Sitocalciferol or Vitamin D5 is one of six different forms of vitamin D, which are numbered from D2 to D7. All six of these forms are based upon calcitrol, and will be converted into calcitrol by the body when they are consumed. They differ in their origin, however, with vitamin D2 and D3 being naturally available. Vitamin D5 is a synthetically produced form of the vitamin.
Vitamin D is a fat-soluble chemical. It is only found naturally in a few types of food, but in some countries including the US, vitamin D is added to other foods such as milk. Stores of vitamin D can be built up in the body. Having too much or too little vitamin D in the body can be harmful.
Maintaining the optimum levels of this vitamin is very important in order to stay healthy. Vitamin D has a particularly strong effect on the bones. If the body does not get enough vitamin D then the bones can become weak and can grow abnormally. If the level of vitamin D in the body become too high, and reaches toxic concentrations, then the bones can be weakened.
Common Forms
The most common forms of vitamin D are D2 and D3. Vitamin D2 is produced by plants and can therefore be obtained from food. Vitamin D3 is produced in the body. When the skin is exposed to the ultraviolet B or UVB rays in sunlight, the synthesis of vitamin D3 in stimulated in the skin. People can also obtain both D2 and D3 from foods that have been artificially fortified with vitamin D.
Vitamin D5 is an artificially produced analog of vitamin D3. An analog is a chemical that shares some structural properties with another chemical, but which can behave differently from it. Vitamin D5 is structurally similar to vitamin D3, and both can be used by the body in similar ways. The D5 form is less toxic than the D3 analog, however, which makes vitamin D5 a better option for medicinal uses of vitamin D.
The 1α-Hydroxyvitamin D5 form of the vitamin was designed and produced by a team of scientists at the University of Illinois, Chicago and has since been studied in a number of experiments to test its safety and efficacy as a treatment for various cancers, particularly cancers of the breast, prostate and colon.
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Chemistry
Vitamin D is a prohormone rather than being a true vitamin. When it is consumed, the body metabolizes it into a number of chemicals that are hormones. Hormones are chemical signals that are used by the body to control various functions.
Vitamin D5 is an analog of vitamin D3. They have very similar structures, but vitamin D5 has been slightly modified. Just a few of the atoms have been changed. Many different analogs of vitamin D3 were designed by scientists searching for a less toxic version of the vitamin that could be used for medicinal purposes without causing problems with toxicity.
Over 1500 of these analogs were produced. The available forms of vitamin D are now classified into six primary forms, named D2, D3, D4, D5, D6 and D7. Each form has a slightly different molecular structure, although they are all still basically the same molecule, and have similar functions in the body. The least toxic of these forms is vitamin D5, which has now undergone a number of experiments to test its efficacy and safety for the prevention and treatment of cancer.
Function
Vitamin D is essential for the maintenance of adequate levels of phosphorus and calcium in the blood. Vitamin D helps the body to absorb calcium from the intestine. Both phosphorous and calcium are required for the development and maintenance of strong bones. Vitamin D may also be able to help to protect the body against high blood pressure, cancer, osteoperosis and certain autoimmune diseases, although the scientific evidence for these functions is less clear-cut that that which shows the importance of vitamin D for the skeleton.
The vitamin D which is obtained from food or which is produced in the skin following stimulation by the sunlight is an inactive chemical. It must be converted through two hydroxylation reactions into its active forms in order to be used. The first reaction occurs in the liver, where the vitamin D is converted into calcidol. Next, the second reaction, which takes place in the kidneys, converts this calcidol into calcitrol.
The most active metabolite of vitamin D is calcitrol. Conversion of vitamin D into calcitrol is regulated according to how much calcium and phosphorus is in the blood, the concentration of calcitrol that is already present in the body, and by the parathyroid hormone. This regulation ensures that the calcitrol levels are maintained at the correct level, as long as there is enough vitamin D available from which to produce more calcitrol when it is needed.
Important Function
The most important function of vitamin D in the body is in the maintenance of calcium and phosphorus levels, and so for ensuring there is proper bone growth and development. There are also some other important functions played by this vitamin in the body. It is involved in the working of the immune system, neuromuscular function, and in reducing inflammation. Vitamin D also plays a role, along with other chemicals, in the modulation of a number of genes that regulate cell division, growth, differentiation and death.
Since most of the vitamin D that is consumed in food, fortified foods and supplements, are in the form of vitamin D2 and D3, these are the most important forms for humans. Vitamin D5, however, may have some important uses, particularly in medicine. Vitamin D5 can also perform similar functions to other versions of the vitamin, when it is consumed.
Deficiency
Vitamin D deficiencies are one of the more common vitamin deficiencies, since the levels of this chemical in food are so low. The chances of suffering a deficiency in vitamin D are related not only to a poor diet, and therefore to poverty, but to certain lifestyle choices and to the climate and latitude at which people live. This is because people do not only obtain vitamin D ready made from their food, but can synthesize it themselves. This synthesis relies on sunlight in order to work, however, therefore exposure to the sun is an important guard against vitamin D deficiencies.
The most well known effect of a deficiency in vitamin D is rickets, which is a condition in which skeletal abnormalities and deformities develop in children. Adults who are not obtaining enough vitamin D can also suffer from weaknesses in their bones, and their muscles may also become weakened. This condition is called osteomalacia. Without a sufficient intake of vitamin D, there will not be enough calcium or phosphate in the blood to ensure that bone mineralization and development occurs properly. This will lead to the bones becoming too thin, weak and brittle. They can also become misshapen and deformed.
Risk Factors
Certain groups of people are at a higher risk of developing a vitamin D deficiency than others. People who are elderly or obese are at an increased risk of vitamin D deficiency, as are infants who have been fed exclusively on breast milk, which contains only low levels of vitamin D, and anyone who has experienced very limited exposure to the sun. Some diseases can also increase the risk of a vitamin D deficiency. These are conditions that affect the absorption of fats, such as cystic fibrosis, or disorders that affect the digestive system, such as Crohn’s disease and inflammatory bowel disease.
A vitamin D deficiency can be treated by increasing the uptake of vitamin D through dietary supplements, or, if possible, increasing exposure to sunlight.
Toxicity
An excess of vitamin D in the body can be toxic, but D5 is the least toxic form of this vitamin. It is therefore the most suitable for medicinal uses, since it is less likely to cause adverse side effects than the other types of vitamin D. If vitamin D, in any form, does build up to toxic levels, however, it can be very harmful.
Vitamin D toxicity can result in a condition called hypocalcaemia that can lead to bone loss. In the most serious cases of hypocalcaemia, the damage can be very serious and may even lead to life threatening side effects. The earliest symptoms of toxicity may include nausea and vomiting. Anorexia, which presents as a loss of weight and appetite may also occur. This can be followed by excess thirst and urination, fatigue, weakness, headache, a metallic taste, dry mouth, tinnitus or ringing ears, vertigo and unsteadiness. The functioning of the kidneys can be impaired, and calcium may be deposited in them and around the organs of the rest of the body. This deposition is known as metastatic calcification.
Hypercalcaemia is treated by stopping further intake of calcium or vitamin D, and gradually reducing the calcium levels in the body. This must be done under medical supervision, in order to ensure that the calcium levels can be monitored. In some cases, it may also be necessary for the condition to be treated with corticosteroids and acidification of the urine.
Medicinal Uses
Research into the potential of vitamin D for the prevention and treatment of cancer was stimulated by epidemiological studies that showed people who had high levels of vitamin D in their diet, or who had high levels of sunlight-induced formation of vitamin D in their skins, were less likely to develop cancer. An epidemiological study is one that looks at what is happening in real populations of people rather than setting up an experiment or testing a particular treatment.
In studies that were conducted in vitro, that is in isolated cells in a laboratory, Vitamin D3 was found to be effective at preventing cancer. However, there was the problem of toxicity.
The doses that were high enough to reduce the chances of a cell developing cancer were also so high that they would be toxic to patients. This meant that vitamin D3 treatment for the prevention of cancer was not possible. In order to be effective, vitamin D3 treatment would require doses that were hundreds of times greater than those that are normal in the body.
The use of vitamin D as a treatment was limited by the toxic effects that it can have when it is present at high concentrations in the body. In order to test the efficacy of vitamin D against cancer, and to have a prospect of using it as a safe treatment if it was found to be effective, it was first necessary to find a safer alternative form of vitamin D, one which would not have the same toxic effects as vitamins D2 and D3.
Studies of Usage
Vitamin D5 was developed as a possible safe analog of the vitamin for medical use. It is a low calcemic analog of vitamin D. D5 is, in fact, the least toxic form of this vitamin and therefore the safest for medicinal use. A number of studies have been carried out to examine the possible therapeutic uses of the D5 form of vitamin D. Despite the research that has been conducted, vitamin D5 is not yet being used by doctors. Further research is necessary before it can be determined whether vitamin D5 is a suitable treatment.
It is the differences between vitamin D5 and the more common forms of the vitamin, D2 and D3 that make D5 a suitable candidate for clinical trials. The reactions which these different forms undergo in the body have different consequences that make D2 and D3 unsuitable for therapeutic use against cancer. The products of the reactions that take place when vitamins D2 and D3 enter the body are hypercalcemic.
Raising Levels of Calcium
This means that they are very effective at raising the levels of calcium in the blood serum, and D2 and D3 are therefore not a suitable medication for cancer prevention or treatment. They are very effective at playing their role in maintaining the appropriate levels of calcium in the body, as long as they are only present in low concentrations. Vitamin D5, however, can exist in the body at much higher concentrations without causing any problems with toxicity.
Studies have been carried out that have looked at both the therapeutic and preventative potentials of vitamin D5. Trials have been conducted in animals to determine whether vitamin D5 can affect the growth of cancer cells, or prevent animals from developing cancers.
D5 has been found to be effective in both of these types of animal-based study. Work has also been begun which will lead to studies of vitamin D5 in humans. The initial studies have been carried out to determine the doses that should be used in future clinical trials in order to avoid toxicity and adverse reactions. These studies investigated the toxicity of vitamin D5 in animals.
Cancer
The scientific evidence points towards an influence of vitamin D on the risk of developing cancer. It appears to be particularly effective in the prevention of colon cancer, and to have some effect in the prevention of breast and prostate cancer. Results from studies of other types of cancer have been more variable and inconclusive. There is as yet no definitive scientific proof that vitamin D can be effective as a treatment against cancer, or that a high vitamin D intake can help to reduce the risks of developing cancer. Further research is required in order to determine the efficacy of vitamin D against cancer.
Sources
Vitamin D2 and D3 are the most common forms of vitamin D in nature. Vitamin D is still a rare vitamin, even in these forms, and it is only found at low levels in food. The vitamin D that is found in plants is in the form of vitamin D2, while some vitamin D3 can be obtained from certain animal-based products.
The best sources of vitamin D are fish and fish liver oil. Cheese, egg yolks and beef liver also contain some vitamin D3. All of these food sources contain the vitamin in its D3 form.
Vitamin D2 can be obtained at fairly high levels from some mushrooms. The amount of vitamin D2 that is available in mushrooms can be increased by growing them under an ultraviolet light.
Other Ways to Get Vitamin D
Vitamin D does not have to be obtained from food. It can also be manufactured in the skin, and this is the method through which most people obtain a sufficient amount of vitamin D to remain healthy. Anyone who does not get enough exposure to sunlight, either through remaining indoors or living in a part of the world that does not receive enough sunshine, is at risk of a vitamin D deficiency.
For example, the region that is north of the line of 42 degrees of latitude will not be receiving enough sunlight during the winter months, between November and February to produce adequate amounts of vitamin D during these months.
Exposure
The amount of sun exposure that is necessary is fairly low. Although there is no consensus on the amount of time that needs to be spent in the sun to ensure sufficient production of vitamin D, it is probably enough in most climates to spend between 5 and 30 minutes out of doors between the hours of 10 am and 3 pm, with the face, legs, arms or back exposed to the light, twice a week. Excessive exposure to the sun should be avoided, since it can lead to sunburn and an increased risk of skin cancer.
A vitamin D deficiency can be avoided or treated by increasing the amount of vitamin D that is consumed in food, increasing exposure to sunlight, or by taking vitamin D supplements. A traditional treatment for a deficiency of vitamin D was to take cod liver oil, since this is a rich source of vitamin D3.
Supplements
Vitamin D5 is not a naturally occurring form of vitamin D. It can be artificially produced, however, and it was designed as a safer form of the vitamin for medicinal use. Vitamin D5 or sitocalciferol is manufactured from the chemical 7-Dehydrositosterol.
Both the D2 and D3 forms of the vitamin are available in dietary supplements and as fortified foods, although D3 is the most commonly used form. Vitamin D2 and D3 supplements are available in different forms including tablets and injections. Different strengths are available to treat severe deficiencies and to provide an additional source of vitamin D for long term supplementation in people who are at risk of developing a deficiency.
Food Products
In addition to naturally occurring vitamin D, some food products are artificially enriched with vitamin D in order to ensure that people are getting enough of this scarce vitamin in their diets. Food that has been fortified with vitamin D is available in the US and in numerous other countries. Most milk that is sold in the US has been fortified with vitamin D.
A cup of fortified milk contains 100 IU (International Units) of vitamin D per cup. This is equivalent to 50% of the adequate daily intake of vitamin D for people who are between 14 and 50 years of age. Other dairy products such as cheese or ice cream are not usually fortified.
Other products that may be fortified with vitamin D in the US are breakfast cereals, cereal flours, margarine, orange juice and yogurt. The amount of vitamin D that can be added to a food product is legally restricted in order to prevent anyone suffering from toxic levels of the vitamin.
Most people do not need to take vitamin D supplements, but those who are at an elevated risk of a vitamin D deficiency may benefit from a dietary supplement of the vitamin. People who are elderly, and women who are pregnant or breastfeeding, should consider taking vitamin D supplements.
A dose of 10 micrograms per day is recommended by the UK Food Standards Agency. People who are in one of the other risk groups may also benefit from vitamin D supplementation.
Sources
Mayo clinic: Vitamin D
The Merck Manuals: Vitamin D
National institute of health, office of dietary supplements: Dietary Supplement Fact Sheet, Vitamin D
Food standards agency: Vitamin D
Patient UK: Vitamin D Deficiency
IITRI: Vitamin D5 Ready for Clinical Trials in Breast Cancer
University of Illinois at Chicago medical center, this week, April 5 1999: US Defense Department OKs UIC Vitamin D5 study
International journal of cancer 108: 6: 922-929, 2003: Punj, Graves and Mehta, Cancer Diagnosis and Therapy
Journal of the national cancer institute, 89:3:211-218, 1997: Mehta, Moriarty, Mehta, Penmasta, Lazzaro, Constantinous and Guo, Prevention of Preneoplastic Mammary Lesion Development by a Novel Vitamin D Analogue, 1 alpha-Hydroxyvitamin D5
Journal of steroid biochemistry and molecular biology, 97: 1-2:129-136, 2005: Murillo and Rajendra, Chemoprevention of chemically-induced mammary and colon carcinogenesis by 1alpha-hydroxyvitamin D5
United States PAtent number 6900191: 1 alpha-hydroxyvitamin D5, its synthesis and use in cancer prevention
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