Why do you need vitamin D and how does it work?

You have undoubtedly heard that Vitamin D is really good for you and that it is important that you have sufficient levels in your body.   But why is this so?  Or is it just a way for supplement companies to make a quick dollar? And if it is so beneficial, then why are doctors not recommending it more often?

Unfortunately, I am unable to definitively answer why this important micronutrient is not suggested more often by doctors, other than to say that as a vitamin it cannot be patented and thus can be found in pharmacies, supermarkets and health food stores.

To answer the first question, we need to understand what this vitamin is, how it is activated, and then what role it plays in the body.

Vitamin D, sometimes called the sunshine vitamin, is a fat-soluble vitamin that acts more like a hormone than a vitamin.  While this micronutrient can be supplied in the diet from animal sources, such as fatty fish, veal, beef, liver, and egg yolks (cholecalciferol D3), or from plant origin (ergocalciferol-D2), such as sun-exposed mushrooms, it is unique in that the body is able to synthesize all its needs given sufficient sunlight [1]. In fact, the levels of vitamin D when the body is exposed to sunlight with one minimal erythema dose (MED), i.e. the exposure that causes redness of the skin, can be compared to oral intake of 10,000 – 25,000 IU vitamin D [2]. (Compare this with most of the supplements found on the shelves, which come in a daily dose of 1,000 IU). Once synthesized in the skin, under the influence of ultraviolet light, vitamin D3 is transported to the liver where it is converted to 25-hydroxyvitamin D3 (25-(OH)D3). This is the major circulating form and is used to measure a patient’s vitamin D status. The final stage of activation occurs in the kidneys, where the mitochondrial enzyme, 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) further hydroxylates 25-(0H)D3 to the active form, 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3], also known as calcitriol. While this stage takes place mainly in the kidneys, it is now been shown that most cells and tissues in the body, including bone, immune cells, skin cells and the parathyroid gland, have a vitamin D receptor, and possess the enzyme necessary to produce the active form of vitamin D3 [3].

One of the most studied roles of vitamin D is the one it plays in calcium and phosphorus metabolism and consequently in the promotion of bone health. It achieves this by increasing the intestinal absorption efficiency of these bone-building minerals from 10-15% to 30-40%, making them more available for bone mineralisation [2].  Additionally it further regulates calcium levels by maintaining parathyroid hormone (PTH) levels in the body.  It therefore stimulates bone building activity by exerting a direct and indirect action on cartilage and bone to promote normal skeletal development and turnover. The negative effect of vitamin D deficiency on musculoskeletal health is evident in the severe bone deforming disease seen in children, called rickets, which is characterised by growth retardation, deformities of the legs, beaded ribs, weak muscles and bending of the spine [8]. Sadly, even though this disease was rampant in the mid-1600s, it is still a major health concern in Australia and New Zealand today. In adults¸  low levels of 25-(OH)D3 can lead to osteomalacia, a condition characterized by defective mineralization of the collagen matrix, causing bones to become increasingly soft, deformed and brittle, increasing the risk of fracture [8]. Furthermore, conditions such as osteopenia and osteoporosis, and as a consequence, the increased incidence of possible hip fracture, can develop later in life [3]. As it has been found that there is a positive dose-response relationship between vitamin D supplementation and fracture prevention, vitamin D is thought to play a vital role in the prevention of osteoporosis and may contribute to improving quality of life for individuals suffering from this condition [5].

Apart from this fundamental role in bone and calcium homeostasis, vitamin D receptors (VDRs), which regulate numerous genes across the genome, have been found present in so many different types of tissues. This fact,  as well as the discovery that a variety of cells have the ability to synthesize the active form, has led to further studies showing the possible roles that vitamin D plays in many other extra-skeletal physiological processes. In fact, a variety of recent studies have implicated vitamin D in the prevention of such conditions as cardiovascular disease, owing to the participation of 1,25(OH)2 D3 in the regulation of blood pressure regulation; respiratory diseases; obesity; autoimmune conditions such as multiple sclerosis and psoriasis; diabetes; and certain forms of cancer such as colon, breast, prostate, ovarian and melanoma [4]. It is also thought to be involved in muscle function, red blood cell synthesis, aging, as well as reducing inflammation and regulating immune responses [4].

Wow! Such a wide variety of conditions. It definitely appears to be an unsung hero.

Lets look a bit closer to some of these conditions and how vitamin D has been demonstrated to be beneficial.

One of the important responses of our immune system to disease-causing micro-organisms, is to produce our own “antibiotic” medication. Yes, you heard correctly!  Our bodies are capable of producing antimicrobial substances, known as Antimicrobial Peptides or AMPs that protect us against bacteria, viruses, fungi, and even certain parasites. Two important AMPs, known as the defensins and the cathelicidins, are produced by white blood cells, and epithelial cells, which line the areas of the body that are typically exposed to microbes present in the external environment, such as the gut, skin, lungs and urinary tract.  Importantly, these AMPs are regulated by vitamin D! Indeed, our lungs have the ability to fight off colds and flu, and consequently maintaining optimal vitamin D levels is crucial for a robust defense against these common conditions [7]. Interestingly, it has been suggested that one of the reasons that colds are more prevalent in winter is due to the lack of sun exposure during these months.

Vitamin D deficiency has been strongly linked to such autoimmune conditions as multiple sclerosis (MS), type 1 diabetes (T1DM), and systemic lupus erythematosus (SLE).  This is not surprising as this micronutrient stimulates our immune system to produce regulatory T cells, which are responsible for differentiating between dangerous invaders and “self” cells [7].

The active form of vitamin D has been successfully shown to inhibit the proliferation, stimulate the differentiation, and suppress the immune activity associated with both psoriasis, an autoimmune disorder, and non-melanoma skin cancer [5].

Obese individuals who are more likely to develop metabolic syndrome, insulin resistance and diabetes, have been shown to have typically lower levels of 25-(0H)D3 levels in the blood [5].  In fact, in one study it was demonstrated that the deficiency was 35% higher in obese subjects compared to subjects of normal weight and 24% higher than in the overweight group [6].  This has been partially explained by the trapping of cholecalciferol produced through the skin via sunlight, or through the diet, by excess body fat, before it has a chance to be transported to the liver for its first conversion into 25-(0H)D3. [6].

Furthermore, there appears to be an association between vitamin D deficiency and insulin resistance.  This could be due to promotion of insulin secretion as a result of the interaction between the expression of the VDR, which are present on pancreatic β cell, by the active form of vitamin D [5]. Indeed, it has been suggested that those individuals who have been shown to suffer from diabetes, or who are pre-diabetic, may benefit from vitamin D supplementation with respect to improving or preventing the development of frank diabetes [5].

 Promising animal studies have demonstrated that the active form of vitamin D can prevent cancer development or retard its progress/metastasis once developed.  The mechanisms responsible are thought to include blocking elements of the cell cycle or interfering with signaling by growth factors, inducing cell death, and reducing blood supply to the cancer cells [5].  However, most of the clinical data stem from observational studies. More human clinical studies are needed to verify these results.

Severe vitamin D deficiency in humans is associated with cardiomyopathy and increased cardiovascular disease (CVD) risk [5]. Unfortunately however, presently there are very few large randomized clinical trials that have been designed specifically to test the role of vitamin D in cardiovascular disease.

Owing to the important roles that this micronutrient plays, it is highly concerning that vitamin D or insufficiency exists in 1 billion people worldwide [2]. In fact, low levels of 25-(OH)D3, are said to be present in as many as 1/3 to ½ of otherwise healthy middle-aged to elderly adults; a major cause being the lack of sun exposure [10] . Moreover, there are factors that can decrease the cutaneous vitamin D production, such as skin exposure during most of winter, darker skin colour, age, adults over 65 years,  being veiled or covered due to religious reasons, as well as the application of sunscreen. Sadly, while individuals are strongly encouraged to wear sunscreen of  SPF ≥15 all year, including  during the summer months, to prevent melanoma, their bodies will make virtually no vitamin D [11].  Paradoxically, melanoma patients can increase their chances of survival with moderate sun exposure [11].

In Australia, mild deficiency of vitamin D for adults has been defined as serum 25-(OH)D levels between 25 and 50nmol/L; moderate deficiency, as between 12.5 and 25nmol/L, and severe, below 12.5nmol/L [9]. However, It has even been suggested that for the prevention and risk of chronic illnesses, levels of 50 nmol/L are considered sub-optimal and one should aim for a level of at least 75nmol/L, with levels of 100-150 nmol/L being optimal [3].

Until recently the criteria used to set a recommended level of vitamin D intake was for the prevention of rickets and osteomalacia [12].  However studies have shown that these levels were totally inadequate to prevent vitamin D deficiency [13]. In the US, the Recommended Daily Allowance was tripled to 600IU for all children over one year of age and adults up to the age of 50 [13].  In Australia, the Adequate Intake value for vitamin D, as set out by the National Health and Medical Research Council (NHMRC), (2013), which assumes no, or minimal, exposure to sunlight, is 5 micrograms/per day (200IU) for children and adults up to the age of 50, 10 micrograms (400 IU) for adults between the ages of 51 to and 70, and 15 micrograms (600 IU) for those adults over the age of 70 years [8]. These levels have been studied to be highly inadequate for those individuals who are at high risk of vitamin D deficiency such as the elderly (especially those in residential care nursing homes), people with skin conditions where sunlight should be avoided,  those who have malabsorption issues, have dark skin, or who cover exposed skin for religious or cultural reasons, or who need to wear protective clothing for their occupation.  Instead, at least 3,000-5,000 IU/day of a vitamin D supplement is recommended [9]. Overweight individuals may need vitamin D supplementation of up to 9000IU [14]

While deficiency of this micronutrient is extremely common, toxicity is quite rare [3]. Hypercalcaemia (high serum calcium levels) causes most of the symptoms of vitamin D toxicity and can include gastrointestinal disorders, bone, muscle and joint pain, drowsiness, headaches, irregular heartbeat, frequent urination and kidney stones [14}. Toxicity cannot be caused by excessive sunlight as sunlight degrades any excess vitamin D, but rather by chronic consumption of supplementation in excess of 40,000IU per day over an extended period of time. As a consequence an Upper Limit at 80 micrograms/day (32,000 IU) for individuals aged from 1 to 50 years and 25 micrograms (10,000 IU) for infants from birth to 12 months [15].

In conclusion, vitamin D plays an essential role in the maintenance of bone health and in many extra-muskuloskeletal physiological processes in the body.  However, studies have shown that vitamin D insufficiency and deficiency is a global public health issue.  As a result of most people having inadequate exposure to the sun and dietary vitamin D intake, and with an increase in many chronic conditions especially osteoporosis, it is advisable to ask your GP to check your levels, and if low, ensure adequate exposure to sunlight (before or after 11 am to 3 pm in summer) and/or adequate supplementation.

If you can relate to this article, and need some assistance, please do not hesitate to contact me.  Also, if you have still not read my other blogs, please click here. Furthermore, I have a facebook page that not only shares some of my blogs and videos but provides valuable health information.  If you gain insight from some of the contributions, don’t forget to click on the “Like” button.

[1] Insel, P., Turner, R. E. & Ross, D. (2007).  Nutrition (3rd ed.). Ontario: Jones and Bartlett.

[2] Wacker, M. & Holick, M. F. (2013). Vitamin D – Effects of skeletal and extraskeletal health and the need for supplementation. Nutrients, 5(1), 111–148.

[3] Holick, M. F. (2007). Vitamin D deficiency. New England Journal of Medicine, 357, 266-281

[4] Christakos, S., Hewison, M., Gardner, D. G., Wagner, C. L., Sergeev, I. N., Rutten, E., Pittas, A. G., Boland, R., Ferrucci, L. & Bikle, D. D. (2013). Vitamin D: beyond bone. Annals of the New York Academy of Sciences, 1287(1), 45-58.

[5] Bikle, D. D. (2014). Vitamin D metabolism, mechanism of action, and clinical applications. Chemistry & biology, 21(3), 319-329.

[6] Pereira‐Santos, M., Costa, P. R. F., Assis, A. M. O., & Santos, D. B. (2015). Obesity and vitamin D deficiency: a systematic review and meta‐analysis. Obesity reviews, 16(4), 341-349.

[7] Kamen, D. L., & Tangpricha, V. (2010). Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity. Journal of molecular medicine, 88(5), 441-450.

[8] National Health and Medical Research Council (2013). Nutrient reference values for Australia and New Zealand. Nutrients: vitamin D. Retrieved from http://www.nrv.gov.au/nutrients/vitamin%20d.htm

[9] (Working Group of the Australian and New Zealand Bone and Mineral Society, the Endocrine Society of Australia and Osteoporosis Australia, 2005, p. 281).

[10] Wang, T. J., Pencina, M. J., Booth, S. L., Jacques, P. F., Ingelsson, E., Lanier, K., Benjamin, E. J., D’Agostino, R. B., Wolf, M. & Vasan, R. S. (2008). Vitamin D Deficiency and Risk of Cardiovascular Disease. Circulation, 117, 503-511.

[11] Godar, D. E., Pope, S. J., Grant, W. B., & Holick, M. F. (2011). Solar UV doses of adult Americans and vitamin D3 production. Dermatoendocrinology, 3(4), 243–250.

[12] Cosenza, L., Pezzella, V., Nocerino, R., Di Costanzo, M., Coruzzo, A., Passariello, A., Leone, L., Savoia, M., Del Puente, A., Esposito, A., Terrin, G. & Canani (2013).  Calcium and vitamin D intakes in children: a randomized controlled trial. BMC Pediatrics, 13(86). doi: 10.1186/1471-2431-13-86.

[13] Holick, M. F. (2012). Evidence-based D-bate on health benefits of vitamin D revisited. Dermatoendocrinology, 4(2), 183–190.  Medi

[14] Wortsman, J., Matsuoka, L. Y., Chen, T. C., Lu, Z., & Holick, M. F. (2000). Decreased bioavailability of vitamin D in obesity–. The American journal of clinical nutrition, 72(3), 690-693.

 [15] Alshahrani, F. & Aljohani N. (2013). Vitamin D: deficiency, sufficiency and toxicity. Nutrients, 5(9), 3605-16.

[16] Saccone, D., Asani, F., & Bornman, L. (2015). Regulation of the vitamin D receptor gene by environment, genetics and epigenetics. Gene, 561(2), 171-180.