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How is vitamin D3 cholecalciferol made?

4 min read

Vitamin D3 synthesis was first accurately determined in the 1930s by Windaus et al., revealing the key roles of precursor molecules and UV light in how is vitamin D3 cholecalciferol made in animals and for supplements.

Quick Summary

Vitamin D3 is synthesized from 7-dehydrocholesterol via UVB irradiation, a process occurring naturally in skin or industrially from sources like lanolin and lichen.

Key Points

  • Natural Production: Vitamin D3 is made in human skin from a precursor molecule, 7-dehydrocholesterol, when exposed to UVB radiation from sunlight.

  • Industrial Sourcing: Commercial vitamin D3 is primarily derived from lanolin, a wax extracted from sheep's wool, or from lichens for vegan products.

  • Conversion Process: Both natural and industrial synthesis rely on exposing a precursor compound (7-dehydrocholesterol) to UV light, which triggers a photochemical reaction.

  • Metabolic Activation: The cholecalciferol produced is biologically inactive until it is converted by hydroxylation in the liver and then the kidneys.

  • Safety Mechanism: Prolonged sun exposure will not cause vitamin D3 toxicity because the body converts excess previtamin D3 into inactive forms.

  • Lanolin Method: The most common industrial method starts with lanolin, extracts cholesterol, converts it to 7-dehydrocholesterol, and then uses UV light to produce vitamin D3.

In This Article

The Natural Synthesis of Vitamin D3

In the human body, the creation of vitamin D3 is a remarkable photochemical process that occurs in the skin. It begins with a precursor molecule called 7-dehydrocholesterol (7-DHC), which is naturally present in high concentrations in the epidermis. This process is not enzymatic and is entirely dependent on sufficient exposure to ultraviolet B (UVB) radiation from sunlight, specifically within the 290–320 nm wavelength range. When UVB photons penetrate the skin, they are absorbed by the 7-DHC molecule. This energy absorption causes the molecule's B-ring to break, initiating a chemical transformation.

The Photochemical and Thermal Steps

  1. Photolysis of 7-DHC: Exposure to UVB light triggers a photolytic cleavage, converting 7-DHC into a short-lived, intermediate compound known as previtamin D3. The amount of previtamin D3 produced is dependent on several factors, including the intensity of the UVB radiation, the duration of sun exposure, and the individual's skin pigmentation.
  2. Thermal Isomerization: Once previtamin D3 is formed, it does not immediately become cholecalciferol. Instead, it undergoes a temperature-dependent rearrangement, or thermal isomerization, to produce the more stable vitamin D3 molecule. This process is gradual and continues for hours after sun exposure ends.
  3. Preventing Toxicity: The body has an ingenious safeguard against overproduction. Prolonged or excessive sun exposure does not lead to toxic levels of vitamin D3. Instead, extra previtamin D3 and vitamin D3 are converted into biologically inactive, non-toxic photoproducts, such as lumisterol3 and tachysterol3. This photoequilibrium ensures that the body's vitamin D stores are naturally regulated by the sun.

Industrial Production of Vitamin D3

For dietary supplements and food fortification, vitamin D3 is not harvested from human skin but rather manufactured on an industrial scale using a process that mimics the natural one. The two primary methods rely on different precursor sources to create cholecalciferol.

Lanolin-Based (Animal-Sourced)

This is the most common industrial method and is not vegan.

  • Source: The process begins with lanolin, a waxy substance derived from sheep's wool during the shearing process.
  • Extraction: Lanolin is washed and processed to extract the raw cholesterol.
  • Conversion to 7-DHC: The extracted cholesterol undergoes a multi-step chemical conversion to produce 7-dehydrocholesterol.
  • Irradiation: The purified 7-DHC is then irradiated with ultraviolet light under controlled conditions to generate previtamin D3.
  • Purification: After thermal isomerization converts the previtamin D3 to cholecalciferol, the product is purified to remove unwanted isomers and yield a highly potent, concentrated form of vitamin D3.

Lichen-Based (Vegan-Sourced)

This method offers a plant-based alternative for those following a vegan diet.

  • Source: Certain species of lichens, a symbiotic organism of algae and fungi, are a natural source of vitamin D3.
  • Extraction: The vitamin D3 is extracted from the lichens using solvents like water and plant ethanol.
  • Refinement: The extracted vitamin D3 is then purified and concentrated to the required potency for supplements.

Natural vs. Industrial Vitamin D3 Production

Aspect Natural Synthesis (in Skin) Industrial Synthesis (Lanolin) Industrial Synthesis (Lichen)
Starting Material 7-dehydrocholesterol (in skin) Lanolin (from sheep's wool) Lichen (algae and fungus)
Key Precursor 7-dehydrocholesterol 7-dehydrocholesterol (synthesized from lanolin cholesterol) Vitamin D3 (extracted directly)
Energy Source Solar UVB radiation Artificial ultraviolet light Water and ethanol extraction
Main Product Cholecalciferol (Vitamin D3) Cholecalciferol (Vitamin D3) Cholecalciferol (Vitamin D3)
Key Process Photochemical and Thermal Chemical conversion, Irradiation, Purification Extraction and Purification

The Activation Pathway: From Cholecalciferol to Active Vitamin

Regardless of its origin (skin or supplement), cholecalciferol is biologically inactive. It must undergo further metabolic conversions to become the potent hormone, 1,25-dihydroxyvitamin D, that regulates calcium metabolism and other body functions.

  1. First Hydroxylation in the Liver: Cholecalciferol is transported via the bloodstream to the liver, where it is hydroxylated at the 25th carbon position. This conversion is catalyzed by the enzyme 25-hydroxylase, producing 25-hydroxyvitamin D. This is the major circulating form of vitamin D and is what blood tests measure to determine an individual's vitamin D status.
  2. Second Hydroxylation in the Kidneys: The 25-hydroxyvitamin D is then transported to the kidneys, where the enzyme 1-alpha-hydroxylase adds another hydroxyl group at the 1st carbon. This final step yields the biologically active form of vitamin D, 1,25-dihydroxyvitamin D (calcitriol).

Conclusion

The creation of vitamin D3, or cholecalciferol, is a multi-stage process whether it happens naturally or industrially. In our skin, a photochemical reaction triggered by sunlight converts a cholesterol-like precursor into previtamin D3, which then thermally rearranges into vitamin D3. Commercially, this process is replicated by extracting a similar precursor from animal-derived lanolin or plant-based lichen and subjecting it to UV radiation. The final product, cholecalciferol, is then metabolically activated in the liver and kidneys before it can fulfill its crucial roles in maintaining health. For more details on vitamin D's function, consult authoritative sources such as the National Institutes of Health (NIH).

Frequently Asked Questions

Sunlight's UVB rays convert 7-dehydrocholesterol in the skin into previtamin D3, which then isomerizes with body heat to become vitamin D3 (cholecalciferol).

The primary precursor for vitamin D3 is 7-dehydrocholesterol, a compound related to cholesterol and found in the skin and certain animal-derived products.

Industrial vitamin D3 is typically sourced from lanolin, a wax from sheep's wool. Vegan versions are derived from lichens.

Yes, some vitamin D3 supplements are produced from lichens, offering a plant-based option for vegans.

Yes. Vitamin D3 is produced from 7-dehydrocholesterol, while vitamin D2 is produced from ergosterol, a compound found in fungi and yeast, also via UV irradiation.

For commercial production, 7-dehydrocholesterol is chemically synthesized from cholesterol, which is extracted and purified from lanolin.

No, excessive sun exposure will not cause vitamin D3 toxicity. The body has a natural regulatory mechanism where excess previtamin D3 and vitamin D3 are degraded into inactive photoproducts.

Once created, vitamin D3 is transported to the liver where it is converted to 25-hydroxyvitamin D. A second conversion in the kidneys turns it into the active hormone, 1,25-dihydroxyvitamin D.

References

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Medical Disclaimer

This content is for informational purposes only and should not replace professional medical advice.