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The Discovery of Vitamin D Part II: From Chemical Structure to Biological Function

Adolf Otto Reinhold Windaus (1876-1959) (universität-freiburg, 2025)

In the late 1920s, another breakthrough was achieved: The German chemist Adolf Windaus, together with his team, isolated an anti-rachitic substance from irradiated plant sterols and initially named it vitamin D1. Although it was later discovered to be a mixture of vitamin D2 and tachysterol, Windaus's work led to an intensive investigation into the chemical structure of vitamin D. A British research group led by Askew eventually isolated pure vitamin D2 (ergocalciferol) from plant sources. In parallel, Windaus identified in animal tissues what we now know as vitamin D3 (cholecalciferol) and its precursor, 7-dehydrocholesterol.

For these achievements, which involved not only vitamin D3 but also related compounds such as cholesterol and other sterols, Adolf Windaus was awarded the Nobel Prize in Chemistry in 1928. With the structural elucidation of vitamin D, the path was cleared for more detailed biochemical and physiological studies. In the following decades, research focused on understanding how vitamin D functions in the body.

A milestone came in 1967 with the discovery of 1,25-dihydroxyvitamin D, the active form of vitamin D. This form is produced in the body through a two-step hydroxylation of cholecalciferol: first in the liver to 25-hydroxyvitamin D (25(OH)D), then in the kidney to the hormonally active compound 1,25(OH)₂D. These insights opened up a completely new understanding of vitamin D's effects - not merely as a vitamin, but as a hormone of systemic significance.

Vitamin D influences not only calcium and phosphate metabolism but also numerous other processes in the body. It acts via specific receptors, so-called vitamin D receptors (VDR), which are present in nearly all tissues, including the intestines, bones, immune system and even the brain. Numerous studies now confirm that vitamin D deficiency is not only associated with rickets or osteomalacia but also linked to an increased risk of infections, autoimmune diseases, diabetes, cardiovascular diseases and certain types of cancer.

The modern definition of vitamin D deficiency includes the defective maturation of chondrocytes and insufficient mineralization of the growth plate. This leads to a soft bone matrix, which manifests especially in children as rickets, characterized by typical deformations of the long bones, enlarged joints and pain. In more severe cases, deformities of the rib cage can cause breathing problems, described in Chinese texts as “pigeon chest.” In girls, a deficiency may lead to pelvic deformities, which can later cause complications during childbirth.

A key risk factor for vitamin D deficiency is insufficient exposure to sunlight. This is especially relevant in northern latitudes, in individuals with darker skin pigmentation, during winter, or among people who cover their skin for cultural or religious reasons, which impairs the body’s own synthesis. Since vitamin D is found in only a few foods in sufficient amounts, supplementation through fortified products or dietary supplements is often necessary.

The history of vitamin D clearly illustrates how medical observation, biochemical research and public health measures can work together. From the early documentation of deficiency-related diseases to structural elucidation and therapeutic application, centuries have passed. Today, vitamin D serves as a prime example of how science can contribute to improving quality of life in the long term - not only by preventing bone diseases but also through its wide-ranging importance for many bodily systems.

Sources: 

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

Holick, M. F. (2023). The One-Hundred-Year Anniversary of the Discovery of the Sunshine Vitamin D3: Historical, Personal Experience and Evidence-Based Perspectives. Nutrients, 15(3), 593. Source

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

universität-freiburg. (2025). Adolf Otto Reinhold Windaus – Universität Freiburg. Source

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