To the Editor: 

We read with great interest the article by Uwitonze and Razzaque¹ about the important role of magnesium in vitamin D activation and function. It is known that several steps in vitamin D metabolism depend on magnesium as a cofactor,^1,2 and taking large doses of a vitamin D supplement can induce severe depletion of magnesium.² 

Aiming to determine the influence of vitamin D replacement therapy on magnesium status, we retrospectively analyzed data from previous studies,^3,4 specifically looking at serum magnesium levels before and after 4 months of cholecalciferol supplementation among 186 patients with vitamin D deficiency and Hashimoto thyroiditis (HT) (173 women and 13 men; mean [SD] age, 37.3 [5.6] years). A 25-hydroxyvitamin D (25[OH]D) level less than 10 ng/mL was considered as severe vitamin D deficiency; 10 to 19.9 ng/mL, moderate deficiency; 20 to 29.9 ng/mL, mild deficiency (or insufficiency); and 30 ng/mL or greater, sufficiency. The normal range for serum intact parathyroid hormone (PTH) and magnesium was 15 to 68 pg/mL and 1.7 to 2.7 mg/dL, respectively. 

All 186 patients were euthyroid (with or without medication) and vitamin D deficient. All patients had a normal calcium level and normal estimated glomerular filtration rate. None of the patients had diabetes or alcoholism. Of the 186 patients, 15 (8.1%) had severe vitamin D deficiency; 109 (58.6%), moderate deficiency; 62 (33.3%), mild deficiency; and 182 (97.8%), elevated serum intact PTH levels. Cholecalciferol supplementation with target serum 25(OH)D levels of 40 ng/mL or greater resulted in 213% increase in mean (SD) serum 25(OH)D levels, from 14.6 (7.2) ng/mL to 45.7 (4.3) ng/mL (P<.001); a 45% decrease in serum intact PTH levels, from 102.5 (15.2) pg/mL to 56.3 (18.4) pg/mL (P<.001); and a 2.6% decrease in serum magnesium levels, from 1.92 (0.3) mg/dL to 1.87 (0.2) mg/dL (P=.059). After cholecalciferol supplementation, all patients remained normocalcemic and none had serum magnesium levels below 1.7 mg/dL or clinical signs of hypomagnesemia. The reduction in serum magnesium levels was greater among the 15 patients with severe vitamin D deficiency (−9.5%). 

The results of investigation revealed that vitamin D deficiency is a common cause of secondary hyperparathyroidism in patients with HT.⁴ Although serum magnesium levels decreased after 4 months of cholecalciferol supplementation, hypomagnesemia or clinical manifestations of hypomagnesemia did not develop in any patient. However, a periodic assessment of serum magnesium levels among these patients is necessary because with continued cholecalciferol supplementation as maintenance therapy,⁵ further depletion of magnesium with possible clinical consequences could result. The depletion of magnesium is expected to be serious among patients who take vitamin D supplements and have coexisting conditions that increase the risk of magnesium deficiency, including insufficient dietary magnesium intake, hypoalbuminemia, chronic alcoholism, type 2 diabetes mellitus, gastrointestinal diseases (eg, celiac disease, chronic diarrhea, Crohn disease), and use of drugs (eg, insulin, loop and thiazide diuretics, aminoglycosides, proton pump inhibitors, and certain chemotherapies).⁶