Vitamin D metabolites, D3 and D2, and their independent associations with depression symptoms among adults in the United States

Background: The two metabolites of vitamin D; serum 25-hydroxyvitamin D3 (25(OH)D3) and D2 (25(OH)D2), and their independent roles in mood regulation are unexplored. This study aims to examine 25(OH)D3 and 25(OH)D2 and their interplay with depression symptoms.Materials and Methods: Utilizing data from the U.S. National Health and Nutrition Examination Survey (2007-2011, 2013-2014), a cross-sectional study was conducted. Depression was assessed using the 9-item Patient Health Questionnaire, and those with total score ≥5 were considered as having mild to severe depression symptoms. 25(OH)D3 and 25(OH)D2, the clinical markers of vitamins D3 and D2, were measured. Weighted logistic regressions were utilized to examine the adjusted association between 25(OH)D3 and depression, and the effect modification of 25(OH)D2.Results: The sample included 11,471 participants aged 20-80 years. Of those, 23.4% reported symptoms of depression, 28.9% had 25(OH)D3 deficiencies(<20 ng/mL), and 21.5% exhibited presence of 25(OH)D2(>0.6 ng/mL). After adjustment, among participants with presence of 25(OH)D2, those who had 25(OH)D3 deficiencies were more likely by 54% to report depression symptoms (OR = 1.54,95%CI:1.14-2.07). In fact, among participants with nearly no 25(OH)D2 presence, a significant effect estimate between 25(OH)D3 deficiency and depression symptom was not observed(OR = 1.11,95%CI:0.94-1.31).Conclusions: Both vitamin D metabolites retain an independent and significant role in mood regulation. The study provides valuable insights on vitamin D3 and its significant relationship with depression symptoms in the presence of vitamin D2. Further research is required to elucidate the distinct mechanisms of these two vitamin D metabolites on depression.