Vitamin D, a fat-soluble sterol compound and hormone precursor, plays a critical role in various physiological functions (1). Among these, its involvement in human energy metabolism has garnered significant attention over the past decade (2). Research has shown that vitamin D status is a positive predictor of resting energy expenditure in adults, independent of obesity or metabolic syndrome (3). This has led to the hypothesis that vitamin D insufficiency or deficiency may be an independent risk factor for unfavorable metabolic phenotypes such as obesity, type 2 diabetes, and dyslipidemia — primarily supported by observational studies (4). In the Framingham Heart Study, for example, vitamin D status was inversely associated with waist circumference and visceral adipose tissue in non-diabetic individuals (5). Similar associations have been observed across various populations, including obese adults (6), healthy children (7), and older adults (8). Given this body of evidence, vitamin D supplementation has been explored as a potential strategy to improve metabolic health. However, many intervention studies have not demonstrated a causal effect of vitamin D status on obesity metrics or weight loss (9, 10). Despite this, the prevalence of poor vitamin D status among individuals with metabolic diseases highlights the need for further research into the relationship between vitamin D and energy metabolism.

There are three main limitations in research on vitamin D’s role in energy metabolism. First, while rodent models often provide valuable insights into human disease development and treatments, the effects of vitamin D metabolism on energy homeostasis differ significantly between animal and human studies (11). Given this limitation, more rigorously controlled experimental studies in humans are necessary. Second, most studies in this field rely on metabolic cart measurements to estimate whole-body energy metabolism (3, 12). Methodologically, metabolic cart-based assessments of energy expenditure and macronutrient oxidation, especially through short-term measurements, may yield inaccurate results (13). In contrast, metabolic chambers, which allow unrestricted human movement and locomotion, provide not only more accurate measurements but also a better representation of real-life energy metabolism. Yet, the high costs and demanding research conditions (e.g., 24-hour observation) associated with metabolic chambers pose significant challenges. To our knowledge, studies in this area using metabolic chambers are scarce. Given the sensitivity needed to detect small yet meaningful effects of vitamin D on physiological functions, more studies utilizing metabolic chambers are required. Third, vitamin D deficiency and essential mineral deficiencies in general are common worldwide (14), affecting not only obese populations but also healthy individuals. From a preventive medicine perspective, understanding vitamin D’s role in energy metabolism among healthy individuals is of significant public health interest. In vitamin D-sufficient young adults, for example, additional vitamin D supplementation has been shown to have no effect on resting energy expenditure (12). As outlined above, due to the limited data from representative 24-hour energy metabolism studies, there are currently no conclusive guidelines to determine vitamin D requirements for metabolic health in the general population. Specifically, data on young individuals with vitamin D insufficiency or deficiency remain scarce.

Therefore, the purpose of this study was to explore the impact of vitamin D status, measured by 25-hydroxyvitamin D (25(OH)D), on energy expenditure and substrate oxidation in young, healthy, non-obese adults. To address the limitations of previous research, a metabolic chamber was utilized to measure energy metabolism over a 24-hour period during typical daily activities. The findings are expected to provide new insights into the effects of vitamin D status on metabolic health in the general population.

Based on the two-way ANOVA, no significant interaction effect was detected, with F-test values ranging from 0.22 to 2.52 and p-values between 0.22 and 0.95. Therefore, we can conclude that seasonality did not influence the primary outcomes of this study. A one-way ANOVA was used to assess the main effect of 25(OH)D status, and Figures 2 and 3 illustrate energy metabolism across the three groups. In summary, neither energy expenditure nor substrate oxidation rates were significantly affected by 25(OH)D status, even after adjusting energy metabolism for fat-free mass (as shown in Figure 2 ), body weight (not shown here), or muscle mass (not shown here). The main effect of seasonality is detailed in Table 3 , where participants tested in the spring exhibited significantly higher values across most energy metabolism metrics.

Table 4 summarizes the correlations between 25(OH)D status and the lipid profile. Although statistically significant relationships were observed for total cholesterol, high-density lipoprotein, and free fatty acid, these correlations were weak.

In a group of young, healthy, non-obese adults, we demonstrate that total 25(OH)D status does not influence energy expenditure or lipid profiles typically associated with overweight and obesity. A novel aspect of this study is that the findings are based on 24-hour continuous measurements of typical human activities conducted in a metabolic chamber. The comprehensiveness of this data set provides new insights into the role of vitamin D in human energy metabolism.

In rodent models, vitamin D receptor-null or vitamin D-deficient mice exhibit an enhanced rate of fatty acid β-oxidation in white adipose tissue and reduced lipid accumulation in the liver, both of which are beneficial for weight management (18, 19). However, it is now clear that these results are not transferable to humans. A substantial body of literature demonstrates an inverse relationship between circulating 25(OH)D levels and fat mass in children (20), adults (21), and even athletes (22). Emerging cellular evidence suggests a potential causal relationship (23), leading to new hypotheses that propose vitamin D status could serve as an adjuvant therapy for unfavorable metabolic phenotypes (24, 25). This existing research prompted the present study, which aimed to clarify the relationship between vitamin D status and human energy metabolism. However, none of the key metrics — energy expenditure or substrate oxidation — differed among non-obese adults with deficient, insufficient, or sufficient 25(OH)D status. Similarly, the significant yet weak correlations between 25(OH)D status and lipid profile do not provide conclusive evidence regarding vitamin D’s role in body weight regulation. To our knowledge, this is the first study to report negative evidence under controlled metabolic chamber conditions.

Despite the well-established inverse association between 25(OH)D status and obesity, our findings suggest that low vitamin D status may not be the cause of unfavorable metabolic phenotypes but rather a consequence. This helps explain the conflicting results between observational and intervention studies (9). Several plausible explanations support this notion. First, aside from dietary sources and supplementation, sun exposure is the main contributor to endogenous cholecalciferol production in the skin. Overweight and obese individuals, often due to low mobility and motivation, engage in less outdoor physical activity (26, 27), which limits natural vitamin D synthesis. Second, overweight and obesity disrupt adipose tissue homeostasis and induce hepatic dysfunction, both of which can affect vitamin D metabolism. In obese individuals, the expression of the cytochrome P450 gene family — the primary 25(OH)D hydroxylase — is down-regulated (28, 29), interfering with downstream circulating 25(OH)D activity. Evidence from obese patients undergoing gastric bypass surgery demonstrates that obesity impacts vitamin D metabolizing enzyme expression in the liver, indicating that being overweight leads to lower 25(OH)D status rather than the reverse (30). Relatedly, since vitamin D is fat-soluble and stored in adipose tissue, individuals with higher adiposity tend to have lower circulating 25(OH)D levels (31) and exhibit a blunted response to vitamin D supplementation (32). Our findings align with the theory that low 25(OH)D status is a result of unfavorable metabolic phenotypes (33), suggesting that non-obese, metabolically active young individuals are unlikely to develop overweight solely due to vitamin D deficiency. Given the potential adverse effects of large doses of vitamin D supplementation (34), healthy young individuals are not advised to take additional vitamin D solely for weight management purposes.

Of note, only 20% of participants met the Chinese standard for vitamin D sufficiency. This poor vitamin D status is consistent with epidemiological studies from other regions in China (35, 36). Vitamin D status is linked to a wide range of health benefits, including immunity (37), epigenetics, and gene regulation, particularly in the context of healthy aging (38). Our participants may lack not only professional knowledge about the benefits of vitamin D but also the resources to regularly check their vitamin D status. From a population management perspective, we recommend that the government include vitamin D status assessments in residents’ optional annual medical check-ups. Furthermore, we suggest that school-aged adolescents be required to complete a mandatory health course covering nutrition, health behavior, and other essential life skills.

Additionally, it is important to note that while seasonality does not affect the main conclusions of the study, participants enrolled during the spring season exhibited significantly higher energy expenditure and substrate oxidation rates. Although all participants were recruited from the Shanghai University of Sport, they are not all alike. For example, ball sports athletes may have elevated daily energy metabolism. As a result, certain group of participants who took part in the experiment during spring may have higher basal metabolic rate. This seasonal effect could create a misleading impression that the general population’s energy metabolism is higher in the spring.

Several limitations apply to our study. First and foremost, the results should be interpreted with caution due to the current analytical approach to measuring 25(OH)D. Similar to steroid hormones (39), 25(OH)D is transported in the blood by vitamin D binding protein and albumin, with only a small fraction of free 25(OH)D entering most cells and exerting physiological functions (40). Therefore, measuring only total 25(OH)D may not accurately reflect an individual’s true vitamin D status, particularly in those with higher body mass index (41). As such, free 25(OH)D may provide a more accurate assessment of vitamin D status than total 25(OH)D (42). Future studies should consider including free 25(OH)D as a complementary measure for a more comprehensive evaluation of vitamin D status. In addition, this study recruited participants from a sport-specialized university. From a practical standpoint, this population may be more metabolically active, potentially diminishing any small effects of vitamin D status on energy metabolism. Conversely, typical Chinese youth tend to be less physically active (43). Furthermore, there was considerable individual variation in the main results (see Figures 2 and 3 ), indicating significant heterogeneity in metabolic profiles. Therefore, caution is advised when generalizing these findings to the broader population. Finally, vitamin D status may be influenced by genetic variations, such as mutations in the CYP2R1 gene (44). However, this is less well-documented in the Chinese population (45) and warrants further investigation.

In conclusion, there is no relationship between serum 25(OH)D status and energy metabolism among young, healthy, non-obese adults. The current body of evidence indicates that being overweight and obesity are the causes of low vitamin D status, rather than the reverse. While further research may be needed to strengthen the overall evidence, we recommend that future studies prioritize intervention approaches, such as exercise, to improve metabolic health and explore their secondary effects on vitamin D status.