Vitamin D metabolites, D3and D2, and their independent associations with depression symptoms among adults in the United States

Background:The two metabolites of vitamin D; serum 25-hydroxyvitamin D-3(25(OH)D-3) and D-2(25(OH)D-2), and their independent roles in mood regulation are unexplored. This study aims to examine 25(OH)D(3)and 25(OH)D(2)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)D(3)and 25(OH)D-2, the clinical markers of vitamins D(3)and D-2, were measured. Weighted logistic regressions were utilized to examine the adjusted association between 25(OH)D(3)and depression, and the effect modification of 25(OH)D-2. Results:The sample included 11,471 participants aged 20-80 years. Of those, 23.4% reported symptoms of depression, 28.9% had 25(OH)D(3)deficiencies(<20 ng/mL), and 21.5% exhibited presence of 25(OH)D-2(>0.6 ng/mL). After adjustment, among participants with presence of 25(OH)D-2, those who had 25(OH)D(3)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)D(2)presence, a significant effect estimate between 25(OH)D(3)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 D(3)and its significant relationship with depression symptoms in the presence of vitamin D-2. Further research is required to elucidate the distinct mechanisms of these two vitamin D metabolites on depression.