Vitamin D deficiency has been closely associated with rickets, a scourge of the nineteenth century that health professionals thought was largely conquered through dietary supplementation. However, emerging knowledge has shown that vitamin D can have very wide ranging effects. Directly or indirectly, the metabolically active form of vitamin D controls more than 200 genes. (Holick)
Humans Obtain Vitamin D From Three Sources
- Sunlight- solar ultraviolet radiation penetrates the skin and converts 7-dehydrocholesterol to vitamin D3. Under intense summer sun, optimal accumulation of vitamin D can be obtained with an exposure of only 10-15 minutes per day, three times per week. However, in northern climates little or no vitamin D will be obtained from sun exposure in the winter months.
- Diet - Very few natural foods have significant levels of vitamin D, and are largely limited to oily fish.
- Supplements - Vitamin D can be obtained from a variety of fortified foods, as well as in vitamin tablets. Vitamin D2 (ergosterol) is is manufactured by ultraviolet irradiation of ergosterol from yeast, and is the prescription form of vitamin D. Vitamin D3 (cholecholesterol) is manufactured from ultraviolet irradiation of 7-dehydrocholesterol from lanolin, and is the form commonly found in supplements. Vitamin D3 is three times more biologically active than Vitamin D2.
The Active Form of Vitamin D is Actually a Hormone
Vitamin D obtained from the skin or diet is further metabolized by the body to 25-hydroxy vitamin D, which is the primary storage form of the vitamin. 25-hydroxy vitamin D is further metabolized to its active form 1,25-dihydroxyvitamin D. A wide variety of tissues have vitamin D receptors that respond to 1,25-dihydroxy vitamin D. These receptors are essential for hormone action, and account for the broad range of vitamin D effects.
How Widespread is Vitamin D Deficiency?
Most experts define vitamin D deficiency as a 25-hydroxy vitamin D blood serum level of less than 20 ng per milliliter. Likewise, there is a general consensus (Gordon) that a 25-hydroxy vitamin D level of less than 30 ng per milliliter is suboptimal. Given these criteria, Gordon and co-workers found that 12.1% of healthy infants and toddlers were vitamin D deficient,and 40% had suboptimal levels of vitamin D. An earlier study showed that 24.1% of healthy adolescents were vitamin D deficient, and 42% were vitamin D insufficient. A review article from the Mayo Clinic indicated that from one-third to one-half of healthy middle-aged to elderly adults have low levels of 25-hydroxy vitamin D.
Vitamin D Deficiency and Osteoporosis
Studies of post-menopausal women receiving treatment for osteoporosis indicated that 50-70% of the patients had suboptimal 25-hydroxy vitamin D levels. Recognizing the importance of vitamin D for calcium absorption from the intestines, manufacturers now routinely add vitamin D3 in calcium tablets. Although classical rickets is rather uncommon today, clinicians are concerned that suboptimal vitamin D status could lead to skeletal deformities later in life.
Vitamin D Deficiency and Cancer
1,25-dihydroxy vitamin D is one of the most potent hormones for regulating cell growth. 1,25-dihydroxy vitamin D inhibits proliferation and induces differentiation of cells. The hormone reduces cancer spread by reducing angiogenesis (blood vessel growth in tumors) and by increasing apoptosis (cell death). Epidemiologic (population) studies indicate that 1,25-dihydroxy vitamin D levels below 20 ng per milliliter are associated with a 30 to 50% increased risk of colon, prostate, and breast cancers.
Vitamin D Deficiency and Cardiovascular Disease
Vitamin D receptors are common in tissues important to cardiovascular disease, including smooth muscle, endothelium, and cardiomyocytes. When 1,25-dihydroxy vitamin D binds to these receptors, they activate a variety of physiological functions, such as regulating smooth muscle proliferation, inflammation, and thrombosis (blood clots). A Framingham Heart Study involving 1739 subjects without prior cardiovascular disease found that individuals with less than 15 ng per milliliter of 25-hydroxy vitamin D had a significantly increased incidence of heart disease.
Vitamin D Deficiency Has Been Implicated in Many Other Diseases
Several studies indicate that vitamin D inadequacy contributes to muscle weakness and falls. Studies have also indicated that men and women who are vitamin D deficient had an approximately 40% greater risk of developing multiple sclerosis. There is some evidence that vitamin D intake is inversely associated with rheumatoid arthritis, and osteoarthritis.
Are Current Recommendations of Vitamin D Adequate?
The Institute of Medicine recommends a daily intake of 200 IU for children and adults up to 50 years of age, increasing to 400 IU for adults from 51 to 70 years of age, and 600 IU for older adults. The FDA recommends 400 IU regardless of age. Currently, experts agree that without adequate sun exposure, children and adults require from 800-1000 IU per day to achieve 25-hydroxy vitamin D serum levels of at least 30 ng per milliliter. Supplementation is even more critical for women who are breast feeding infants.
Vitamin D toxicity is very rare, and has only been observed when daily supplementation exceeds 10,000 IU per day. Linda Mundorff provides an excellent summary of conditions and medications in which vitamin D supplementation is contraindicated.
References
- Gordon, C.,et.al. Prevalence of Vitamin D Deficiency Among Healthy Infants and Toddlers. Arch Pediatr Adolesc Med. 2008 June; 162(6):505-512.
- Gordon, C.,et.al. Prevalence of Vitamin D Deficiency Among Healthy Adolescents. Arch Pediatr Adolesc Med. 2004 June;158:531-536.
- Holick, M. Vitamin D Deficiency. N Eng J Med 2007 July 19; 357(3):266-279.
- Holick, M. High Prevalence of Vitamin D Inadequacy and Implications for Health. Mayo Clin Proc. 2006;81(3);353-373.
- Mundorff, L. Vitamin D. 2009 Feb 19; Suite 101.com.
- Wang, T., et.al. Vitamin D Deficiency and Risk of Cardiovascular Disease. Circulation. 2008;117:503-511.
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