Vitamin D supplementation is widely recognised by clinical bodies including the Scientific Advisory Committee on Nutrition (SACN), the National Institute for Clinical Health and Excellence (NICE) and Public Health England (PHE) as being an area of health intervention that can support a healthy and active lifestyle and help maintain independence. The most well-documented function of Vitamin D is to facilitate the absorption of calcium by the body. Calcium is crucial to the maintenance of skeletal mass and bone health, and also plays a key role in functions such as cell signaling, blood clotting, muscle contraction and nerve function.

Fast Facts

  • Vitamin D is fat-soluble and has an essential role in maintaining health.1

  • A key role of vitamin D is to help regulate calcium and phosphate homeostasis. In this regard it is vital for the maintenance of musculoskeletal health.2,3

  • Vitamin D deficiency manifests mainly as osteomalacia in adults and rickets in children, which the SACN suggests are generally associated with increased risk at plasma 25-hydroxyvitamin D (25(OH)D) concentrations below 20-25 nmol/L4.

  • There is emerging evidence that being deficient in vitamin D may also associate with other health outcomes including some cancers, cardiovascular, respiratory, immune modulation and infectious diseases.5,6

  • Between 80 and 90% of vitamin D intake is produced by dermal synthesis following exposure to natural sunlight, while only 10 to 20% is obtained from the diet.4,5 Unlike with other micronutrients, a healthy, balanced diet is not enough by itself to provide sufficient levels of vitamin D.7 Supervised supplementation provides a solution to manage shortfalls in vitamin D levels.5,7

  • There are five recognised forms of vitamin D, with the two most important for health being vitamins D2 and D3.1

How does vitamin D work?

  • The vast majority (between 80 and 90%) of vitamin D is produced in the skin following exposure to UVB rays. 4,9,10 During direct sun exposure, 7-dehydrocholesterol (stored under the skin following conversion from cholesterol) absorbs UVB and is converted to pre-vitamin D3 which in turn isomerises with the help of the body’s heat into vitamin D3 (colecalciferol).

  • The remaining amount (10 to 20%) of total vitamin D comes from dietary intake of vitamins D2 and D3. The latter can be obtained in small quantities from certain foods, while the former can be ingested in supplements or from certain types of mushrooms.

  • The liver processes both types of vitamin D to form the major circulating metabolite 25–hydroxyvitamin D (25(OH)D calcidiol), the concentration of which in the blood is tested to indicate vitamin D status4,9,10

  • 25(OH)D is further hydroxylated to form the active metabolite and steroid hormone 1,25–dihydroxyvitamin D (1,25(OH)2calcitriol), primarily in the kidney. Calcitrol can also be activated in non-renal tissues and cells, including breast, colon, prostate, skin, and immune tissue following hydroxylation in the liver.4,9,10

  • 1,25(OH)2D binds to the vitamin D receptor (VDR) in cell nuclei of target tissues around the body and is responsible for cellular pathways linked to key physiological processes, including maintenance of serum calcium concentrations, bone mineralisation, and neuromuscular function.2 Given VDRs are widespread around the body, extra-renal production of calcitriol results in activation within the cell (autocrine/paracrine behaviour) This differs from renally activated calcitriol, that is carried in the bloodstream to the intestine & bones (endocrine behaviour).2,7

Who is at increased risk of vitamin D deficiency?

Despite the important role it plays in physiological health and the two available routes to production, low vitamin D is highly prevalent and affects people across all age groups in all geographical areas. The growth of cells brings an increased need for vitamin D, while ageing brings a reduced ability for the skin to produce the required levels. A 70-year-old adult has 70% less capacity for vitamin D production compared to a young adult, when exposed to the same amount of natural sunlight.

There are some patient groups who may be at higher risk of vitamin D deficiency as a result of compromised UVB exposure or concomitant disease/diet related factors or indeed a combination of both throughout the stages of life. NICE and SACN stated that the following groups are at increased risk of vitamin D deficiency in the UK:


1. Martineau A. Vitamin D deficiency: people at risk need access to supplements 2015. Available at:

2. Dusso AS, et al. Am J renal physiol 2005:298:F8-28. Available at:

3. Colorado State University Books. Available at: (this reference used in INTERNIS training manual)

4. National Osteoporosis Society Practical Guidelines. Vitamin D and Bone Health: A practical clinical guideline for patient management. December 2018.

5. Fraser WD, Milan AM. Calcified Tissue Intl 2013;92(2):118¬–127.

6. Hossein-Nezhad A, Holick M. Mayo Clin Proc 2013;88:720–755.

7. Muszkat P et al. Arq Bras Endocrin Metabo 2010;54(2):110–17. Available at

8. Ross AC, et al. editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011. Available at:

9. Bikle D. Chem Biol Rev 2014;319–29. Available at:

10. Christakos S, et al. Endocrin Metab Clin North Am 2010;39(2):243–253. Available at:

11. Arthritis and Musculoskeletal Alliance 2018. Available at:

12. Holick M. The Vitamin D Solution: A 3-Step Strategy to Cure Our Most Common Health Problems. Hudson Street Press 2010. ISBN 9780452296886.

Job Code: FUL-519 Date of Preparation: June 2019 Date of Revision: January 2020