Childhood obesity, potentially coupled with vitamin D deficiency, is one of the most significant modifiable risk factors for numerous chronic diseases. We have presented genetic evidence indicating that childhood obesity may lead to a lower level of vitamin D. These findings suggest that while increasing vitamin D levels may unlikely contribute to weight regulation, a heightened risk of vitamin D deficiency could lead to adverse health effects associated with obesity. According to our results, all odds ratios (OR) were less than 1, suggesting that childhood obesity may lead to decreased levels of 25(OH)D in the body, paralleling findings observed in adult studies. A meta-analysis also confirmed an association between obesity and vitamin D deficiency within pediatric populations(17). Recent intervention studies have indicated that individuals with obesity require a higher dose of vitamin D than lean individuals do to achieve the same serum concentrations of 25(OH)D(18). However, neither deficient nor excessive levels of vitamin D have a causal relationship with the onset of obesity. Vitamin D deficiency and obesity are two concurrent pandemics, that are sometimes interlinked. Although a close relationship between these two health issues has been recognized, the underlying pathophysiological mechanisms have yet to be fully elucidated. Indeed, on the one hand, obesity itself seems to involve low circulating levels of vitamin D due to diminished sunlight exposure, low physical activity, also Obesity causes increased fat cells, and vitamin D sequestration in adipose tissue, thus relatively reduced circulating levels (19). Conversely, low levels of vitamin D may play a role in adipogenesis due to the expression of receptors by preadipocytes and adipocytes and participation in vitamin D metabolism, thereby contributing to the development of obesity. This link is particularly critical when considering diseases associated with obesity(20). Moreover, low levels of vitamin D and severe obesity are significantly associated with several cardiometabolic risk factors, including high body mass index, waist circumference, blood pressure, impaired lipid and glucose profiles, and insulin resistance. These findings seem to correlate with worse cardiovascular outcomes and higher incidence and mortality rates from cancer(21). Vitamin D is an essential nutrient for children's growth and development(22, 23). A deficiency in vitamin D during the critical periods of childhood growth can lead to rickets and osteomalacia through primary or secondary causes(24, 25).A meta-analysis suggested that lower levels of 25(OH)D may contribute to the occurrence of asthma in children(26). Vitamin D has anti-inflammatory effects, and children with asthma or obesity tend to have lower serum levels. Supplementing with vitamin D is considered a simple, safe, and cost-effective adjunctive treatment (27). One possible reason for the lower levels of vitamin D in obese children is that, as vitamin D is fat-soluble, it is hypothesized to be sequestered in excess by adipose tissue, which is the most accepted physiopathologic explanation(28). The finding that excessive screen time (television, computers, and tablets) is also related to lower vitamin D levels reinforces the idea that the association between childhood obesity and hypovitaminosis D appears to be multifactorial, also influenced by diminished exposure to outdoor activities and sunlight(29). Dietary intake and sunlight exposure are also significant factors that affect vitamin D levels. Therefore, in obese children, the levels of vitamin D may be lower than those in normal weight children. To prevent vitamin D deficiency, oral vitamin D supplementation can be considered. Enhancing the importance of lifestyle changes in the pediatric population is equally critical. It is necessary to promote physical exercise, decrease screen time, and promote healthy dietary habits to reduce the prevalence of overweight and obesity among children and adolescents, as well as the impact of related comorbidities, including vitamin D deficiency (30).
Nonetheless, there are several limitations to this study. First, our findings, which are based primarily on participants of European ancestry, may not apply to populations of other ethnic groups. Second, although we did not find the presence of horizontal pleiotropy, there may be residual bias because the exact function of most of these SNPs is unknown. Third, because our study used GWAS of vitamin D level summary data rather than individual-level data, we were unable to stratify our analyses according to other factors, such as age and sex. Finally, we cannot completely disregard the possibility of diet-gene or gene-environment interactions influencing our findings. Our study also has several strengths. First, this is the first MR study to assess childhood obesity and vitamin D levels, and the association is causal. Second, this MR study was based on two large sample GWAS data from a European population, which provided us with sufficient power to estimate causality. Third, the MR analysis revealed no causal association between vitamin D levels and childhood obesity, which is unlikely to be affected by confounding factors.