Few molecules are as vital to human health yet so thoroughly misunderstood as vitamin D. There exists a tremendous gap between scientifically sound principles and clinical applications. Careful evaluations of clinical trials that examined health and disease relationships associated with vitamin D indicate that the actual daily requirement is closer to 1,000 IU instead of the current recommendation of 400 IU.
Bischoff-Ferrari et al. (2005, 2006) showed that the culmination of clinical evidence supports the assertion that a higher intake of vitamin D results in improved functional outcomes, including a decreased incidence of fractures, improved muscle strength and thus a reduction in falls, enhanced oral health, and reduced risk of colorectal and other cancers.
Thus, vitamin D may be viewed as an important "functional food" nutrient that reaches beyond the results of vitamin deficiency. Hyppönen and Power (2007) reported that in a study of nearly 7,500 subjects in Great Britain, the general population was at high risk of vitamin D deficiency in spring and winter and affected more women than men. The risk of vitamin deficiency was reduced in this population during the summer and fall months, yet nearly 61% of the subjects exhibited serum 25-hydroxy vitamin D levels below 75 nmol/L.
Calvo et al. (2004) championed a call for global increase in vitamin D intake because of the increased prevalence of rickets and elevated risk of osteoporosis, diabetes, some cancers, and several autoimmune disorders that may be related to reduced exposure to sunlight (UVB) and subsequent vitamin D insufficiency. The absence of adequate exposure to UVB and the increased risks of melanoma from unprotected outdoors living in sunny climates indicate that vitamin D fortification of the global food supply is the logical alternative.
Hathcock et al. (2007) reassessed the safe Tolerable Upper Intake Level (UL) of vitamin D based on Food and Nutrition Board (FNB) methodologies and revised it from 2,000 IU/day to >10,000 IU/day. This is supported by numerous clinical studies and the absence of apparent toxicity in healthy adult humans having consumed 100,000 IU/day for 4 days or a bolus every 4 mo for 5 years (Trivedi et al., 2003).
Clinical trials with elevated doses of vitamin D did not result in any significant alterations in serum calcium or phosphorus levels, except for those with granulomatous disease such as sarcoidosis, Mycobacterium infections, Crohn’s disease, and infantile fat necrosis, and those treated with thiazide diuretics who are extremely sensitive to excessive vitamin D. For example, Adams and Lee (1997) reported that vitamin D intoxication (1,000-1,200 IU/day for up to 3 years) produced hypercalcuria and increased bone turnover in only 4 of 39 subjects. Obviously, there are many factors that determine whether someone may present symptoms of vitamin D deficiency, such as efficiency of conversion of vitamin D3 by 25-hydroxylase in the liver and theoretical polymorphisms in vitamin D receptor or binding protein.
Froicu and Cantorna (2007) showed that the active form of vitamin D (1,25-(OH)2 D3) inhibits the development of inflammatory bowel disease in IL-10 knock out mice. In models of Crohn’s disease and ulcerative colitis, research demonstrated epithelial resistance to injury as well as suppression of immune response to luminal antigens through vitamin D receptor signaling. The macrophage was also discussed as an important vitamin D target. This pointed to a potential critical role for the vitamin D receptor and 1,25-(OH)2 D3 in response to colonic injury.
Abreu et al. (2004) studied the autocrine and paracrine effects of vitamin D and found that the low bone mineralization observed in subjects with Crohn’s disease was inversely correlated with serum 1,25-(OH)2D levels and that the mineralization defect in the skeleton might be improved by controlling intestinal inflammation. Adams (2006) found that vitamin D may function as a defensin, a function typically ascribed to small, cysteine-rich peptides.
The innate stability of vitamin D in food products, the very low likelihood of developing vitamin D hypervitaminosis, and the accumulated clinical evidence for health benefits associated with increased vitamin D intake support two important opportunities. One is for domestic and international agencies, such as FNB and the European Commission’s Health and Consumer Protection Directorate-General, to reassess the dietary recommendations for vitamin D. The other is for food companies to include higher levels of vitamin D in food products. The simple addition of vitamin D to appropriate food products may have a prophylactic impact on several health conditions, including but not limited to osteoporosis, diabetes, and cardiovascular disease.
References for the studies mentioned above are available from the authors.
by Jordan Geller, M.D.
Clinical Instructor of Medicine, UCLA School of Medicine, Los Angeles, Calif.
by Peter Pressman, M.D.,
Attending Staff, Internal Medicine, Cedars-Sinai Medical Center, Los Angeles, Calif.