Dr. Kumar’s Take:
This is a narrative historical review, not a clinical trial, and it charts vitamin D from a poorly understood cure for rickets to a hormone with a dedicated set of transport proteins, metabolic enzymes, and a receptor. What I find useful clinically is the reminder that vitamin D acts through a receptor-mediated transcriptional mechanism regulating hundreds of genes in many tissues, which is why its effects reach past bone into muscle contraction, immune function, and cellular function throughout the body. The historical arc also shows how long it took to connect sunlight to the disease: the deficiency was described in the 1600s, but the role of sunlight was not worked out until the 1900 to 1920 period.
Key Takeaways:
✔ Rickets was recognized as a specific disease in the 15th century in Europe, and the earliest printed record of it causing death was in the London Bill of Mortality in 1634.
✔ The role of sunlight in vitamin D deficiency was defined in the 1900 to 1920 period, roughly 250 years after the first descriptions of the disease.
✔ The active hormonal form, 1,25-dihydroxyvitamin D, was discovered after vitamin D metabolism was first described in 1967.
✔ Vitamin D acts through a 1,25-dihydroxyvitamin D₃ and vitamin D receptor transcriptional mechanism that binds cellular chromatin and regulates hundreds of genes in many tissues.
Actionable tip:
Vitamin D reaches the body two ways: through the skin and through the diet. If sunlight exposure is limited, dietary and supplemental sources carry more of the load, so talk with your physician about whether your intake is adequate.
Brief Summary:
This article reviews more than 350 years of vitamin D history, organized into four distinct eras: the first recognition of rickets, the discovery of the nutritional factor and its chemical structure, the elucidation of vitamin D metabolites including the hormonal form 1,25-dihydroxyvitamin D₃, and the delineation of the vitamin D cellular machinery, functions, and vitamin D related diseases. It traces how vitamin D moved from a nutritional deficiency disease to a hormone understood to regulate gene transcription in many target cells.
History of Vitamin D:
This was a narrative historical review published in Endocrine Connections in 2022. It organizes the history of vitamin D research into four chronological eras:
- 1650 to 1890: History of vitamin D deficiency (rickets)
- 1890 to 1930: Discovery of vitamin D and its structural elucidation
- 1930 to 1975: Discovery of vitamin D metabolites including 1,25-(OH)₂D₃
- 1975 to present: Vitamin D cellular machinery, functions, and vitamin D related human diseases
Rickets was prevalent in Europe long before it was recognized as a specific disease in the 15th century. The earliest documentation of the word “rickets” appears in the domestic receipt book of an English family in 1632. The term may derive from the Dorset dialect verb “rucket,” meaning to breathe with difficulty, though others trace it to the Anglo-Saxon “wrikken,” meaning to twist. Daniel Whistler first clearly described rickets and osteomalacia in the Netherlands in 1645 as a condition of poorly mineralized and deformed bone, and Francis Glisson provided the first documented records in De Rachitide, published in Latin in 1650 and translated into English in 1671, which features a lithograph of children with bowed legs and skeletal deformities.
Highlights:
- Rickets in children and osteomalacia in adults were first described in the early 1600s, with bone deformities recorded in treatises and lithographs of the period.
- It took another 250 years to define the cause: in the 1900 to 1920 period, physicians and biochemists elucidated the role of sunlight and identified the chemical structures of vitamin D₂ and vitamin D₃.
- Vitamin D metabolism was first described in 1967, and the active form, 1,25-dihydroxyvitamin D, was discovered in that era.
- Vitamin D₃ (cholecalciferol) is of animal origin and vitamin D₂ (ergocalciferol) is of plant or fungal origin; the two forms have roughly equal potencies, similar metabolic patterns, and identical effects in the body.
- Vitamin D has its own dedicated machinery: transport proteins, metabolic enzymes, and the vitamin D receptor, which mediate its actions in bone and many other tissues.
- The name “vitamin D” was coined by nutritionists, not chemists, and is defined as a substance with anti-rachitic properties that will cure rickets.
How Vitamin D Works in the Body
Vitamin D is a steroidal substance required by all vertebrates, including humans, to keep blood calcium and phosphate within a narrow normal range. That, in turn, supports a healthy skeleton, muscle contraction, immune function, and cellular function in many locations around the body.
Its physiological functions include increasing intestinal calcium and phosphate absorption, mobilizing bone resorption, and driving renal reabsorption of calcium, alongside a range of pleiotropic actions. Many of the hormonal effects of vitamin D are believed to run through a 1,25-dihydroxyvitamin D₃ and vitamin D receptor mediated transcriptional mechanism, in which the complex binds cellular chromatin and regulates hundreds of genes across many tissues. When vitamin D is deficient, the skeleton is poorly mineralized and deformed, which is the picture Whistler and Glisson described in the 1600s: rickets in children and osteomalacia in adults.
Related Studies and Research
Global Prevalence of Vitamin D Deficiency: A Meta-Analysis: Provides modern context for historical intake patterns.
Historical Aspects of Vitamin D Research and Public Health Impact: Detailed narrative of vitamin D’s discovery and fortification efforts.
Clinical Overview of Vitamin D Deficiency by Holick et al.: Describes how historical definitions of deficiency evolved.
Analysis of Vitamin D Status in Traditionally Living Maasai and Hadzabe Communities: Compares ancestral vitamin D levels to modern homes.
Comprehensive Review of Vitamin D’s Immunomodulatory Effects in Immune-Related Disorders: Connects historical use to current immune research.
Frequently Asked Questions
What is vitamin D’s main role in the body?
It keeps blood calcium and phosphate within a narrow normal range by increasing intestinal calcium and phosphate absorption, mobilizing bone resorption, and promoting renal reabsorption of calcium. That supports a healthy skeleton, muscle contraction, and immune function.
What does vitamin D deficiency look like?
The classic picture is a poorly mineralized and deformed skeleton: rickets in children and osteomalacia in adults. The historical hallmarks illustrated in Glisson’s 1650 work are bowing of the legs and other skeletal deformities.
What is the difference between vitamin D₂ and vitamin D₃?
Vitamin D₃, cholecalciferol, is of animal origin. Vitamin D₂, ergocalciferol, comes from plants or fungi. This review states that the two have roughly equal potencies, similar metabolic patterns, and identical effects in the body.
What is the active form of vitamin D?
1,25-dihydroxyvitamin D, also written 1,25-(OH)₂D. It was discovered after vitamin D metabolism was first described in 1967, and it is the form that binds the vitamin D receptor and regulates gene transcription.
Conclusion
This historical review traces vitamin D across more than 350 years, from the first descriptions of rickets and osteomalacia in the early 1600s, through the elucidation of sunlight’s role and the vitamin’s chemical structure between 1900 and 1920, to the discovery of its metabolism in 1967 and the modern understanding of its receptor, enzymes, and transport proteins. Reading it, I am struck by how much of what I rely on clinically, the idea that vitamin D is a hormone regulating hundreds of genes in many tissues, rests on work done within the last half century.
