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673 - ‘Vitamin D Metabolism, Mechanism of Action, and Clinical Applications’. Chem Biol.. 21(3): 319–329

Reference Number: 673

Year: 2014

Authors: Daniel D. Bikle

Link: Link to original paper

Nutrition: Vitamin D

Summary

Abstract

Vitamin D3 is made in the skin from 7-dehydrocholesterol under the influence of UV light. Vitamin D2 (ergocalciferol) is derived from the plant sterol ergosterol. Vitamin D is metabolized first to 25 hydroxyvitamin D (25OHD), then to the hormonal form 1,25-dihydroxyvitamin D (1,25(OH)2D). CYP2R1 is the most important 25-hydroxylase; CYP27B1 is the key 1-hydroxylase. Both 25OHD and 1,25(OH)2D are catabolized by CYP24A1. 1,25(OH)2D is the ligand for the vitamin D receptor (VDR), a transcription factor, binding to sites in the DNA called vitamin D response elements (VDREs). There are thousands of these binding sites regulating hundreds of genes in a cell-specific fashion. VDR-regulated transcription is dependent on comodulators, the profile of which is also cell specific. Analogs of 1,25(OH)2D are being developed to target specific diseases with minimal side effects. This review will examine these different aspects of vitamin D metabolism, mechanism of action, and clinical application.

Summary of Findings

What is Vitamin D and How Is It Made?

  • Vitamin D3 is made in the skin when exposed to sunlight (UVB rays).
  • Vitamin D2 comes from plants and fungi (like mushrooms) and is often used in food fortification.
  • Both forms are converted in the liver to 25-hydroxyvitamin D (25OHD), the main circulating form.
  • Then, in the kidney and other tissues, 25OHD is converted to the active hormone 1,25-dihydroxyvitamin D (1,25(OH)?D).

Key Enzymes in Vitamin D Metabolism

  • CYP2R1: Main enzyme in the liver that converts vitamin D to 25OHD.
  • CYP27B1: Converts 25OHD to the active hormone 1,25(OH)?D, mainly in the kidney.
  • CYP24A1: Breaks down both 25OHD and 1,25(OH)?D to prevent toxic buildup.
  • Other enzymes and pathways (like CYP11A1 and 3-epimerase) also play roles in specific tissues.

How Vitamin D Works in the Body

  • The active form binds to the Vitamin D Receptor (VDR), which is found in nearly every tissue.
  • VDR acts as a transcription factor, turning genes on or off depending on the cell type.
  • Vitamin D influences hundreds of genes, affecting bone health, immune function, cell growth, and more.
  • It also has non-genomic effects, acting quickly on cells through membrane receptors.

Vitamin D Analogs

  • Scientists have developed modified versions of vitamin D to target specific diseases with fewer side effects.
  • Examples include:
    • Calcipotriol and maxacalcitol for psoriasis
    • Paricalcitol and doxercalciferol for secondary hyperparathyroidism
    • Eldecalcitol for osteoporosis
  • These analogs differ in how they bind to transport proteins, receptors, and how quickly they are broken down.

Clinical Applications

Vitamin D plays a role in many health conditions:

  • Bone health: Prevents rickets and osteomalacia; may reduce fractures and falls.
  • Parathyroid gland: Helps regulate calcium and suppress excess hormone production.
  • Skin: Used to treat psoriasis and may protect against skin cancer.
  • Metabolic health: Linked to obesity, insulin resistance, and diabetes risk.
  • Cancer: Promising lab data, but clinical trials are still inconclusive.
  • Heart disease: May reduce blood pressure and heart enlargement, but more research is needed.
  • Immune system: Boosts innate immunity and may help regulate autoimmune responses.

Conclusions

Vitamin D is far more than a bone vitamin. It acts like a hormone, influencing many body systems. While analogs show promise for targeted treatments, more clinical trials are needed to confirm benefits in cancer, heart disease, and immune disorders. 

Significance for the Baker

Research into vitamin D is an ongoing area which is going to lead to abilities to really personalise baking. For the moment watching all the new areas being discovered that are influenced by vitamin D is fascinating and offering symbiotic eating to include vitamin D and advising on short periods of sun exposure (especially in the Northern Hemisphere) and ensure that natural intake is good. Try the mushroom traybake and remember to leave your mushrooms in the sun before using them as they continue to absorb vitamin D themselves.

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Disclaimer

All reasonable care is taken when advising about health aspects of bread, but the information that we share is not intended to take the place of treatment by a qualified medical practitioner. You must seek professional advice if you are in any doubt about any medical condition. Any application of the ideas and information contained on this website is at the reader's sole discretion and risk.

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