Vitamin D, or calciferol, is a vitamin present naturally both in some sources of food and produced endogenously in the skin, and is a key component in many different biological pathways in the body. Foods rich in vitamin D include fish, red meats and egg yolks. Since its discovery, through the work of Mellanby and separately McCollum, there have been many studies on vitamin D and its potential applications in medicine, with over 50000 studies and articles being published since 1922. There is currently great scientific interest surrounding this vitamin, there have been reports of using it to assist in the treatment of Covid-19. However, other studies dispute the efficacy in combatting Covid-19. This short essay will explore the physiological effects of vitamin D, whilst also examining what can happen in those with serious vitamin D deficiency, and how individuals with a deficiency may be treated.
Production and Physiological Effects of Vitamin D
Vitamin D is technically not a vitamin, due to the body’s ability to produce it when ultraviolet light penetrates the skin. Instead, it is better described as a type of fat-soluble steroid hormone. When ultraviolet (B, wavelengths 290-315nm) radiation is absorbed by the skin a molecule called 7-DHC, which is mostly concentrated in the lowest layers of the epidermis, is synthesized into an isomer of vitamin D3 (also called cholecalciferol) named preD3. Next, a protein called VDBP will carry D3 into the bloodstream through capillaries, after isomerization of preD3 into D3. This reaction requires a body temperature of around 37C and will last for around three days even if there is no exposure to the sun again during that time. D3 is then transported to the liver, where it is hydroxylated into 25(OH)D3, which in turn can either be stored or circulated in blood plasma. This intermediary metabolite acts as a type of reservoir, in which a second hydroxylation reaction can occur in the kidneys forming 1,25(OH)2D3, the active form of D3. Individuals with higher skin melanin content, those who are obese and those who are older produce less vitamin D via sunlight exposure, in addition to numerous other factors also lowering its production.
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As mentioned previously, vitamin D can also be found in a small number of foods. The main source of dietary vitamin D is in fish, however there are vast differences in vitamin D content across different types of fish, with oily fishes such as salmon containing higher concentrations. A second type of vitamin D, vitamin D2, is present in some other foods, namely plants and mushrooms. They produce D2 (also called ergocalciferol) via the irradiation of ergosterol, a sterol comparable to mammalian cholesterol in that it helps to maintain the structure of the cell membrane. A clinical trial, performed by Trang et al. (1998, pp.854-856), examined the differences in the effect of D2 and D3 on increasing 25(OH)D. The trial was carried out between February and May, when 25(OH)D levels were deemed to be at the lowest concentrations during the year. 34 volunteers were assigned to a double-blind group, where they would take either D2 or D3. Remaining volunteers were assigned D3 or to no vitamin at all. The results shown, despite the small sample (n=89), are reasonably reliable as p = 0.03. We can conclude from these results that while both D2 and D3 showed a dramatic increase in 25(OH)D levels, D3 showed the larger increase.
Vitamin D has two major effects, which have different functions in the body. Firstly, it regulates calcium metabolism. The main way it achieves this is by raising the amount of calcium absorption in the intestine. Enterocytes are a form of simple columnar epithelial cell in the intestine which are stimulated by the hormonally active 1,25(OH)2D3, to further increase the rate of calcium transportation along the cell. Calcium metabolism is also regulated through bone resorption. The second major effect that vitamin D has on the body is through the binding of 1,25(OH)2D3 to the VDR, a transcription factor, where it acts as a ligand. VDR is present on the surface of most immune cells. An example of how 1,25(OH)2D3 can help with the immune system is in B-lymphocytes, where apoptosis of activated B-lymphocytes is increased and T-lymphocyte activation is decreased. We can therefore deduce that 1,25(OH)2D3 plays a pivotal role in regulating the immune system which may help in cases of autoimmune. VDRs also help to increase and maintain muscle strength. There have been multiple studies in which the VDR gene in mice is blocked, causing atrophy in the muscles. The way in which VDR affects muscular function is not entirely clear and more research needs to be done.
Effects of Vitamin D Surplus or Deficiency
In the recommended daily intake of vitamin D is 400IU, equivalent to 10mcg. This dosage is recommended during the fall and winter months, as less vitamin D will be synthesized from sunlight during this time. A safe level is around ten times the recommended intake (4000IU), but ingesting any more of this would put an individual at risk of hypercalcemia, meaning calcium levels in the blood are above a safe level. Side effects of this can weaken bones, cause issues with the kidneys, and in more serious cases damage the heart and brain, causing a threat to life.
A diet consisting of less than 400IU of vitamin D a day can result in deficiency. The main disorders caused by vitamin D deficiency are generally seen in the bones. Two examples of disorders are rickets, which mainly affects children, and osteomalacia which is a similar condition, but generally found in adults. Rickets can usually be observed by the presence of bowlegs, a bending outward of the legs. Due to many foods being fortified and better nutrition, rickets has mainly become a thing of the past in the Western world. Children with rickets also have growth problems and an increased diameter of the wrists, all caused by the weakening of epiphyseal growth plates. In a small number of cases, rickets can be inherited via any form of genetic conditions, such as a kidney disorder, that affect vitamin D content in the body. Osteomalacia is caused by a lack of mineralization in the bones, following the closing of growth plates. Both osteomalacia and rickets can cause painful bone sensations and individuals with said conditions may experience more bone fractures.
In a large proportion of individuals (around 60-70%) are considered to have insufficient vitamin D intake, meanwhile around a sixth are vitamin D deficient. If you are considered to have vitamin D levels in the insufficient or deficient range, then treatment is required.
Conclusion
Vitamin D is a vital component of many different biological pathways. It helps with bone and muscle maintenance as well as regulation of calcium levels and the immune system. The consumption of vitamin D has greatly increased over the past hundred years, leading to a decrease in those with a deficiency. There are still risks of vitamin D deficiencies due to a multitude of factors, including diet, environment and age. The associated complications are often painful and can cause serious issues if not attended to. In many people do not ingest the 400IU of vitamin D recommended as a minimum level by the NHS in the winter months. It is important that an individual maintains a healthy level of vitamin D in their body, and more people are now taking supplements to achieve the required amount. It is still a topic many are unaware of, and more public campaigns would be useful.
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