1930s-1950s: Early synthesis and mechanisms: 

In the 1930s, vitamin D₂ and D₃ were chemically synthesized for the first time, paving the way for research into their biological functions. Scientists discovered that vitamin D plays a central role in regulating calcium and phosphate metabolism in the body. It acts through three main mechanisms:

• Stimulating the absorption of calcium and phosphate in the intestine.

• Mobilizing calcium from the bones into the bloodstream.

• Promoting renal reabsorption of calcium in the kidneys.

In the 1940s and 1950s, researchers examined the interaction of vitamin D with hormones such as parathyroid hormone (PTH) and calcitonin, which also regulate calcium metabolism. It also became clear that vitamin D not only promotes calcium absorption but also supports its mobilization from bones to maintain a stable blood calcium concentration.

1960s: Discovery of Metabolites: 

During the 1960s, intensive research focused on whether vitamin D is biologically active in its original form or must be metabolized. Radioactively labeled forms of vitamin D₂ and D₃ enabled the study of their metabolic pathways.

• Cambridge: Egon Kodicek’s group investigated vitamin D activity, initially (and incorrectly) assuming it was active without conversion.

• University of Wisconsin-Madison: It was shown that vitamin D is converted in the liver to 25-hydroxyvitamin D₃ (25-OH-D₃), the main circulating form of vitamin D and crucial for calcium metabolism.

1970s: Hormonal active form and therapeutic use

In the early 1970s, another potent metabolite, 1,25-dihydroxyvitamin D₃ (1,25-(OH)₂D₃), was discovered, formed in the kidneys. This metabolite proved to be hormonally active and regulates both calcium and phosphate levels in the blood. This definitively demonstrated that vitamin D must be activated in multiple steps to exert its full biological effect.

By the mid-1970s, 1,25-(OH)₂D₃ was synthesized and clinically used under the name calcitriol, for example in the treatment of rickets and osteomalacia. Other metabolites, such as 24,25-dihydroxyvitamin D₃, were also identified as inactive forms.

The research from the 1930s through the 1970s laid the foundation for our current understanding of vitamin D metabolism. From the first chemical syntheses to the discovery of the main circulating form, 25-OH-D₃, and the identification of the hormonally active 1,25-(OH)₂D₃, these stepwise scientific advances clarified fundamental biological processes and created new therapeutic possibilities.

In the next and final part of this series, the history of vitamin D from 1975 onward will be continued. The focus will be on discoveries related to the vitamin D receptor, signal transduction mechanisms, the role of vitamin D in gene regulation, as well as clinical applications and modern therapies built upon these earlier findings.

Sources: 

DeLuca, H. F. (2014). History of the discovery of vitamin D and its active metabolites. BoneKEy Reports, 3, 479. Source

Jones, G. (2022). 100 YEARS OF VITAMIN D: Historical aspects of vitamin D. Endocrine Connections, 11(4), e210594. Source