D Vitamins

Vitamin D: How the Body is Affected by its Promotion and Deficiency

Vitamin D is an extraordinarily important vitamin which promotes the overall health of the body. Produced naturally in the human skin or in plant life through the exposure to sunlight, vitamin D, found in various forms in life, is necessary to regulate normal levels of calcium metabolism, which promotes the health of bones and blood and the possible prevention of various diseases.

The metabolism of vitamin D in the body is a complex process that begins with the photochemical process caused by the exposure of ultraviolet B rays in the sunlight on the epidermis of the skin, through the ingestion of foods that are a natural source of or are fortified with vitamin D, and through the ingestion of vitamin D supplements.

While there is still a great deal of ongoing research into how Vitamin D affects and prevents deficiencies, one thing is certain is that Vitamin D deficiency can be serious and life-threatening. It can not only affected the way the body functions and grows, but can quite possibly affect an individual’s mental and psychological well-being.

What Is It?

Vitamin D is a class of fat soluble vitamins that are made of secosteroids. Secosteroids are found naturally in the skin of vertebrates, including humans, and in plant life. They are divided into five forms of calciferols

• Vitamin D1 (a molecular compound of ergocalciferol and lumisterol)
• Vitamin D2 (ergocalciferol)
• Vitamin D3 (cholecalciferol, which is produced by 7-dehydrocholesterol in the skin)
• Vitamin D4 (22-dihydroergocalciferol)
• Vitamin D5 (sitocalciferol, produced by 7-dehydrositosterol)

The two significant forms of calciferols are Vitamin D2 and Vitamin D3. Vitamin D3, once activated by sunlight, will target at least 2000 genes found in the body, making up at least 10% of the human genome.

Sources and Discoveries

Vitamin D2 is synthesized mainly in plants, fungi, and invertebrates through the exposure of UVB light. There are some questions as to how Vitamin D2 functions in nonvertebrates. Vitamin D3 is synthesized in human skin after it has been exposed to UVB light. The process of synthesizing Vitamin D into fat-soluble vitamins first began in 1923, when scientists such as Alfred Fabian Hess, was able to irradiate 7-dehyrdocholesterol to produce the fat-soluble vitamin.

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Later, Adolf Windaus of the University of Gottingen in Germany discovered a connection between the constitution of sterols and vitamins. His work won him the Nobel Prize in Chemistry in 1928. During the 1930s, the chemical structure of Vitamin D3 was established.

Chemical Structure

The chemical structure of Vitamin D is composed of secosteroids, a form of steroids in which one bond of the ring is broken. Both Vitamin D2 and Vitamin D3 differ in their chemical compositions. For instance, Vitamin D2, unlike Vitamin D3, has a double bond between carbons 22 and 23, as well as a methyl group of carbon 24 in its side chain. It is also found mainly in invertebrates, fungi, and plants, and responds to UV radiation.

Ergosterol absorbs UV radiation to protect the DNA, RNA, and protein and might possibly act as a protective mechanism for organisms. Choleciferol, or Vitamin D3, becomes synthesized when the chemical compound 7-dehyrdocholesterol is exposed to UVB light. This metabolism occurs in the skin of vertebrates. Humans and other vertebrates produce large quantities of choleciferol in the skin, so therefore the vast quantity of vitamin D metabolism occurs through exposure to the sun.

Activation and Function

Vitamin D generally maintains normal levels of calcium and phosphorus in the blood and helps absorb calcium for bone strength. The process vitamin D undergoes after it has been synthesized by UVB light is complex and varied. Generally, vitamin D is inactive until it is metabolized biologically within the system.

This occurs either through the digestion of its food source or its supplemental form or when it is exposed in the epidermis of the skin through sunlight. Once activated, vitamin D circulates in the bloodstream and enters the liver. There, it is hydroxylated or synthesized into a prohormone called calcidiol (25-hydroxyvitamin D). This conversion is made possible through the circulation process within the bloodstream, thus making it more active in the kidneys as vitamin D or in the immune system as a monocyte-macrophages.

Increased exposure to sun or dietary intake also increases the 25-hydroxyvitamin D serum which is composed of calcidiol. The calcidiol is then converted into calcitriol. Once this synthesized process takes place, the calcitriol behaves like a cytokine, operating as a defensive mechanism against localized, invasive microbials. When the synthesized calcitriol reaches the kidneys, it circulates as a hormone and is transported to certain organs with vitamin D-binding protein binders, which in turn regulates calcium and a concentration of phosphate in the bloodstream. The vitamin d-binding protein (VDBP), which is a protein found in the plasma, binds itself to the calcitriol, acting as a transportational agent through the body.

Calcitriol

Calcitriol also binds to a vitamin D receptor (VDR), a nuclei of target cells found in such organs as the brain, heart, skin, gonads, prostate, and breast. The vitamin d receptor belongs to a nuclear receptor superfamily of steroid/thyroid hormone receptors. These receptors perform any number of duties such as the promotion of healthy bone mineralization and the prevention of hypercalcemic tenany.

When the vitamin D receptor is activated in the intestines, bone, kidney, and parathyroid gland cells, it maintains levels of calcium and phosphorus in the blood and promotes bone strength. Vitamin D receptors help proliferate and differentiate cells to prevent the growth and proliferation of cancer. Vitamin D receptors are concentrated in white blood cells, including monocytes and activated T and B cells, as well.

Sun Effect

The sun is the most important factor in the metabolism of vitamin D in human and plant life. The photochemical process begins with the exposure of UVB light, but the length of exposure to sunlight is extremely significant. For instance, 10 to 20 minutes of exposure to the summer sun can produce in the skin at least 10,000 IU. This is 50 times more than the 200 IU the United States government recommends on a daily basis. Some researchers suggest that adequate exposure to UV radiation to synthesize vitamin D should occur twice a week for approximately 5 to 30 minutes between 10 AM to 3 PM, when the sun is at its peak of UV radiation intensity.

Yet factors such as season, geographic latitude, time of day, weather, smog, melanin content, and sunscreen use can all affect whether vitamin D will be properly synthesized in the skin due to UV radiation. For instance, during the winter months between November and February, some areas aligned along the northern border of California to Boston, lack the UV radiation intensity to generate vitamin D synthesis in the epidermis of the skin. In other northern latitudinal areas, this decrease in intensity can stretch up to 6 months.

Areas below latitudes of 34 degrees, found generally in the United States in an alignment between Los Angeles and Columbia, South Carolina, have conditions that allow for adequate vitamin D metabolism throughout the entire calendar year.

Other Weather Factors

Weather factors and indirect exposure to the sun can greatly affect the photochemical synthesis of vitamin D. Overcast skies can decrease UV radiation by 50%, while shade or shadowy cover from the sun can decrease it by 60%. Sunlight filtered through windows does not create the photochemical process to synthesize vitamin D in the skin.

However sun exposure is primarily the means in which vitamin D is synthesized in the skin and provide and maintain health benefits in humans. For instance, ten minutes of sun exposure is sufficient enough to prevent most deficiencies such as rickets or osteomalacia. In order to make up the daily recommendation of sun light exposure, one will have to ingest 50 glasses of milk or digest 10 tablets of multivitamins a day to maintain comparable levels of vitamin D in the system, neither of which is feasible.

A combination of sun exposure, diet, and dietary supplements are recommended to reach the full benefits of vitamin D in the body.

Health and Deficiencies

Vitamin D plays a tremendous role in maintaining health and the possible prevention of certain diseases. Vitamin D deficiencies have been known to cause pathogens for at least 17 types of cancer, heart disease, stroke, hypertension, autoimmune disease, diabetes, chronic pain, osteoarthritis, osteoporosis, muscle weakness, muscle wasting, birth defects and periodontal disease.

The lack of sun exposure might also explain outbreaks of influenza during the winter season. Researchers are continuously discovering the potential benefits of vitamin D sufficiency in preventing or treating any one of these diseases.

Rickets

Vitamin D deficiency or a severely limited exposure to the sun can also lead to such deficiencies as rickets in infants and children. Rickets is primarily the failure of bones to mineralize. Its effects are most prominent in rapidly growing bones, which explains why infants and children are the most vulnerable to contracting the deficiency, since their bones are constantly growing at a fast rate.

While rickets does not slow down the expansion rates of bone growth, it does cause the bowing of bones in arms and legs and the disfigurement of the rib cage. In the most severe cases of rickets, infants and children suffer from seizures caused by hypercalcemia.

Osteomalacia

Vitamin D deficiency can lead to osteomalacia in adults. Osteomalacia is a condtion that causes the weakening or softening of bones. While bones in adults stop growing, they do continue a process called remodeling, which maintains bone strength.

Osteomalacia causes a progressive loss of bone minerals which can lead to bone pain and the weakening and softening of bones.

Weakness and Pain in the Muscles

A lack of exposure to sunlight and a vitamin D deficiency can lead to weakness and pain in the muscles. This condition is often prevalent in the elderly. In a randomized controlled study, scientists discovered that elderly women who were placed on a three month regimen that included vitamin D supplements at 800 IU per day along with 1,200mg per day of calcium saw an increase in muscle strength and a 50% decreased risk of falling.

Cancer

The lack of differentiation or specialization and the rapid growth define the characteristic behavior of cancer cells. Epidemiological studies have suggested that vitamin D can aid the growth and differentiation of these cells, though a cautionary note should be added that such studies can’t adequately prove an association between the two. What is known is that vitamin D plays some vital role in preventing at least 17 different forms of cancer.

This is largely because vitamin D receptors are present in malignant tumors, usually prevalent in breast, lung, skin (melanoma), colon and bone cancers. Biologically, once certain forms of vitamin D, such as 1,25-dihydroxyvitamin D and its analogs are activated, it has the possibility to stimulate cell differentiation that are both cancerous and noncancerous in some cell cultures.

The limitation of sun exposure as it applies to geography might also play a role in who is considered to have a high factor risk in contracting cancer. In a 2006 study, using data collected on over 4 million cancer patients spread throughout 13 different countries, scientists have uncovered the possibility that individuals living in countries with a low exposure to the sun are most likely to have high risk factors.

Mental Health

Though the research in how vitamin D affects mental health is still ongoing, there have been some studies which suggest a correlation between vitamin D deficiency and depression and other mental health afflictions. Geographical factors regarding low sun exposure might also play a role in mental health risks.

Aging and Mortality

Researchers, using data collected by the National Health and Nutrition Examination Survey, have uncovered a link between vitamin D and mortality. Following a group of 13,331 Americans over the age of 20 over a 6 year period, the study was able to correlate possible links between vitamin D deficiency and mortality rates through cancer and cardiovascular diseases. Vitamin D might play a role in preventing premature aging as well.

This is occurs through the preventative nature of vitamin D in the inflammation of leukocyte telomeres, a gene that marks aging, and through the lengthening of the gene which can slow down aging.

High Risk Factors

People with a high risk for these deficiencies generally tend to be found among the elderly, who have a reduced capability to generate vitamin D through naturalized forms of sunlight exposure. They are also more likely to stay indoors and use sunscreen, which blocks the metabolism of vitamin D.

The obese, infants who are primarily breastfed (mother’s milk only has 25 IU of Vitamin D3 per liter, which is an insufficient amount for infants according to the American Academy of Pediatrics, which recommends 400 IU of vitamin D per day); those who have a severely limited exposure to sunlight; and victims of malabsorption syndromes such as cystic fibrosis, and inflammatory bowel diseases such as Chrohn’s Disease are all likely to fall within the risk factors of individuals who suffer from vitamin D deficiency.

Skin Color

Skin color can play a role in vitamin D deficiency as well. Individuals with dark skin are less capable of metabolizing vitamin D through exposure to UVB light. Those who live further away from the equator are at a higher risk of vitamin D deficiency. In a U.S. study, researchers have determined that African American women are 42% more likely to develop vitamin D deficiency, as opposed to white women who only have a 4% risk factor.

Body Coverage

Vitamin D deficiency is also documented among women who cover all areas of their skin due to religious or cultural practices, which conforms to a study performed on Arab and Danish Muslim women in Denmark who have shown a higher propensity toward muscle pain and weakness, two symptoms of vitamin D deficiency. Sunscreen can block the metabolism of vitamin D in the skin as well. Sunscreens with a SPF factor of 8 greatly decreases vitamin D by 95%.

Nutritional Value

Vitamin D is produced naturally by sunlight, with different forms (Vitamin D2 and Vitamin D3) found in plant life and the skin of vertebrates, including humans. Vitamin D, though, can also be found in food, though this source is rather limited.

Foods that have a natural source of Vitamin D can include fatty fishes (catfish; cooked salmon, mackerel, and eel; sardines cooked in oil and drained; and tuna that has been canned in oil); whole eggs, particularly the yolks, cooked beef liver, 1 Tbs of fish liver oils, such as cod liver oil; and mushrooms, which make up the only vegetable containing vitamin D.

In certain countries such as the United States, other foods are fortified with Vitamin D3. These include milk, yogurt, margarine or oil spreads, breakfast cereals, pastries, and breads.

Dosage

The general dosage of vitamin D varies between children and adults. For adults, the Adequate Intake (AI) recommendation of vitamin D for adults is 50 IU to 1,000 IU. This differs depending on age. Adults under 50 are generally recommended to take 50mg of vitamin D a day. Adults between the ages of 50 and 70 are recommended to take 10mg daily, while adults over the age of 70 are recommended to take 15mg a day.

There are differing opinions on exactly how much Vitamin D adults should take daily based on how much sun a person is exposed to during the day. Some opinions suggest that the AI recommendations might be inadequate for such exceptions. Not all doses, though, are effective for all conditions, such as rickets or osteomalacia. Generally, in such cases, it is recommended that a person takes 400 IU to 800 IU per day, while an oral dose of vitamin D might be necessary to combat and prevent osteoporosis.

Children’s Dosage

It is recommended that children older than 1 year should not exceed 50mg of vitamin D a day, while children 1 year and younger are recommended to take 25mg a day.

Other Forms of Intake

While the more popular form of vitamin D supplements are found in softgels, capsules, and tablets, they can also be taken in liquid form.

Warnings and Side Effects

There are various side effects and warnings associated with vitamin D. Overdosage is possible. The Adequate Intake limit of dosage is set at 2,000 IU. Anything higher is extremely toxic. Anything within the Adequate Intake levels though are tolerable for ingestion. Excessive amounts of vitamin D can cause hypercalcemia, or excessive bone loss. Hypercalcemia can also cause kidney stones and the hardening of the heart and kidneys if left untreated. Some vitamin D analogues have been known to cause some daytime drowsiness.

Some allergens are also caused by Vitamin D, so it is important to know beforehand if one is allergic to vitamin D. Excessive amounts of orally ingested vitamin D in infants can cause health risks as well in the form of high blood calcium levels (hypercalcemia), which can lead to major bone loss. Individuals with a high risk for hyperparathyroidism, kidney disease, sarcoidosis, tuberculosis, histoplasmosis, and chronic hypercalcemia are steered away from taking vitamin D, as this might lead to serious and possibly life threatening health problems.

Pregnant mothers are recommended to take the same daily dosage of vitamin D as nonpregnant women. It is recommended that infants who are exclusively breastfed take vitamin D supplements after the age of 2 months to make up for the insufficient amount of the vitamin found in breast milk.

Interactions with other Medications

Vitamin D supplements can be inhibited or enhanced through the interaction of other drugs. Drugs that increase the metabolism of vitamin D and serum 25-hydroxyvitamin D levels include:

• phenytoin (Dilantin)
• fosphenytoin (Cerebyx); phenobarbital (Luminal)
• carbamazepine (Tegretol)
• rifampin (Rimactane).

Drugs and other agents that decrease absorption of vitamin D in the intestines and should be avoided when taking the supplement include:

• Cholestyramine (Questran)
• Colestipal (colestid)
• Orlistat (Xenical)
• Mineral oil
• Olestra

Otherwise healthy men who take ketoconazole with vitamin D will experience a decrease in seum levels of 1,25-hydroxyvitamin D. The drug also blocks the 25-hydroxyvitamin D3-1-hydroxylase enzyme.

Sources

• http://lpi.oregonstate.edu/infocenter/vitamins/vitaminD/
• http://en.wikipedia.org/wiki/Vitamin_D
• http://www.mayoclinic.com/health/vitamin-d/ns_patient-vitamind
• http://www.vitamindcouncil.org/
• http://ods.od.nih.gov/factsheets/vitamind.asp