Vitamin D is the name given to a group of prehormones (secosteroids) essential in small quantity for healthy bodily function. Vitamin D is responsible for maintaining healthy bone structure and its deficiency has been implicated as playing a role in a number of chronic diseases and cancers. There are two mains types of vitamin D which can be absorbed by the human body. The first, vitamin D3 (or cholecalciferol), is produced in the skin of humans upon exposure to direct sunlight. The other, vitamin D2 (or ergocalciferol), is found naturally in plants or yeasts and can be obtained through diet.
Vitamin D presents a controversial issue in modern day dermatology since the main source (over 90%) comes through dermal contact with solar radiation. Given the known effects of extended skin exposure to ultraviolet (UV) rays, such as skin cancer and photoaging, many people try to gain an adequate intake through dietary changes or supplements. Despite these advancements, there is a troubling trend towards increase in vitamin D deficiency, perhaps due to public health campaigns on sun protection and an increase in the awareness of the harmful effects of UV radiation.
Vitamin D levels can vary greatly within a person’s lifetime, dependant on factors such as the level of air pollution, latitude and season. In addition, the use of sunscreen and high degrees of melanin pigmentation reduce the ability of the skin to synthesize vitamin D. While some experts argue that brief periods of sun exposure remains the most practical way to source vitamin D, dietary intake and supplementation are doubtless the safest methods.
Biological functions of vitamin D in humans
Vitamin D is largely responsible for regulating calcium and phosphate levels in the blood and therefore is crucial for skeletal health; playing a vital role in bone development, maintenance and repair. Since vitamin D is key to bone growth and health it is no surprise that deficiency can lead to rickets in children and osteomalacia in adults; both conditions characterised by soft, weak bones with insufficient mineralisation. In contrast, an adequate supply of vitamin D has been shown to significantly reduce the risk of osteoporosis and bone fractures.
Calcium uptake, which is aided by vitamin D, also has a significant effect on muscles and nerves, thus vitamin D is required for proper neuromuscular function. Consequently it is also useful in prevention of the condition hypocalcemic tetany, marked by continuous, painful muscle spasm. A portion of vitamin D within the body is also used in communication between several types of white blood cells; hence vitamin D is known to play a vital part in the immune system and protection against infection.
It has been recognized that vitamin D receptors exist on over 60 different types of cells in a range of target organs (including intestines, brain, heart, skin and gonads) and influence more than 200 genes. These findings indicate that vitamin D is likely to have implications far beyond those biological pathways already understood. Our knowledge of the influence of vitamin D will no doubt grow as research into its affects on a number of these cells continues.
Though not all the roles of vitamin D are clear yet, studies have found it is likely to be beneficial in a variety of conditions including: diabetes mellitus; some forms of internal cancer (particularly breast, colon and colorectal); hypertension; mental illnesses (including depression and Seasonal Affective Disorder); autoimmune diseases; metabolic disorders; muscle weakness and cardiovascular diseases.
Sources of vitamin D
The main source of vitamin D for humans is photochemical synthesis within the skin upon exposure of UVB radiation, through direct sunlight. Thus UV protection by limiting sun exposure can often result in vitamin D deficiency. In order to obtain sufficient amounts of vitamin D, whilst still protecting the body from the damaging effects of UV radiation, many people opt to take an oral vitamin D supplement. The need to prevent deficiency is particularly important for individuals with photosensitive conditions necessitating sun avoidance, or those who live in a region lacking adequate sunlight. Extended exposure to sunlight causes degradation of the excess vitamin D, thus toxicity of vitamin D3 rarely occurs.
The current recommendations for recommended dietary allowance of vitamin D, according to the Institute of Medicine (IOM), are listed in the table below; these figures are based on an absence of adequate sun exposure. The recommendations were revised in November 2010 and are based on evidence from over 1000 studies.
Table 1. Current daily recommended dietary allowances (RDAs) for vitamin D (Institute of Medicine)
|400 international units (5 mcg)*
600 IU (10 mcg)
800 IU (15 mcg)
|400 international units (5 mcg)*
600 IU (10 mcg)**
800 IU (15 mcg)
*Adequate intake (AI) only
**Includes pregnancy and lactation
Though it can be obtained through diet, there are very few natural food sources of vitamin D2. These include cod liver oil, egg yolk and oily fish such as tuna, salmon or sardines. In addition, many dairy producers now formulate milk, yoghurt and margarine that have been fortified with vitamin D2 during manufacture. Orange juice and cereals are other products often fortified with vitamin D.
Table 2. Some examples of common food sources of vitamin D and the amounts which they contain. (National Institute of Health)
|Food||International units (IU) per serving||Percent of daily intake (%)|
|Cod liver oil, 1 tablespoon||1,360||340|
|Salmon, cooked, 85g||794||199|
|Mackerel, cooked, 85g||388||97|
|Tuna fish, canned in water, 35g||154||39|
|Vitamin D-fortified milk, 1 cup||115-124||29-31|
|Vitamin D-fortified orange juice, 1 cup (amount varies per product)||100||25|
|Margarine, fortified, 1 tablespoon||60||15|
|Sardines, canned in oil, 2 whole||46||12|
|Liver, beef, cooked, 100g||46||12|
|Egg, 1 whole||25||6|
|Swiss cheese, 28g||6||2|
It is important to note that excess dosage of vitamin D is dangerous and can elicit symptoms of nausea, vomiting, constipation, loss of appetite and weight loss. Extended excess has been associated with high levels of calcium in the blood, leading to heart arrhythmia, mental confusion and an increased risk of kidney stones. The upper tolerable limits of vitamin D per day are: 1000 international units for infants up to six months; 1500 IU for infants six to 12 months; 2500 IU for children one to three years; 3000 IU for children four to eight years and 4000 IU for males and females 9 years to adult. Dietary intake (with the exception of large amounts of cod liver oil) is unlikely to cause toxicity. Oral supplementation however can be dangerous if not monitored; therefore it is imperative that it be supervised by a medical professional.
Vitamin D levels status is monitored by measuring the serum concentration of the inactive storage form of vitamin D, called calcidiol (25-hydroxycholecalciferol or 25-OH-D), understood to reflect total body stores. Vitamin D deficiency is defined as a level below 20 ng/ml (nanograms per millilitre), while toxicity is defined as a level above 150 ng/ml.
Vitamin D synthesis
Vitamin D3 is produced when UVB radiation (280-315nm) impacts upon the skin and excites a particular lipid (7-dehydrocholesterol) in the cell membrane, causing a structural change to form pre-vitamin D3. The pre-vitamin D3 is then converted to vitamin D3 (cholecalciferol), through the addition of heat. Finally, it is transferred into the bloodstream with the aid of a carrier protein, its concentration reaches maximum level approximately 24 hours subsequent to contact with sunlight. Vitamin D3 is manufactured mostly in the outer layer of the skin, the epidermis. This in turn, is comprised of five separate levels or strata. Of these, it is cells in the lower two layers, the stratum spinosum and stratum basale, where vitamin D3 is commonly found (see Figure 1.).
A similar process in plants, fungi and some invertebrates is also used to synthesize vitamin D2.
Vitamin D, obtained either by photochemical synthesis within the skin or intestinal absorption of natural and fortified food or supplements, enters the bloodstream. From there it travels to the liver, where it is converted to a prehormone known as calcidiol (25-hydroxycholecalciferol or 25-OH-D). Calcidiol represents the inactive storage form of vitamin D; this is the form that is measured in a blood sample when vitamin levels are monitored. It is then further metabolized in the kidney and becomes the biologically active calcitriol (1,25-dihydroxycholecalciferol). Calcitriol exerts its biological effects by binding to vitamin D receptors located in many target organs and tissues.
Vitamin D structure
The various forms of vitamin D are secosteroids; i.e., steroids compounds with a partial steroid ring; they differ in the composition of their side chains. The D3 form of the vitamin comes primarily from cutaneous production whereas the D2 form is produced by plants, fungi and invertebrates, which we obtain through food sources.
- Aloia, J.F & Li-Ng, M, 2007, ‘Re: epidemic influenza and vitamin D’, Epidemiology and Infection, 135: 1095-1096, author reply 1097-1098.
- Biser-Rohrbaugh, A & Hadley-Miller, N, 2001, ‘Vitamin D deficiency in breast-fed toddlers’, Journal of Pediatric Orthopaedics, 21: 508-511.
- Chesney, R.W, 1989,‘Vitamin D: can an upper limit be defined?’, Journal of Nutrition, 119 (suppl. 12): 1825-1828.
- David S.H. Bell, MB, 2011, Protean Manifestations of Vitamin D Deficiency Part 1, South Med J. 104(5):331-334. Accessed online at <http://www.medscape.com/viewarticle/742623_2>.
- Diehl, J.W & Chiu, M.W, 2010, ‘Effects of ambient sunlight and photoprotection on vitamin D status’, Dermatologic Therapy, 23: 48-60.
- Favus, M.J & Christakos, S, 1996, Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 3rd ed., Lippincott-Raven, Philadelphia.
- Ginde, A.A, Liu, M.C & Camargo, C.A Jr, 2009, ‘Demographic differences and trends of vitamin D insufficiency in the US population’, Archives of Internal Medicine 1988-2004, 169: 626-632.
- Grant, W.B, 2002, ‘An estimate of premature cancer mortality in the U.S. due to inadequate doses of solar ultraviolet-B radiation’, Cancer 2002, 94: 1867-1875.
- Holick, M.F, 2004, ‘Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis’, American Journal of Clinical Nutrition, 79: 362-371.
- Holick, M.F, 2007, ‘Vitamin D deficiency’, New England Journal of Medicene, 357: 266-281.
- Institute of Medicine, 2001, Dietary Reference Intakes: Vitamins, accessed 30th April 2010, <http://nationalacademies.org/hmd/activities/nutrition/summarydris/dri-tables.aspx>.
- Looker, A.C et al., 2008, ‘Serum25-hydroxyvitamin D status of the US population: 1988-1994 compared with 2000-2004’, American Journal of Clinical Nutrition, 88: 1519-1527.
- Malabanan, A, Veronikis, I.E & Holick, M.F, 1998, ‘Redefining vitamin D insufficiency’, The Lancet, 351: 805-806.
- National Institute of Health, Office of Dietary Supplements, 2009, Dietary Supplement Fact Sheet: Vitamin D, accessed 30th April 2010, <http://ods.od.nih.gov/factsheets/vitamind.asp>.
- Perrine, C.G et al., 2010, ‘Adherence to Vitamin D Recommendations Among US Infants’, Pediatrics, 125:627-632.
- Reddy, K.K & Gilchrest, B.A, 2010, ‘What is All The Commotion about Vitamin D?’, Journal of Investigative Dermatology’, 130: 321-326.
- Reichrath, J, 2009, ‘Skin cancer prevention and UV-protection: how to avoid vitamin D-deficiency?’, British Journal of Dermatology, 161 (suppl. 3): 54-60.
- Sage, R.J & Lim, H.W, 2010, ‘Therapeutic Hotline: Recommendations on Photoprotection and vitamin D’, Dermatologic Therapy’, 23: 82-85.
- Tracey, D et al., 2000, Anatomica, Random House, Sydney.
- University of California Riverside, 2004, About Vitamin D, accessed 30th April 2010, <http://vitamind.ucr.edu/>.
- Wolpowitz, D & Gilchrest, B.A, 2006, ‘Vitamin D questions: How much do you need and how should you get it?’, Journal of the American Academy of Dermatology, 54: 301-317.