Areas of Interest
Vitamin D Deficiency - The Cause of Everything?
Vitamin D, a fat-soluble vitamin, is essential for normal calcium metabolism and homeostasis. Vitamin D is also considered a hormone since it meets the basic definition for a hormone: it can be synthesized in the body, it has specific target tissues, and it doesn't have to be supplied by the diet. Vitamin D is also responsible for maintaining normal blood levels of calcium and phosphorus which are vital for normal neuro function and bone growth. Vitamin D also works in concert with other vitamins, minerals and hormones to promote optimal bone mineralization.
Vitamin D is known as the sunshine vitamin since modest exposure to sunlight is generally adequate for most people to meet their vitamin D needs. There are two ingested forms of vitamin D -- D3 and D2. Vitamin D3 (cholecalciferol) can be produced in the skin after exposure to ultraviolet-B (UVB) radiation from sunlight, or it can be supplied by the diet. Plants also produce a form of vitamin D called vitamin D2 (or ergocalciferol), which also has activity in people. Both vitamin D3 and D2 are used to fortify foods and dietary supplements in the US.
Vitamin D2 and D3 are biologically inactive, and therefore must be metabolized to their biologically active forms. After consumed in the diet or synthesized in the skin, vitamin D2 and D3 enter the circulation and are transported to the liver where they are hydroxylated (changed by enzymes)to calcitriol, or 25-hydroxyvitamin D, the major circulating form of vitamin D. Increased exposure to sunlight or increased intake of vitamin D increases blood levels of 25(OH)D, making the serum 25(OH)D concentration a useful indicator of vitamin D nutritional status. In the kidney and other tissues, an enzyme changes 25(OH)D, producing 1alpha,25-dihydroxyvitamin D [1,25(OH)2D] -- the most potent form of vitamin D (Holick, 2005). Most of the physiological effects of vitamin D in the body are related to the activity of 1,25(OH)2D.
Over 50 genes in tissues throughout the body are known to be regulated by 1,25(OH)2D, and the vitamin D receptor has been identified on almost every cell in the body.
Insufficient vitamin D impairs calcium absorption. Subsequently, the parathyroid glands increase their production of parathyroid hormone to mobilize calcium from the skeleton in order to maintain normal serum calcium levels. In cases of severe vitamin D deficiency, rapidly growing bones fail to mineralize resulting in rickets. Although the growth-plates continue to enlarge, in the absence of bone mineralization, weight-bearing limbs begin to bow, resulting in skeletal abnormalities. Though the fortification of foods with vitamin D (primarily milk) has practically eradicated rickets; there are a large number of children and adults worldwide who are vitamin D insufficient without apparent skeletal or calcium metabolism abnormalities.
Assessing Vitamin D Status
Serum vitamin D level is the best indicator of vitamin D deficiency and sufficiency, but the cutoff values have not been clearly defined. While laboratory reference ranges for serum vitamin D levels are often based on average values from populations of healthy individuals, recent research suggests that health-based cutoff values aimed at preventing an over-functioning parathyroid and bone loss are likely considerably higher. Severe deficiency, which is associated with rickets and weakened bones, is generally associated with serum vitamin D values less than 20. Although 50 has been suggested as the low end of the normal range, more recent research suggests that parathyroid function and calcium absorption are not optimized until vitamin D levels reach approximately 80 . Data from supplementation studies indicates that vitamin D intakes of at least 800-1,000 IU/day are required by adults living in temperate latitudes to achieve serum vitamin D levels of at least 80 nmol/L (Vieth, 1999; Tangpricha et al., 2003).
Very few foods are naturally rich in vitamin D, therefore, fortified foods are the most common sources of vitamin D. Due to the rickets epidemic in the 1930s, the U.S. established and implemented a milk fortification program to combat this problem. As a result, rickets was nearly eliminated in the U.S. Most of the milk supply in the U.S. is fortified with 10 micrograms (ìg) (equal to 400 International Units or IU) of vitamin D per quart.
Although milk is fortified with vitamin D, other dairy products produced from milk, such as cheese and ice creams, are typically not fortified with vitamin D and therefore, may only contain small amounts. Commercially-prepared fortified breakfast cereals generally provide 10-15% of the vitamin D of the Daily Value. There is also some vitamin D in eggs, organ meats, and fish such as salmon, sardines, and herring. The following table provides a listing of foods that provide vitamin D in varying amounts.
|Food||Serving Size||Vitamin D (I.U.)|
|Pink salmon, canned||3 ounces||530|
|Sardines, canned||3 ounces||231|
|Tuna, canned||3 ounces||200|
|Cow's milk||8 ounces||100|
|Orange juice fortified w/ Vit D||8 ounces||100|
|Fortified breakfast cereals||1 serving (1 cup)||40-50|
|Cod liver oil||1 ounce||1,360|
Disease Prevention and Intervention
Components of the immune system, including its special cells called macrophages, monocytes, and T and B lymphocytes, also have a vitamin D receptor, thereby allowing vitamin D to have an impact proper functioning, etc (Holick, 2005). The risk of developing Type 1 diabetes and multiple sclerosis (MS) was significantly reduced or prevented in animals receiving vitamin D supplements. Reportedly, living at a latitude above 37° increases the risk of developing multiple sclerosis>100% during one's lifetime (Holick, 2005). The risk for both multiple sclerosis and rheumatoid arthritis was decreased by ~40% in women taking a multi-vitamin supplement with 400 I.U. of vitamin D (Holick, 2005).
It is estimated that over 28 million adults in the United States have, or are at risk of developing low bone density and osteoporosis, and osteoporosis is expected to become epidemic. Given the magnitude of this problem, prevention and early intervention is paramount.
Osteoporosis is most often associated with inadequate calcium intake. However, a deficiency of vitamin D also contributes to the development of osteoporosis due to inadequate calcium and phosphorus absorption. This results in a decrease in serum calcium levels. In response, the parathyroid facilitates the mobilization of calcium from the skeleton. As a result of vitamin D deficiency, increased parathyroid activity develops causing continued leaching of calcium from the skeleton thereby weakening the skeleton which subsequently results in low bone density.
While rickets is an extreme examples of vitamin D deficiency, osteoporosis is an example of a long-term effect of vitamin D insufficiency. Adequate storage levels of vitamin D help keep bones strong and may help prevent osteoporosis in older adults, in non-ambulatory individuals (those who have difficulty walking and exercising), in post-menopausal women, and in individuals on chronic steroid and antiepileptic therapies.
A number of studies have examined the impact of vitamin D supplementation on bone loss in older adults, showing that vitamin D supplementation daily with 400-800 I.U., given alone or in conjunction with calcium, can reverse vitamin D insufficiency, prevent bone loss, and improve bone density (Bischoff-Ferrari et al., 2005; Gennari, 2001). Sufficient vitamin D intake is also associated with a reduction in falls (Graafsman et al., 1996). Vitamin D supplementation for the prevention and management of osteoporosis is considered an effective public health benefit due to its low costs, excellent tolerance, and overall health benefits.
Alzheimer's disease is associated with an increased risk of hip fractures. This may be because many Alzheimer's patients are older, homebound, and exposed less to sunlight. With aging, less vitamin D is converted to its active form. One study, which included elderly women with Alzheimer's disease, found that decreased bone mineral density was associated with a low intake of vitamin D and inadequate sunlight exposure (Sato et al., 2005). However, with regular sunlight exposure and calcium supplementation, bone mineral density increased by 2.7% and serum 25(OH)D levels increased from 24 nmol/L to 52 (Sato et al., 2005). The need for vitamin D supplementation should be considered as part of an overall treatment plan for adults with Alzheimer's disease.
Laboratory, animal, and epidemiologic evidence suggests that vitamin D may be protective against some cancers. Epidemiologic studies suggest that a higher dietary intake of calcium and vitamin D, and/or sunlight-induced vitamin D synthesis, correlates with lower incidence of cancer. In fact, for over 60 years researchers have observed an inverse association between sun exposure and cancer mortality, however, it wasn’t until the late 1980s that Garland and colleagues found that the mortality rate associated with colon cancer was higher in the Northeastern states of the US compared to southern states (Garland et al., 1985). A wealth of accumulated data reveals that the risk of developing and dying of breast, colon, esophageal, non-Hodgkin’s Lymphoma, ovarian, and prostate cancers is associated with living at higher latitudes and being at a greater risk for vitamin D deficiency (Holick, 2005; Hanchette & Schwartz, 1992; Grant, 2002).
Assessment of vitamin D status is a vital component of an integrative medicine evaluation.