Vitamin D Supplementation for the Treatment of Depressive Symptoms in Women with Type 2 Diabetes: A Randomized Clinical Trial

Abstract

Aim: To determine the efficacy and safety of vitamin D₃ supplementation in reducing depressive symptoms in women with type 2 diabetes (T2D), depression, and low vitamin D.

Methods: In this double-blind randomized active comparator-controlled trial, women with significant depressive symptoms as assessed by the Center for Epidemiologic Studies Depression (CES-D) scale received weekly oral vitamin D₃ supplementation (50,000 IU) or an active comparator (5,000 IU) for 6 months. Assessments of vitamin D, 25-hydroxyvitamin D [25 (OH) D], and depression were measured at baseline, 3 months, and 6 months.

Results: A total of 129 women were randomized, from which 119 completed the study (57 in lower dose and 62 in higher dose). Participants had an average 25 (OH) D and HbA1c of 20.8 ng/mL and 7.8%, respectively, at baseline. They were diverse (48% Black) and had a mean age of 50 and T2D for about 8 years. Upon completion of vitamin D₃ supplementation, serum 25 (OH) D levels increased with 50,000 IU (+34 ng/mL) and 5,000 IU (+10 ng/mL). There was no difference in CES-D scores by treatment dose. Overall, depressive symptoms significantly improved over time with an average CES-D decline of 12.98 points (95% CI: -15.04 to -10.93; p < 0.001). Among women with moderate baseline depressive symptoms, those receiving the lower dose had nominally lower depression scores at follow-up than those in the higher dose cohort. Among women with severe baseline depressive symptoms, the improvement in follow-up depression scores was the same regardless of dose.

Conclusions: There was no difference in the dosing effect of vitamin D₃ supplementation for the treatment of depressive symptoms in women with T2D who present with significant symptoms and low vitamin D. Regardless of the dose, participants' mood improved over time. Further study of vitamin D to target depressive symptoms in comorbid populations is needed.

Figure 1

Recruitment and retention flow diagram. Prior to the three-month follow-up visit, four participants in the high CES-D stratum and three participants in the low CES-D stratum discontinued treatment (n = 3) or were lost to follow-up (n = 4). Similarly, prior to the six-month follow-up visit an additional three participants from the high CES-D stratum discontinued treatment (n = 1) or were lost to follow-up (n = 2).

Figure 2

Mean CES-D score by treatment allocation and time. The mean change in CES-D as a function of elapsed time since baseline, treatment assignment, and their interaction from a linear mixed-effects model based on 129 participants contributing 370 CES-D observations.

Figure 3

Mean serum vitamin D (25 OH D) by treatment allocation and time. The mean change in the vitamin D level as a function of elapsed time since baseline, treatment assignment, and their interaction from a linear mixed-effects model based on 129 participants contributing 370 vitamin D laboratory measurements.

Figure 4

Mean CES-D score with stratification by treatment allocation and time. The mean change in CES-D with stratification as a function of elapsed time since baseline, treatment assignment, and their interaction from a linear mixed-effects model based on 129 participants contributing 370 CES-D observations.