Letters to the Editor  |   December 2018
Investigating the Influence of Vitamin D Replacement Therapy on Magnesium Status
Author Notes
  • Department of Internal Medicine, Naval Hospital of Crete, Chania, Crete, Greece 
  • School of Production Engineering and Management, Technical University of Crete, Chania, Crete, Greece 
Article Information
Addiction Medicine / Endocrinology / Gastroenterology / Hypertension/Kidney Disease / Diabetes
Letters to the Editor   |   December 2018
Investigating the Influence of Vitamin D Replacement Therapy on Magnesium Status
The Journal of the American Osteopathic Association, December 2018, Vol. 118, 772-773. doi:
The Journal of the American Osteopathic Association, December 2018, Vol. 118, 772-773. doi:
Web of Science® Times Cited: 1
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 
Uwitonze AM, Razzaque MS. Role of magnesium in vitamin D activation and function. J Am Osteopath Assoc. 2018;118(3):181-189. doi: 10.7556/jaoa.2018.037 [CrossRef] [PubMed]
Reddy P, Edwards LR. Magnesium supplementation in vitamin D deficiency. Am J Ther. Published online May 3, 2017. doi: 10.1097/MJT.0000000000000538
Mazokopakis EE, Papadomanolaki MG, Tsekouras KC, Evangelopoulos AD, Kotsiris DA, Tzortzinis AA. Is vitamin D related to pathogenesis and treatment of Hashimoto's thyroiditis? Hell J Nucl Med. 2015;18(3):222-227. [PubMed]
Mazokopakis E, Papadomanolaki M, Skarakis SN, Tsekouras K. Primary and secondary hyperparathyroidism among vitamin D deficient Hashimoto's thyroiditis patients and the need for a parathyroid scan [letter]. Hell J Nucl Med. 2017;20(3):258-259. doi: 10.1967/s002449910613 [PubMed]
Pfotenhauer KM, Shubrook JH. Vitamin D deficiency, its role in health and disease, and current supplementation recommendations. J Am Osteopath Assoc. 2017;117(5):301-305. doi: 10.7556/jaoa.2017.055 [CrossRef] [PubMed]
Martin KJ, González EA, Slatopolsky E. Clinical consequences and management of hypomagnesemia. J Am Soc Nephrol. 2009;20(11):2291-2295. doi: 10.1681/ASN.2007111194 [CrossRef] [PubMed]