sectional Study Using the National Health and Nutrition Examination Survey

Provisionally accepted
Weirui  RenWeirui Ren1Chuang  ZhangChuang Zhang2Jie  YinJie Yin3Jingyi  RenJingyi Ren4Hongzhao  SongHongzhao Song4Xiaoya  WangXiaoya Wang4Junmin  WangJunmin Wang1*
  • 1Third Hospital of Hebei Medical University, Shijiazhuang, China
  • 2Shijiazhuang Medical College,, Shijiazhuang, Hebei Province, China
  • 3Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China
  • 4Hebei Medical University, Shijiazhuang, Hebei Province, China

The final, formatted version of the article will be published soon.

Carotenoids, known for their antioxidant properties and potential health benefits, have attracted considerable attention. Nonetheless, the association between carotenoid levels and gallstone prevalence has not been adequately explored. This study aimed to investigate the association between serum carotenoid levels and gallstone risk in an adult population. This cross-sectional study utilized the 2017-2018 NHANES data. Multivariate logistic regression analyses were performed to assess the association between serum carotenoid levels and gallstone prevalence. Subgroup and interaction analyses were conducted to confirm these findings. Additionally, generalized additive model (GAM) regression combined with smooth curve fitting techniques was utilized to clarify potential nonlinear associations, and a mediation analysis was conducted to identify possible mediators in the association between serum carotenoid levels and gallstones. This study included 3,809 participants aged ≥20 years, among whom 412 had gallstones. After adjusting for confounders (Model 3), serum carotenoid levels were inversely associated with gallstone prevalence. The participants in the highest quartile of total carotenoid levels had a 48% lower gallstone risk than those in the lowest quartile (Q4: odds ratio [OR] = 0.52, P = 0.0005).Individual carotenoids showed similar trends: α-carotene (49% lower risk, OR = 0.51, P = 0.0010), α-cryptoxanthin (54% lower risk, Q4: OR = 0.46, P < 0.0001), β-carotene (47% lower risk, Q4: OR = 0.53, P = 0.0010), β-cryptoxanthin (42% lower risk, Q4: OR = 0.58, P = 0.0061), lutein/zeaxanthin (44% lower risk, Q4: OR = 0.56, P = 0.0025), and lycopene (30% lower risk, Q4: OR = 0.70, P = 0.0441). GAM analysis detected nonlinear associations between carotenoids and gallstone risk. The subgroup and interaction analyses confirmed these results. Mediation analysis revealed that body mass index (BMI) accounted for 16.7% of the total effect. Observational data demonstrated inverse associations between serum carotenoid levels and gallstone prevalence, with BMI mediating 16.7% of the total effect. These findings suggest that maintaining high serum carotenoid levels may reduce the gallstone risk. Future studies should explore the protective mechanisms of carotenoids and validate their causal relationships using longitudinal studies.

Keywords: Serum carotenoids, Gallstones, NHANES, BMI, Cross-sectional study, Antioxidants, Inflammation, Mediation analysis

Received: 27 Mar 2025; Accepted: 23 Jun 2025.

Copyright: © 2025 Ren, Zhang, Yin, Ren, Song, Wang and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Junmin Wang, Third Hospital of Hebei Medical University, Shijiazhuang, China

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