Vitamin D safety and requirements

Abstract

Vitamin D an ancient secosteroid is essential for mineral homeostasis, bone remodeling, immune modulation, and energy metabolism. Recently, debates have emerged about the daily vitamin D requirements for healthy and elderly adults, the safety and efficacy of long term supplementation and the role of vitamin D deficiency in several chronic disease states. Since this molecule acts as both a vitamin and a hormone, it should not be surprising that the effects of supplementation are multi-faceted and complex. Yet despite significant progress in the last decade, our understanding of vitamin D physiology and the clinical relevance of low circulating levels of this vitamin remains incomplete. The present review provides the reader with a comprehensive and up-to-date understanding of vitamin D requirements and safety. It also raises some provocative research questions.

Fig 1

This figure shows some of the most relevant studies, which are used to justify beneficial and detrimental effects of high serum levels of vitamin D as well as efficiency and inefficiency of vitamin D treatment.

Fig 2

Vitamin D has a complex relationship with obesity: top left) obesity is considered a condition associated with vitamin D deficiency, showing low serum levels of 25-OHD and high 1,25(OH)₂D. Previous studies suggest association between vitamin D levels and insulin resistance; top right) VDR null mice, VDR heterozygote male mice and CYP27B null mice have a lean phenotype and there are studies showing that VDR null mice have metabolic advantages when exposed to a diabetogenic diet; botton) 1,25(OH)₂D signaling through membrane and nuclear receptors inhibits lipolysis and promotes lipogenesis, there are studies showing that hypercalcemic diet induces weight loss [2,23,61-66]. VDR- vitamin D receptor, CYP27B- 25-hydroxyvitamin D-1α-hydroxylase.

Fig 3

A) Sun-induced synthesis of vitamin D includes an ingenious process to prevent intoxication in cases of excessive exposure. High temperature drives pre-vitamin D and vitamin D to form inactive molecules, respectively lumisterol or tachisterol and suprasterol I, suprasterol II or 5,6-transvitamin D₃; B) Oral vitamin D₃ (cholecalciferol) and Vitamin D₂ (ergocalciferol) bypass skin control in synthesis of vitamin D and deliver substrates that will be forwarded to the synthesis of 25-OHD and 1,25(OH)₂D.