Combined oral supplementation with magnesium plus vitamin D alleviates mild to moderate depressive symptoms related to long-COVID: an open-label randomized, controlled clinical trial

Background. Individuals with long-COVID exhibit a higher frequency of hypomagnesemia, vitamin D deficiency, and depression. Objective. To evaluate the efficacy and safety of oral supplementation with magnesium chlo- ride plus vitamin D in alleviating depressive symptoms related to long-COVID. Methods. A total of 60 subjects, aged 52.8 +/- 12.6 years, with a diagnosis of hypomagnesemia, vitamin D deficiency, and mild-to-moderate depression (MMD) related to long-COVID, were enrolled in an open-label randomized, controlled clinical trial. Participants were randomly allocated into an intervention group (n=30) that received magnesium chloride (1300 mg) plus vitamin D (4000 IU), or a control group (n=30) that received vitamin D (4000 IU), for four months. Using the Beck Depression Inventory (BDI), diagnosis of MMD was established based on a score of >= 11<30. The primary trial endpoint was improvement in de- pressive symptoms (BDI <11). Results. Mild adverse events that did not require withdrawal from intervention were documented in six (20.0%) and three (10%) individuals of the intervention and control group, respectively. By comparing baseline vs. final measurements, the BDI score was significantly reduced in in- dividuals in the intervention (28.8 +/- 3.7 to 9.2 +/- 7.5, p<0.01) and control (28.4 +/- 3.8 to 21.6 +/- 9.1, p<0.05) group. A total of 22 (73.2%) subjects in the intervention group and 10 (34.5%) in the control group reached a BDI <11, p=0.006. Conclusion. Our results show that, among patients with hypomagnesemia and vitamin D deficiency, combined oral supplementation with magnesium plus vitamin D is effective and safe in alleviating MMD related to long-COVID.