How Is Vitamin D Cholecalciferol Made? A Look at Natural and Industrial Production

Over 80% of the vitamin D in most people's bodies comes from sunlight exposure, but the process of how is vitamin D cholecalciferol made involves a precise chemical reaction that can also be replicated industrially for supplements and fortified foods.

Quick Summary

Cholecalciferol, or vitamin D3, is produced in human skin by converting 7-dehydrocholesterol using UVB radiation. It is also manufactured commercially by irradiating 7-dehydrocholesterol extracted from lanolin or from sources like lichen for vegan alternatives.

Key Points

• Skin Synthesis: Cholecalciferol (vitamin D3) is made in the skin from 7-dehydrocholesterol upon exposure to UVB sunlight.

• Two-Step Reaction: The natural process involves photolysis by UVB to form previtamin D3, followed by a heat-driven conversion to cholecalciferol.

• Industrial Sources: Commercially, cholecalciferol is produced by irradiating 7-dehydrocholesterol extracted from lanolin (sheep's wool) or lichen.

• Safety Mechanism: The body has a built-in safety mechanism where prolonged sun exposure creates inactive photoproducts instead of toxic levels of vitamin D.

• Limiting Factors: Natural vitamin D production is affected by latitude, season, time of day, age, and skin pigmentation.

• Inactivation: Whether naturally or industrially produced, cholecalciferol is inactive until metabolized in the liver and kidneys into its active form.

Natural Production: Sunlight and the Skin

The most common way for humans and animals to get vitamin D cholecalciferol is through natural synthesis in the skin. This process is a non-enzymatic photochemical reaction that relies on exposure to a specific wavelength of sunlight: ultraviolet B (UVB) radiation, with a wavelength of 290 to 320 nm.

The journey begins with a cholesterol precursor found in the epidermis, the outer layer of the skin. This molecule is known as 7-dehydrocholesterol (7-DHC). When UVB photons from sunlight penetrate the epidermis, they strike the 7-DHC molecule, causing a chemical reaction.

The Photochemical Conversion Steps

1. Photolysis: The high-energy UVB photons break a specific bond within the 7-DHC molecule's B-ring, causing it to open. This ring-opening creates an unstable intermediate compound called previtamin D3 (pre-D3).
2. Thermal Isomerization: The previtamin D3 is biologically inactive, but it is thermodynamically unstable. Over a period of several hours, body heat causes the pre-D3 to undergo a molecular rearrangement known as thermal isomerization, which converts it into stable cholecalciferol (vitamin D3).

This process is self-regulating; prolonged sun exposure does not lead to toxic levels of vitamin D. If previtamin D3 is exposed to continued UV radiation, it is converted into biologically inactive photoproducts like lumisterol and tachysterol, preventing excess cholecalciferol from forming.

Industrial Manufacturing of Cholecalciferol

For dietary supplements and fortified foods, cholecalciferol must be produced on a large scale. This industrial process mimics the natural one but uses controlled, high-yield methods to produce a consistent and pure product. The primary raw material for conventional industrial vitamin D3 is lanolin, a waxy substance found in sheep's wool.

The Manufacturing Process from Lanolin

1. Source Collection: Lanolin is collected from sheep's wool during the shearing and washing process.
2. Lanolin Processing: The raw lanolin is purified through saponification, a process that separates the waxy alcohol component from other fatty elements.
3. Cholesterol Extraction: The refined lanolin alcohols are further processed to extract cholesterol, which is the precursor for the synthesis of cholecalciferol.
4. Conversion to 7-DHC: The extracted cholesterol undergoes a multi-step chemical conversion to produce 7-dehydrocholesterol, the same precursor found in human skin.
5. UV Irradiation: The purified 7-DHC is irradiated with ultraviolet light under controlled conditions to convert it into previtamin D3.
6. Thermal Isomerization and Purification: The previtamin D3 then undergoes thermal isomerization to form cholecalciferol. Further purification steps, such as chromatography, are used to remove any unwanted isomers and ensure high purity.

Vegan and Plant-Based Cholecalciferol

For vegan supplements, an alternative source for industrial cholecalciferol production is lichen, a symbiotic organism containing fungi and algae. The process is similar to the lanolin-based method, involving extraction and UV irradiation, but uses entirely plant-based materials. This provides a suitable option for those with dietary or ethical restrictions against animal products.

Factors Affecting Natural Vitamin D Production

While industrial production offers a consistent supply, several factors influence the amount of vitamin D a person's skin can naturally produce. These limitations highlight the importance of dietary and supplement sources for many individuals.

• Skin Pigmentation: Melanin, the pigment that gives skin its color, acts as a natural sunscreen. Individuals with darker skin pigmentation have more melanin, which absorbs UVB radiation and reduces the amount reaching the 7-dehydrocholesterol, slowing down vitamin D synthesis.
• Latitude and Season: The intensity and angle of UVB rays reaching the earth's surface vary with latitude and season. At higher latitudes, especially during winter months, the sun's angle is too low for sufficient UVB to penetrate the atmosphere, limiting natural production.
• Time of Day: The sun's rays are most intense around midday, typically between 10 am and 3 pm, when the sun is higher in the sky. Exposure during these hours is most effective for vitamin D synthesis.
• Age: As people get older, the skin's ability to produce 7-dehydrocholesterol decreases, reducing the efficiency of vitamin D synthesis.
• Sunscreens and Clothing: Using sunscreen with a high sun protection factor (SPF) blocks UVB radiation, effectively preventing the skin from producing vitamin D. Similarly, covering exposed skin with clothing inhibits synthesis.

Comparison Table: Natural vs. Industrial Cholecalciferol

Feature	Natural Production (in skin)	Industrial Production (for supplements)
Source	7-dehydrocholesterol (7-DHC) in the skin	7-DHC derived from lanolin or lichen
Radiation	UVB component of natural sunlight	Controlled UV lamps in a lab setting
Regulation	Self-regulating; excess UV leads to inactive byproducts	Highly controlled to ensure purity and dose accuracy
Factors Affected By	Latitude, season, skin color, age, sunscreen use	Manufacturing process, source material
Primary Purpose	Internal body supply	Supplements, food fortification

Conclusion: The Multiple Origins of a Crucial Vitamin

In conclusion, vitamin D cholecalciferol is made through two primary pathways: the natural process in the skin driven by UVB light and controlled industrial synthesis for commercial products. While the natural method is effective for many, its efficiency is influenced by a range of environmental and personal factors. Industrial manufacturing, whether from lanolin or lichen, provides a reliable and consistent way to produce the vitamin for supplements and fortified foods, helping to meet dietary needs and prevent deficiencies, especially in populations with limited sun exposure. Understanding these different origins is key to appreciating the versatility and importance of this vital nutrient. Learn more about vitamin D production and metabolism by visiting the National Institutes of Health.

Frequently Asked Questions

What is the starting material for making cholecalciferol in the skin?

The starting material for the synthesis of cholecalciferol in the skin is 7-dehydrocholesterol, a cholesterol precursor found in the epidermis.

Does prolonged sun exposure cause vitamin D toxicity?

No, prolonged sun exposure does not cause vitamin D toxicity. The body has a natural regulatory mechanism where excess UVB exposure converts previtamin D3 into inactive photoproducts like lumisterol and tachysterol.

What is lanolin and how is it used to make vitamin D3?

Lanolin is a waxy substance found in sheep's wool. It is processed to extract cholesterol, which is then chemically converted to 7-dehydrocholesterol and irradiated with UV light to create vitamin D3.

How is vegan cholecalciferol produced?

Vegan-friendly cholecalciferol can be produced industrially by extracting 7-dehydrocholesterol from lichens, which are then irradiated with ultraviolet light.

Why do people with darker skin produce less vitamin D from sunlight?

People with darker skin have more melanin. Melanin absorbs UVB radiation, reducing the amount that can reach the 7-dehydrocholesterol in the skin, which slows the rate of vitamin D synthesis.

Why is vitamin D from the sun considered more effective in some ways than from supplements?

Some sources suggest that vitamin D produced from sensible sun exposure stays in the blood longer than ingested vitamin D, contributing to sustained levels. However, D3 supplements are often more effective than D2 at maintaining levels.

Where does cholecalciferol go after it is produced in the skin?

After cholecalciferol is produced in the skin, it is transported to the liver, where it undergoes a first hydroxylation step to become calcidiol (25-hydroxyvitamin D3).