The discovery and synthesis of the nutritional factor vitamin D

Although vitamin D deficiency was first recognized as rickets/osteomalacia in the early 1600s, it was only a century ago that vitamin D, the nutritional factor responsible, was discovered. This discovery was made difficult by the fact that the substance could be synthesized in human skin by exposure to UV light and could also be present in the diet in animal-derived (D-3) and plant-derived forms (D-2). Prior to 1920, the frequency of vitamin D deficiency in the general population of industrialized cities was high. The discovery of vitamin D led to the widespread fortification of foods e.g. milk and the virtual eradication of rickets in developed nations. Vitamin D-3 was first chemically synthesized in the 1930s and its metabolism to the active form 1,25-dihydroxyvitamin D-3 and its mode of action in calcium and phosphate homeostasis were elucidated in the latter half of the 20th century. Synthetic vitamin D analogs that mimic the physiological effects of vitamin D are now used therapeutically in diseases such as bone disease, chronic kidney disease and psoriasis. Thus, a wide range of disciplines played critical roles in the rich history of vitamin D and these are described in this short historical overview.