Safety Issues of Vitamin D Supplementation

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)

Volume 16, 12 Issues, 2016

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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex

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Safety Issues of Vitamin D Supplementation

Anti-Cancer Agents in Medicinal Chemistry, 13(1): 4-10.

Author(s): Armin Zittermann, Sylvana Prokop, Jan F. Gummert and Jochen Borgermann.

Affiliation: Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Georgstraße 11, 32545 Bad Oeynhausen, Germany.


Vitamin D deficiency is a re-emerging global health problem, which is primarily due to inadequate vitamin D synthesis in the skin. Supplement use is an effective measure to improve vitamin D status. However, some safety issues have to be considered, which are highlighted in this review article: The concept of vitamin D safety consists of two models, the safe tolerable upper intake level (UL) method, and the idea of adequate circulating 25-hydroxyvitamin D (25[OH]D) levels. Oral vitamin D intakes up to 250 μg/d have not been associated with harm. Hypercalcemia, the hallmark of vitamin D intoxication, may only occur if circulating 25(OH)D levels are consistently above 375-500 nmol/l. However, some observational studies indicate that already circulating 25(OH)D levels > 125 nmol/l are related to an increased morbidity and mortality risk. Therefore, the Institute of Medicine has set the UL for adults at 100 μg/d, and the adequate circulating 25(OH)D level at 50 to 125 nmol/l. In clinical practice, oral vitamin D dosing has to consider that the increment in circulating 25(OH)D depends on baseline 25(OH)D levels and the person’s body weight. It is reasonable to assess 25(OH)D before and 3-6 months after initiation of oral vitamin D administration and to adjust the dose, if necessary. In future, two issues have to be clarified: First, would it be more appropriate to define instead of a fixed UL a variable UL, based on the individual’s body weight? Second, what are the underlying mechanisms, if any, for potentially harmful vitamin D effects at circulating 25(OH)D levels between 125 and 375 nmol/l.


Vitamin D, Vitamin D3, Vitamin D2, 25-hydroxyvitamin D, Intoxication, Toxicity, Safety, Hypercalcemia, Hypercalciuria, Death, No observed adverse effect level, Lowest observed adverse effect level, Tolerable upper intake level, Body weight, Vitamin D binding protein, Parathyroid hormone, Fibroblast growth factor 23, Hyperphosphatemia, Food fortification, Sarcoidosis.

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Article Details

Volume: 13
Issue Number: 1
First Page: 4
Last Page: 10
Page Count: 7
DOI: 10.2174/1871520611307010004

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