builtbeast

Vitamin D has been in the news recently with the latest research suggesting some exposure could help prevent cancer. This thread will be for information on it's properties, mechanisms, efficacy and potential cancer prevention.

builtbeast

Vitamin D (Cholecalciferol)

Vitamin D is a steroid hormone that has long been known for its important role in regulating body levels of calcium and phosphorus, and in mineralization of bone. More recently, it has become clear that receptors for vitamin D are present in a wide variety of cells, and that this hormone has biologic effects which extend far beyond control of mineral metabolism.


Structure and Synthesis

The term vitamin D actually refers to a group of steroid molecules. Vitamin D3, also known as cholecalciferol is generated in the skin of animals when light energy is absorbed by a precursor molecule 7-dehydrocholesterol. Vitamin D is thus not a true vitamin, because individuals with adequate exposure to sunlight do not require dietary supplementation. There are dietary sources of vitamin D, including egg yolk, fish oil and a number of plants. The plant form of vitamin D is called vitamin D2 or ergosterol. However, natural diets typically do not contain adequate quantities of vitamin D, and exposure to sunlight or consumption of foodstuffs purposefully supplemented with vitamin D are necessary to prevent deficiencies.

Vitamin D, as either D3 or D2, does not have significant biological activity. Rather, it must be metabolized within the body to the hormonally-active form. This transformation occurs in two steps, as depicted in the diagram below:

1. Within the liver, cholecalciferal is hydroxylated to 25-hydroxycholecalciferol by the enzyme 25-hydroxylase.
   
   
2. Within the kidney, 25-vitamin D serves as a substrate for 1-alpha-hydroxylase, yielding 1,25-dihydroxycholecalciferol, the biologically active form of vitamin D.

Each of the forms of vitamin D is hydrophobic, and is transported in blood bound to carrier proteins. The major carrier is called, appropriately, vitamin D-binding protein. The halflife of 25-hydroxycholecalciferol is several weeks, while that of 1,25-dihydroxycholecalciferol is only a few hours.

Control of Vitamin D Synthesis

Hepatic synthesis of 25-hydroxycholecalciferol is only loosely regulated, and blood levels of this molecule largely reflect the amount of amount of vitamin D produced in the skin or ingested. In contrast, the activity of 1-alpha-hydroxylase in the kidney is tightly regulated and serves as the major control point in production of the active hormone. The major inducer of 1-alpha-hydroxylase is parathyroid hormone; it is also induced by low blood levels of phosphate.

The Vitamin D Receptor and Mechanism of Action

The active form of vitamin D binds to intracellular receptors that then function as transcription factors to modulate gene expression. Like the receptors for other steroid hormones and thyroid hormones, the vitamin D receptor has hormone-binding and DNA-binding domains. The vitamin D receptor forms a complex with another intracellular receptor, the retinoid-X receptor, and that heterodimer is what binds to DNA. In most cases studied, the effect is to activate transcription, but situations are also known in which vitamin D suppresses transcription.

The vitamin D receptor binds several forms of cholecalciferol. Its affinity for 1,25-dihydroxycholecalciferol is roughly 1000 times that for 25-hydroxycholecalciferol, which explains their relative biological potencies.

Physiological Effects of Vitamin D

Vitamin D is well known as a hormone involved in mineral metabolism and bone growth. Its most dramatic effect is to facilitate intestinal absorption of calcium, although it also stimulates absorption of phosphate and magnesium ions. In the absence of vitamin D, dietary calcium is not absorbed at all efficiently. Vitamin D stimulates the expression of a number of proteins involved in transporting calcium from the lumen of the intestine, across the epithelial cells and into blood. The best-studied of these calcium transporters is calbindin, an intracellular protein that ferries calcium across the intestinal epithelial cell.

Numerous effects of vitamin D on bone have been demonstrated. As a transcriptional regulator of bone matrix proteins, it induces the expression of osteocalcin and suppresses synthesis of type I collagen. In cell cultures, vitamin D stimulates differentiation of osteoclasts. However, studies of humans and animals with vitamin D deficiency or mutations in the vitamin D receptor suggest that these effects are perhaps not of major physiologic importance, and that the crutial effect of vitamin D on bone is to provide the proper balance of calcium and phosphorus to support mineralization.

It turns out that vitamin D receptors are present in most if not all cells in the body. Additionally, experiments using cultured cells have demonstrated that vitamin D has potent effects on the growth and differentiation of many types of cells. These findings suggest that vitamin D has physiologic effects much broader that a role in mineral homeostasis and bone function. This is an active area of research and a much better understanding of this area will likely be available in the near future.

Vitamin D toxicity

Excessive exposure to sunlight does not lead to overproduction of vitamin D. Vitamin D toxicity is inevitably the result of overdosing on vitamin D supplements. Don't do this! Ingestion of milligram quantities of vitamin D over periods of weeks of months can be severely toxic to humans and animals. In fact, baits laced with vitamin D are used very effectively as rodenticides.



ref: http://arbl.cvmbs.colostate.edu/hboo.../vitamind.html

builtbeast

Food

Fortified foods are common sources of vitamin D. In the 1930s, rickets was a major public health problem in the United States (U.S.). A milk fortification program was implemented to combat rickets, and it nearly eliminated this disorder in the U.S. About 98% to 99% 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. One cup of vitamin D fortified milk supplies one-half of the recommended daily intake for adults between the ages of 19 and 50, one-fourth of the recommended daily intake for adults between the ages of 51 and 70, and approximately 15% of the recommended daily intake for adults age 71 and over.

Although milk is fortified with vitamin D, dairy products made from milk, such as cheese and ice creams, are generally not fortified with vitamin D and contain only small amounts. Some ready-to-eat breakfast cereals may be fortified with vitamin D, often at a level of 10% to 15% of the Daily Value*. There are only a few commonly consumed foods that are good sources of vitamin D. Suggested dietary sources of vitamin D are listed in Table 1.

Table 1: Selected food sources of vitamin D



Sun exposure

Sun exposure is perhaps the most important source of vitamin D because exposure to sunlight provides most humans with their vitamin D requirement. UV rays from the sun trigger vitamin D synthesis in skin. Season, geographic latitude, time of day, cloud cover, smog, and sunscreen affect UV ray exposure and vitamin D synthesis. For example, sunlight exposure from November through February in Boston is insufficient to produce significant vitamin D synthesis in the skin. Complete cloud cover halves the energy of UV rays, and shade reduces it by 60%. Industrial pollution, which increases shade, also decreases sun exposure and may contribute to the development of rickets in individuals with insufficient dietary intake of vitamin D. Sunscreens with a sun protection factor (SPF) of 8 or greater will block UV rays that produce vitamin D, but it is still important to routinely use sunscreen to help prevent skin cancer and other negative consequences of excessive sun exposure. An initial exposure to sunlight (10 -15 minutes) allows adequate time for Vitamin D synthesis and should be followed by application of a sunscreen with an SPF of at least 15 to protect the skin. Ten to fifteen minutes of sun exposure at least two times per week to the face, arms, hands, or back without sunscreen is usually sufficient to provide adequate vitamin D. It is very important for individuals with limited sun exposure to include good sources of vitamin D in their diet.


ref: http://ods.od.nih.gov/factsheets/vitamind.asp

builtbeast

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. The inverse relationship between higher vitamin D levels in blood and lower cancer risk in humans is best documented for colon and colorectal cancers. Vitamin D emerged as a protective factor in a study of over 3,000 adults (96% of whom were men) who underwent a colonoscopy between 1994 and 1997 to look for polyps or lesions in the colon. About 10% of the group was found to have at least one advanced neoplastic (cancerous) lesion in the colon. There was a significantly lower risk of advanced cancerous lesions among those with the highest vitamin D intake.


ref: http://ods.od.nih.gov/factsheets/vitamind.asp