From ATLANTA Medicine, Vol. 85, No. 5
The human body requires Vitamin D to function, yet how we obtain the essential vitamin – and what we as physicians can safely recommend to our patients – is constantly up for debate.
Just one hundred years ago, rickets debilitated more than 80 percent of children living in New York City, Boston and London. In many northern cities, increasing industrialization, and the resulting factory work, shifted adults and children indoors, creating a disease not seen in the squalor of much poorer rural communities or cities of more equatorial climates.
By 1921, JAMA editorials touted cod liver oil as an effective antirachitic; scientists later isolated Vitamin D and recognized the connection to solar radiation. Two decades later, the USDA had instituted fortification of milk, breads and cereals. Rickets was largely eradicated, Vitamin D dropped off physician’s radar, and cod liver oil became a distant, distasteful memory.
Transportation and technology catapulted us into the age of trains, automobiles, air travel, indoor plumbing, electricity, radio, television, Hollywood, appliances, grocery stores, computers and the Internet – all of which made it more convenient, conducive, climate controlled and safer to work and play indoors
Many physicians and patients assume that a well-balanced, vitamin-fortified diet is adequate to meet all nutritional needs – including Vitamin D. Unfortunately, Vitamin D occurs naturally in only a few types of foods. The rest is naturally formed when sunshine strikes skin, cycling semiannually. (Figure 1).
Milwaukee-based Schlitz Brewing Company, maker of the now-defunct “Sunshine Vitamin Beer,” boasted in a 1936 ad, “As the summer sun heads south; as days grow shorter and stormier – we get less and less of sunshine’s benefits. Likewise, our ordinary foods are lacking in Sunshine Vitamin D, so essential to robust vitality. … [Our beer] gives you the sunny source of health you need the whole year around … and at no increase in price.”
Dermatologists discourage deliberate ultraviolet radiation exposure; 90 percent of cutaneous malignancies are linked to cumulative and delayed effects of sun on our skin. Despite these efforts, one fifth of the United States (U.S.) population can expect to develop skin cancer in their lifetime. The National Cancer Institute estimatesone death per hour from melanoma in the U.S. this year.
Many risk factors for skin cancer are largely unavoidable (family history, natural skin pigmentation, history of childhood sunburns, altitude and latitude of residence) but lifestyle adjustments can limit ongoing exposure. These include staying inside during the middle of the day when the ultraviolet (UV) B rays are the most intense; avoiding tanning beds; wearing protective clothing, hats and glasses; and correctly applying (and reapplying!) a sufficient amount of sunscreen to exposed skin. In a December 2010 position paper, the American Academy of Dermatology issued a strong monition, warning that “There is no scientifically validated, safe threshold level of UV exposure from the sun or indoor tanning devices that allows for maximal vitamin D synthesis without increasing skin cancer risk.”
The epidermis protects against solar damage and also makes Vitamin D3 for systemic use. Increased melanin content in the epidermis, either genetically directed or developed due to radiation damage as a tan, confers some barrier to penetration of longer wavelengths of light into the dermis. High concentrations of melanin also dampen Vitamin D synthesis in the skin so that darker complexions take longer to form the same amount of Vitamin D when compared to fair complexions exposed to the same intensity of light for the same amount of time.
DIFFERENCES IN LATITUDE
Figure 2 depicts rough, relative latitudes of countries and continents. Hundreds of years ago, before significant mass transportation, many people lived within walking distances of their ancestors’ habitats. Natives near the Arctic Circle, such as the Inuit of Alaska, tolerate months of complete darkness each winter, but their typical diet includes fish rich in Vitamin D.
Compare the latitude of the United Kingdom to that of Australia, used by colonial England as a penal colony. Australia’s indigenous peoples have darker complexions to compensate for their proximity to the equator, but, in general, the transplanted criminals did not, resulting in high rates of skin cancer that persist today. Compare also how much further north the United Kingdom is to the southern United States. The striking difference in latitude demands awareness and lifestyle accommodation for skin cancer prevention and subsequent Vitamin D supply.
There are two sources of Vitamin D: the sun and our diet. There are also two forms of Vitamin D supplements, D2 and D3, which are bioequivalent and handled identically by the GI tract. D2, a vegan source, is available in a prescription form of 50,000 IU; D3 – the form made in the skin – is the most commonly used over-the-counter supplement.
Both D2 and D3 have two names. D2 is also known as ergocalciferol; D3 is also known as cholecalciferol. Together they are called calciferol. Supplements are dosed in either international units (IU) or in micrograms, with 40 IU equal to 1 microgram.
Vitamin D can be measured as two metabolites in the serum called 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D; 25-OH is the best form for screening and is the best marker of available bodily stores, working in concert with the parathyroid hormone to maintain calcium homeostasis. The 1,25-dihydroxyvitamin D form is complexly regulated and used to finesse levels in renal failure and sarcoidosis. (Figure 3) Test results are also given using two units. Most U.S. laboratories use ng/mL units for serum Vitamin D levels; others report using the international system of nmol/L. To convert from ng/mL to nmol/L, multiply by 2.5.
Vitamin D deficiency in infants is classically associated with rickets in children, osteomalacia and osteoporosis in adults. The distribution of Vitamin D receptors throughout the body, including in the brain, breast, prostate and macrophages, indicates a much wider role than in calcium homeostasis, including in autoimmune diseases, certain cancers and cardiovascular disease. It is hard to pick up a journal in any specialty without seeing ongoing studies of the effect of Vitamin D.
25-hydroxyvitamin D blood levels (CPT code 82306) determine whether current supply is adequate. Fasting is not required. Medicare will not cover checking Vitamin D levels unless the patient has a documented Vitamin D deficiency or a limited number of diseases. (Figure 4) Consider testing – or perhaps empiric supplementation – in patients with those conditions or at increased risk of deficiency: people of color; who are elderly, obese or shut-ins; people on medications including anticonvulsants, HAART and cholestyramine; those with poor absorption due to inflammatory bowel disease, cystic fibrosis and celiac disease; and sun avoiders either due to cultural preferences or practicing “safe sun” for skin cancer prevention and anti-aging benefits.
Vitamin D levels are not static; they are highest in late summer and lowest in early spring, proportionate to the length and intensity (angle) of seasonal sunshine. The World Health Organization (WHO) defines 25-OH Vitamin D insufficiency as serum levels <30 ng/ml and Vitamin D deficiency if levels are < 20 ng/ml. Variations in Vitamin D binding protein levels in some people and certain medical conditions (malnutrition, liver disease) may affect the circulating levels.
Ideal levels and safe upper levels are still being discussed and studied. Some have suggested that African Americans have lower “normal” level than European Americans. However, a 2012 study from the British Journal of Nutrition revealed that Hadzabe and Maasai natives of East Africa, hunter-gathers wearing sparse clothes but avoiding sun during the hottest part of the day, had average levels of 44 ng/ml. Studies across eclectic populations including Hawaiian skateboarders, pregnant women on prenatal supplements, and resident physicians in Boston, Southern Brazil and India, show the majority (sometimes 80 percent or more) as Vitamin D deficient using WHO’s criteria.
Vitamin D is absorbed in the distal duodenum and proximal jejunum of the small intestine. Patients with inflammatory bowel conditions, small bowel resection and bariatric surgery may need substantially higher supplement dosing. Food fortification will not be beneficial to people who avoid them due to lactase deficiency and/or gluten avoidance.
Dosing compliance and intestinal absorptive capacity are the driving factors. For many adults, 1000-2000 IU a day may be sufficient, but for post-bariatric surgery obese patients, significantly higher doses may be needed. Toxicity has been reported but is rare.
The Kaiser Permanente Center for Health Research assayed Vitamin D supplements andnoted a startling difference between the printed strength and the assayed activity (from 9 percent to 146 percent of the stated dose) of calciferol. The U.S. Pharmacopeial Convention (USP), an independent, nonprofit organization, annually audits voluntarily participating manufacturers of dietary supplements; approved Vitamin D products tend to test more closely to the stated dose than those from non-participating labs.Consider looking for the USP Verified Mark on supplement packaging to increase the likelihoodof quality, potency and purity of the product.
“The devil is in the details.” More work needs to be done before we have a satisfactory solution to keep our patients and ourselves simultaneously protected from carcinogenic radiation while adequately providing for Vitamin D needs. We might have been spared this dilemma if our forefathers had not left the lands, latitudes and lifestyles of our ancestors. Personally, I prefer to stay in my current climate and maintain my mainly indoor lifestyle – even if I have to be mindful of the sun and Vitamin D.
- American Academy of Dermatology and AAD Association . 2009. Position statement on vitamin D. http://www.aad.org/Forms/Policies/Uploads/PS/PS-Vitamin%20D.pdf Accessed August 20, 2014.
- Kennel KA, Drake MT, Hurley DL. Vitamin D Deficiency in Adults: When to Test and How to Treat. Mayo Clin Proc. 2010;85(8):752-758.
- Vanchinathan V, Lim HW. A Dermatologist’s Perspective on Vitamin D. Mayo Clin Proc. 2012;87(4):372-380.
- National Institutes of Health Office of Dietary Supplements Vitamin D June 24, 2011.
- Holick MF. The Vitamin D Deficiency Pandemic: a Forgotten Hormone Important for Health. Public Health Reviews 2010; 32:267-283.