Hyperuricemia, characterized by elevated serum uric acid levels, arises due to urate overproduction or its impaired excretion through the kidneys and gastrointestinal tract (1). The prevalence of hyperuricemia varies widely across populations, ranging from 8.9 to 24.4% (2–5). It serves as a major risk factor for gout (6) and is independently associated with chronic conditions, including type 2 diabetes (7), hypertension (8), metabolic syndrome (9), and chronic kidney disease (10). Various factors contribute to the onset of hyperuricemia, in addition to genetic predisposition and environmental influences, dietary habits like excessive alcohol consumption (11), high-purine diets (12), and the intake of high-fructose or sugary beverages (13) are well-established contributors to elevated serum uric acid levels. Additionally, previous studies have suggested potential associations between hyperuricemia and the intake levels of various vitamins, including vitamins C, D, E, and B1 (1, 14–16).

Retinol is an effective exogenous antioxidant and is believed to be involved in uric acid metabolism (17). Several studies have observed a positive correlation between serum retinol and uric acid levels (18–20), suggesting that higher retinol intake might elevate the risk of hyperuricemia. However, findings from retinol intake studies have been inconsistent. For instance, a study in Korea found lower dietary retinol intake in hyperuricemic individuals compared to controls (21), while a comparative study involving Australian and Norwegian cohorts reported a positive correlation between retinol intake and uric acid levels only in the Australian cohort (22). Furthermore, a cross-sectional survey in Taiwan found no significant association between retinol intake and hyperuricemia (23). These inconsistencies might be attributed to population-specific genetic variations in vitamin A metabolism (24), differences in overall dietary patterns affecting nutrient interactions (25), and varying environmental factors that influence vitamin bioavailability (26, 27). Such variations highlight the importance of population-specific investigations to better understand the relationship between retinol intake and hyperuricemia.

Given these inconsistent and limited findings on the relationship between dietary retinol intake and hyperuricemia, further research is warranted. This study aims to evaluate the relationship between dietary retinol intake and the risk of hyperuricemia in the population of Southwest China, using data from the China Health and Nutrition Survey (CHNS).

Our study reveals that increased dietary retinol intake is linked to a higher prevalence of hyperuricemia, especially in men. Additionally, a J-shaped dose–response relationship between hyperuricemia and dietary retinol was observed. This suggests that excessive intake of retinol may potentially elevate uric acid levels. Previous studies exploring the relationship between retinol intake and hyperuricemia or serum uric acid levels relied on cross-sectional analyses. Data from the 1988–1994 NHANES highlighted a positive correlation between serum retinol levels and uric acid in the U.S. adult population (19). Similarly, research conducted among Korean adults robusted the results, demonstrating that higher retinol intake was associated with elevated uric acid levels (18, 36). Moreover, the use of isotretinoin, a retinoid medication for acne treatment, has been linked to increased uric acid levels, further supporting this relationship (37). The mechanistic link between retinol levels and hyperuricemia remains inadequately elucidated. One plausible explanation involves the role of elevated serum retinol in enhancing xanthine oxidase activity. This enzyme not only catalyzes the conversion of retinol to retinoic acid but also facilitates the oxidation of xanthine, leading to increased uric acid production (38, 39). However, to our knowledge, no prospective studies have yet explored the association between individual dietary retinol intake and uric acid levels or hyperuricemia.

The gender-stratified analysis highlights a pronounced susceptibility among men to hyperuricemia associated with elevated retinol intake. This finding aligns with established literature, which underscores the pivotal role of hormonal modulation in uric acid homeostasis. Specifically, prior studies have elucidated that estrogen facilitates uric acid excretion, thereby conferring a protective advantage against hyperuricemia in premenopausal women (40, 41). Conversely, testosterone has been implicated in upregulating uric acid synthesis, potentially exacerbating the risk of hyperuricemia in men (42). These results underscore the necessity for gender-specific dietary recommendations to mitigate the risk of hyperuricemia, particularly in populations with high retinol consumption.

Dose–response analysis revealed that exceeding the recommended dietary retinol intake (3,538 IU/day for men and 4,504 IU/day for women) was linked to a higher prevalence of hyperuricemia, regardless of dietary supplement use. These values notably exceed the current recommended daily intakes of 3,000 IU for men and 2,310 IU for women (43), highlighting the potential health risks of excessive consumption. These findings are consistent with previous studies indicating that excessive vitamin A can influence metabolic pathways related to uric acid production and excretion (44). Although hypervitaminosis A is uncommon under typical dietary conditions, the rising prevalence of nutritional supplements as a primary source of vitamins raises the possibility of inadvertent overconsumption. For instance, during the 2003–2006 NHANES survey, 53% of participants reported using dietary supplements, with 33% specifically consuming multivitamin/multimineral products that often contain retinol (45). However, this pattern differs significantly in our study population from Southwest China, a lower-income region where supplement use is minimal. According to the 2010–2012 CNHS survey, only 0.71% (95% CI: 0.49–0.94%) of the Chinese population aged 6 and older reported using nutritional supplements in the past month, with usage rates in impoverished areas as low as 0.09% (46). This low prevalence reflects both economic constraints and adherence to Chinese dietary guidelines, which emphasize obtaining nutrients primarily from food sources rather than supplements (47). Given the limited supplement use in our study population, we did not include this variable in the main analysis. While this aligns with local dietary patterns, the lack of comprehensive supplement use data represents a limitation that should be addressed in future research, particularly as supplement use patterns may evolve with economic development.

Our findings contribute to the growing body of evidence supporting a positive association between retinol intake and hyperuricemia. However, the relationship appears to vary across different populations, highlighting the importance of population-specific factors in this association. For instance, studies from different regions of China have yielded varying results: while research in northern China observed a positive correlation between serum vitamin A levels and uric acid concentrations in adults (48), a cross-sectional survey in Taiwan found no significant association between retinol intake and hyperuricemia (23). Similarly, a study conducted in Korea reported lower dietary retinol intake among individuals with hyperuricemia (21). These disparate findings may be partly explained by regional dietary habits. The distinctive dietary characteristics in Southwest China, characterized by lower consumption of vegetables, fruit, and animal products, along with a higher intake of grain and oil (49), may uniquely influence both retinol intake and uric acid metabolism. Such regional variations in dietary habits underscore the importance of considering local dietary contexts when developing nutritional guidelines for hyperuricemia prevention.

Additionally, results in the present study indicate that individuals with higher retinol intake frequently consume more dark vegetables, organ meats, and fish. These consumption habits possibly reflect broader lifestyle choices that influence hyperuricemia risk. Therefore, we adjusted for potential confounders, including physical activity, smoking, and alcohol consumption, to more accurately assess the relationship between retinol intake and hyperuricemia. On the other hand, understanding the influence of lifestyle factors on retinol intake and hyperuricemia is crucial for developing effective prevention strategies. Physical activity represents another critical lifestyle factor in this relationship, as regular exercise has been shown to help maintain healthy uric acid levels (50), whereas sedentary behavior may increase hyperuricemia risk (51). These findings suggest that managing hyperuricemia requires a comprehensive lifestyle approach. Indeed, previous research has demonstrated that combined interventions incorporating balanced dietary choices, regular physical activity, limited alcohol consumption, and weight management are more effective in preventing hyperuricemia than modifications to single factors (52). This integrated approach to lifestyle management may be particularly important for individuals with elevated retinol intake, as it involves multiple pathways that influence uric acid metabolism.

In summary, this study provides valuable insights into the association between dietary retinol intake and hyperuricemia within a Southwest China population, demonstrating a significant relationship through comprehensive dietary assessments and a large, representative sample. The dose–response analysis reveals specific threshold levels associated with increased risk, while gender-stratified results highlight the need for sex-specific recommendations. Despite methodological limitations inherent to our cross-sectional design and dietary assessment methods, which preclude causal inference and may introduce recall bias, these findings make a substantial contribution to our understanding of the retinol-hyperuricemia relationship. The regional dietary patterns characteristic of Southwest China, while potentially limiting broader generalizability, offer unique insights into population-specific nutritional factors affecting hyperuricemia. Future longitudinal and experimental studies are crucial to validate these observations and elucidate underlying mechanisms, particularly focusing on population-specific dietary patterns and their impact on hyperuricemia risk.