The Initial Search for the Anti-Rickets Factor
Before the specific chemical structure of vitamin D3 was identified, scientists in the early 20th century sought to understand and cure rickets. Observations from the 17th century linked lack of sunlight and poor diet to the disease. In 1919, Kurt Huldschinsky showed that ultraviolet light treated rickets in children, suggesting sunlight created a therapeutic substance.
Elmer McCollum's 1922 experiments with cod liver oil led to the discovery of the broader 'Vitamin D'. By heating the oil, he destroyed Vitamin A but found it still cured rickets, identifying a separate, fat-soluble nutrient. This was the discovery of the vitamin D class, but not yet vitamin D3.
The Role of Sterols and Ultraviolet Light
Researchers like Harry Steenbock in the 1920s focused on how irradiation affected sterols, molecules in plants and animals. Steenbock patented irradiating foods to add Vitamin D, which reduced rickets. Nobel laureate Adolf Windaus also researched irradiated sterols with antirachitic properties.
The Chemical Characterization of Vitamin D3
Adolf Windaus and his team were crucial in characterizing vitamin D forms. In 1935, they isolated and identified cholecalciferol, or vitamin D3, from animal sources. They found it's produced in skin from 7-dehydrocholesterol when exposed to UVB radiation. This linked sunlight, skin sterols, and the specific vitamin D3 molecule. Windaus received the Nobel Prize in 1928 for his work on sterols, contributing to the understanding of these compounds.
The Two Primary Forms: Vitamin D2 vs. Vitamin D3
Vitamin D3 comes from animals and human skin, while Vitamin D2 (ergocalciferol) comes from irradiated plants and fungi. Vitamin D2 was identified in 1931 and D3 in 1935. Though similar chemically, their origins and how the body processes them differ.
Comparison Table: Vitamin D2 vs. Vitamin D3
| Feature | Vitamin D2 (Ergocalciferol) | Vitamin D3 (Cholecalciferol) |
|---|---|---|
| Origin | Plants and fungi (e.g., mushrooms) | Skin of animals (incl. humans) and some animal foods |
| Precursor | Ergosterol | 7-Dehydrocholesterol |
| Synthesis | UV irradiation of ergosterol in plants/fungi | UVB irradiation of skin |
| Common Sources | Fortified milk, cereals, and supplements; UV-treated mushrooms | Sun exposure, fatty fish, cod liver oil, and supplements |
| Potency in Humans | Generally considered less effective at raising and sustaining blood levels of 25(OH)D | More effective at increasing and maintaining serum 25(OH)D levels |
The Modern Understanding of Vitamin D
Since its discovery, our understanding of vitamin D has grown. It's now seen not as a traditional vitamin, but a precursor to calcitriol, a steroid hormone crucial for calcium and phosphorus regulation, bone health, and the immune system. The journey from treating rickets with cod liver oil to understanding its hormonal function shows the progress in nutritional science. While many contributed, Windaus and his team's 1930s work precisely defined when vitamin D3 was discovered. This knowledge led to interventions like food fortification, combating diseases like rickets.
Milestones in Vitamin D Discovery
- 1645-1650s: Early descriptions of rickets.
- 1820s: Link between sunlight and less rickets observed.
- 1919: UV light shown to cure rickets.
- 1922: Elmer McCollum isolates Vitamin D factor.
- 1924: Harry Steenbock patents food irradiation for Vitamin D.
- 1928: Adolf Windaus receives Nobel Prize for sterols work.
- 1931: Structure of Vitamin D2 characterized.
- 1935: Chemical structure of Vitamin D3 determined.
- 1968: First vitamin D metabolite, 25-hydroxyvitamin D, discovered.
- 1970s: Hormonally active form, 1,25-dihydroxyvitamin D, identified.
Conclusion: The Final Piece of the Puzzle
The discovery of vitamin D3 is a multi-decade scientific story. While Elmer McCollum identified the general vitamin D factor in 1922, the specific molecule of vitamin D3 (cholecalciferol) was isolated and chemically characterized by Adolf Windaus's team in the mid-1930s. This distinction was a crucial biochemical advancement, explaining how the body uses sunlight to prevent bone disease and revolutionizing nutritional science. For more on vitamin D metabolism, see the National Institutes of Health review(https://pmc.ncbi.nlm.nih.gov/articles/PMC8074587/).
Frequently Asked Questions
1. When was vitamin D discovered, as opposed to vitamin D3? Elmer McCollum and his team discovered the broader vitamin D factor in 1922 when they found an anti-rachitic substance in cod liver oil, distinct from vitamin A.
2. Who was Adolf Windaus and what was his role? Adolf Windaus was a German chemist who won the Nobel Prize in 1928 for his work on sterols. His team later characterized the chemical structure of vitamin D3 in 1935.
3. How did scientists figure out that sunlight produces vitamin D? Early research by Kurt Huldschinsky in 1919 demonstrated that ultraviolet light could cure rickets. This led researchers to discover that UV rays act on a sterol in the skin, 7-dehydrocholesterol, to produce vitamin D3.
4. What is the difference between vitamin D2 and vitamin D3? Vitamin D2 (ergocalciferol) is produced from plants and fungi, while vitamin D3 (cholecalciferol) comes from animals and is synthesized in human skin. The chemical structures are slightly different, and vitamin D3 is often considered more effective in humans.
5. Why was the discovery of vitamin D3 so important? The discovery of vitamin D3 was crucial because it provided a precise understanding of the chemical basis for how the body prevents rickets, leading to effective food fortification programs and supplements that significantly reduced the disease.
6. Did people know about rickets before the discovery of vitamin D? Yes, rickets was described in medical literature as early as the 17th century, though its cause was unknown. It was sometimes referred to as 'the English disease' due to its prevalence in industrial Britain.
7. What is 7-dehydrocholesterol? 7-dehydrocholesterol is a sterol found in the skin that acts as the precursor to vitamin D3. When exposed to UVB radiation from sunlight, it undergoes a chemical change that initiates the production of vitamin D3.
8. How did Harry Steenbock contribute to the vitamin D story? In the mid-1920s, Harry Steenbock patented a process for irradiating foods to increase their vitamin D content. This innovation made food fortification widely accessible and helped to virtually eliminate rickets in the U.S..
9. What happened to the initial 'Vitamin D1'? 'Vitamin D1' was a name given to an early preparation of the vitamin by Windaus, but it was later found to be an adduct (a mixture) of vitamin D2 and another substance. It was not a distinct vitamin itself.
10. How does the modern understanding of vitamin D differ from earlier views? Initially considered a simple nutrient, vitamin D is now understood to be a precursor to an active hormone, calcitriol, that plays a broad regulatory role in the body, impacting more than just bone health.
