Dietary Creatine and Hydration Biomarkers in the General Population: <scp>NHANES</scp> 1999–2023

Creatine is widely recognized for its performance-enhancing and neuroprotective properties; however, its impact on hydration status at the population level remains poorly understood. This study investigated the relationship between dietary creatine intake and hydration biomarkers in a nationally representative sample derived from the National Health and Nutrition Examination Survey (NHANES). Data from the biannual 1999 and 2023 NHANES cycles were harmonized and analyzed, including dietary recall data and hydration biomarkers such as plasma osmolality, urine specific gravity (USG), total body water (TBW), intracellular fluid (ICF), and extracellular fluid (ECF) volumes. Valid data on dietary creatine intake were obtained from 98,681 participants, with serum osmolality measured in 69,144 individuals, fluid volumes assessed in 12,369, and USG evaluated in 6274 respondents. Total daily dietary creatine intake was expressed in milligrams per kilogram of body mass and categorized into quantiles. Associations were evaluated using multivariate regression models, adjusted for potential confounders, including gender, age, daily intake of caffeine, alcohol, sodium, water, protein, and total caloric intake. Both the lowest and highest creatine intake quantiles were significantly associated with altered plasma osmolality levels and an increased prevalence of hypoosmolality (<i>p</i> < 0.01), relative to moderate creatine intake (4.27-10.19 mg/kg). Higher creatine intake was also associated with reduced TBW, ICF, and ECF volumes (<i>p</i> < 0.01). Notably, a significantly lower risk of hypoosmolality was observed in the 50th percentile (OR = 0.861; <i>p</i> = 0.035) and the 75th percentile (OR = 0.832; <i>p</i> = 0.010) of creatine intake. Our findings challenge the prevailing notion that dietary creatine universally enhances hydration. While moderate intake from regular foods appears to have a neutral effect, higher intake levels may disrupt systemic fluid balance. Further research is warranted to explore the underlying physiological mechanisms and evaluate the long-term effects of creatine intake on hydration homeostasis.