As I prepared to write this article, the Spring 2008 issue of Holistic Primary Care arrived in my mail. There were four articles about vitamin D and its effects on cardiovascular risk, diabetes, polycystic ovary syndrome, autoimmune disease, and cancer. This vitamin, or perhaps better described as a prohormone or “vitamone,” has risen to great prominence in recent years.
Over the last decade we have learned quite a lot about the broad sphere of influence of the vitamin D prohormone. Vitamin D receptors (VDR) are present in over thirty human tissues and organs, and vitamin D targets more than 200 human genes. Different shapes of 1,25(OH)2D3 act as molecular switches through VDRs in different cellular locations to selectively mediate gene expression; this is in addition to vitamin D’s direct and more rapid effects on various tissues (Norman AW. Endocrinology. 2006 Dec; 147(12): 5542–5548).
Heightened clinical awareness of vitamin D and its deficiency are definitely warranted. A recent meta-analysis of 18 randomized controlled trials revealed that supplemental vitamin D significantly reduced all-cause mortality by seven percent, and these studies used low doses (mean 538 IU) and were relatively short (Autier P, Gandini S. Arch Intern Med. 2007; 167: 1730–1737). Another recent study shows that statin drugs significantly increase 25(OH)D, suggesting that some of the mortality reduction attributed to statins may be due to elevated vitamin D levels (Aloia JF, et al. Am J Cardiol. 2007; 100: 1329).
But along with all the promising new findings come new questions. Some of the new research challenges long-held ideas about this vitamin. Like many things in medicine, the vitamin D story may not be as simple as we would like it to be.
Vitamin D deficiency has been found in association with many chronic diseases. But for most of these disorders it is not yet clear whether the deficiency is a causal factor or a result of the disease processes. Vitamin D has both immune-enhancing and immunosuppressive effects. There is speculation that supplemental vitamin D may actually block VDR activation, and promote rather than improve certain immune responses (Marshall TG. BioEssays. 2008; 30(2): 173–182).
Since 25(OH)D is called a “vitamin,” there is a common misconception that we can obtain adequate amounts from a healthy diet. But most diets contain minimal vitamin D. Dietary sources are limited to fatty fish, reindeer meat, sun-dried Shiitake mushrooms, and fortified foods (milk, juices, cereals).
Our main source of vitamin D comes from its production in the skin. Thirty minutes of full-body summer sun exposure produces approximately 20,000 IU in a fair-skinned person.
The Sunshine Vitamin—or Not?
But again, it may not be as simple as it seems. Three studies, from Honolulu, Tucson, and Miami, have shown that contrary to popular belief, serum vitamin D levels do not necessarily correlate with sun exposure (Binkley N, et al. J Clin Endocrinol Metab. 2007 Jun; 92(6): 2130–2135; Jacobs ET, et al. Am J Clin Nutr. 2008; 87(3): 608–613; Levis S, et al. J Clin Endocrinol Metab. 2005 Mar; 90(3): 1557–1562). There was no correlation between serum 25(OH)D levels and age, lightest or darkest skin color, hours per week of sun exposure without sunscreen, or total hours/week of sun exposure.
This lack of correlation seems surprising. But consider that many factors affect vitamin D production, including: skin color, current tan level, amount of time spent in the sun, weather conditions (cloud cover and pollution, ozone layer, surface reflection, etc.), latitude and altitude, season, use of sunscreen and/or sun protective clothing.
Body weight also factors in, because fat absorbs vitamin D (Yanoff LB, et al. Clin Endocrinol (Oxf). 2006; 64: 523–529), and the vitamin stores in fat are not measurable in serum. Age is also a factor: elderly people produce much less than 20-year-olds after the same amount of sun exposure (Holick MF. Am J Clin Nutr. 1994; 60: 619–630). Other possible explanations include: inadequate cutaneous production of vitamin D3; increased cutaneous destruction of previtamin D3; down-regulation of cutaneous synthesis by sun-induced melanin production; and abnormalities of transport from skin to the blood.
Given the complexity of cutaneous vitamin D production and transfer to the bloodstream, it is not so surprising that by looking at just one factor alone, without controlling for the others, none of these studies showed correlations.
Treatment of Vitamin D Deficiency
We know vitamin D deficiency is quite common, and it does warrant treatment. Vitamin D supplementation is the most rational solution, but in severely deficient people, repletion may require very high doses, ranging from 400 IU/day for infants to 10,000 IU/day for obese patients. In severely deficient people, a dose of 1,000 IU/day for 3–4 months will generally result in approximately a 10 ng/mL increase of 25(OH)D from baseline. Vitamin D kinetics are not linear, however, and a similar dose will not increase higher baseline levels by a similar amount (Cannell JJ, Hollis BW. Alt Med Rev. 2008; 13: 6–20).
For healthy people, dosage should be individualized. The question of optimal level depends on the individual’s health status and health objectives. To optimize intestinal calcium absorption, 34 ng/mL is the target (Heaney RP, et al. J Am Coll Nutr. 2003; 22: 142–146). To optimize neuromuscular performance, 38 ng/mL is needed (Hollis BW, Wagern CL. Am J Clin Nutr. 2004; 80: 1752S–1758S). To effect a 50-percent reduction in breast cancer incidence, 52 ng/mL is the estimated level (Garland CF, et al. J Steroid Biochem Mol Biol. 2007; 103: 708–711).
I recommend measuring 25(OH)D at least twice yearly on any patient at risk, once in the early spring for the nadir, and again in the late summer for a peak level. Since the kidneys exert tight control over serum 1,25(OH)2D3 levels, measurement of this activated form of vitamin D is not a reliable indicator of hypovitaminosis D.
With the exception of osteoporosis and psoriasis, vitamin D has not been conclusively proven effective as a therapy for other conditions. There are certainly a lot of suggestive findings in cardiovascular disease, metabolic syndrome, and autoimmune diseases, but so far the evidence is anecdotal, from epidemiological studies or open trials. Hopefully, further research will permit us to make more solid therapeutic recommendations.
Michael Traub, ND, DHANP, FABNO, past-president of the American Association of Naturopathic Physicians, practices on the Big Island of Hawaii. He is designing a study to compare the relative efficacy of an emulsified liquid vitamin D with a capsulated vitamin D. Interested parties may contact him at michaeltraub@earthlink.net.
