Which of the following is an inactivated vitamin D?

An estimated one billion people worldwide have vitamin D deficiency, a fat-soluble prohormone that plays a critical role in calcium absorption and overall bone health. However, this essential compound exists in multiple forms, with only one being the biologically active form, while the others are considered an inactivated vitamin D.

Quick Summary

Explaining which forms of vitamin D are inactive precursors, how they are converted into their active hormonal state, and how this metabolic pathway is regulated by the body.

Key Points

• Cholecalciferol (D3) and Ergocalciferol (D2) are Inactive: The initial forms of vitamin D are inactive prohormones.

• Two-Step Activation is Required: D3 and D2 are activated in the liver and kidneys.

• 25-Hydroxyvitamin D is a Storage Form: This is the major circulating form but is largely inactive.

• Calcitriol is the Active Form: 1,25-dihydroxyvitamin D (calcitriol) is the active hormone.

• Inactivation prevents Toxicity: The conversion process is controlled to avoid excessive accumulation.

• Regulation depends on PTH and Mineral Levels: Active vitamin D production is regulated by hormones and mineral levels.

• Measuring 25(OH)D is standard practice: Blood tests for 25-hydroxyvitamin D are used to measure vitamin D status.

Understanding the Inactive Forms of Vitamin D

Vitamin D is considered a prohormone because the body can produce it, unlike traditional vitamins. It starts as an inactive precursor and needs two hydroxylation steps in the liver and kidneys to become the active steroid hormone, calcitriol. The initial forms from the body or diet, such as cholecalciferol (D3) and ergocalciferol (D2), are biologically inactive.

Cholecalciferol (Vitamin D3)

Cholecalciferol is made in the skin from UVB light exposure and is also in some animal foods like fatty fish. It is inactive until metabolized.

Ergocalciferol (Vitamin D2)

Ergocalciferol comes from plants and is made by radiating ergosterol in yeast and fungi. It's often used in fortified foods and supplements and, like D3, needs liver and kidney conversion to be active.

25-Hydroxyvitamin D [25(OH)D]

After D3 and D2 are made or eaten, they go to the liver. Here, they're changed into 25-hydroxyvitamin D. This is the main type in the blood, but it's still mostly inactive before its final conversion. Measuring 25(OH)D levels is the usual way to check someone's vitamin D status.

The Activation Pathway: From Inactive to Active

Turning inactive vitamin D into its active form is a controlled two-step process. This ensures the body makes the right amount of the active hormone, 1,25-dihydroxyvitamin D, for mineral balance without becoming toxic.

1. Liver Step: Inactive D2 and D3 go to the liver. An enzyme called 25-hydroxylase adds a hydroxyl group, making 25-hydroxyvitamin D (calcidiol), the main form in circulation.
2. Kidney Step: In the kidneys, another enzyme, 1-alpha-hydroxylase, changes 25-hydroxyvitamin D into the active hormone, 1,25-dihydroxyvitamin D (calcitriol).

For more information on the regulation of this process, including the role of parathyroid hormone (PTH) and mineral levels, refer to {Link: Linus Pauling Institute https://lpi.oregonstate.edu/mic/vitamins/vitamin-D}.

Comparison of Vitamin D Forms

Feature	Cholecalciferol (Vitamin D3)	Ergocalciferol (Vitamin D2)	25-Hydroxyvitamin D (Calcidiol)	1,25-Dihydroxyvitamin D (Calcitriol)
Source	Skin synthesis via UVB exposure, fatty fish, egg yolks	Plant sterols, mushrooms, fortified foods	Metabolized from D2 and D3 in the liver	Metabolized from 25(OH)D in the kidneys
Biological Activity	Inactive	Inactive	Largely inactive until converted	Active steroid hormone
Role	Prohormone, precursor to active form	Prohormone, precursor to active form	Major circulating form, indicator of vitamin D status	Promotes intestinal calcium absorption and bone mineralization
Regulation	Production in skin regulated by UVB exposure; dietary intake	Dietary intake	Tightly controlled by negative feedback loop	Tightly regulated by PTH, calcium, and phosphate levels

Conclusion

Both cholecalciferol (D3) and ergocalciferol (D2) are inactive vitamin D forms, requiring metabolism to become active. They are first converted to 25-hydroxyvitamin D in the liver, and then to the active form, 1,25-dihydroxyvitamin D (calcitriol), in the kidneys. This regulated process is essential for mineral balance and preventing toxicity. Inactivated forms include cholecalciferol, ergocalciferol, and 25-hydroxyvitamin D as they all need further metabolic steps to become fully active. For more details, see {Link: NCBI https://www.ncbi.nlm.nih.gov/books/NBK278935/}.

Frequently Asked Questions

What are the two most common inactive forms of vitamin D?

The two most common inactive forms are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol).

Where does the first step of vitamin D activation occur?

The first step of vitamin D activation occurs in the liver, converting D2 and D3 into 25-hydroxyvitamin D.

Which form of vitamin D is used to measure a person's vitamin D status?

Serum levels of 25-hydroxyvitamin D [25(OH)D] are the best indicator of vitamin D status.

What is the biologically active form of vitamin D called?

The biologically active form is 1,25-dihydroxyvitamin D, or calcitriol, produced mainly in the kidneys.

How is the production of active vitamin D regulated?

Active vitamin D (calcitriol) production is regulated by hormones and mineral levels like parathyroid hormone (PTH), calcium, and phosphate.

Why is vitamin D considered a prohormone rather than a vitamin?

Vitamin D is a prohormone because the body can synthesize it and it requires metabolic conversion to its active form.

Is 25-hydroxyvitamin D active or inactive?

While the main circulating form, 25-hydroxyvitamin D is largely inactive until its final activation in the kidneys.