Vitamin D

It is believed by many health care professionals that vitamin D intake (through all sources) is below recommended levels for a large amount of the population across the world. As that is the case, this article will investigate everything vitamin D. This article will be comprehensive and cover what vitamin D is, its function, digestion and absorption, metabolism, sources of vitamin D, and recommended dosages according to varying official institutions.

What is Vitamin D?

Vitamin D (aka, calciferol) is a prohormone, meaning it is a “precursor” to being made into a hormone [1]. Vitamin D is one of 4 fat soluble vitamins and comes in two major forms – vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) [1].

Function of Vitamin D?

Vitamin D has been strongly associated with calcium and phosphorous in the formation of bone tissue [2]. However, it is also implicated in immune function, gene regulation, reducing risk of cancer, blood pressure regulation, insulin production, and more; so, to be clear, vitamin D is of utmost importance and necessary [3].

Digestion, Absorption, and Metabolism

Vitamin D is an interesting molecule when it comes to absorption, because unlike almost every other molecule we need, which are absorbed via the intestines, Vitamin D is not only absorbed in the intestine by passive diffusion, as well as facilitated diffusion using proteins integrated in the enterocyte (intestinal cell) membrane, but can be taken up by the skin when exposed to sunlight [4]. Its absorption is enhanced over 30% with fat intake [12].

Intestinal Lumen (Inside)

Vitamin D

Blood/Lymph Side

Intestinal Enterocytes

Vitamin D enters the intestinal lining (enterocytes) by facilitated transport using a protein to enter the cell (red) and passive diffusion (blue).

Intestinal Absorption & Metabolism

Once taken up in the enterocyte, cholecalciferol (Vitamin D3) is carried across the cytosol by carrier proteins, then repackaged into chylomicrons and sent through the lymphatic system to the blood [5]. Vitamin D3 is then transported to a variety of tissues, but primarily to the liver, where the CYP enzymes (25-hydroxylases) in the endoplasmic reticulum, and even the mitochondria, act on it to convert it to 25-hydroxyvitamin-D, also known as calcifediol ((25(OH)D) [6][7]. Once metabolized, it is exported to the kidneys, mainly, where it is converted to calcitriol ((1,25(OH)2D)); other tissues, like the skin, lungs, intestines, breasts, and others also have the capacity for this conversion [6][7].

Now calcitriol, vitamin D, leaves the kidneys (or other tissue) and is carried by albumin, vitamin binding proteins, or freely into circulation to be passed on, in steroid fashion (meaning, across the membrane), to the cytosol of each actionable cell, where a Vitamin D Receptor (VDR) binds to calcitriol and carries it into the nucleus where it binds to genes and either activates or inhibits the expression of that gene for a particular purpose [6][8].

 

Skin Synthesis & Metabolism

Vitamin D is unique in that it is produced from a type of cholesterol, 7-dihydrocholesterol, as the keratinocytes of the epidermis (aka, the most distal layer of skin) use UV-B radiation from the sun to break a ring in the cholesterol and isomerizes the molecule based on heat [6]. Once the cholecalciferol has been produced, it is exported from the keratinocyte to vitamin D binding proteins and circulated to the liver and metabolized as explained before [6].

As a quick note on vitamin D2 (ergocalciferol), all of these processes can occur for this type of vitamin D, as well, but the binding affinity of this isoform to binding proteins in circulation is less than for D3, so it does not remain in circulation (lower conversion to metabolically viable versions and faster clearance) for as long as D3, hence the focus on D3 [6].

Sources of Vitamin D

There are a few sources of vitamin D, but fish is the most potent source, aside from supplementation; other sources are fish oil, milk, and orange juice [10].

Dose

The recommended dose for adults is 15 mcg (600 IU) [11]. Do not overconsume vitamin D as it is fat soluble and not readily excreted [11].

Safety
Overdose

Overdosing vitamin D (>10,000 IU) can lead to polyuria (using the bathroom frequently), anorexia, weight loss, elevated calcium, and heart arrhythmias [11].

Underdosing

Under consuming vitamin D (<600 IU) chronically leads to increased risk of osteoperosis and bone fractures, decreased immune function, as well as the development of rickets (aka, softening of the bones) [7][11].

SUMMARY

Vitamin D is a fat soluble vitamin that comes in two forms – D2 and D3. It is necessary for the formation of bone, immunity, gene regulation, and more. Vitamin D is absorbed via passive and facilitated diffusion, and then, like many fats, is released into the lymph system to be delivered to the liver for the beginning of metabolism. Vitamin D is also synthesized through a reaction in our skin. As for sources – fish, fish oil, milk are a few. Vitamin D can be dangerous if overconsumed chronically leading to heart arrhythmias and other pathologies, while under consuming can lead to rickets, immune deficiencies, and bone abnormalities.

Writer: Nicolas Verhoeven

References

[1] Yaktine, C. L. (2011). Overview of Vitamin D. In Dietary Reference Intakes for Calcium and Vitamin D. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK56061/

[2] Khazai, N., Judd, S. E., & Tangpricha, V. (2008). Calcium and vitamin D: Skeletal and extraskeletal health. Current Rheumatology Reports, 10(2), 110-117. doi:10.1007/s11926-008-0020-y

[3] Nair, R. (2012). Vitamin D: The “sunshine” vitamin. Journal of Pharmacology & Pharmacotherapeutics, 3(2), 118-126. doi:10.4103/0976-500X.95506

[4] Silva, M. C., & Furlanetto, T. W. (2017). Intestinal absorption of vitamin D: a systematic review. Nutrition Reviews, 76(1), 60-76. doi:10.1093/nutrit/nux034

[5] Blomhoff, R., Helgerud, P., Dueland, S., Berg, T., Pedersen, J. I., Norum, K. R., & Drevon, C. A. (1984). Lymphatic absorption and transport of retinol and vitamin D-3 from rat intestine Evidence for different pathways. Biochimica et Biophysica Acta (BBA) - Biomembranes, 772(2), 109-116. doi:10.1016/0005-2736(84)90033-6

[6] Bikle, D. (2014). Vitamin D Metabolism, Mechanism of Action, and Clinical Applications. Chemistry & Biology, 21(3), 319-329. doi:10.1016/j.chembiol.2013.12.016

[7] Bowen, R. (n.d.). Vitamin D (Calcitriol). Retrieved from Colorado State website: http://www.vivo.colostate.edu/hbooks/pathphys/endocrine/otherendo/vitamind.html

[8] Groot, L. J. (2017). Vitamin D: Production, Metabolism, and Mechanisms of Action. In Endotext. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK278935/

[9] Mostafa, W. Z., & Hegazy, R. A. (2015). Vitamin D and the skin: Focus on a complex relationship: A review. Journal of Advanced Research, 6(6), 793-804. doi:10.1016/j.jare.2014.01.011

[10] Appendix 12. Food Sources of Vitamin D - 2015-2020 Dietary Guidelines - health.gov (8th). (2015). Retrieved from Office of Disease Prevention and Health Promotion website: https://health.gov/dietaryguidelines/2015/guidelines/appendix-12/

[11] Nair, R. (2012). Vitamin D: The “sunshine” vitamin. Journal of Pharmacology & Pharmacotherapeutics, 3(2), 118-126. doi:10.4103/0976-500X.95506

[12] Dawson-Hughes, B., Harris, S. S., Lichtenstein, A. H., Dolnikowski, G., Palermo, N. J., & Rasmussen, H. (2015). Dietary Fat Increases Vitamin D-3 Absorption. Journal of the Academy of Nutrition and Dietetics, 115(2), 225-230. doi:10.1016/j.jand.2014.09.014

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