Vitamin D

Vitamin D Dr.Ahmed Noureldin Ahmed (MBBCH, DCH, DTM&H (Cairo Senior Pediatrician

Vitamin D is a group of fat-soluble Pro-hormones , the two major forms of which are : Vitamin D2 or Ergocaciferol -1 Vit. D2 is derived from Fungal and Plant sources, and is not produced by the human .body vitamin D3 or Cholecalciferol-2 Vitamin D3 is derived from animal sources and is produced in skin exposed to sunlight, .Specifecally UVB Radiation

.Vitamin D plays an important role in the maintenance of Organ System Vitamin D regulates the Calcium and Phosphorus levels in the Blood by promoting their absorption in the intestines, and by promoting re-absorption of calcium in the Kidneys, which enables normal mineralization of bones and prevents hypocalcemic .Tetany Vitamin D is an essential hormone for bone growth and development in children and promotes skeletal health in adults. Currently, an adequate daily intake of 200 IUs of vitamin D for children is recommended. This is also the recommendation from the AAP. These levels, however, may not be adequate for bone growth and musculoskeletal health in children and adolescents .It is also needed for bone growth and bone remodeling by osteoblasts and osteoclasts .Vitamin D can promote soft tissue calcification• .It inhibits Parathyroid Hormone secretion from the Parathyroid gland• Vitamin D affects the immune System by promoting, phagocytosis , anti-tumor• .activity, and immunomodulatory functions (1(

Vitamin D deficiency is a growing problem around the world, including in developed countries where children spend little time outside. Questions have existed for some time regarding the adequacy of the

current RDA, particularly for older children and adolescents, who undergo a great deal of bone growth. As the researchers of this study note, Vitamin D levels during adolescence have bearing on a child’s .future bone density and risk for other diseases Vit.D and RDA for Children Science Daily (May 28, 2008) — The current (RDA) of vitamin D for children is 200 IU, but new research reveals that children may need and can safely take 10-times that amount. According to new research this order-of-magnitude increase could improve the bone health of children .worldwide and may have other long-term health benefits Study 1 : New research published in the Journal of Clinical Endocrinology and Metabolism suggests that the current children’s RDA for Vitamin D (200 IUs( does not sufficiently support the “bone growth and musculoskeletal health of children and adolescents.”The RDA value for children was set at 200 IUs because, unlike testing for adults’ dosage, there wasn’t .adequate research into the benefits of higher amounts For this placebo-controlled study, researchers gave children various doses of vitamin D at various intervals and measured the impact this had on serum levels of 25-OHD. For the short-term study, 25 students (15 boys and 10 girls( received one-weekly, 14,000 IU doses of vitamin D for eight weeks. Serum levels of 25-OHD were then measured for an additional eight weeks. This portion of the test was conducted during the summer and early fall, when the highest natural levels of vitamin D are reached. For the long-term, one-year study, 340 students (172 boys and 168 girls( received either a low dose of vitamin D (1,400 IUs each .(week( or a high dose (14,000 IUs each week The study notes that previous research has indicated no difference between daily and weekly supplementation of Vitamin D. To ensure full compliance, the researchers required weekly, .on-site administration of the supplement At the end of the study periods, only those children who had received the “high” dosage of vitamin D had the recommended optimum serum (blood) levels as they are defined for adults. (There is less agreement about an ideal serum level for children.( Other benefits were seen in those who received the higher dose. Researchers observed “substantial increments in lean mass, bone area and bone mass” particularly in girls. Their observations from the study caused them to suggest that serum OHD-25 (vitamin D( levels in the midthirties (ng/ml( may be a reasonable and beneficial target for this age group. The researchers noted that adolescents would be less likely candidates for toxicity because of their body’s use of the vitamin for constant growth.Our research reveals that vitamin D, at doses equivalent to 2,000 IUs a day, is not only safe for adolescents, but it is actually necessary for ",achieving desirable vitamin D levels (2( Vitamin D3 is one of the most common forms of vitamin D, and is easily converted to 25.OHD (25-hydroxyvitamin(, which is the active form of vitamin D found in the blood For this placebo-controlled study, researchers gave children various doses of vitamin D at .various intervals and measured the impact this had on serum levels of 25-OHD For the short-term study, 25 students (15 boys and 10 girls( received one-weekly, 14,000 IU doses of vitamin D for eight weeks. Serum levels of 25-OHD were then measured for an

additional eight weeks. This portion of the test was conducted during the summer and early .fall, when the highest natural levels of vitamin D are reached For the long-term, one-year study, 340 students (172 boys and 168 girls( received either a .(low dose of vitamin D (1,400 IUs each week( or a high dose (14,000 IUs each week Only children given the equivalent of 2,000 IUs a day of vitamin D increased 25-OHD levels from the mid-teens to the mid-thirties (ng/ml(--the level considered optimal for adults. .None of the children in either trial showed any evidence for vitamin D intoxication Although many experts agree that a 25-OHD level of 30 ng/ml is desirable in adults, what constitutes an optimal D level for children and adolescents is more debatable. According to the researchers, due to rapid skeletal growth, children and adolescents are more likely to be vitamin D deficient, and are far less likely to reach vitamin D levels that doctors would .consider toxic Supplementation of children and adolescents with 2,000 IUs a day of vitamin D3 is well" tolerated and safe," said Dr. Fuleihan. "This is particularly relevant in light of the increasingly recognized health benefits of vitamin D for adults and children Study2 : Low Vitamin D Levels May Be Common In Otherwise Healthy Children ScienceDaily (July 10, 2007( — Many otherwise healthy children and adolescents have low vitamin D levels, which may put them at risk for bone diseases such as rickets. African American children, children above age nine and with low dietary vitamin D intake were the most likely to have low levels of vitamin D in their blood, according to researchers from The .Children's Hospital of Philadelphia A study in the current issue of the American Journal of Clinical Nutrition measured blood levels of vitamin D in 382 healthy children between six years and 21 years of age living in the northeastern U.S. Researchers assessed dietary and supplemental vitamin D intake, as well as body mass, and found that more than half of the children had low blood levels of vitamin D. Of the subjects, 55 percent of the children had inadequate vitamin D blood levels and 68 percent overall had low blood levels of the vitamin in the wintertime."The best indicator of a person's vitamin D status is the blood level of a vitamin D compound called 25-hydroxyvitamin D," said Babette Zemel, Ph.D., a nutritional anthropologist at Children's Hospital and primary investigator of this study. "Vitamin D deficiency remains an under".recognized problem overall, and is not well studied in children (3( Vitamin D is crucial for musculoskeletal health. The primary dietary source of the vitamin is fortified milk, but the best way to increase vitamin D levels is from exposure to sunshine. Severe deficits in vitamin D may lead to muscle weakness, defective bone mineralization and rickets. In addition to musculoskeletal effects, vitamin D is important for immune function, and low blood levels of the vitamin may contribute to diseases such as hypertension, cancer, multiple sclerosis and type 1 diabetes. Decreased blood levels of vitamin D have also been linked to obesity.ScienceDaily (Oct. 14, 2008( — The American Academy of Pediatrics (AAP( is doubling the amount of vitamin D it recommends for infants, children and adolescents. The new clinical report, "Prevention of Rickets and Vitamin D Deficiency in Infants, Children, and Adolescents," recommends all children .receive 400 IU a day of vitamin D, beginning in the first few days of life

The change in recommendation comes after reviewing new clinical trials on vitamin D and the historical precedence of safely giving 400 IU per day to the pediatric population. Clinical data show that 400 units of vitamin D a day will not only prevent rickets, but treat it. This bone-softening disease is preventable with adequate vitamin D, but dietary sources of vitamin D are limited, and it is difficult to determine a safe amount of sunlight exposure to synthesize vitamin D in a given individual. Rickets continues to be reported in the United States in infants and adolescents. The greatest risk for rickets is in exclusively breastfed .infants who are not supplemented with 400 IU of vitamin D a day Adequate vitamin D throughout childhood may reduce the risk of osteoporosis. In adults, new evidence suggests that vitamin D plays a role in the immune system and may help .prevent infections, autoimmune diseases, cancer and diabetes We are doubling the recommended amount of vitamin D children need each day because" evidence has shown this could have life-long health benefits," said Frank Greer, MD, FAAP, chair of the AAP Committee on Nutrition and co-author of the report. “Supplementation is “.important because most children will not get enough vitamin D through diet alone Breastfeeding is the best source of nutrition for infants. However, because of vitamin D" deficiencies in the maternal diet, which affect the vitamin D in a mother’s milk, it is important that breastfed infants receive supplements of vitamin D,” said Carol Wagner, MD, FAAP, member of the AAP Section on Breastfeeding Executive Committee and co-author of the report. “Until it is determined what the vitamin D requirements of the lactating motherinfant dyad are, we must ensure that the breastfeeding infant receives an adequate supply of “.vitamin D through a supplement of 400 IU per day The new recommendations include: Breastfed and partially breastfed infants should be supplemented with 400 IU a day of .vitamin D beginning in the first few days of life All non-breastfed infants, as well as older children, who are consuming less than• one quart per day of vitamin D-fortified formula or milk, should receive a vitamin .D supplement of 400 IU a day (4( Adolescents who do not obtain 400 IU of vitamin D per day through foods should• .receive a supplement containing that amount Children with increased risk of vitamin D deficiency, such as those taking certain• .medications, may need higher doses of vitamin D Given the growing evidence that adequate vitamin D status during pregnancy is important for fetal development, the AAP also recommends that providers who care for pregnant .women consider measuring vitamin D levels in this population Vitamin D deficiency is common across populations and particularly among people with darker skin. Nutritional rickets among nursing infants whose mothers have insufficient .levels of vitamin D is an increasingly common, yet preventable disorder Carol Wagner, MD, Sarah Taylor, MD, and Bruce Hollis, PhD, from the Department of Pediatrics, Medical University of South Carolina (Charleston(, emphasize the need for clinical studies to determine the dose of vitamin D needed to achieve adequate vitamin D .levels in breastfeeding mothers and their infants without toxicity The authors point out that vitamin D is now viewed not simply as a vitamin with a role in promoting bone health, but as a complex hormone that helps to regulate immune system

function. Long-term vitamin D deficiency has been linked to immune disorders such as .multiple sclerosis, rheumatoid arthritis, type I diabetes, and cancer Vitamin D is a hormone not a vitamin and it is not just for kids anymore," writes Ruth A." Lawrence, MD, Editor-in-Chief of Breastfeeding Medicine, from the Department of Pediatrics, University of Rochester School of Medicine and Dentistry, in an accompanying editorial. "Perhaps the most startling information is that adults are commonly deficit in modern society. Vitamin D is now recognized as a pivotal hormone in the human immune system, a role far beyond the prevention of rickets, as pointed out in the article by Wagner et ".al in this month's issue of Breastfeeding Medicine ScienceDaily (Dec. 11, 2008( — Insufficient vitamin D can stunt growth and foster weight gain during puberty, according to a new study published in the Journal of Clinical Endocrinology & Metabolism. Even in sun-drenched California, where scientists from the McGill University Health Centre (MUHC( and the University of Southern California conducted their study, vitamin D deficiency was found to cause higher body mass and .shorter stature in girls at the peak of their growing spurt Penckofer and colleagues concluded that diet alone is not sufficient to manage vitamin D levels. Treatment options to correct this level, such as vitamin D2 or D3, may decrease the risk of severe disease or death from cardiovascular disorders. The preferred range in the .body is 30 - 60 ng/mL of 25(OH( vitamin D Most physicians do not routinely test for vitamin D deficiency," said Penckofer. "However," most experts would agree that adults at risk for heart disease and others who experience ".fatigue joint pain or depression should have their vitamin D levels measured (5( So the Canadian Cancer Society recommends that during the winter, Canadians take at least “.1,000 units a day of Vitamin D, dubbed “the sunshine vitamin Dr. Parker says 1,000 units a day is well beyond what you can obtain from your diet. Vitamin D is a bit of a rare vitamin, appearing only in fatty fish, cod liver oil and egg yolks. .Even if you were to sunbathe in southern climates, you would not take in 1,000 units If you were to lie naked on a beach in the Bahamas, and I don’t recommend that because of” skin cancer, you cannot get up to the equivalent of 1,000 units of Vitamin D a day,” says Dr. .Parker She notes Vitamin D as a factor is turning up in study after study. It turns out people with lung and colon cancer are Vitamin D deficient. And it helps the body absorb calcium. In a study examining whether women who took Vitamin D had a lower risk of osteoporosis, it was found the women taking Vitamin D had stronger bones than those who did not take the vitamin. Years later, researchers went back to that study and found that the women who took Vitamin D also had fewer cancers.But before Vitamin D becomes the “new aspirin,” more .research needs to be carried out Vitamin D works in very complicated ways, she says. It changes the way cells work. In fact, there is medical speculation that it may block cancer cell proliferation or improve immune .system functions. But its role is not fully understood Lifestyle also has to be part of the equation. Dr. Parker is looking at how obesity, which we know can cause cancer, and exercise, which we know prevents cancer, could interact with Vitamin D. “At the population level, I am trying to understand how all these things fit together,” says Dr. Parker. “It’s very complex.” Dr. Parker describes it as looking for a piece

of a jigsaw puzzle. “We know some of the jigsaw pieces, but not all,” she says.Meanwhile, there is very little evidence that taking Vitamin D can harm you. Perhaps in huge doses it .could cause kidney stones, but that has not been proven On the average, 1,000 units a day is safe and is probably effective in reducing the risk of” colon cancer, and maybe other cancers as well,” says Dr. Parker.So does she take Vitamin D and recommend it? Absolutely. “I take 1,000 units of Vitamin D The authors point out that vitamin D is now viewed not simply as a vitamin with a role in promoting bone health, but as a complex hormone that helps to regulate immune system function. Long-term vitamin D deficiency has been linked to immune disorders such as multiple sclerosis, rheumatoid .arthritis, type I diabetes, and cancer Vitamin D is a hormone not a vitamin and it is not just for kids anymore," writes Ruth A." Lawrence, MD, Editor-in-Chief of Breastfeeding Medicine, from the Department of Pediatrics, University of Rochester School of Medicine and Dentistry, in an accompanying editorial. "Perhaps the most startling information is that adults are commonly deficit in modern society. Vitamin D is now recognized as a pivotal hormone in the human immune system, a role far beyond the prevention of rickets, as pointed out in the article by Wagner et ".al in this month's issue of Breastfeeding Medicine (6( :Vitamin

D NEWS

Further Evidence Supports Vitamin-D-Deficiency Link to CHD “Hypovitaminosis D, especially at levels less than 30 ng/mL, is associated with an increased risk for MI in men. • Vitamin D is likely to exert its effect on the risk for cardiovascular disease via vascular smooth muscle cell proliferation, inflammation, “.vascular calcification, the renin-angiotensin system, and blood pressure Key Gaps Remain in Understanding Health Effects of Vitamin D “Despite considerable progress in research to understand the health effects of vitamin D, experts convened by the NIH to review the available data found major gaps in the evidence. The data are strongest in the area of bone health among elderly men and post-menopausal women, suggesting that increased vitamin D intake can improve bone health and prevent falls. For other age groups and health issues, though, it is too early to say conclusively whether more “.vitamin D might be beneficial Kids May Need 10 Times More Vitamin D: Study: Kids Need 2,000 IU of Vitamin D, Not 200 IU Now Recommended Lack Of Vitamin D Causes Weight Gain And Stunts Growth In Girls Lack of vitamin D may cause juvenile diabetes Low vitamin D tied to back pain in older women “For men, there was no relationship between vitamin D levels and pain. Women with vitamin D deficiency, on the other hand, were nearly twice as likely to have back pain that was moderate or worse, but vitamin D status wasn't related to pain in other parts of the body. The gender- and back-specific effects of vitamin D found in the study could be because lack of the vitamin can cause osteomalacia, or bone softening, which is more common in women and often manifests itself as low back pain, the researchers say. But before vitamin D supplementation can be widely recommended for treating back pain, they add, randomized controlled trials should be undertaken to determine if giving “.people the vitamin is indeed helpful Low Vitamin D Levels Independent Predictor of Fatal Stroke“Low levels of vitamin D appear to be an independent predictor of fatal stroke — a finding that suggests supplementation may be a promising approach for stroke prevention. Investigators at the University of Heidelberg, in Germany, found that among individuals referred for coronary angiography, low levels of 25-hydroxyvitamin D were more likely to suffer fatal stroke even after adjusting for cardiovascular risk factors, physical activity level, and calcium and parathyroid hormone levels. "Vitamin D supplementation in stroke patients has already been shown to reduce osteopenia, fractures, and falls while improving muscle strength. Apart from these beneficial effects, ” .our results suggest that vitamin D might also directly protect against stroke," the authors write

Low vitamin D linked to sudden cardiac death “Vitamin D deficiency is associated with heart dysfunction, sudden cardiac death, and death due to heart failure, German researchers report. An association between vitamin D deficiency and heart trouble is physiologically plausible, the researchers note. For example, ”.vitamin D is known to affect contractility of the heart Most Kids With Type 1 Diabetes Lack Vitamin D “Almost 75 percent of children and adolescents with type 1 diabetes have insufficient levels of vitamin D, researchers at the Joslin Diabetes Center in Boston report. A deficit in vitamin D can lead to bone problems later in life, especially among those with type 1 diabetes. While vitamin D is usually gotten from exposure to sunlight or from the diet, researchers suggest that supplements are needed to boost vitamin D levels. … Whether or not supplementing vitamin D would prevent all diabetes-related bone disease in diabetic children, the practice makes sense, particularly in light of a recent American Academy of Pediatrics recommendation doubling the intake of vitamin D for all children, Katz said. "All children should get ample vitamin D, at least 400 IU daily, from some combination of sun exposure, dairy products, and/or supplements," Katz said. "Those at high risk of deficiency, but not “".all children, should have levels monitored Mother's Vitamin D Status During Pregnancy Will Affect Her Baby's Dental Health Oral Vitamin D May Help Prevent Some Skin Infections “A study led by researchers at the University of California, San Diego School of Medicine suggests that use of oral Vitamin D supplements bolsters production of a protective chemical normally found in the skin, and may help prevent skin infections that “.are a common result of atopic dermatitis, the most common form of eczema Pain 'linked with low vitamin D' “Low levels of the sunshine vitamin, vitamin D, may contribute to chronic pain among women, scientists believe. The link does not apply to men, suggesting hormones may be involved, according to a study published in the Annals of Rheumatic Diseases said. The team from the Institute of Child Health in London said studies were now needed to see if vitamin D supplements can guard ” .against chronic pain. About one in 10 people are affected by chronic pain at any one time in the UK Some Seek Guidelines to Reflect Vitamin D's Benefits “A flurry of recent research indicating that Vitamin D may have a dizzying array of health benefits has reignited an intense debate over whether federal guidelines for the "sunshine vitamin" are outdated, leaving millions unnecessarily vulnerable to cancer, heart disease, diabetes and other ailments. The studies have produced evidence that low levels of Vitamin D make men more likely to have heart attacks, breast and colon cancer victims less likely to survive, kidney disease victims more likely to die, and children more likely to develop diabetes. Two other studies suggested that higher Vitamin D levels reduce the risk of dying prematurely from any cause. … But many leading experts caution that it remains premature for people to start taking large doses of Vitamin D. While the new research is provocative, experts argue that the benefits remain far from proven. Vitamin D can be toxic at high doses, and some studies suggest it could increase the risk for some health problems, experts say. No one knows what consequences might emerge from exposing millions of people to megadoses of the vitamin for long periods. … Physicians should routinely test their patients for Vitamin D deficiencies, and more people -- especially African Americans -- should take supplements and increase their exposure to the sun, they say. … The Canadian Cancer Society upped its recommendation to 1,000 units a day last year. Hollis and others believe Americans should routinely consume at least 2,000 international units a day. … Holick urges people to take 1,000 international units a day along with a multivitamin with 400 international units, as well as exposing their arms and legs to the sun for about 15 minutes several times a week. … But others have reservations. Dermatologists worry that encouraging people to get unprotected sun exposure or use tanning salons may increase the rate of skin cancer. "We're in the middle of a skin cancer epidemic," said C. William Hanke, president of the American Academy of Dermatology. "Tanning is risky and dangerous behavior. Ultraviolet light is classified as a carcinogen. We need to protect our skin. … "We call it a vitamin, but it's really a steroid," said Trevor G. Marshall, a molecular biologist at Murdoch University ".in Australia. "It's not something we should be playing with Too Little Vitamin D May Soften Baby's Skull “Vitamin D deficiency during pregnancy may be linked to a softening of bones in a baby's skull, Japanese researchers report. They also found that breast-feeding without vitamin D supplementation could prolong the deficiency, which might lead to a risk of serious ”.health problems later in life, including decreased bone density and type 1 diabetes Too Little Vitamin D Puts Heart at Risk “Getting too little vitamin D may be an underappreciated heart disease risk factor that's actually easy to fix. Researchers say a growing body of evidence suggests that vitamin D deficiency increases the risk of heart disease and is linked to other, well-known heart disease risk factors such as high blood pressure, obesity, and diabetes. For example, several large studies have shown

that people with low vitamin D levels were twice as likely to have a heart attack, stroke, or other heart” .related event during follow-up, compared with those with higher vitamin D levels Vitamin D A Surprising Champion Of Back Pain Relief, Report Says “According to Stewart B. Leavitt, MA, PhD, editor of Pain Treatment Topics and author of the report, "our examination of the research, which included 22 clinical investigations of patients with pain, found that those with chronic back pain almost always had inadequate levels of vitamin D. When sufficient vitamin D supplementation was provided, their pain either vanished or was at least helped to a significant extent." … -- Vitamin D is essential for calcium absorption and bone health. Inadequate vitamin D intake can result in a softening of bone surfaces, or osteomalacia, that causes pain. The lower back seems to be particularly vulnerable to this effect. -- In one study of 360 patients with back pain, all of them were found to have inadequate levels of vitamin D. After taking vitamin D supplements for 3 months, symptoms were improved in 95% of the patients. All of them with the most severe vitamin D deficiencies experienced back-pain relief. -- The currently recommended adequate intake of vitamin D up to 600 IU per day is outdated and too low. According to the research, most children and adults need at least 1000 IU per day, and persons with chronic back pain would benefit from 2000 IU or more per day of supplemental vitamin D3 (also called cholecalciferol(. … In conclusion, Leavitt stresses that vitamin D should not be viewed as a cure for all back pain and in all patients. It also is not necessarily a replacement for other pain treatments. "While further research would be helpful," he says, "current best evidence indicates that recommending supplemental vitamin D for patients with chronic back “".pain would do no harm and could do much good at little cost Vitamin D and Musculoskeletal Health “Vitamin D is critical for calcium homeostasis. Following cutaneous synthesis or ingestion, vitamin D is metabolized to 25(OH(D and then to the active form 1,25(OH(2D. Low serum vitamin D levels are common in the general population and cause a decline in calcium absorption, leading to low serum levels of ionized calcium, which in turn trigger the release of parathyroid hormone, “.promoting skeletal resorption and, eventually, bone loss or osteomalacia Vitamin D deficiency makes bowel disease worse “A vitamin D deficiency can make inflammatory bowel disease more severe and worsen the quality of life for affected individuals, according to a study presented this week at the 73rd annual scientific meeting of the American College of Gastroenterology. Inflammatory bowel disease, or IBD, refers to a group of conditions, including Crohn's disease and ulcerative colitis, marked by chronic inflammation in the intestines, leading to symptoms like abdominal pain and diarrhea. A number of medications are effective for IBD, but surgical removal of a portion of the intestines is often required. People with IBD are also known to be at increased risk of developing colon cancer. Vitamin D deficiency is common in patients with IBD, but whether vitamin D deficiency parallels disease severity or adversely impacts quality of life is not known, Dr. Alex Ulitsky and colleagues at the Medical College of ” .Wisconsin in Milwaukee point out in a meeting abstract Vitamin D Deficit in Pregnancy Tied to Caesarean Risk: Women with deficiency at time of delivery had almost 4 times the odds, study says “He noted that previous research has linked vitamin D deficiency with proximal muscle weakness and suboptimal muscle performance and strength, which may help explain the ”.findings Vitamin D Insufficiency Linked to Increased Body Fat Vitamin D: Builds Bones And Much More Vitamin D Deficiency Common in Patients With Chronic Migraine “New research showing that vitamin D deficiency is common in patients with chronic migraine suggests that this patient group, like other vitamin D–deficient populations, is at increased risk for cardiovascular disease, malignancy, and other serious illnesses that have been linked to low levels of this "good-health" vitamin. … "Clinicians generally don't recognize the importance of vitamin D deficiency, and so they don't screen for it — not just in migraineurs, but in all of their patients. But it is a condition that is easily treated and may confer major, wide-ranging “.health benefits," he said Vitamin D Deficiency Linked To Tuberculosis Vitamin D Deficiency May Be Common in Infants and Toddlers Vitamin D deficiency tied to higher blood pressure “Low blood concentrations of vitamin D may be associated with higher blood pressure in whites, indicating a risk of developing hypertension, or high blood that requires medical treatment, researchers report. However, this relationship was not noted among blacks.

"Though easily corrected by taking a vitamin D supplement or having causal sunlight exposure, vitamin D ”.insufficiency is highly prevalent in the United States," Dr. Vin Tangpricha told Reuters Health Vitamin D for Babies May Prevent Type 1 Diabetes Vitamin D Important In Brain Development And Function “Vitamin D has long been known to promote healthy bones by regulating calcium levels in the body. Lack of sufficient vitamin D in very young children results in rickets, which can be easily prevented by vitamin D supplements. Only recently the scientific community has become aware of a much broader role for vitamin D. For example, we now know that, in addition to its role in maintaining bone health, vitamin D is involved in differentiation of tissues during development and in proper functioning of the immune system. … Vitamin D is present in only a few foods (e.g., fatty fish(, and is also added to fortified milk, but our supply typically comes mostly from exposure to ultraviolet rays (UV( in sunlight. UV from the sun converts a biochemical in the skin to vitamin D, which is then metabolized to calcitriol, its active form and an important hormone. Formation of vitamin D by UV can be 6 times more efficient in light skin than dark skin, which is an important cause of the known widespread vitamin D deficiency among African Americans living in northern latitudes. Dark skin has been selected during evolution because it protects against the burning UV rays of the sun in the tropics. … Many vitamin D experts advise that the currently recommended level of vitamin D intake is much too low and should be raised to protect against bone fractures and possibly cancer in addition to rickets (2(. Indeed, even using present guidelines, too many Americans have low vitamin D blood levels. McCann & Ames propose that, despite uncertainty regarding all of the deleterious effects of vitamin D inadequacy, the evidence overall indicates that supplementation, which is both inexpensive and prudent, is warranted for groups whose vitamin D status is exceptionally low, particularly nursing infants, the elderly, and African Americans (e.g., “.((see (3 (Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration (Am J Clin Nutr 2008 Vitamin D Linked To Reduced Mortality Rate In Chronic Kidney Disease Vitamin D protects cells from stress that can lead to cancer “By inducing a specific gene to increase expression of a key enzyme, vitamin D protects healthy prostate cells from the damage and injuries that can “.lead to cancer, University of Rochester Medical Center researchers report :ARTICLES

Position statement on vitamin D “The American Academy of Dermatology recommends that an adequate amount of vitamin D should be obtained from a healthy diet that includes foods naturally rich in vitamin D, foods/beverages fortified with vitamin D, and/or vitamin D supplements; it should not be obtained from “.unprotected exposure to ultraviolet (UV( radiation Supplement Your Knowledge of Vitamin D “How much vitamin D do I need? The current recommended daily dose of vitamin D is 200 IU for people up to age 50, 400 IU for people aged 51 to 70, and 600 IU for people over age 70. That's not enough, Boston University vitamin D expert Michael Holick, MD, PhD, tells WebMD. Holick recommends a dose of 1,000 IU a day of vitamin D for both infants and adults -- unless they're getting plenty of safe sun exposure. In 2008, the American Academy of Pediatrics recommended that breastfed infants receive 400 IU of vitamin D every day until they are weaned and drink at least 1 liter of vitamin D-fortified formula or whole milk each day. The AAP also recommends 400 IU/day of vitamin D for children and teens who drink less than a liter of vitamin D-fortified milk per day. The Vitamin D Council recommends that healthy adults take 2,000 IU of vitamin D daily -- more if they get little or no sun “.exposure The virtues of vitamin D “What’s special about vitamin D? This fat-soluble vitamin is exceptional among vitamins in three ways. First, it has a unique mechanism of action in the body. Second, you can’t get very much of it naturally through your diet. And third, many Americans are deficient in this vital nutrient. That final point is keenly important, in light of burgeoning evidence that vitamin D’s health benefits extend far beyond its reputation for building healthy bones. Over the past decade, studies suggest that adequate amounts of vitamin D may lessen the risk of several types of cancer and may also play a role in preventing high blood pressure, multiple sclerosis, and even schizophrenia. And a 2007 meta-analysis of 18 ”.randomized controlled trials showed that vitamin D supplementation may even help people to live longer The Vitamin That Could Add Years to Your Life “D seems to be particularly relevant to a cellular yardstick of aging called a telomere. These "end caps" on your chromosomes get shorter and shorter with age, but having high blood levels of vitamin D seems to help ensure longer telomeres. That's a good thing, because

when telomeres get really short and disappear, cells stop dividing and start to die. Translation: You age and “.become more vulnerable to disease Vitamin D Deficiency and Related Disorders Vitamin D3 for 1 Year Is Safe in Adolescents “Vitamin D3 at doses equivalent to 2000 IU/day for 1 year is safe in adolescents and results in desirable vitamin D levels … Current recommendations indicate that a daily intake of at least 200 IU of vitamin D among children is adequate. In the current study, the use of 14,000 IU of vitamin D3 weekly improved 25-OHD levels at 1 year among children. Vitamin D supplementation did not affect levels of calcium or 1,25-OHD, and there were no reported cases of vitamin “.D intoxication Vitamin D Deficiency: Implications Across the Lifespan “The role of vitamin D and calcium absorption in the eldery with osteoporosis has been well documented. However, as more evidence is developed, it is becoming clear that vitamin D deficiency is not only affecting the elderly population, it has negative effects across the lifespan. It is estimated that 1 billion people worldwide have vitamin D deficiency or insufficiency.[1] Review of research in medical, nursing, and nutritional literature reveals the need for “.vitamin D education, supplementation, and follow-up in all ages and treatment settings Vitamin D: New Guidelines for Children: American Academy of Pediatricians Doubles Its Minimum Daily Amount of Vitamin D for Babies, Children, and Teens “The American Academy of Pediatrics has doubled its recommendation for the minimum amount of vitamin D that infants, children, and teens should get daily. The new recommendation is to get at least 400 international units (IU(, according to guidelines published by the American Academy of Pediatrics (AAP( in November's edition of Pediatrics. "We know that 400 international units a day is safe and it will prevent rickets," Frank R. Greer, MD, chairman of the AAP's committee on nutrition, tells WebMD. The new guidelines are especially important for breastfed babies, since breast milk isn't rich in vitamin D, notes Greer, who recommends supplements to ensure adequate ”.vitamin D intake. Some vitamin D experts say the AAP's new vitamin D guidelines don't go far enough :JOURNAL ARTICLES

Hydroxyvitamin D and Risk of Myocardial Infarction in Men ( Arch Intern Med. 2008( “Conclusion-25 Low levels of 25(OH(D are associated with higher risk of myocardial infarction in a graded manner, even “.after controlling for factors known to be associated with coronary artery disease Hydroxyvitamin D Levels and the Risk of Mortality in the General Population (Arch Intern Med. 2008(-25 “Conclusion The lowest quartile of 25(OH(D level (<17.8 ng/mL( is independently associated with all”.cause mortality in the general population (Assessing the vitamin D status of the US population1 (American Journal of Clinical Nutrition 2008 Associations Between Vitamin D Status and Pain in Older Adults: The Invecchiare in Chianti Study (Journal of the American Geriatrics Society 2008( “CONCLUSION: Lower concentrations of 25(OH(D are associated with significant back pain in older women but not men. Because vitamin D deficiency and chronic pain are fairly prevalent in older adults, these findings suggest it may be worthwhile to query older “.adults about their pain and screen older women with significant back pain for vitamin D deficiency Comparison of Daily, Weekly, and Monthly Vitamin D3 in Ethanol Dosing Protocols for Two Months in Elderly Hip Fracture Patients (The Journal of Clinical Endocrinology & Metabolism 2008( “Conclusions: Supplementation with vitamin D can be achieved equally well with daily, weekly, or monthly dosing frequencies. Therefore, the choice of dose frequency can be based on whichever approach will optimize an “.individual’s adherence with long-term vitamin D supplementation Depression Is Associated With Decreased 25-Hydroxyvitamin D and Increased Parathyroid Hormone Levels in Older Adults (Arch Gen Psychiatry. 2008( “Conclusion The results of this large population-based study show an association of depression status and severity with decreased serum 25(OH(D levels and “.increased serum PTH levels in older individuals (Estimation of the dietary requirement for vitamin D in healthy adults (Am J Clin Nutr 2008 Higher Serum Vitamin D(3( Levels Are Associated with Better Cognitive Test Performance in Patients with Alzheimer's Disease. (Dement Geriatr Cogn Disord. 2008( “Conclusions: These data support the idea that a relationship exists between vitamin D status and cognition in patients with probable AD. However, given the cross-sectional design of this study, no causality can be concluded. Further prospective studies are “.needed to specify the contribution of vitamin D status to the onset and course of cognitive decline and AD

(Hypovitaminosis D among rheumatology outpatients in clinical practice. (Rheumatology (Oxford(. 2008 Hypovitaminosis D: a stealthy epidemic that requires treatment. (Geriatrics. 2008( “Increasing evidence strongly supports the benefits of vitamin D supplementation and also reveals that present recommendations are inadequate, especially for older individuals. Although additional studies are still needed to further optimize diagnostic and therapeutic approaches, physicians should consider prescribing cholecalciferol - at least 2000 international units (IU( per day - to all elderly patients. Oral cholecalciferol supplementation at that level is inexpensive, safe, and effective, and has great potential to improve the quality of life of the “.elderly Importance of calcium, vitamin D and vitamin K for osteoporosis prevention and treatment. (Proc Nutr Soc. (2008 Independent Association of Low Serum 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Levels With All-Cause and Cardiovascular Mortality (Arch Intern Med. 2008( “Conclusions Low 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels are independently associated with all-cause and cardiovascular “.mortality. A causal relationship has yet to be proved by intervention trials using vitamin D (Intake of vitamin D and risk of breast cancer-A meta-analysis. (J Steroid Biochem Mol Biol. 2008 Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis. (Int J Epidemiol. 2008( “CONCLUSIONS: Low serum vitamin D levels are associated with higher risk of active tuberculosis. Although more prospectively designed studies are needed to firmly establish the direction of this association, it is more likely that low body vitamin D levels increase the risk of active tuberculosis. In view of this, the potential role of vitamin D supplementation in people with tuberculosis and hypovitaminosis D“.associated conditions like chronic kidney disease should be evaluated Optimal serum 25-hydroxyvitamin D levels for multiple health outcomes. (Adv Exp Med Biol. 2008( “An intake of no less than 1000 IU (25 mcg( of vitamin D3 (cholecalciferol( per day for all adults may bring at least 50% of the population up to 75 nmol/l. Thus, higher doses of vitamin D are needed to bring most individuals into the desired range. While estimates suggest that 2000 IU vitamin D3 per day may successfully and safely achieve this goal, the implications of 2000 IU or higher doses for the total adult “.population need to be addressed in future studies Prevalence of Vitamin D Deficiency Among Healthy Infants and Toddlers (Arch Pediatr Adolesc Med. 2008( “Conclusions Suboptimal vitamin D status is common among otherwise healthy young children. Predictors of vitamin D status vary in infants vs toddlers, information that is important to consider in the care of these young patients. One-third of vitamin D–deficient participants exhibited demineralization, “.highlighting the deleterious skeletal effects of this condition Prevalence of Vitamin D Insufficiency in Patients With Parkinson Disease and Alzheimer Disease (Arch Neurol. 2008( “Conclusions This report of 25(OH(D concentrations in a predominantly white PD cohort demonstrates a significantly higher prevalence of hypovitaminosis in PD vs both healthy controls and patients with AD. These data support a possible role of vitamin D insufficiency in PD. Further studies are needed to determine the factors contributing to these differences and elucidate the potential role of vitamin “.D in pathogenesis and clinical course of PD (Prevalence & potential significance of vitamin D deficiency in Asian Indians. (Indian J Med Res. 2008 Progression of malignant melanoma is associated with reduced 25-hydroxyvitamin D serum levels. (Exp Dermatol. 2008( “In conclusion, our findings add to the growing body of evidence that 25-hydroxyvitamin “.D serum levels may be of importance for pathogenesis and progression of malignant melanoma Serum 25-hydroxyvitamin D and functional outcomes in the elderly (American Journal of Clinical Nutrition 2008( “Many elderly persons in the United States and elsewhere have serum 25-hydroxyvitamin D concentrations below these levels. For this reason, supplementation is likely to provide significant benefit to “.this segment of the population Serum 25-Hydroxyvitamin D Concentrations and Risk for Hip Fractures (Annals 2008( “Conclusion: Low ” .serum 25(OH( vitamin D concentrations are associated with a higher risk for hip fracture Serum Vitamin D and Subsequent Occurrence of Type 2 Diabetes. (Epidemiology. 2008( “CONCLUSIONS:: The results support the hypothesis that high vitamin D status provides protection “.against type 2 diabetes. Residual confounding may contribute to this association

SHORT-TERM AND LONG-TERM SAFETY OF WEEKLY HIGH-DOSE VITAMIN D3 SUPPLEMENTATION IN SCHOOL CHILDREN. (J Clin Endocrinol Metab. 2008( “Conclusion: Vitamin D3 at doses equivalent to 2,000 IU/day for one year is safe in adolescents and results in desirable vitamin D “.levels Summary of evidence-based review on vitamin D efficacy and safety in relation to bone health. (Am J Clin Nutr. 2008 ( “The evidence of an association between serum 25(OH(D concentration and some clinical outcomes (fractures, performance measures( in postmenopausal women and older men was inconsistent, and the evidence of an association with falls was fair. We found good evidence of a positive effect of consuming vitamin D-fortified foods on 25(OH(D concentrations. The evidence for a benefit of vitamin D on falls and fractures varied. We found fair evidence that adults tolerated vitamin D at doses above current dietary reference intake levels, but we had no data on the association between long-term harms and higher “.doses of vitamin D (Sun exposure and vitamin D sufficiency. (Am J Clin Nutr. 2008 The association between ultraviolet B irradiance, vitamin D status and incidence rates of type 1 diabetes in 51 regions worldwide. (Diabetologia. 2008( “CONCLUSIONS/INTERPRETATION: An association was found between low UVB irradiance and high incidence rates of type 1 childhood diabetes after controlling for per capita health expenditure. Incidence rates of type 1 diabetes approached zero in regions worldwide with high UVB irradiance, adding new support to the concept of a role of vitamin D in reducing the risk of “.the disease (The resurgence of the importance of vitamin D in bone health. (Asia Pac J Clin Nutr. 2008 Vitamin D and chronic widespread pain in a white middle-aged British population: evidence from a cross(sectional population survey. (Ann Rheum Dis. 2008 (Vitamin D and fracture reduction: an evaluation of the existing research. (Altern Med Rev. 2008 Vitamin D and living in northern latitudes--an endemic risk area for vitamin D deficiency. (Int J Circumpolar Health. 2008( “CONCLUSIONS: Vitamin D plays a fundamental role in calcium and phosphate homeostasis. A deficiency of vitamin D has been attributed to several diseases. Since its production in the skin depends on exposure to UVB-radiation via the sunlight, the level of vitamin D is of crucial importance for the health of inhabitants who live in the Nordic latitudes where there is diminished exposure to sunlight during the winter season. Therefore, fortification or supplementation of vitamin D is necessary for most of the people living in the northern latitudes during the winter season to maintain “.adequate levels of circulating 25(OH(D3 to maintain optimal body function and prevent diseases Vitamin D and multiple sclerosis. (J Cell Biochem. 2008( “Vitamin D is a principal regulator of calcium homeostasis. However, recent evidence has indicated that vitamin D can have numerous other physiological functions including inhibition of proliferation of a number of malignant cells including breast and prostate cancer cells and protection against certain immune mediated disorders including multiple sclerosis (MS(. The geographic incidence of MS indicates an increase in MS with a decrease in sunlight exposure. Since vitamin D is produced in the skin by solar or UV irradiation and high serum levels of 25-hydroxyvitamin D (25(OH(D( have been reported to correlate with a reduced risk of MS, a protective role of vitamin D is “.suggested Vitamin D and neurocognitive dysfunction: Preventing "D"ecline? (Mol Aspects Med. 2008( “Vitamin D exhibits functional attributes that may prove neuroprotective through antioxidative mechanisms, neuronal calcium regulation, immunomodulation, enhanced nerve conduction and detoxification mechanisms. Compelling evidence supports a beneficial role for the active form of vitamin D in the developing brain as “.well as in adult brain function Vitamin D and Prevention of Colorectal Adenoma: A Meta-analysis (Cancer Epidemiology Biomarkers & Prevention 2008( “Conclusions: Both circulating 25(OH(D and vitamin D intake were inversely associated with colorectal adenoma incidence and recurrent adenomas. These results further support a role of vitamin “.D in prevention of colorectal adenoma incidence and recurrence Vitamin D and Sunlight: Strategies for Cancer Prevention and Other Health Benefits. (Clin J Am Soc Nephrol. 2008( “Lack of sun exposure and vitamin D deficiency have been linked to many serious chronic diseases, including autoimmune diseases, infectious diseases, cardiovascular disease, and deadly cancers. It is estimated that there is a 30 to 50% reduction in risk for developing colorectal, breast, and prostate cancer by either increasing vitamin D intake to least 1000 IU/d vitamin D or increasing sun exposure to raise blood

levels of 25(OH(D >30 ng/ml. Most tissues in the body have a vitamin D receptor. The active form of vitamin D, 1,25-dihydroxyvitamin D, is made in many different tissues, including colon, prostate, and breast. It is believed that the local production of 1,25(OH(2D may be responsible for the anticancer benefit of vitamin D. Recent studies suggested that women who are vitamin D deficient have a 253% increased risk for developing colorectal cancer, and women who ingested 1500 mg/d calcium and 1100 IU/d vitamin D3 “.for 4 yr reduced risk for developing cancer by >60% (Vitamin D Deficiency and Risk of Cardiovascular Disease (Circulation 2008 (Vitamin D deficiency in patients with active systemic lupus erythematosus. (Osteoporos Int. 2008 Vitamin D deficiency: a worldwide problem with health consequences (Am J Clin Nutr 2008( “Vitamin D deficiency causes rickets in children and will precipitate and exacerbate osteopenia, osteoporosis, and fractures in adults. Vitamin D deficiency has been associated with increased risk of common cancers, autoimmune diseases, hypertension, and infectious diseases. A circulating level of 25-hydroxyvitamin D of >75 nmol/L, or 30 ng/mL, is required to maximize vitamin D's beneficial effects for health. In the absence of adequate sun exposure, at least 800–1000 IU vitamin D3/d may be needed to achieve this in children and “.adults Vitamin D improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D levels (Diabetic Medicine 2008( “Conclusions Vitamin D insufficiency is common in patients with Type 2 diabetes during winter in Scotland. A single large dose of oral vitamin D2 improves endothelial function in “.patients with Type 2 diabetes and vitamin D insufficiency (Vitamin D in Health and Disease. (Clin J Am Soc Nephrol. 2008 Vitamin D in pregnancy and lactation: maternal, fetal, and neonatal outcomes from human and animal (studies. (Am J Clin Nutr. 2008 Vitamin D inadequacy in French osteoporotic and osteopenic women. (Joint Bone Spine. 2008( “CONCLUSION: Vitamin D deficiency is common among postmenopausal women with osteoporosis or “.osteopenia in France Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors (American Journal of Clinical Nutrition 2008( “Conclusions: In these breast cancer survivors, the prevalence of vitamin D insufficiency was high. Clinicians might consider monitoring vitamin D status in breast cancer patients, together with “.appropriate treatments, if necessary Vitamin D intake and breast cancer risk: a case-control study in Italy. (Ann Oncol. 2008( “CONCLUSIONS: This study adds to the existing evidence that vitamin D intake in inversely associated “.with breast cancer risk (Vitamin D levels and patient outcome in chronic kidney disease. (Kidney Int. 2008 (Vitamin d status of females in an elite gymnastics program. (Clin J Sport Med. 2008 (Vitamin D status in gastrointestinal and liver disease. (Curr Opin Gastroenterol. 2008 (Vitamin D Status: Measurement, Interpretation, and Clinical Application. (Ann Epidemiol. 2008 :INTERNET SITES

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Dietary Supplement Fact Sheet: Vitami Office of Dietary Supplements • National Institutes of Health Table of Contents Introduction Reference Intakes Sources of Vitamin D Vitamin D Intakes and Status Vitamin D Deficiency Groups at Risk of Vitamin D Inadequacy Vitamin D and Health Health Risks from Excessive Vitamin D Interactions with Medications Vitamin D and Healthful Diets References Introduction Vitamin D is a fat-soluble vitamin that is naturally present in very few foods, added to others, and available as a dietary supplement. It is also produced endogenously when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis [1-3]. Vitamin D obtained from sun exposure, food, and supplements is biologically inert and must undergo two hydroxylations in the body for activation. The first occurs in the liver and converts vitamin D to 25hydroxyvitamin D [25(OH)D], also known as calcidiol. The second occurs primarily in the kidney and forms the physiologically active 1,25.[dihydroxyvitamin D [1,25(OH)2D], also known as calcitriol [4 Vitamin D is essential for promoting calcium absorption in the gut and maintaining adequate serum calcium and phosphate concentrations to enable normal mineralization of bone and prevent hypocalcemic tetany. It is also needed for bone growth and bone remodeling by osteoblasts and osteoclasts [4-6]. Without sufficient vitamin D, bones can become thin, brittle, or misshapen. Vitamin D sufficiency prevents rickets in children and osteomalacia in adults [3,7,8]. Together with calcium, vitamin D also helps .protect older adults from osteoporosis Vitamin D has other roles in human health, including modulation of neuromuscular and immune function and reduction of inflammation. Many genes encoding proteins that regulate cell proliferation, differentiation, and

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apoptosis are modulated in part by vitamin D [4,6,9,10]. Many laboratorycultured human cells have vitamin D receptors and some convert 25(OH)D to 1,25(OH)2D [11]. It remains to be determined whether cells with vitamin D .receptors in the intact human carry out this conversion Serum concentration of 25(OH)D is the best indicator of vitamin D status. It reflects vitamin D produced cutaneously and that obtained from food and supplements [5] and has a fairly long circulating half-life of 15 days [15]. However, serum 25(OH)D levels do not indicate the amount of vitamin D stored in other body tissues. Circulating 1,25(OH)2D is generally not a good indicator of vitamin D status because it has a short half-life of 15 hours and serum concentrations are closely regulated by parathyroid hormone, calcium, and phosphate [15]. Levels of 1,25(OH)2D do not typically decrease until .[vitamin D deficiency is severe [6,11 There is considerable discussion of the serum concentrations of 25(OH)D associated with deficiency (e.g., rickets), adequacy for bone health, and optimal overall health (Table 1). A concentration of <20 nanograms per milliliter (ng/mL) (or <50 nanomoles per liter [nmol/L]) is generally considered .inadequate Table 1: Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and *Health **ng/mL **nmol/L 11< 27.5< 10-15< 30≥

Consistentl y <200

Health status Associated with vitamin D deficiency and rickets in .[infants and young children [5 25-37.5< Generally considered inadequate for bone and overall .[health in healthy individuals [5,13 75≥ Proposed by some as desirable for overall health and disease prevention, although a recent governmentsponsored expert panel concluded that insufficient data are available to support these higher levels .[[13,14 Consistentl Considered potentially toxic, leading to y <500 hypercalcemia and hyperphosphatemia, although human data are limited. In an animal model, concentrations ≥400 ng/mL (≥1,000 nmol/L) .[demonstrated no toxicity [15,16

Serum concentrations of 25(OH)D are reported in both nanograms per * .(milliliter (ng/mL) and nanomoles per liter (nmol/L .ng/mL = 2.5 nmol/L 1 ** Reference Intakes Intake reference values for vitamin D and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of The National Academies (formerly National Academy of Sciences) [5]. DRI is the general term for a set of reference values used to plan and assess nutrient intakes of healthy people. :These values, which vary by age and gender [5], include

Recommended Dietary Allowance (RDA): average daily level of• intake sufficient to meet the nutrient requirements of nearly all (97.98%) healthy people Adequate Intake (AI): established when evidence is insufficient to• develop an RDA and is set at a level assumed to ensure nutritional .adequacy Tolerable Upper Intake Level (UL): maximum daily intake unlikely to• .[cause adverse health effects [5 The FNB established an AI for vitamin D that represents a daily intake that is sufficient to maintain bone health and normal calcium metabolism in healthy people. AIs for vitamin D are listed in both micrograms (mcg) and International Units (IUs); the biological activity of 1 mcg is equal to 40 IU (Table 2). The AIs for vitamin D are based on the assumption that the vitamin is not synthesized .[by exposure to sunlight [5

Age Birth to 13 years years 14-18

years 19-50

years 51-70

years +71

[Table 2: Adequate Intakes (AIs) for Vitamin D [5 Childr Wome Pregna Lactati Men en n ncy on mcg 5 200) (IU mcg 5 mcg 5 mcg 5 mcg 5 200) 200) (IU 200) (IU 200) (IU (IU mcg 5 mcg 5 mcg 5 mcg 5 200) 200) (IU 200) (IU 200) (IU (IU 10 10 mcg mcg 400) 400) (IU (IU 15 15 mcg mcg 600) 600) (IU (IU

In 2008, the American Academy of Pediatrics (AAP) issued recommended intakes for vitamin D that exceed those of FNB [18]. The AAP recommendations are based on evidence from more recent clinical trials and the history of safe use of 400 IU/day of vitamin D in pediatric and adolescent populations. AAP recommends that exclusively and partially breastfed infants receive supplements of 400 IU/day of vitamin D shortly after birth and continue to receive these supplements until they are weaned and consume ≥1,000 mL/day of vitamin D-fortified formula or whole milk [18]. (All formulas sold in the United States provide ≥400 IU vitamin D3 per liter, and the majority of vitamin D-only and multivitamin liquid supplements provide 400 IU per serving.) Similarly, all non-breastfed infants ingesting <1,000 mL/day of vitamin D-fortified formula or milk should receive a vitamin D supplement of 400 IU/day. AAP also recommends that older children and adolescents who do not obtain 400 IU/day through vitamin D-fortified milk and foods should take a .[400 IU vitamin D supplement daily [18

Sources of Vitamin D Food Very few foods in nature contain vitamin D. The flesh of fish (such as salmon, tuna, and mackerel) and fish liver oils are among the best sources [5]. Small amounts of vitamin D are found in beef liver, cheese, and egg yolks. Vitamin D in these foods is primarily in the form of vitamin D3 (cholecalciferol) and its metabolite 25(OH)D3 [19]. Some mushrooms provide vitamin D2 .[(ergocalciferol) in variable amounts [20-22 Fortified foods provide most of the vitamin D in the American diet [5,22]. For example, almost all of the U.S. milk supply is fortified with 100 IU/cup of vitamin D (25% of the Daily Value or 50% of the AI level for ages 14-50 years). In the 1930s, a milk fortification program was implemented in the United States to combat rickets, then a major public health problem. This program virtually eliminated the disorder at that time [5,14]. Other dairy products made from milk, such as cheese and ice cream, are generally not fortified. Ready-to-eat breakfast cereals often contain added vitamin D, as do some brands of orange juice, yogurt, and margarine. In the United States, foods allowed to be fortified with vitamin D include cereal flours and related products, milk and products made from milk, and calcium-fortified fruit juices .and drinks [22]. Maximum levels of added vitamin D are specified by law .Several food sources of vitamin D are listed in Table 3 [Table 3: Selected Food Sources of Vitamin D [23-25 Food Cod liver oil, 1 tablespoon Salmon, cooked, 3.5 ounces Mackerel, cooked, 3.5 ounces Tuna fish, canned in oil, 3 ounces Sardines, canned in oil, drained, 1.75 ounces Milk, nonfat, reduced fat, and whole, vitamin D-fortified, 1 cup Margarine, fortified, 1 tablespoon Ready-to-eat cereal, fortified with 10% of the DV for vitamin D, 0.75-1 cup (more heavily fortified cereals (might provide more of the DV (Egg, 1 whole (vitamin D is found in yolk Liver, beef, cooked, 3.5 ounces Cheese, Swiss, 1 ounce

IUs per Percent *serving **DV 1,360 340 360 90 345 90 200 50 250 70 98

25

60

15

40

10

20 15 12

6 4 4

.IUs = International Units* DV = Daily Value. DVs were developed by the U.S. Food and Drug** Administration to help consumers compare the nutrient contents of products within the context of a total diet. The DV for vitamin D is 400 IU for adults and children age 4 and older. Food labels, however, are not required to list vitamin D content unless a food has been fortified with this nutrient. Foods providing .20% or more of the DV are considered to be high sources of a nutrient

The U.S. Department of Agriculture's Nutrient Database Web site, http://www.nal.usda.gov/fnic/foodcomp/search/ [26], lists the nutrient content .of many foods; relatively few have been analyzed for vitamin D content Sun exposure Most people meet their vitamin D needs through exposure to sunlight [6,27]. Ultraviolet (UV) B radiation with a wavelength of 290-315 nanometers penetrates uncovered skin and converts cutaneous 7-dehydrocholesterol to previtamin D3, which in turn becomes vitamin D3 [11,27-28]. Season, geographic latitude, time of day, cloud cover, smog, skin melanin content, and sunscreen are among the factors that affect UV radiation exposure and vitamin D synthesis [28]. The UV energy above 42 degrees north latitude (a line approximately between the northern border of California and Boston) is insufficient for cutaneous vitamin D synthesis from November through February [6]; in far northern latitudes, this reduced intensity lasts for up to 6 months. Latitudes below 34 degrees north (a line between Los Angeles and Columbia, South Carolina) allow for cutaneous production of vitamin D [throughout the year [14 Complete cloud cover reduces UV energy by 50%; shade (including that produced by severe pollution) reduces it by 60% [29]. UVB radiation does not penetrate glass, so exposure to sunshine indoors through a window does not produce vitamin D [30]. Sunscreens with a sun protection factor of 8 or more appear to block vitamin D-producing UV rays, although in practice people generally do not apply sufficient amounts, cover all sun-exposed skin, or reapply sunscreen regularly [31]. Skin likely synthesizes some vitamin D even .when it is protected by sunscreen as typically applied The factors that affect UV radiation exposure and research to date on the amount of sun exposure needed to maintain adequate vitamin D levels make it difficult to provide general guidelines. It has been suggested by some vitamin D researchers, for example, that approximately 5-30 minutes of sun exposure between 10 AM and 3 PM at least twice a week to the face, arms, legs, or back without sunscreen usually lead to sufficient vitamin D synthesis and that the moderate use of commercial tanning beds that emit 2-6% UVB radiation is also effective [11,28]. Individuals with limited sun exposure need .to include good sources of vitamin D in their diet or take a supplement Despite the importance of the sun to vitamin D synthesis, it is prudent to limit exposure of skin to sunlight [31]. UV radiation is a carcinogen responsible for most of the estimated 1.5 million skin cancers and the 8,000 deaths due to metastatic melanoma that occur annually in the United States [31]. Lifetime cumulative UV damage to skin is also largely responsible for some ageassociated dryness and other cosmetic changes. It is not known whether a desirable level of regular sun exposure exists that imposes no (or minimal) risk of skin cancer over time. The American Academy of Dermatology advises that photoprotective measures be taken, including the use of sunscreen, whenever .[one is exposed to the sun [83 Dietary supplements In supplements and fortified foods, vitamin D is available in two forms, D2

(ergocalciferol) and D3 (cholecalciferol). Vitamin D2 is manufactured by the UV irradiation of ergosterol in yeast, and vitamin D3 is manufactured by the irradiation of 7-dehydrocholesterol from lanolin and the chemical conversion of cholesterol [11]. The two forms have traditionally been regarded as equivalent based on their ability to cure rickets, but evidence has been offered that they are metabolized differently. Vitamin D3 could be more than three times as effective as vitamin D2 in raising serum 25(OH)D concentrations and maintaining those levels for a longer time, and its metabolites have superior affinity for vitamin D-binding proteins in plasma [6,32,33]. Because metabolite receptor affinity is not a functional assessment, as the earlier results for the healing of rickets were, further research is needed on the comparative physiological effects of both forms. Many supplements are being reformulated to contain vitamin D3 instead of vitamin D2 [33]. Both forms (as well as vitamin D in foods and from cutaneous synthesis) effectively raise serum 25(OH)D .[levels [6 Vitamin D Intakes and Status In 1988-1994, as part of the third National Health and Nutrition Examination Survey (NHANES III), the frequency of use of some vitamin D-containing foods and supplements was examined in 1,546 non-Hispanic African American women and 1,426 non-Hispanic white women of reproductive age (15-49 years) [34]. In both groups, 25(OH)D levels were higher in the fall (after a summer of sun exposure) and when milk or fortified cereals were consumed more than three times per week. The prevalence of serum concentrations of 25(OH)D ≥15 ng/mL (≥37.5 nmol/L) was 10 times greater for the African .(American women (42.2%) than for the white women (4.2% The 2000-2004 NHANES provided the most recent data on the vitamin D nutritional status of the U.S. population [35]. Generally, younger people had higher serum 25(OH)D levels than older people; males had higher levels than females; and non-Hispanic whites had higher levels than Mexican Americans, who in turn had higher levels than non-Hispanic blacks. Depending on the population group, 1-9% had serum 25(OH)D levels <11 ng/mL (<27.5 nmol/L), 8-36% had levels <20 ng/mL (<50 nmol/L), and the majority (50-78%) had levels <30 ng/mL (<75 nmol/L). Among adults in the United Kingdom, nationally representative data collected between 1992 and 2001 show that 520% in most age groups on average had serum 25(OH)D levels <10 ng/ml (<25 nmol/L); the prevalence of deficiency was greater (range 20-40%) for older people <65 years of age in residential care homes and among women <85 years. Among all adults, 20-60% had levels ≥20 ng/ml (≥50 nmol/L) and .[90% had levels ≥32 ng/ml (≥80 nmol/L) [36 Vitamin D Deficiency Nutrient deficiencies are usually the result of dietary inadequacy, impaired absorption and use, increased requirement, or increased excretion. A vitamin D deficiency can occur when usual intake is lower than recommended levels over time, exposure to sunlight is limited, the kidneys cannot convert vitamin D to its active form, or absorption of vitamin D from the digestive tract is inadequate. Vitamin D-deficient diets are associated with milk allergy, lactose .[intolerance, and strict vegetarianism [37 Rickets and osteomalacia are the classical vitamin D deficiency diseases. In

children, vitamin D deficiency causes rickets, a disease characterized by a failure of bone tissue to properly mineralize, resulting in soft bones and skeletal deformities [29]. Rickets was first described in the mid-17th century by British researchers [29,38]. In the late 19th and early 20th centuries, German physicians noted that consuming 1-3 teaspoons of cod liver oil per day could reverse rickets [38]. In the 1920s and prior to identification of the structure of vitamin D and its metabolites, biochemist Harry Steenbock patented a process to impart antirachitic activity to foods [14]. The process involved the addition of what turned out to be precursor forms of vitamin D followed by exposure to UV radiation. The fortification of milk with vitamin D has made rickets a rare disease in the United States. However, rickets is still reported periodically, particularly among African American infants and children [29,38]. A 2003 report from Memphis, for example, described 21 cases of .[rickets among infants, 20 of whom were African American [38 Prolonged exclusive breastfeeding without the AAP-recommended vitamin D supplementation is a significant cause of rickets, particularly in dark-skinned infants breastfed by mothers who are not vitamin D replete [6]. Additional causes of rickets include extensive use of sunscreens and placement of children in daycare programs, where they often have less outdoor activity and sun exposure [29,38]. Rickets is also more prevalent among immigrants from Asia, Africa, and the Middle East, possibly because of genetic differences in vitamin D metabolism and behavioral differences that lead to less sun .[exposure [29 In adults, vitamin D deficiency can lead to osteomalacia, resulting in weak muscles and bones [7,8,15]. Symptoms of bone pain and muscle weakness can indicate inadequate vitamin D levels, but such symptoms can be subtle .and go undetected in the initial stages Groups at Risk of Vitamin D Inadequacy Obtaining sufficient vitamin D from natural food sources alone can be difficult. For many people, consuming vitamin D-fortified foods and being exposed to sunlight are essential for maintaining a healthy vitamin D status. In some groups, dietary supplements might be required to meet the daily need for .vitamin D Breastfed infants Vitamin D requirements cannot be met by human milk alone [5,39], which provides only about 25 IU/L [17]. A recent review of reports of nutritional rickets found that a majority of cases occurred among young, breastfed African Americans [40]. The sun is a potential source of vitamin D, but AAP advises keeping infants out of direct sunlight and having them wear protective clothing and sunscreen [41]. As noted earlier, AAP recommends that exclusively and partially breastfed infants be supplemented with 400 IU of .[vitamin D per day [18 Older adults Americans aged 50 and older are at increased risk of developing vitamin D insufficiency [28]. As people age, skin cannot synthesize vitamin D as efficiently and the kidney is less able to convert vitamin D to its active hormone form [5,42]. As many as half of older adults in the United States with

.[hip fractures could have serum 25(OH)D levels <12 ng/mL (<30 nmol/L) [6 People with limited sun exposure Homebound individuals, people living in northern latitudes (such as New England and Alaska), women who wear long robes and head coverings for religious reasons, and people with occupations that prevent sun exposure are .[unlikely to obtain adequate vitamin D from sunlight [43,44 People with dark skin Greater amounts of the pigment melanin result in darker skin and reduce the skin's ability to produce vitamin D from exposure to sunlight. Some studies suggest that older adults, especially women, with darker skin are at high risk of developing vitamin D insufficiency [34,45]. However, one group with dark skin, African Americans, generally has lower levels of 25(OH)D yet develops fewer osteoporotic fractures than Caucasians (see section below on .(osteoporosis People with fat malabsorption As a fat-soluble vitamin, vitamin D requires some dietary fat in the gut for absorption. Individuals who have a reduced ability to absorb dietary fat might require vitamin D supplements [46]. Fat malabsorption is associated with a variety of medical conditions including pancreatic enzyme deficiency, Crohn's disease, cystic fibrosis, celiac disease, surgical removal of part of the stomach .[or intestines, and some forms of liver disease [15 People who are obese Individuals with a body mass index (BMI) ≥30 typically have a low plasma concentration of 25(OH)D [47]; this level decreases as obesity and body fat increase [48]. Obesity does not affect skin's capacity to synthesize vitamin D, but greater amounts of subcutaneous fat sequester more of the vitamin and alter its release into the circulation. Even with orally administered vitamin D, BMI is inversely correlated with peak serum concentrations, probably because .[some vitamin D is sequestered in the larger pools of body fat [47 Vitamin D and Health Optimal serum concentrations of 25(OH)D for bone and general health throughout life have not been established [6,11] and are likely to vary at each stage of life, depending on the physiological measures selected. The three-fold range of cut points that have been proposed by various experts, from 16 to 48 ng/mL (40 to 120 nmol/L), reflect differences in the functional endpoints chosen (e.g., serum concentrations of parathyroid hormone or bone fractures), as well as differences in the analytical methods used. The numerous assays for 25(OH)D provide differing results. One reason for these issues of precision and variability is that no standard reference preparations or calibrating materials are available commercially to help reduce the variability of results between methods and laboratories. Efforts are underway to standardize the .quantification of 25(OH)D to measure vitamin D status In March 2007, a group of vitamin D and nutrition researchers published a controversial and provocative editorial contending that the desirable concentration of 25(OH)D is ≥30 ng/mL (≥75 nmol/L) [12]. They noted that supplemental intakes of 400 IU/day of vitamin D increase 25(OH)D

concentrations by only 2.8-4.8 ng/mL (7-12 nmol/L) and that daily intakes of approximately 1,700 IU are needed to raise these concentrations from 20 to .(32 ng/mL (50 to 80 nmol/L Osteoporosis More than 25 million adults in the United States have or are at risk of developing osteoporosis, a disease characterized by fragile bones that significantly increases the risk of bone fractures [50]. Osteoporosis is most often associated with inadequate calcium intakes (generally <1,000-1,200 mg/day), but insufficient vitamin D contributes to osteoporosis by reducing calcium absorption [51]. Although rickets and osteomalacia are extreme examples of the effects of vitamin D deficiency, osteoporosis is an example of a long-term effect of calcium and vitamin D insufficiency [52]. Adequate storage levels of vitamin D maintain bone strength and might help prevent osteoporosis in older adults, nonambulatory individuals who have difficulty exercising, postmenopausal women, and individuals on chronic steroid therapy .[[53 Normal bone is constantly being remodeled. During menopause, the balance between these processes changes, resulting in more bone being resorbed than rebuilt. Hormone therapy with estrogen and progesterone might be able to delay the onset of osteoporosis. However, some medical groups and professional societies recommend that postmenopausal women consider using other agents to slow or stop bone resorption because of the potential adverse .[health effects of hormone therapy [54-56 Most supplementation trials of the effects of vitamin D on bone health also include calcium, so it is not possible to isolate the effects of each nutrient. The authors of a recent evidence-based review of research concluded that supplements of both vitamin D3 (at 700-800 IU/day) and calcium (500-1,200 mg/day) decreased the risk of falls, fractures, and bone loss in elderly individuals aged 62-85 years [6]. The decreased risk of fractures occurred primarily in elderly women aged 85 years, on average, and living in a nursing home. Women should consult their healthcare providers about their needs for vitamin D (and calcium) as part of an overall plan to prevent or treat .osteoporosis African Americans have lower levels of 25(OH)D than Caucasians, yet they develop fewer osteoporotic fractures. This suggests that factors other than vitamin D provide protection [57]. African Americans have an advantage in bone density from early childhood, a function of their more efficient calcium economy, and have a lower risk of fracture even when they have the same bone density as Caucasians. They also have a higher prevalence of obesity, and the resulting higher estrogen levels in obese women might protect them from bone loss [57]. Further reducing the risk of osteoporosis in African Americans are their lower levels of bone-turnover markers, shorter hip-axis length, and superior renal calcium conservation. However, despite this advantage in bone density, osteoporosis is a significant health problem among .[African Americans as they age [57 Cancer

Laboratory and animal evidence as well as epidemiologic data suggest that vitamin D status could affect cancer risk. Strong biological and mechanistic bases indicate that vitamin D plays a role in the prevention of colon, prostate, and breast cancers. Emerging epidemiologic data suggest that vitamin D has a protective effect against colon cancer, but the data are not as strong for a protective effect against prostate and breast cancer, and are variable for cancers at other sites [58-59]. Studies do not consistently show a protective effect or no effect, however. One study of Finnish smokers, for example, found that subjects in the highest quintile of baseline vitamin D status have a three.[fold higher risk of developing pancreatic cancer [60 Vitamin D emerged as a protective factor in a prospective, cross-sectional study of 3,121 adults aged ≥50 years (96% men) who underwent a colonoscopy. The study found that 10% had at least one advanced cancerous lesion. Those with the highest vitamin D intakes (<645 IU/day) had a significantly lower risk of these lesions [61]. However, the Women's Health Initiative, in which 36,282 postmenopausal women of various races and ethnicities were randomly assigned to receive 400 IU vitamin D plus 1,000 mg calcium daily or a placebo, found no significant differences between the groups in the incidence of colorectal cancers over 7 years [62]. More recently, a clinical trial focused on bone health in 1,179 postmenopausal women residing in rural Nebraska found that subjects supplemented daily with calcium (1,400-1,500 mg) and vitamin D3 (1,100 IU) had a significantly lower incidence of cancer over 4 years compared to women taking a placebo [63]. The small number of cancers reported (50) precludes generalizing about a protective effect from either or both nutrients or for cancers at different sites. This caution is supported by an analysis of 16,618 participants in NHANES III, where total cancer mortality was found to be unrelated to baseline vitamin D status [64]. However, colorectal cancer mortality was inversely related to serum 25(OH)D concentrations; levels <80 nmol/L were associated with a 72% .risk reduction than those <50 nmol/L Further research is needed to determine whether vitamin D inadequacy in particular increases cancer risk, whether greater exposure to the nutrient is protective, and whether some individuals could be at increased risk of cancer .[because of vitamin D exposure [58 Other conditions A growing body of research suggests that vitamin D might play some role in the prevention and treatment of type 1 [65] and type 2 diabetes [66], hypertension [67], glucose intolerance [68], multiple sclerosis [69], and other medical conditions [70-71]. However, most evidence for these roles comes from in vitro, animal, and epidemiological studies, not the randomized clinical trials considered to be more definitive. Until such trials are conducted, the implications of the available evidence for public health and patient care will be .debated A recent meta-analysis found that use of vitamin D supplements was associated with a reduction in overall mortality from any cause by a statistically significant 7% [72-73]. The subjects in these trials were primarily healthy, middle aged or elderly, and at high risk of fractures; they took 300-

.2,000 IU/day of vitamin D supplements Health Risks from Excessive Vitamin D Vitamin D toxicity can cause nonspecific symptoms such as nausea, vomiting, poor appetite, constipation, weakness, and weight loss [74]. More seriously, it can also raise blood levels of calcium, causing mental status changes such as confusion and heart rhythm abnormalities [8]. The use of supplements of both calcium (1,000 mg/day) and vitamin D (400 IU/day) by postmenopausal women was associated with a 17% increase in the risk of kidney stones over 7 years in the Women's Health Initiative [75]. Deposition of calcium and phosphate in the kidneys and other soft tissues can also be caused by excessive vitamin D levels [5]. A serum 25(OH)D concentration consistently <200 ng/mL (<500 nmol/L) is considered to be potentially toxic [15]. In an animal model, concentrations ≥400 ng/mL (≥1,000 nmol/L) were not .[associated with harm [16 Excessive sun exposure does not result in vitamin D toxicity because the sustained heat on the skin is thought to photodegrade previtamin D3 and vitamin D3 as it is formed [11,30]. High intakes of dietary vitamin D are very unlikely to result in toxicity unless large amounts of cod liver oil are .consumed; toxicity is more likely to occur from high intakes of supplements Long-term intakes above the UL increase the risk of adverse health effects [5] (Table 4). Substantially larger doses administered for a short time or periodically (e.g., 50,000 IU/week for 8 weeks) do not cause toxicity. Rather, the excess is stored and used as needed to maintain normal serum 25(OH)D .[concentrations when vitamin D intakes or sun exposure are limited [15,76 [Table 4: Tolerable Upper Intake Levels (ULs) for Vitamin D [5 Childre n mcg 25 Birth to 12 1,000) months (IU mcg 50 years 1-13 2,000) (IU Age

years +14

Men

Women

Pregna Lactati ncy on

mcg 50 mcg 50 mcg 50 mcg 50 2,000) 2,000) 2,000) 2,000) (IU (IU (IU (IU

Several nutrition scientists recently challenged these ULs, first published in 1997 [76]. They point to newer clinical trials conducted in healthy adults and conclude that the data support a UL as high as 10,000 IU/day. Although vitamin D supplements above recommended levels given in clinical trials have not shown harm, most trials were not adequately designed to assess harm [6]. Evidence is not sufficient to determine the potential risks of excess vitamin D .in infants, children, and women of reproductive age Interactions with Medications Vitamin D supplements have the potential to interact with several types of medications. A few examples are provided below. Individuals taking these

medications on a regular basis should discuss vitamin D intakes with their .healthcare providers Steroids Corticosteroid medications such as prednisone, often prescribed to reduce inflammation, can reduce calcium absorption [77-79] and impair vitamin D metabolism. These effects can further contribute to the loss of bone and the .[development of osteoporosis associated with their long-term use [78-79 Other medications Both the weight-loss drug orlistat (brand names Xenical® and alli™) and the cholesterol-lowering drug cholestyramine (brand names Questran®, LoCholest®, and Prevalite®) can reduce the absorption of vitamin D and other fat-soluble vitamins [80-81]. Both phenobarbital and phenytoin (brand name Dilantin®), used to prevent and control epileptic seizures, increase the hepatic metabolism of vitamin D to inactive compounds and reduce calcium .[absorption [82 Vitamin D and Healthful Diets According to the 2005 Dietary Guidelines for Americans, "nutrient needs should be met primarily through consuming foods. Foods provide an array of nutrients and other compounds that may have beneficial effects on health. In certain cases, fortified foods and dietary supplements may be useful sources of one or more nutrients that otherwise might be consumed in less than recommended amounts. However, dietary supplements, while recommended ".in some cases, cannot replace a healthful diet The Dietary Guidelines for Americans describes a healthy diet as one that Emphasizes a variety of fruits, vegetables, whole grains, and fat-free• .or low-fat milk and milk products Milk is fortified with vitamin D, as are many ready-to-eat cereals and a few brands of yogurt and orange juice. Cheese naturally contains small .amounts of vitamin D .Includes lean meats, poultry, fish, beans, eggs, and nuts• Fish such as salmon, tuna, and mackerel are very good sources of vitamin D. Small amounts of vitamin D are also found in beef liver and .egg yolks Is low in saturated fats, trans fats, cholesterol, salt (sodium), and• .added sugars .Vitamin D is added to some margarines .Stays within your daily calorie needs• For more information about building a healthful diet, refer to the Dietary Guidelines for Americans (http://www.health.gov/dietaryguidelines/dga2005/document/default.htm) and the U.S. Department of Agriculture's food guidance system, My Pyramid .((http://www.mypyramid.gov

References

Office of Dietary Supplements National Institutes of Health Bethesda, Maryland 20892 USA Web: http://ods.od.nih.gov E-mail: [email protected]

:Vitamin D deficiency can result from Inadequate intake -1 ,Inadequate sunlight exposure-2 ,Disorders that limit its absorption-3 Conditions that impair conversion of vitamin D into active metabolites, such as Liver or-4 .kidney disorders, or, rarely, by a number of hereditary disorders Deficiency results in impaired bone mineralization, and leads to Rickets in children and .Osteomalacea in adults, and possibly contributes to Osteoporosis and is made in the skin when 7- Dehydrocholesterol reacts with UVB at Wavelengths between 270–300 nm, with peak synthesis occurring between 295-297 nm. These Wavelengths are present in sunlight when the UV index is greater than 3. At this solar elevation, which occurs daily within the tropics, daily during the spring and summer seasons .in temperate region Adequate amounts of vitamin D3 can be made in the skin after only 10-15 minutes of sun exposure at least 2 times per wk to the face, arms, hands, or back without sunscreen , before 10 am or after 4 pm. With longer exposure to UVB rays, an equilibrium .is achieved in the skin, and the vitamin simply degrades as fast as it is generated In humans, Vit.D3 is as effective as D2 at increasing the levels of vitamin D hormone in circulation, although others state that D3 is more effective than D2. Both vitamin D2 and D3 are used for human nutritional supplementation, and Pharmaceutical forms include .Calcterol (1alpha, 25-dihydroxycholecalciferol), doxercalciferol and calcipotriene

Biochemistry Vitamin D is a prohormone, meaning that it has no hormone activity itself, but is converted to the active hormone 1,25-D through a tightly regulated synthesis mechanism. Production of vitamin D in nature always appears to require the presence of some UV light; even vitamin D in foodstuffs is ultimately derived from organisms, from mushrooms to animals, which are not able to synthesize it except through the action of sunlight at some point in the synthetic chain. For example, fish contain vitamin D only because they ultimately exist on calories from ocean algae which synthesize vitamin D in shallow waters from the action of .solar UV Vitamin D3 is produced photochemically in the skin from 7-dehydrocholesterol. The highest concentrations of 7-dehydrocholesterol are found in the epidermal layer of skin, specifically in the .[stratum basale and stratum spinosum.[8

Synthesis in the skin involves UVB radiation which effectively penetrates only the epidermis. While 7Dehydrocholesterol absorbs UV light at wavelengths between 270–300 nm, optimal synthesis occurs in a narrow band of UVB spectra between 295-300 nm. Peak isomerization is found at 297 nm. This narrow segment is sometimes referred to as D-UV.[9] The two most important factors that govern the generation of pre-vitamin D3 are the quantity (intensity) and quality (appropriate wavelength) of the UVB irradiation reaching the 7-dehydrocholesterol deep in the stratum basale and stratum [ spinosum.[8 A critical determinant of vitamin D3 production in the skin is the presence and concentration of melanin. Melanin functions as a light filter in the skin, and therefore the concentration of melanin in the skin is related to the ability of UVB light to penetrate the epidermal strata and reach the 7dehydrocholesterol-containing stratum basale and stratum spinosum. Under normal circumstances, ample quantities of 7-dehydrocholesterol (about 25-50 µg/cm² of skin) are available in the stratum spinosum and stratum basale of human skin to meet the body's vitamin D requirements,[8] and melanin content does not alter the amount of vitamin D that can be produced.[14] Thus, individuals with higher skin melanin content will simply require more time in sunlight to produce the same amount of vitamin D as individuals with lower melanin content. As noted below, the amount of time an individual requires to produce a given amount of Vitamin D may also depend upon the person's .distance from the equator and on the season of the year Mechanism of action

Once vitamin D is produced in the skin or consumed in food, it is converted in the liver and kidney to form 1,25 dihydroxyvitamin D, (1,25(OH)2D) the physiologically active form of vitamin D .This metabolically active form of vitamin D is known as calcitriol. Following this conversion, calcitriol is released into the circulation, and by binding to a carrier protein in the plasma, vitamin D binding protein (VDBP(, it is [ transported to various target organs.[7 Vitamin D also affects the immune system, and VDR are expressed in several white blood cells including [ monocytes and activated T and B cells.[13 ----------------------------------------------------------------------------------------------------------------------------Ultraviolet Radiation All energies that move at the speed of light are collectivelly referred to as electromagnetic radiation or 'light'. Various types of light differ in their wavelength, frequency and energy; higher energy waves have higher frequencies and shorter wavelengths. Pigments inside the retina of our eyes absorb wavelengths of light between 400nm-700nm, .collectively referred to as 'visible light'. A "nm'' is a nanometer which is one billionth, or 10e-9, meters

Stratospheric Oxygen and Ozone molecules absorb 97-99% of the sun's high freguency Ultraviolet light, light with wavelengths between 150 and 300nm. Ultraviolet-B(UV-B) is a section of the UV spectrum, with wavelengths .between 270 and 320nm

:The amount of UV-B light recieved by a location is strongly dependent on latitude and elevation of the location. At the high-latitude polar regions the sun is always low in the sky;• because the sunlight passes through more atmosphere so more of ithe UV-B is absorbed. For this reason .average UV-B exposure at the poles is over a thousand times lower than at the equator .cloud cover ; the reduction in UV-B exposure depends the cover's thickness• proximity to an industrial area because of the protection offered by photochemical smog. Industrial• processes produce ozone, one of the more irritaiting components of smog, which aborbs UV-B. This is thought to be one of the main reasons that significant ozone losses in the southern hemisphere have not .been mirrored in the northern hemisphere Health effects of UV-B light Genetic damage DNA absorbs UV-B light and the absorbed energy can break bonds in the DNA. Most of the DNA breakages are repaired by proteins present in the cells nucleus but unrepaired genetic damage of the DNA can lead to skin cancers. In fact one method that scientists use to analyze amounts of 'genetically-damaging UV-B is to expose samples of DNA to the light and then count the number of breaks in the DNA. For example J.Regan's work at the Florida Institute of Technology used human DNA to find that genetically significant doses of solar radiation could .penetrate as far as 9 feet into non-turbulant ocean water The Cancer link The principle danger of skin cancer is to light-skinned peoples. A 1%decrease in the ozone layer will cause a estimated 2%increase in UV-B irradiation; it is estimated that this will lead to a 4%increase in basal carcinomas and 6%increase in squamous-cell carcinomas.[Graedel&Crutzen]. 90% of the skin carcinomas are attributed to UV-B exposure [Wayne] and the chemical mechanism by which it causes skin cancer has been identified [Tevini]. The above named carcinomas are relatively easy to treat, if detected in time, and are rarely fatal. But the much more dangerous malignant melanoma is not as well understood. There appears to be a correlation between brief, high intensity exposures to UV and eventual appearance (as long as 10-20yrs!) of melanoma. Twice as many deaths due to melanomas are seen in the southern states of Texas and Florida, as in the northern states of Wisconsin and Montana, but there could be many other factors involved. One undisputed effect of long-term sun exposure is the premature aging of the skin due to both UV-A, UV-B and UV-C. Even careful tanning kills skin cells, damages DNA and causes permanent changes in skin connective tissue which leads to wrinkle formation in later life. There is no .such thing as a safe tan Possible eye damage can result from high doses of UV light, particularly to the cornea which is a good absorber of UV light. High doses of UV light can causes a temporary clouding of the cornea, called 'snow-blindness', and chronic doses has been tenitively linked to the formation of cataracts. Higher incidences of cataracts are found at high .(elevations,Tibet and Bolivia; and higher incidences are seen at lower latitudes(approaching the equator Damage to marine life The penetration of increased amounts of UV-B light has caused great concern over the health of marine plankton that densly populate the top 2 meters of ocean water. The natural protective-responce of most chlorophyll containing cells to increased light-radiation is to produce more light-absorbing pigments but this protective responce is not triggered by UV-B light. Another possible responce of plankton is to sink deeper into the water but this reduces the amount of visible light they need for photosynthesis, and thereby reduces their growth and reproduction rate. In other words, the amount of food and oxygen produced by plankton could be reduced by UV exposure without :killing individual organisms. There are several other considerations Ultraviolet levels are over 1,000 times higher at the equator than at the polar regions so it is presumed• that marine life at the equator is much better adapted to the higher enviromental UV light than organisms in the polar regions. The current concern of marine biologists is mostly over the more sensitive antarctic phytoplankton which normally would recieve very low doses of UV. Only one large-scale field survey of

Anarctic phytoplankton has been carried out so far [Smith et.al _Science_1992] ; they found a 6-12% drop in phytoplankton productivity once their ship entered the area of the spring-time ozone hole. Since the hole only lasts from 10-12weeks this translates into a 2-4%loss overall, a measurable but not yet .catastrophic loss Both plants and phytoplankton vary widely in their sensitivity to UV-B. When over 200 agricultural plants• were tested, more than half showed sensitivity to UV-B light. Other plants showed neglible effects or even a small increase in vigor. Even within a species there were marked differences; for example one variety of soybean showed a 16% decrease in growth while another variety of the same soybean showed no effect [R.Parson]. An increase in UV-B could cause a shift in population rather than a large die-off of plants An increase in UV-B will cause increased amounts of Ozone to be produced at lower levels in the• atmosphere. While some have hailed the protection offered by this 'pollution-sheild' many plants have .shown themselves to be very sensitive to photochemical smog

Ultraviolet Radiation Gary Zeman, ScD, CHP Ultraviolet (UV( radiation is defined as that portion of the electromagnetic spectrum between x rays and visible light, i.e., between 40 and 400 nm (30–3 eV(. The UV spectrum is divided into Vacuum UV (40-190 nm(, Far UV (190-220 nm(, UVC (220-290 nm(, UVB (290-320(, and UVA (320-400 nm(. The sun is our primary natural source of UV radiation. Artificial sources include tanning booths, black lights, curing lamps, germicidal lamps, mercury vapor lamps, halogen lights, high-intensity discharge lamps, fluorescent and incandescent sources, and some types of lasers (excimer lasers, nitrogen lasers, and third harmonic Nd:YAG lasers(. Unique hazards apply to the different sources depending on the wavelength range of the .emitted UV radiation UVC is almost never observed in nature because it is absorbed completely in the atmosphere, as are Far UV and Vacuum UV. Germicidal lamps are designed to emit UVC radiation because of its ability to kill bacteria. In humans, UVC is absorbed in the outer dead layers of the epidermis. Accidental overexposure to UVC can cause corneal burns, commonly termed welders' flash, and snow blindness, a severe sunburn to .the face. While UVC injury usually clears up in a day or two, it can be extremely painful UVB is typically the most destructive form of UV radiation because it has enough energy to cause photochemical damage to cellular DNA, yet not enough to be completely absorbed by the atmosphere. UVB is needed by humans for synthesis of vitamin D; however, harmful effects can include erythema (sunburn(, cataracts, and development of skin cancer. Individuals working outdoors are at the greatest risk of UVB effects. Most solar UVB is blocked by ozone in the atmosphere, and there is concern that reductions in .atmospheric ozone could increase the prevalence of skin cancer UVA is the most commonly encountered type of UV light. UVA exposure has an initial pigment-darkening effect (tanning( followed by erythema if the exposure is excessive. Atmospheric ozone absorbs very little of this part of the UV spectrum. UVA is needed by humans for synthesis of vitamin D; however, overexposure to UVA has been associated with toughening of the skin, suppression of the immune system, and cataract .formation. UVA light is often called black light. Most phototherapy and tanning booths use UVA lamps The photochemical effects of UV radiation can be exacerbated by chemical agents including birth control pills, tetracycline, sulphathizole, cyclamates, antidepressants, coal tar distillates found in antidandruff shampoos, lime oil, and some cosmetics. Protection from UV is provided by clothing, polycarbonate, glass, acrylics, and plastic diffusers used in office lighting. Sun-blocking lotions offer limited protection against .UV exposure Accidental UV overexposure can injure unaware victims due to the fact UV is invisible and does not produce an immediate reaction. Labeling on UV sources usually consists of a caution or warning label on the product or the bulb packaging cover or a warning sign on the entryway. Some type of emission indicator as required with laser products is rarely found. Reported UV accident scenarios often involve work near UV sources with protective coverings removed, cracked, or fallen off. Depending on the intensity of the UV source and length of exposure, an accident victim may end up with a lost-time injury even though totally unaware of the hazardous condition. Hazard communication training is especially important to help prevent .accidental exposures in the workplace Exposure guidelines for UV radiation have been established by the American Conference of Governmental Industrial Hygienists and by the International Commission on Non-Ionizing Radiation Protection. Handheld

meters to measure UV radiation are commercially available, but expert advice is recommended to ensure .selecting the correct detector and diffuser for the UV wavelengths emitted by the source Some of the most frequently recognized types of energy are heat and light. These, along with others, can be classified as a phenomenon known as electromagnetic radiation. Other types of electromagnetic radiation are gamma rays, X-rays, visible light, infrared rays, and radio waves. The progression of electromagnetic radiation through space can be visualized in different ways. Some experiments suggest that these rays travel in the form of waves. A physicist can actually measure the length of those waves (simply called their wavelength (. It turns out that a smaller wavelength means more energy. At other times, it is more plausible .to describe electromagnetic radiation as being contained and traveling in little packets, called photons The distinguishing factor among the different types of electromagnetic radiation is their energy content. Ultraviolet radiation is more energetic than visible radiation and therefore has a shorter wavelength. To be more specific: Ultraviolet rays have a wavelength between approximately 100 nanometers and 400 .nanometers whereas visible radiation includes wavelengths between 400 and 780 nanometers ?Where does it come from The sun is a major source of ultraviolet rays. Though the sun emits all of the different kinds of electromagnetic radiation, 99% of its rays are in the form of visible light, ultraviolet rays, and infrared rays (also known as heat(. Man-made lamps can also emit UV radiation, and are often used for experimental .purposes ?What does it do Light enables us to see, and heat keeps us from being cold. However, ultraviolet rays often carry the unfortunate circumstance of containing too much energy. For example, infrared rays create heat in much the same way as rubbing your hands together does. The energy contained in the infrared rays causes the molecules of the substance it hits to vibrate back and forth. However, the energy contained in ultraviolet rays is higher, so instead of just causing the molecules to shake, it actually can knock electrons away from the atoms, or causes molecules to split. This results in a change in the chemical structure of the molecule. This change is especially detrimental to living organisms, as it can cause cell damage and deformities by .actually mutating its genetic code ?What stops it Ultraviolet rays can be subdivided into three different wavelength bands—UV-A, UV-B, and UV-C. This is simply a convenient way of classifying the rays based on the amount of energy they contain and their effects .on biological matter. UV-C is most energetic and most harmful; UV-A is least energetic and least harmful Luckily,UV-C rays do not reach the earth’s surface because of the ozone layer. When UV-C rays meet the ozone molecules at high layers of the atmosphere, the energy inherent in them is enough to break apart the bond of the molecule and absorb the energy. Therefore, no UV-C rays from the sun ever come into contact .with life on earth, though man-produced UV-C rays can be a hazard in certain professions, such as welders UV-B rays have a lower energy level and a longer wavelength than UV-C. As their energy is often not sufficient to split an ozone molecule, some of them extend down to the earth's surface. UV-A rays do not have enough energy to break apart the bonds of the ozone, so UV-A radiation passes the earth's atmosphere almost unfiltered. As both UV-B and UV-A rays can be detrimental to our health, it is important that we protect ourselves. This can be done through a variety of ways. The most obvious is to reduce the amount of time one spends in the sun, particularly between the hours of 11 am and 3 pm, when the sun is at its highest in the sky. However, especially during the summer holidays, this does not always work out. More ways to .protect ourselves can be found here Variability of UV UV levels are not constant over the course of a day, or even over the course of a year. An obvious factor is the position of the sun in the sky. At noon, for example, the electromagnetic waves emitted from the sun travel a much shorter path through the earth’s atmosphere then they would at, say, 5 pm, and thus noon-time

intensity is stronger. A second important parameter determining UV at the ground is the amount of ozone present in the stratosphere. Low ozone correlates with much UV. However, there are many other features of the environment that contribute to UV radiation variability. Most important are clouds. On cloudy days, UV levels are usually lower than during clear skies as clouds can deflect rays up into space. Clouds can, however, also lead to increased UV levels. This happens, for example, when the sun is not obscured by clouds but clouds in the vicinity of the sun reflect additional radiation to the ground. So a general rule is not !to feel save from UV radiation just because it's cloudy The amounts of UV one is exposed to also varies with altitude. As a rule of thumb, UV levels increase about 4% for every 1,000 foot gain in altitude. This increase has nothing to do with being closer to the sun—any elevation you might gain would be miniscule in comparison to the distance from the earth to the sun, and so would have an insignificant outcome on UV levels. Instead, the increase is the result of a thinner atmosphere with a smaller number of molecules being present to absorb or scatter UV. Examples of such molecules are tropospheric ozone (commonly associated with smog( and aerosols, molecules that remain suspended in the air. Aerosols can be a multitude of substances—dust, soot, sulfates, etc. These aerosols .absorb and scatter UV rays, and so cut down on the ultimate UV irradiance Other factors that have an influence on UV levels are the physical features of the land—sand, snow, and water all tend to reflect UV rays. This phenomenon is called albedo. Some of the ultraviolet rays reflected off the ground encounter scattering by air molecules, aerosols or clouds back down to the earth, thus increasing the total irradiance. When there is snow on the ground the amount of time it takes for sunburn to .occur is therefore significantly reduced Also, the closer one is to the equator, the more ultraviolet rays one is exposed to. This can be explained by the fact that the sun is usually higher at the sky at low latitudes. In addition, the ozone layer is thinner at the .equator as it is over, for example the United States or Europe, and this also contributes to more UV Since the 1980s, polar regions are affected by the ozone hole. Under the ozone hole, biologically relevant UV levels are 2-3 times as high as they were before. Learn, based on real data, how UV levels are affected by the ozone hole by going to the experiments page! Here you can compare UV radiation measured by the .NSF network in Antarctica with satellite ozone data Ultraviolet (UV( light is electromagnetic radiation with a wavelength shorter than that of visible light, but longer than x-rays, in the range 400 nm to 10 nm, and energies from 3 eV to 124 eV. It is so named because the spectrum consists of electromagnetic waves with frequencies higher than those that humans identify as the color violet

Electromagnetic radiation—Any of a number of types of energy (i.e. radio waves, microwaves, ultraviolet rays, infrared or heat rays, light, X-rays, and gamma rays( that travel at .the speed of light Ultraviolet radiation (or UV radiation)— Electromagnetic radiation with wavelengths between 100 and . 400 nanometers. These rays are emitted from the sun and are not visible. They inflict increasingly more damage upon a recipient as the wavelength decreases. Based on its effects, UV radiation is subdivided into :three wavelength ranges named UV-A, UV-B and UV-C UV-A covers the wavelength range 320-400 nm. UV-A is not absorbed by the ozone layer and is• .the least harmful UV radiation UV-B covers the wavelength range 280-320 nm. UV-B is more energetic than UV-A, and is• partially absorbed by the ozone layer. UV-B rays that are not filtered out cause sunburn and other .harmful effects to humans UV-C covers the wavelength range 100-280 nm. UV-C is the most dangerous form of UV• radiation, but is completely absorbed by the ozone layer. Artificial UV-C (for example emitted .by electric discharges( is a threat for certain occupational group, like welders UV Index—UV Index is a way of expressing the amount of sun-burning UV radiation. It was invented to inform the public about the intensity of UV radiation, and is now published in newspapers and on TV. The definition of the UV Index is the same throughout the world, so it's a great way to learn about the UV hazards at your travel destinations. The Index is a simple number. 1-3 means low exposure; 4-6 means .medium; 7-9 means high; and more than 10 means extreme exposure

Mostly wavelengths in the UV-B contribute to the UV Index. The contribution from the UV-A is only about 10%. Therefore, the UV Index is highly affected by the thickness of the ozone layer, in contrast to UV-A .radiation The time you can stay outside in the sun at a given UV Index depends also on on your skin type. For example, if you have fair skin (skin type I( and the UV Index is seven, it takes less than 20 minutes until your skin starts to redden. If you have a dark skin color the same UV level may need more than 40 minutes to cause an effect. Check out the noontime UV Index at San Diego measured by the NSF network! During .summer it is typically 10—this means extreme Visible light—Electromagnetic radiation with wavelengths between 380 and 780 nanometers. It is the only .type of radiation that the human eye can see Wavelength—A concept used to describe the energy of electromagnetic radiation, in which the rays are visualized as traveling in a wave-like pattern. The length of these peaks varies and is the identifying factor .in the type of ray (e.g. x-ray, ultraviolet, visible(. A shorter wavelength means more energy The sun radiates energy in a wide range of wavelengths, most of which are invisible to human eyes. The shorter the wavelength, the more energetic the radiation, and the greater the potential for harm. Ultraviolet (UV( radiation that reaches the Earth’s surface is in wavelengths between 290 and 400 nm (nanometers, or .billionths of a meter(. This is shorter than wavelengths of visible light, which are 400 to 700 nm UV radiation from the sun has always played important roles in our environment, and affects nearly all living organisms. Biological actions of many kinds have evolved to deal with it. Yet UV radiation at different wavelengths differs in its effects, and we have to live with the harmful effects as well as the helpful ones. Radiation at the longer UV wavelengths of 320-400 nm, designated as UV-A, plays a helpful and essential role in formation of Vitamin D by the skin, and plays a harmful role in that it causes sunburn on human skin and cataracts in our eyes. Radiation at shorter wavelengths of 290-320 nm, designated as UV-B, causes damage at the molecular level to the fundamental building block of life— deoxyribonucleic .(acid (DNA

Electromagnetic radiation exists in a range of wavelengths, which are delineated into major divisions for our convenience. Ultraviolet B radiation, harmful to living organisms, represents a small portion of the (spectrum, from 290 to 320 nanometer wavelengths. (Illustration by Robert Simmon DNA readily absorbs UV-B radiation, which commonly changes the shape of the molecule in one of several ways. The illustration below illustrates one such change in shape due to exposure to UV-B radiation. Changes in the DNA molecule often mean that protein-building enzymes cannot “read” the DNA code at .that point on the molecule. As a result, distorted proteins can be made, or cells can die

.The darker the skin, the higher the risk of deficiency of vitamin d Your location on earth and the altitude of where you live also makes a big difference. So does the season .you are in and the UV index

For instance your skin gets to produce much higher vitamin d dosage at 10,000 feet elevation than at sea .level Also if you live near the equator, your skin will produce much higher amounts compared to other locations .on earth But no one of course should intentionally expose his or her skin to UV rays or ultraviolet radiation, .especially if there is a family history of skin cancers Otherwise, it is still considered very dangerous not to have any kind of sun protection or sun protective .clothing while being out doors in the sun .One could get it from a tanning bed too, but even that could be harmful to your skin .The UV rays can lead to skin cancer, with melanoma being one of the deadliest .Therefore, it might be more logical for certain individuals to obtain it thru foods rich in vitamin d Milk, some cereals (1 cup, fortified with 10% daily value, 40 IU( and certain breads have been fortified for .many years now Also cooked fish like salmon (3.5oz, 360 IU( or canned tuna fish in oil (3oz, 200 IU( and sardines in oil .(1.75oz, 250 IU( are considered natural vitamin d rich foods Cod liver oil has the highest amount of vitamin D (1,360 IU per tablespoon( where as one cup of nonfat .fortified milk contains 98 IU

:No Vitamin D Deficiency Facts It is essential to your bone health • (It prevents Rickets in children (deformity and soft bone • (It prevents Osteomalacia in adults (weak bone and muscle • It maintains a healthy immune system • Vitamin D production stops when sunscreen is used • Sunscreen may create deficiency of vitamin d • Skin needs sun exposure a couple of times per week for good vitamin d levels • Eat plenty of fruits, vegetables, grains and low-fat or non-fat dairy products •

s Page 72 -- THE SUN

Three types of ultraviolet radiation UVB as measured by sunburn (Erythema) or damage to cell DNA. On the other hand, 20 times more UVA than UVB reaches the earth in the middle of a summer's day. It is not greatly affected by absorption and scattering in the atmosphere when the sun is low in the sky, and is now known to contribute significantly to the total exposure at moderate levels throughout the whole day and year. UVA penetrates deeper into the

skin and leads to deeper damage than UVB does. It penetrates cloud cover, light clothing and untinted glass relatively easily, and may induce a degree of continuing skin damage over long periods, .even when UVR exposure is not obvious

The spectrum of ultraviolet radiation

Ultraviolet C (UVC, 100-290 nm) are the shortest and most energetic portion of the UV spectrum. These highly energetic wavelengths are the most dangerous in terms of the damage it can inflict on living material. The important wavelengths in the UVC are removed within the atmosphere, mainly by absorption in the ozone layer and not reach the .earth's surface in any quantity Ultraviolet B (UVB, 290-320nm) is the most damaging part of UVR that we encounter. It is currently thought to generate most of the photodamage to skin, though not all. UVB are wavelengths mostly blocked by dense clouds, closely woven clothing and glass window panes. Significant amounts are transmitted from blue sky in the middle of the day in summer. It is less dangerous when the sun is low in the sky, at high latitude in winter, and in early mornings and late .evenings in summer Ultraviolet A (UVA, 320-400nm) is about 1000 times less damaging to the skin than

The depth of penetration of the skin by UV radiation of different wavelengths: UVB mainly affects the epidermis, while UVA .penetrates deeper into the dermis

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?Ultraviolet Radiation: What Is It

Simply put, ultraviolet radiation (also known as UV radiation or ultraviolet rays( is a form of energy traveling through space. UV radiation is greatest when the sun is highest in the sky and rapidly decreases as .the sun approaches the horizon The level of risk varies from place to place, season to season, and hour to hour. There are a number of :factors that affect the level of risk ;In the northern hemisphere the sun's rays are stronger in the spring and summer• ;Heavy cloud cover can block most UV radiation• UV radiation peaks when the sun reaches its highest point in the sky so the best time to be out of• ;the sun is from 11AM to 4PM ;UV radiation increases with altitude due to thinner air• UV radiation is strongest near the equator and declines toward the poles due to the curvature of• the earth; and UV radiation can be scattered by ground surfaces (as much as 80% can be reflected by snow,• .(sand can reflect 15%, and 10% can be reflected by water UV radiation is divided into UV-A, UV-B and UV-C. UV-C is absorbed by the ozone layer and does not present any threat (man made sources of UV-C, like electric welding arcs, are very harmful to the eyes, if you do not use the proper protection(. That's not true of UV-A and UV-B. More and more scientific evidence is showing that exposure to both UV-A and UV-B can have damaging long and short term effects .on your eyes and vision If you are exposed, unprotected, to excessive amounts of UV radiation over a short period of time, you are likely to experience an effect called photokeratitis. Like a "sunburn of the eye" it may be painful and you may have symptoms including red eyes, a foreign body sensation or gritty feeling in the eyes, extreme sensitivity to light and excessive tearing. Fortunately, this is usually temporary and rarely causes permanent .damage to the eyes Long term exposure to UV radiation can be more serious. A number of scientific studies and research have shown that exposure to small amounts of UV-B radiation over a period of many years may increase your chance of developing a cataract and can cause damage to the retina, the nerve-rich lining of your eye that is .used for seeing. Damage to the retina is usually not reversible

UV light is found in sunlight and is emitted by electric arcs and specialized lights such as black lights. As an ionizing radiation it can cause chemical reactions, and causes many substances to glow or fluoresce. Most people are aware of the effects of UV through the painful condition of sunburn, but the UV spectrum has many other effects, both beneficial and damaging, on human health. Natural sources of UV The Sun emits ultraviolet radiation in the UVA, UVB, and UVC bands, but because of absorption in the atmosphere's ozone layer, 98.7% of the ultraviolet radiation that reaches the Earth's surface is UVA. (Some (.of the UVB and UVC radiation is responsible for the generation of the ozone layer Ordinary glass is partially transparent to UVA but is opaque to shorter wavelengths while Silica or quartz glass, depending on quality, can be transparent even to vacuum UV wavelengths. Ordinary window glass [ passes about 90% of the light above 350 nm, but blocks over 90% of the light below 300 nm.[3][4][5 The onset of vacuum UV, 200 nm, is defined by the fact that ordinary air is opaque below this wavelength. This opacity is due to the strong absorption of light of these wavelengths by oxygen in the air. Pure nitrogen

(less than about 10 ppm oxygen( is transparent to wavelengths in the range of about 150–200 nm. This has wide practical significance now that semiconductor manufacturing processes are using wavelengths shorter than 200 nm. By working in oxygen-free gas, the equipment does not have to be built to withstand the pressure differences required to work in a vacuum. Some other scientific instruments, such as circular .dichroism spectrometers, are also commonly nitrogen purged and operate in this spectral region Extreme UV is characterized by a transition in the physics of interaction with matter: wavelengths longer than about 30 nm interact mainly with the chemical valence electrons of matter, while wavelengths shorter than that interact mainly with inner shell electrons and nuclei. The long end of the EUV/XUV spectrum is set by a prominent He+ spectral line at 30.4nm. XUV is strongly absorbed by most known materials, but it is possible to synthesize multilayer optics that reflect up to about 50% of XUV radiation at normal incidence. This technology has been used to make telescopes for solar imaging; it was pioneered by the NIXT and MSSTA sounding rockets in the 1990s; (current examples are SOHO/EIT and TRACE( and for .(nanolithography (printing of traces and devices on microchips

edit] Human health-related effects of UV radiation] edit] Beneficial effects] edit[ Vitamin D [

The Earth's atmosphere blocks UV radiation from penetrating through the atmosphere by 98.7%. A positive effect of UVB exposure is that it induces the production of vitamin D in the skin. It has been estimated that tens of thousands of premature deaths occur in the United States annually from a range of cancers due to vitamin D deficiency.[6] Another effect of vitamin D deficiency is bad absorption of calcium which can lead .to bone diseases [Some studies show most people get adequate Vitamin D through food and incidental exposure,[7 Many countries have fortified certain foods with Vitamin D to prevent deficiency. Eating fortified foods or taking a dietary supplement pill is usually preferred to UVB exposure, due to the increased risk of skin [ cancer from UV radiation.[7 edit[ Aesthetics [

Too little UVB radiation leads to a lack of Vitamin D. Too much UVB radiation leads to direct DNA damages and sunburn. An appropriate amount of UVB (which varies according to skin color( leads to a limited amount of direct DNA damage. This is recognized and repaired by the body. Then the melanin production is increased which leads to a long lasting tan. This tan occurs with a 2 day lag phase after irradiation, but it is much less harmful and long lasting than the one obtained from UVA. However some .tanning lotions and sprays available in the market doesn't require UV exposition edit[ Medical applications [

Ultraviolet radiation has other medical applications, in the treatment of skin conditions such as psoriasis and vitiligo. UVA radiation can be used in conjunction with psoralens (PUVA treatment(. UVB radiation is rarely used in conjunction with psoralens. In cases of psoriasis and vitiligo, UV light with wavelength of [ 311 nm is most effective.[citation needed edit] Harmful effects]

An overexposure to UVB radiation can cause sunburn and some forms of skin cancer. In humans, prolonged exposure to solar UV radiation may result in acute and chronic health effects on the skin, eye, and immune system.[8] However the most deadly form - malignant melanoma - is mostly caused by the indirect DNA damage (free radicals and oxidative stress(. This can be seen from the absence of a UV-signature mutation [ in 92% of all melanoma.[9 UVC rays are the highest energy, most dangerous type of ultraviolet light. Little attention has been given to UVC rays in the past since they are filtered out by the atmosphere. However, their use in equipment such as pond sterilization units may pose an exposure risk, if the lamp is switched on outside of its enclosed pond .sterilization unit

Ultraviolet photons harm the DNA molecules of living organisms in different ways. In one common damage event, adjacent Thymine bases bond with each other, instead of across the ."ladder". This makes a bulge, and the distorted DNA molecule does not function properly edit[ Skin [

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Ultraviolet (UV) irradiation present in sunlight is an environmental human carcinogen. The toxic effects of UV from natural sunlight and therapeutic artificial lamps are a major concern for human health. The major acute effects of UV irradiation on normal human skin comprise sunburn inflammation erythema, .tanning, and local or systemic immunosuppression

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Matsumura and Ananthaswamy —

UVA, UVB and UVC can all damage collagen fibers and thereby accelerate aging of the skin. Both UVA and UVB destroy vitamin A in skin which may cause further damage.[11] In the past UVA was considered less harmful, but today it is known that it can contribute to skin cancer via the indirect DNA damage (free radicals and reactive oxygen species(. It penetrates deeply but it does not cause sunburn. UVA does not damage DNA directly like UVB and UVC, but it can generate highly reactive chemical intermediates, such as hydroxyl and oxygen radicals, which in turn can damage DNA. Because it does not cause reddening of the skin (erythema( it cannot be measured in the SPF testing. There is no good clinical measurement of the blocking of UVA radiation, but it is important that sunscreen block both UVA and UVB. Some scientists blame the absence of UVA filters in sunscreens for the higher melanoma-risk that was found for sunscreen [ users.[12

The reddening of the skin due to the action of sunlight depends both on the amount of sunlight as well as the sensitivity of the skin ("erythemal action spectrum") over the UV .spectrum

UVB light can cause direct DNA damage. The radiation excites DNA molecules in skin cells, causing aberrant covalent bonds to form between adjacent cytosine bases, producing a dimer. When DNA polymerase comes along to replicate this strand of DNA, it reads the dimer as "AA" and not the original "CC". This causes the DNA replication mechanism to add a "TT" on the growing strand. This is a mutation, which can result in cancerous growths and is known as a "classical C-T mutation". The mutations that are caused by the direct DNA damage carry a UV signature mutation that is commonly seen in skin cancers. The mutagenicity of UV radiation can be easily observed in bacteria cultures. This cancer connection is one reason for concern about ozone depletion and the ozone hole. UVB causes some damage to collagen but at a .very much slower rate than UVA As a defense against UV radiation, the amount of the brown pigment melanin in the skin increases when exposed to moderate (depending on skin type( levels of radiation; this is commonly known as a sun tan. The purpose of melanin is to absorb UV radiation and dissipate the energy as harmless heat, blocking the UV from damaging skin tissue. UVA gives a quick tan that lasts for days by oxidizing melanin that was already present and triggers the release of the melanin from melanocytes. UVB yields a tan that takes roughly 2 days to develop because it stimulates the body to produce more melanin. The photochemical properties of melanin make it an excellent photoprotectant. However, sunscreen chemicals can not dissipate the energy of the excited state as efficiently as melanin and therefore the penetration of sunscreen ingredients into the [ lower layers of the skin is increasing the amount of free radicals and ROS.[13 Sunscreen prevents the direct DNA damage which causes sunburn. Most of these products contain an SPF rating to show how well they block UVB rays. The SPF rating, however, offers no data about UVA protection. In the US, the FDA is considering adding a star rating system to show UVA protection. A similar .system is already used in some European countries Some sunscreen lotions now include compounds such as titanium dioxide which helps protect against UVA rays. Other UVA blocking compounds found in sunscreen include zinc oxide and avobenzone. Cantaloupe extract, rich in the compound superoxide dismutase (SOD(, can be bound with gliadin to form glisodin, an orally-effective protectant against UVB radiation. There are also naturally occurring compounds found in rainforest plants that have been known to protect the skin from UV radiation damage, such as the fern .Phlebodium aureum edit] Sunscreen safety debate] Main article: Sunscreen controversy

Medical organizations recommend that patients protect themselves from UV radiation using sunscreen. Five .(sunscreen ingredients have been shown to protect mice against skin tumors (see sunscreen However, some sunscreen chemicals produce potentially harmful substances if they are illuminated while in contact with living cells.[14][15][16] The amount of sunscreen which penetrates through the stratum corneum [may or may not be large enough to cause damage. In one study of sunscreens, the authors write:[17 The question whether UV filters acts on or in the skin has so far not been fully answered. Despite the fact that an answer would be a key to improve formulations of sun protection products, many publications .carefully avoid addressing this question In an experiment that was published in 2006 by Hanson et al, the amount of harmful reactive oxygen species (ROS( had been measured in untreated and in sunscreen treated skin. In the first 20 minutes the film of sunscreen had a protective effect and the number of ROS species was smaller. After 60 minutes however the amount of absorbed sunscreen was so high, that the amount of ROS was higher in the sunscreen treated [ skin than in the untreated skin.[13 edit[ Eye [

High intensities of UVB light are hazardous to the eyes, and exposure can cause welder's flash .(photokeratitis or arc eye( and may lead to cataracts, pterygium,[18][19] and pinguecula formation Protective eyewear is beneficial to those who are working with or those who might be exposed to ultraviolet radiation, particularly short wave UV. Given that light may reach the eye from the sides, full coverage eye protection is usually warranted if there is an increased risk of exposure, as in high altitude mountaineering. Mountaineers are exposed to higher than ordinary levels of UV radiation, both because there is less .atmospheric filtering and because of reflection from snow and ice Ordinary, untreated eyeglasses give some protection. Most plastic lenses give more protection than glass lenses, because, as noted above, glass is transparent to UVA and the common acrylic plastic used for lenses is less so. Some plastic lens materials, such as polycarbonate, inherently block most UV. There are protective treatments available for eyeglass lenses that need it which will give better protection. But even a .treatment that completely blocks UV will not protect the eye from light that arrives around the lens

edit] Degradation of polymers, pigments and dyes] Many polymers used in consumer products are degraded by UV light, and need addition of UV absorbers to inhibit attack, especially if the products are used outdoors and so exposed to sunlight. The problem appears as discoloration or fading, cracking and sometimes, total product disintegration if cracking has proceeded .far enough. The rate of attack increases with exposure time and sunlight intensity It is known as UV degradation, and is one form of polymer degradation. Sensitive polymers include thermoplastics, such as polypropylene and polyethylene as well as speciality fibres like aramids. UV absorption leads to chain degradation and loss of strength at sensitive points in the chain structure. They .include tertiary carbon atoms, which in polypropylene occur in every repeat unit In addition, many pigments and dyes absorb UV and change colour, so paintings and textiles may need extra protection both from sunlight and fluorescent lamps, two common sources of UV radiation. Old and antique paintings such as watercolour paintings for example, usually need to be placed away from direct sunlight. Common window glass provides some protection by absorbing some of the harmful UV, but valuable .artifacts need shielding

edit] Nutrition]

.Milk and cereal grains are often fortified with vitamin D

A blood calcidiol (25-hydroxy-vitamin D( level is the accepted way to determine vitamin D nutritional status. The optimal level of serum 25-hydroxyvitamin D is 35–55 ng/mL; with some debate among medical scientists for the slightly higher value. Supplementation of 100 IU (2.5 mcg( vitamin D3 raises circulating [ 25(OH(D by 2.5 nmol/l (1 ng/ml(.[16 Season, geographic latitude, time of day, cloud cover, smog, and sunscreen affect UV ray exposure and vitamin D synthesis in the skin, and it is important for individuals with limited sun exposure to include good sources of vitamin D in their diet. The 2005 Dietary Guidelines for Americans recommend that older adults, people with dark skin, and those exposed to insufficient ultraviolet radiation (i.e., sunlight( consume extra vitamin D from vitamin D-fortified foods and/or supplements. Individuals in these high-risk groups should consume 25 μg (1000 IU( of vitamin D daily to maintain adequate blood concentrations of 25hydroxyvitamin D. The Canadian Pediatric Society recommends 2,000 IU daily for pregnant and [ breastfeeding women.[17 In many countries, foods such as milk, yogurt, margarine, oil spreads, breakfast cereal, pastries, and bread are fortified with vitamin D2 and/or vitamin D3, to minimize the risk of vitamin D deficiency.[18] In the United States and Canada, for example, fortified milk typically provides 100 IU per glass, or one quarter of [ the estimated adequate intake for adults over the age of 50.[1

.Fatty fish, such as salmon, are natural sources of vitamin D

Very few foods are naturally rich in vitamin D, so much vitamin D intake in the industrialized world is from fortified products including milk, soy milk and breakfast cereals or supplements.[1] Natural sources of [vitamin D include:[1 Fish liver oils, such as cod liver oil, 1 Tbs. (15 mL) provides 1,360 IU (one IU equals• (25 ng :Fatty fish species, such as• Herring, 85g (3 oz) provides 1383 IU○ Catfish, 85g (3 oz) provides 425 IU○ Salmon, cooked, 3.5 oz provides 360 IU○ Mackerel, cooked, 3.5 oz, 345 IU○

Sardines, canned in oil, drained, 1.75 oz, 250 IU○ Tuna, canned in oil, 3 oz, 200 IU○ Eel, cooked, 3.5 oz, 200 IU○ One whole egg, provides 20 IU• Beef liver, cooked, 3.5 ounces, provides 15 IU• edit] Vitamin D as a Vitamin]

Vitamin D is naturally produced by the human body when exposed to direct sunlight. When civilization and the Industrial Revolution enabled humans to work indoors and wear more clothes when in the sun, these cultural changes reduced natural production of vitamin D and caused deficiency diseases. When it was discovered that exogenous supplements of Vitamin D would prevent or correct some of these diseases, [ vitamin D was added to the growing list of vital nutrients.[19

edit] Deficiency] Main article: Hypovitaminosis D

Deficiency of vitamin D can result from a number of factors including: inadequate intake coupled with inadequate sunlight exposure, disorders that limit its absorption, conditions that impair conversion of vitamin D into active metabolites, such as liver or kidney disorders and body characteristics such as skin color and body fat. Rarely deficiency can result from a number of hereditary disorders.[2] Deficiency results :in impaired bone mineralization, and leads to bone softening diseases[20] including Rickets, a childhood disease characterized by impeded growth, and deformity, of• the long bones. The role of diet in the development of rickets was determined by Edward Mellanby between 1918–1920.[21] In 1921 Elmer McCollum identified a substance found in certain fats that could prevent rickets. Prior to the fortification of milk products with vitamin D, rickets was a major public health problem. In the United States the fortification of milk with 10 micrograms (400 IU) of vitamin D per [ quart in the 1930s led to a dramatic decline in the number of rickets cases.[15 Osteomalacia, a bone-thinning disorder that occurs exclusively in adults and is• .characterized by proximal muscle weakness and bone fragility Osteoporosis, a condition characterized by reduced bone mineral density and• .increased bone fragility

Vitamin D malnutrition may also be linked to an increased susceptibility to several chronic diseases such as high blood pressure, tuberculosis, cancer, periodontal disease, multiple sclerosis, chronic pain, depression[22][not in citation given], schizophrenia[22], seasonal affective disorder[23][24], peripheral artery disease[25] and several autoimmune diseases including type 1 diabetes (see role in immunomodulation(.[15][26] There is an association between low vitamin D levels and Parkinson's disease, but whether Parkinson's causes low vitamin D levels, or whether low vitamin D levels play a role in the pathogenesis of Parkinson's disease has [ not been established.[27

edit] Overdose] .For more details on this topic, see hypervitaminosis D

Vitamin D stored in the human body as calcidiol (25-hydroxy-vitamin D( has a large volume of distribution and a half-life of about 20 to 29 days.[13] However, the synthesis of bioactive vitamin D hormone is tightly regulated and vitamin D toxicity usually occurs only if excessive doses (prescription forms or rodenticide analogs( are taken.[28] Although normal food and pill vitamin D concentration levels are far too low to be toxic in adults, because of the high vitamin A content in codliver oil, it is possible to reach toxic levels of vitamin A (but not vitamin D( via this route, [29] if taken in multiples of the normal dose in an attempt to increase the intake of vitamin D. Most historical cases of vitamin D overdose have occurred due to [ manufacturing and industrial accidents.[30 Exposure to sunlight for extended periods of time does not cause vitamin D toxicity.[30] This is because within about 20 minutes of ultraviolet exposure in light skinned individuals (3–6 times longer for pigmented skin( the concentration of vitamin D precursors produced in the skin reach an equilibrium, and any further

vitamin D that is produced is degraded.[31] Maximum endogenous production with full body exposure to [ sunlight is 250 µg (10,000 IU( per day.[30 The exact long-term safe dose of vitamin D is not entirely known, but dosages up to 250 micrograms (10,000 IU( /day in healthy adults are believed to be safe.[13], and all known cases of vitamin D toxicity with hypercalcemia have involved intake of or over 1,000 micrograms (40,000 IU(/day[30]. The U.S. Dietary Reference Intake Tolerable Upper Intake Level (UL( of vitamin D for children and adults is 50 micrograms/day (2,000 IU/day(, although this is widely presumed to be below actual physiological daily requirements. In adults, sustained intake of 2500 micrograms/day (100,000 IU( can produce toxicity within a few months.[2] For infants (birth to 12 months( the tolerable UL is set at 25 micrograms/day (1000 IU/day(, and vitamin D concentrations of 1000 micrograms/day (40,000 IU( in infants has been shown to produce toxicity within 1 to 4 months. In the United States, overdose exposure of vitamin D was reported by 284 individuals in 2004, leading to 1 death.[32] The Nutrition Desk Reference states "The threshold for toxicity is 500 to 600 micrograms [vitamin D] per kilogram body weight per day."[33] The United States Environmental [ Protection Agency published an oral LD50 of 619 mg/kg for female rats.[34 Serum levels of calcidiol (25-hydroxy-vitamin D( are typically used to diagnose vitamin D overdose. In healthy individuals, calcidiol levels are normally between 32 to 70 ng/mL (80 to 175 nmol/L(, but these levels may be as much as 15-fold greater in cases of vitamin D toxicity. Serum levels of bioactive vitamin D [ hormone (1,25(OH2(D( are usually normal in cases of vitamin D overdose.[2 Some symptoms of vitamin D toxicity are a result of hypercalcemia (an elevated level of calcium in the blood( caused by increased intestinal calcium absorption. Vitamin D toxicity is known to be a cause of high blood pressure.[35] Gastrointestinal symptoms of vitamin D toxicity can include anorexia, nausea, and vomiting. These symptoms are often followed by polyuria (excessive production of urine(, polydipsia (increased thirst(, weakness, nervousness, pruritus (itch(, and eventually renal failure. Other signals of kidney disease including elevated protein levels in the urine, urinary casts, and a build up of wastes in the blood stream can also develop.[2] In one study, hypercalciuria and bone loss occurred in four patients with documented vitamin D toxicity.[36] Another study showed elevated risk of ischaemic heart disease when 25D [was above 89 ng/mL.[37 Vitamin D toxicity is treated by discontinuing vitamin D supplementation, and restricting calcium intake. If the toxicity is severe blood calcium levels can be further reduced with corticosteroids or bisphosphonates. [ In some cases kidney damage may be irreversible.[2

edit] Role in immunomodulation] The hormonally active form of vitamin D mediates immunological effects by binding to nuclear vitamin D receptors (VDR( which are present in most immune cell types including both innate and adaptive immune cells. The VDR is expressed constitutively in monocytes and in activated macrophages, dendritic cells, NK cells, T and B cells. In line with this observation, activation of the VDR has potent anti-proliferative, prodifferentiative, and immunomodulatory functions including both immune-enhancing and [ immunosuppressive effects.[38 Effects of VDR-ligands, such as vitamin D hormone, on T-cells include suppression of T cell activation and induction of regulatory T cells, as well as effects on cytokine secretion patterns.[39] VDR-ligands have also been shown to affect maturation, differentiation, and migration of dendritic cells, and inhibits DC-dependent [ T cell activation, resulting in an overall state of immunosuppression.[40 VDR ligands have also been shown to increase the activity of natural killer cells, and enhance the phagocytic activity of macrophages.[13] Active vitamin D hormone also increases the production of cathelicidin, an antimicrobial peptide that is produced in macrophages triggered by bacteria, viruses, and fungi.[41] Vitamin D deficiency tends to increase the risk of infections, such as influenza[42] and tuberculosis[43][44][45]. In a 1997 study, Ethiopian children with rickets were 13 times more likely to get [ pneumonia than children without rickets.[46 These immunoregulatory properties indicate that ligands with the potential to activate the VDR, including supplementation with calcitriol (as well as a number of synthetic modulators(, may have therapeutic clinical applications in the treatment of; inflammatory diseases (rheumatoid arthritis, psoriatic arthritis(, dermatological conditions (psoriasis, actinic keratosis(, osteoporosis, cancers (prostate, colon, breast, myelodysplasia, leukemia, head and neck squamous cell carcinoma, and basal cell carcinoma(, and

autoimmune diseases (systemic lupus erythematosus, type I diabetes, multiple sclerosis( and in preventing [ organ transplant rejection.[38 A 2006 study published in the Journal of the American Medical Association, reported evidence of a link between Vitamin D deficiency and the onset of Multiple Sclerosis; the authors posit that this is due to the [ immune-response suppression properties of Vitamin D.[47

edit] Role in cancer prevention and recovery] The Canadian Cancer Society recommends that adults should consider supplementeing with 1,000 IU of vitamin D per day during the fall and winter. They base this recommendation on the growing evidence for a [ link between vitamin D and a reduced risk for colorectal, breast and prostate cancers.[48 The vitamin D hormone, calcitriol, has been found to induce death of cancer cells in vitro and in vivo. Although the anti-cancer activity of vitamin D is not fully understood, it is thought that these effects are mediated through vitamin D receptors expressed in cancer cells, and may be related to its immunomodulatory abilities. The anti-cancer activity of vitamin D observed in the laboratory has prompted some to propose that vitamin D supplementation might be beneficial in the treatment or prevention of some [ types of cancer.[13 A search of primary and review medical literature published between 1970 and 2007 found an increasing body of research supporting the hypothesis that the active form of vitamin D has significant, protective effects against the development of cancer. Epidemiological studies show an inverse association between sun exposure, serum levels of 25(OH(D, and intakes of vitamin D and risk of developing and/or surviving cancer. The protective effects of vitamin D result from its role as a nuclear transcription factor that regulates cell growth, differentiation, apoptosis and a wide range of cellular mechanisms central to the development of cancer.[49] In 2005, scientists released a metastudy which demonstrated a beneficial correlation between vitamin D intake and prevention of cancer. Drawing from a meta-analysis of 63 published reports, the authors showed that intake of an additional 1,000 international units (IU( (or 25 micrograms( of vitamin D daily reduced an individual's colon cancer risk by 50%, and breast and ovarian cancer risks by 30%.[50] Research has also shown a beneficial effect of high levels of calcitriol on patients with advanced prostate cancer.[51] A randomized intervention study involving 1,200 women, published in June 2007, reports that vitamin D supplementation (1,100 international units (IU(/day( resulted in a 60% reduction in cancer incidence, during a four-year clinical trial, rising to a 77% reduction for cancers diagnosed after the first year (and therefore excluding those cancers more likely to have originated prior to the vitamin D intervention(.[52][53] In 2006, a study at Northwestern University found that taking the U.S. RDA of vitamin D (400 IU per day( cut the risk of pancreatic cancer by 43% in a sample of more than 120,000 people from [ two long-term health surveys.[54][55 A 2006 study using data on over 4 million cancer patients from 13 different countries showed a marked difference in cancer risk between countries classified as sunny and countries classified as less–sunny for a number of different cancers.[56] Research has also suggested that cancer patients who have surgery or treatment in the summer — and therefore make more endogenous vitamin D — have a better chance of surviving their cancer than those who undergo treatment in the winter when they are exposed to less [ sunlight.[57 A scientific review undertaken by the National Cancer Institute found no link between baseline vitamin D status and overall cancer mortality. They did find that vitamin D was beneficial in preventing colorectal cancer, which showed an inverse relationship with blood levels "80 nmol/L or higher associated with a 72% [ risk reduction".[58 Vitamin D regulates the expression of genes associated with cancers and autoimmune disease by controlling the activation of the vitamin D receptor (VDR(, a type 1 nuclear receptor and DNA transcription factor.[59] Research has indicated that vitamin D deficiency is linked to colon cancer and more recently, to breast [ cancer.[60

edit] Role in cardiovascular disease prevention] Research indicates that vitamin D may play a role in preventing or reversing coronary disease.[61][62] Vitamin D deficiency is associated with an increase in high blood pressure and cardiovascular risk. When researchers monitored the vitamin D levels, blood pressure and other cardiovascular risk factors of 1739

people, of an average age of 59 years for 5 years, they found that those people with low levels of vitamin D [ had a 62% higher risk of a cardiovascular event than those with normal vitamin D levels.[63 A report from the National Health and Nutrition Examination Survey (NHANES( found that low levels of vitamin D were associated with an increased risk of peripheral artery disease (PAD(. Researchers divided 4,839 participantes in NHANES into quartiles (four groups( based on their blood levels of vitamin D, and found that increasing levels of vitamin D were associated with a lower prevalence of PAD. The authors adjusted for other factors which could influence the development of PAD (such as smoking and high cholesterol( and found that among participants with the lowest vitamin D levels (<17.8 ng/mL( PAD was [ 80% more common than in individuals with the highest levels (>29.2 ng/mL( of vitamin D. [25 Researchers publishing in the Journal of Circulation studied the blood levels of vitamin D in 1739 middleaged children of partipants in the Framingham Heart Study in Framinhgam, Massachussetts (their mean age was 59 years; 55% were women; all were white( who did not have any prior history of cardiovascular disease. These subjects were followed for a mean of 5.4 years. The authors adjusted for other conventional risk factors for cardiovascular disease which could have confounded the results and still found that among the 120 individuals in this group who suffered a first cardiovascular event, those who had the lowest levels of vitamin D were most likely to have had an event. Individuals with lowest levels of vitamin D (<15 ng/mL( had a 62% increased risk (95% confidence interval 1.11 to 2.36, P=0.01( for having a first cardiovascular event compared with those with vitamin D levels of 15 ng/mL. This effect was evident in [ participants with hypertension, but not in those without hypertension. [64 In a study of 34 middle-aged men, researchers found that low levels of vitamin D were associated with [ hypertension, elevated VLDL triglycerides, and impaired insulin metabolism.[65 As with cancer incidence, a qualitative inverse correlations was found between coronary disease incidence and serum vitamin D levels of 32.0 versus 35.5 ng/mL.[66] Cholesterol levels were found to be reduced in gardeners in the UK during the summer months.[67] Heart attacks peak in winter and decline in summer in [ temperate[68] but not tropical latitudes.[69 The issue of vitamin D in heart health has not yet been settled. Exercise may account for some of the benefit attributed to vitamin D, since vitamin D levels are higher in physically active persons.[70] Moreover, there may be an upper limit after which cardiac benefits decline. One study found an elevated risk of ischaemic heart disease in Southern India in individuals whose vitamin D levels were above 89 ng/mL.[71] These sunliving groups results do not generalize to sun-deprived urban dwellers. Among a group with heavy sun exposure, taking supplemental vitamin D are unlikely to result in blood levels over the ideal range, while urban dwellers not taking supplemental vitamin D may fall under the levels recognized as ideal, and being .below the preferable levels may cause adverse affects on the health of each group

edit] Role in all-cause mortality] Low vitamin D levels are associated with cancer, diabetes, and hypertension, and in increased mortality among patients undergoing dialysis. Using the National Health and Nutrition Examination Survey Melamed and coworkers at the Albert Einstein College of Medicine evaluated whether low serum vitamin D levels were associated with mortality in the general population. The researchers studied the association of low vitamin D levels with all-cause mortality, cancer, and cardiovascular disease (CVD( mortality among 13,331 diverse American adults who were 20 years or older. Vitamin D levels of these participants were collected over a 6-year period (from 1988 through 1994(, and individuals were passively followed for mortality through the year 2000. The researchers found that being older, female, nonwhite, having diabetes, a current smoker, and having a higher body mass index were all independently associated with a greater risk of being vitamin D deficient, while greater physical activity, vitamin D supplementation, and evaluating subjects in a non-winter season (greater exposure to sunshine( were all associated with higher levels. During a median of 8.7 years of follow-up, there were 1806 deaths, including 777 (43%( from CVD. The authors divided the participants into 4 groups (quartiles( based on their serum vitamin D levels, and adjusted for baseline demographics, season, and CVD risk factors. Being in the lowest quartile (vitamin D levels <17.8 ng/mL( was associated with a 26% increased rate of all-cause mortality (mortality rate ratio, 1.26; 95% CI, 1.08-1.46(. The adjusted models of CVD and cancer mortality revealed a higher risk, but it was not statistically significant. The authors concluded that having low levels of vitamin D (<17.8 ng/mL( was [ independently associated with an increase in all-cause mortality in the general population. [72 Among many factors that may be responsible for vitamin D's apparent beneficial effect on all-cause mortality is its effect on telomeres and its potential effect on slowing aging. Richards and coworkers

examined whether vitamin D concentrations would slow the rate of shortening of leukocyte telomeres (a marker of aging(. The authors stated that vitamin D is a potent inhibitor of the proinflammatory response and slows the turnover of leukocytes. Leukocyte telomere length (LTL( predicts the development of agingrelated disease, and length of these telomeres decreases with each cell division and with increased inflammation (more common in the elderly(. Researchers measured serum vitamin D concentrations in 2160 women aged 18-79 years (mean age: 49.4( from a large population-based cohort of twins. This study divided the group into thirds [tertiles http://en.wiktionary.org/wiki/tertile] based on vitamin D levels, and found that increased age was significantly associated with shorter LTL (r = -0.40, P < 0.0001(. Higher serum vitamin D concentrations were significantly associated with longer LTL (r = 0.07, P = 0.0010(, and this finding persisted even after adjustment for age (r = 0.09, P < 0.0001( and other variables that independently could affect LTL (age, season of vitamin D measurement, menopausal status, use of hormone replacement therapy, and physical activity(. The difference in LTL between the highest and lowest tertiles of vitamin D was highly significant (P = 0.0009(, and the authors stated that this was equivalent to 5.0 years of aging. The authors concluded that higher vitamin D levels, (easily modifiable through nutritional supplementation(, were associated with longer LTL, which underscores the potentially beneficial effects of [ vitamin D on aging and age-related diseases. [73 ietary Supplement Fact Sheet: Vitamin D Office of Dietary Supplements • National Institutes of Health Table of Contents Introduction Reference Intakes Sources of Vitamin D Vitamin D Intakes and Status Vitamin D Deficiency Groups at Risk of Vitamin D Inadequacy Vitamin D and Health Health Risks from Excessive Vitamin D Interactions with Medications Vitamin D and Healthful Diets References Introduction Vitamin D is a fat-soluble vitamin that is naturally present in very few foods, added to others, and available as a dietary supplement. It is also produced endogenously when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis [1-3]. Vitamin D obtained from sun exposure, food, and supplements is biologically inert and must undergo two hydroxylations in the body for activation. The first occurs in the liver and converts vitamin D to 25hydroxyvitamin D [25(OH)D], also known as calcidiol. The second occurs primarily in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D [1,25(OH)2D], also known as .[calcitriol [4 Vitamin D is essential for promoting calcium absorption in the gut and maintaining adequate serum calcium and phosphate concentrations to enable normal mineralization of bone and prevent hypocalcemic tetany. It is also needed for bone growth and bone remodeling by osteoblasts and osteoclasts [4-6]. Without sufficient vitamin D, bones can become thin, brittle, or misshapen. Vitamin D sufficiency prevents rickets in children and osteomalacia in adults .[3,7,8]. Together with calcium, vitamin D also helps protect older adults from osteoporosis Vitamin D has other roles in human health, including modulation of neuromuscular and immune function and reduction of inflammation. Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D [4,6,9,10].

Many laboratory-cultured human cells have vitamin D receptors and some convert 25(OH)D to 1,25(OH)2D [11]. It remains to be determined whether cells with vitamin D receptors in the .intact human carry out this conversion Serum concentration of 25(OH)D is the best indicator of vitamin D status. It reflects vitamin D produced cutaneously and that obtained from food and supplements [5] and has a fairly long circulating half-life of 15 days [15]. However, serum 25(OH)D levels do not indicate the amount of vitamin D stored in other body tissues. Circulating 1,25(OH)2D is generally not a good indicator of vitamin D status because it has a short half-life of 15 hours and serum concentrations are closely regulated by parathyroid hormone, calcium, and phosphate [15]. .[Levels of 1,25(OH)2D do not typically decrease until vitamin D deficiency is severe [6,11 There is considerable discussion of the serum concentrations of 25(OH)D associated with deficiency (e.g., rickets), adequacy for bone health, and optimal overall health (Table 1). A concentration of <20 nanograms per milliliter (ng/mL) (or <50 nanomoles per liter [nmol/L]) is .generally considered inadequate *Table 1: Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health **ng/mL **nmol/L Health status 11< 27.5< Associated with vitamin D deficiency and rickets in infants and young .[children [5 10-15< 25-37.5< Generally considered inadequate for bone and overall health in .[healthy individuals [5,13 30≥ 75≥ Proposed by some as desirable for overall health and disease prevention, although a recent government-sponsored expert panel concluded that insufficient data are available to support these higher .[levels [13,14 Consistentl Consistentl Considered potentially toxic, leading to hypercalcemia and y <200 y <500 hyperphosphatemia, although human data are limited. In an animal model, concentrations ≥400 ng/mL (≥1,000 nmol/L) demonstrated .[no toxicity [15,16 Serum concentrations of 25(OH)D are reported in both nanograms per milliliter (ng/mL) and * .(nanomoles per liter (nmol/L .ng/mL = 2.5 nmol/L 1 **

Vitamin D

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Pronunciations

cholecalciferol corticosteroid ergocalciferol hypercalcemia hyperparathyroidism osteoma osteomalacia osteoporosis rifampin

:Two forms of vitamin D are important for nutrition

Vitamin D2 (ergocalciferol): This form is synthesized from plants• and yeast precursors. It is also the form used in very high dose .supplements Vitamin D3 (cholecalciferol): This form is the most active form of• vitamin D. It is formed in the skin when the skin is exposed to direct sunlight. The most common food source is fortified foods, mainly cereals and dairy products. Vitamin D3 is also present in fish liver oils and fatty fish. Human breast milk contains only small amounts of .vitamin D Vitamin D is stored mainly in the liver. Vitamin D2 and D3 are not active in the body. Both forms must be processed (metabolized( by the liver and kidneys into an active form called calcitriol Some Trade Names ROCALTROL This active form promotes absorption of calcium and phosphorus from the . intestine. Calcium and phosphorus, which are minerals, are incorporated into bones to make them strong and dense (a process called mineralization(. Thus, vitamin D is necessary for the formation, growth, and repair of bones. Vitamin D also enhances immune function and improves muscle strength. Requirements for .vitamin D increase as people age Vitamin D Deficiency The most common cause is lack of exposure to sunlight, but certain• .disorders can also cause the deficiency Without enough vitamin D, muscle and bone weakness and pain• .occur Infants develop rickets: The skull is soft, bones grow abnormally, and• .infants are slow to sit and crawl .Blood tests and sometimes x-rays are done to confirm the diagnosis• From birth, breastfed infants should be given vitamin D supplements• .because breast milk contains little vitamin D Vitamin D supplements taken by mouth or given by injection usually• .results in a complete recovery Vitamin D deficiency is common. Most commonly, it occurs when the skin is not exposed to enough sunlight. Almost no one consumes enough vitamin D from .foods to prevent vitamin D deficiency when exposure to sunlight is inadequate In vitamin D deficiency, calcium and phosphate levels in the blood decrease because vitamin D is necessary for absorption of these minerals. Because not enough calcium and phosphate are available to maintain healthy bones, vitamin D deficiency may result in a bone disorder called rickets in children or osteomalacia in adults. In a pregnant woman, vitamin D deficiency causes the deficiency in the fetus, and the newborn has a high risk of rickets. Occasionally, the deficiency is severe enough to cause osteomalacia in the woman. Vitamin D deficiency makes osteoporosis worse. To try to increase the low calcium level in blood caused by vitamin D deficiency, the body may produce more parathyroid hormone. However, as the parathyroid hormone level becomes high (a condition called hyperparathyroidism(, the hormone draws calcium out of bone to increase .the calcium level in blood. Thus, bones are weakened

...Did You Know Lack of exposure to sunlight• can cause vitamin D

.deficiency Most older people need• .vitamin D supplements Causes The most common cause is inadequate exposure to sunlight. Thus, vitamin D deficiency occurs mainly among people who do not spend much time outdoors: older people and people who live in an institution such as a nursing home. The deficiency can also occur in the winter at northern and southern latitudes or in people who keep their bodies covered, such as Muslim women. Because breast milk contains only small amounts of vitamin D, breastfed infants who are not .exposed to enough sunlight are at risk of the deficiency and rickets When the skin is exposed to enough sunlight, the body usually forms enough vitamin D. However, certain circumstances increase the risk of vitamin D :deficiency even when there is exposure to sunlight The skin forms less vitamin D in response to sunlight in certain• groups of people. They include people with darker skin (particularly .blacks(, older people, and people who use sunscreen The body may not be able to absorb enough vitamin D from foods. In• malabsorption disorders, people cannot absorb fats normally (see Malabsorption(. They also cannot absorb vitamin D because it is a fat-soluble vitamin, which is normally absorbed with fats in the small .intestine The body may not be able to convert vitamin D to an active form.• Certain kidney and liver disorders and several rare hereditary disorders interfere with this conversion, as do certain drugs, such as some anticonvulsants and rifampin Some Trade Names RIFADIN RIMACTANE .

Spotlight on Aging Older people are likely to develop vitamin D deficiency for several :reasons Their requirements are• .higher than younger persons They tend to spend less time• outdoors, or stay indoors more in the winter, and thus are not exposed to enough .sunlight They may not be exposed to• enough sunlight because they are housebound, live in longterm care facilities, or need

to stay in the hospital for a .long time When exposed to sunlight,• their skin does not form as .much vitamin D They consume so little• vitamin D in their diet that even taking vitamin D supplements in low doses (such as 400 units per day( does not prevent the .deficiency They may have disorders or• take drugs that interfere with .the processing of vitamin D New studies suggest that older adults may need more vitamin D than the current recommended dietary allowance or even the recommended upper limits. In fact, they may need 1000 to 2000 IU (or more( daily, but taking such high amounts should be done only after consulting a doctor. Older people who take high amounts of vitamin D supplements need to have periodic blood tests to check their levels of calcium, vitamin D, and parathyroid .hormone Symptoms Vitamin D deficiency can cause muscle aches, weakness, and bone pain in people of all ages. Muscle spasms, which are caused by a low calcium level, may .be the first sign of rickets in infants In young infants who have rickets, the entire skull may be soft. Older infants may be slow to sit and crawl, and the spaces between the skull bones (fontanelles( may be slow to close. In children aged 1 to 4 years, bone growth may be abnormal, causing an abnormal curve in the spine and bowlegs or knockknees. These children may be slow to walk. For older children and adolescents, walking is painful. The pelvic bones may flatten, narrowing the birth canal in adolescent girls. In adults, the bones, particularly the spine, pelvis, and leg bones, .weaken. Affected areas may be painful to touch, and fractures may occur .In older people, bone fractures may result from only slight jarring or a minor fall Diagnosis Doctors suspect vitamin D deficiency when people report an inadequate diet or exposure to sunlight. Doctors also suspect the deficiency in older adults, especially in those with decreased bone density (for example, with osteoporosis( or broken bones. Blood tests to measure vitamin D can confirm the deficiency. X-rays may also be taken. The diagnosis of rickets or osteomalacia is based on symptoms, the characteristic appearance of bones on x-rays, and a low level of .vitamin D in the blood Prevention and Treatment Many people need to take vitamin D supplements. Getting enough exposure to

sunlight may be difficult, especially because the skin also needs to be protected from sun damage. The diet rarely contains enough vitamin D to compensate for lack of sunlight. Many multiple vitamins contain little or no vitamin D, so most people need to take vitamin D supplements. These supplements are particularly important for people who are at risk (such as people who are older, housebound, or living in long-term care facilities(. Commercially available liquid milk (but not cheese or yogurt( is fortified in the United States and Canada. Many other countries do not fortify milk with vitamin D. Breakfast cereals may also be .fortified In breastfed infants, starting vitamin D supplements at birth is particularly important because breast milk contains little vitamin D. Commercial infant .formulas contain enough vitamin D Treatment involves taking high doses of vitamin D by mouth or by injection daily or weekly for 1 to 2 months or longer. If muscle spasms are present or calcium is thought to be deficient, calcium supplements are also given. If phosphate is deficient, phosphate supplements are given. Usually, this treatment leads to a complete recovery. People with a chronic liver or kidney disorder may .require special formulations of vitamin D supplements Vitamin D Excess Taking very high daily doses of vitamin D—for example, 50 or more times the recommended daily allowance (RDA(—over several months can cause toxicity and a high calcium level in the blood (hypercalcemia—see Minerals and .(Electrolytes: Hypercalcemia Early symptoms are loss of appetite, nausea, and vomiting, followed by excessive thirst, weakness, nervousness, and high blood pressure. Because the calcium level is high, calcium may be deposited throughout the body, particularly in the kidneys, blood vessels, lungs, and heart. The kidneys may be permanently .damaged and malfunction, resulting in kidney failure Vitamin D excess is usually diagnosed when blood tests detect a high calcium level in a person who takes high doses of vitamin D. The diagnosis is confirmed .by measuring the level of vitamin D in the blood :Treatment consists of the following Stopping vitamin D supplements• Following a low-calcium diet for a while to offset the effects of a high• calcium level in the body Taking drugs (such as corticosteroids or bisphosphonates( to suppress• the release of calcium from the bones Last full review/revision August 2007 by Larry E. Johnson, MD, PhD

Vitamin D Deficiency Vitamin D deficiency is common, particularly in children, pregnant women, breastfed babies, and anyone who stays indoors or covers their skin. It is important to treat and prevent deficiency to ensure good health, growth and strong bones. See your doctor if you think you are at risk of vitamin D deficiency, or if you have symptoms such as muscle or bone pains. Vitamin D deficiency is easily treated and prevented with vitamin supplements. Pregnant and breastfeeding women, breastfed babies, and other people .at risk of vitamin D deficiency should take vitamin D supplements

?What is vitamin D deficiency

Vitamin D deficiency means that there is not enough vitamin D in the body. Vitamins are a group of chemicals that are needed by the body for good health. Vitamin D is important for strong bones and muscles. Possibly, it may also help to prevent other diseases such as cancer, diabetes, tuberculosis and heart .disease

?Who gets vitamin D deficiency It is easiest to understand this if you know where vitamin D comes from. Vitamin D is made in the skin with the help of sunlight – this is the main source of vitamin D. It needs bare skin and direct sunlight (not through a window(. People with darker skins will need more sun to get the same amount of vitamin D. Vitamin D is also found in certain foods: liver, some types of fish, and egg yolk. Some cereals or margarines .contain added vitamin D Growing children, pregnant women, and breastfeeding women need extra vitamin D because it is required :for growth. So, vitamin D deficiency is more likely to develop in the following groups of people .Pregnant or breastfeeding women• Breastfed babies whose mothers are lacking in vitamin D, or with prolonged• breastfeeding. (These babies do not need to stop breastfeeding, they can have .(“breast milk plus vitamin drops – “breast is still best People who get very little sunlight on their skin such as those who are stay indoors• .a lot, or cover up when outside, for example, if wearing a veil People with conditions that affect the way the body handles vitamin D such as those• .with coeliac disease, Crohn’s disease, and some types of liver and kidney disease People taking certain medicines: carbamezepine, phenytoin, primidone or• .barbiturates People with dark skins or of South Asian origin, elderly people, and those with a• .family history of vitamin D deficiency

?How common is vitamin D deficiency It is very common. Research suggests that in the UK around 2 in 10 adults, and 9 in 10 adults of South Asian origin, may be vitamin D deficient. Most people don’t have symptoms and are unaware of the .problem

?What are the symptoms of vitamin D deficiency :Many people have no symptoms, or only vague ones such as tiredness or aches. Other symptoms may be Muscle pains or muscle weakness. In more severe deficiency, this may cause• difficulty standing up or climbing stairs, or can lead to the person walking with a .‘waddling’ pattern .Bone pains, often in the back, hips or legs• Children with severe deficiency may have soft skull or leg bones. This can make the• legs look curved or bow-legged. Other symptoms in children are poor growth and .delayed/weak teeth Muscle spasms (cramps), seizures and breathing difficulties can occur in babies and• .children with very severe deficiency

?How is vitamin D deficiency diagnosed It may be suspected from your medical history, symptoms, or lifestyle. A simple blood test for vitamin D levels can make the diagnosis. Also, blood tests for calcium and liver function may show changes linked to .a low level of vitamin D Sometimes, a wrist x-ray is done for a child. This can assess how severe the problem is by looking for .changes in the wrist bones

Extra tests may be needed if the cause of the deficiency is in doubt, or if there are other vitamin or mineral deficiencies. For example, if anaemia is found as well, you should have a blood test to look for coeliac .disease

?What is the treatment for vitamin D deficiency .Note: if you are pregnant or breastfeeding, see the next section after this The treatment is to take vitamin D supplements. This is a form of vitamin D called ergocalciferol or calciferol. (The dose of ergocalciferol is written in units known as international units or IU. Some people use microgrammes or μg instead, which are not the same as units.( There are various different ways of :taking vitamin D, which are Injection

A single small injection of vitamin D will last for about six months. This is a very effective and convenient treatment. It is useful for people who do not like taking medicines by mouth, or who are likely to forget to .take their tablets High dose tablets or liquids

There are different strengths available and a dose may be taken either daily, weekly or monthly. This will depend on your situation and on which particular treatment guideline your doctor is using. Always check with your doctor that you understand the instructions - with high doses of vitamin D it is important to take the medicine correctly. The advantage of the higher dose treatment is that the deficiency improves quickly .important in growing children Standard dose tablets, powders or liquids

These need to be taken every day for about 12 months in order that the body can "catch up" on the missing vitamin D. This is a rather slow method of replacing vitamin D, but is suitable if the deficiency is mild, or for prevention. A disadvantage is that all these preparations contain either calcium or other vitamins, giving .them a strong taste which some people dislike. Cod liver oil is an alternative :Note: care is needed with vitamin D supplements in certain situations If you are taking certain other medicines: digoxin or thiazide diuretics such as• bendroflumethazide. In this situation, avoid high doses of vitamin D, and digoxin will .need monitoring If you have other medical conditions: kidney stones, some types of kidney disease,• .liver disease or hormone disease. Specialist advice may be needed Vitamin D should not be taken by people who have high calcium levels or certain• .types of cancer You may need more than the usual dose if taking certain medicines which interfere• .with vitamin D. These are: carbamezepine, phenytoin, primidone and barbiturates

If you are pregnant or breastfeeding Vitamin D is especially important for pregnant or breastfeeding women, and their babies, because it is .needed for growth Prevention

Vitamin D supplements are recommended for all pregnant women, breastfeeding women and breastfed .babies Pregnant women and breastfeeding mothers: 400 units (10 micrograms) daily• of vitamin D is recommended. This can be either as a calcium/vitamin D tablet, or as a multivitamin tablet labelled as suitable for use in pregnancy. Some experts think that women who get no sunshine need a higher preventative dose such as 800 units (20 micrograms) daily. Pregnant women can get free prescriptions and .vitamins

Babies: all breastfed babies should be given vitamin drops (Abidec or Dalivit in the• dose advised on the label). Free vitamins are available with the Surestart scheme .via your health visitor Treatment - if you are diagnosed with vitamin D deficiency

Doses of up to 1000 units (25 micrograms( daily of vitamin D can be used. (In some situations, higher doses (.have been used to treat pregnant women Important note: if you are pregnant or breastfeeding you should not use high doses of vitamin D (the injections and high dose tablets/liquids described above(. This is because of uncertainty about whether these doses are too high for the baby. Doctors tend to be cautious about the dose of vitamin D given to pregnant or breastfeeding women, and will often limit the dose to 1,000 units daily. This is a safe dose. It is likely .that higher doses are safe for pregnant women, but we are waiting for more guidance on this subject Important note: if you are pregnant, do not take supplements containing large amounts of vitamin A. Supplements labelled as suitable for pregnancy are safe to use. Also, do not eat liver which contains large .amounts of vitamin A, as too much can harm the baby. Vitamin A is safe if you are breastfeeding

?Are there any side-effects from vitamin D supplements It is very unusual to get side effects from vitamin D if taken in the prescribed dose. However, very high doses can raise calcium levels in the blood. This would cause symptoms such as thirst, passing a lot of urine, nausea or vomiting, dizziness and headaches. If you have these symptoms, see a doctor immediately .so that your calcium level can be checked with a blood test Some guidelines advise that people taking high vitamin D doses should have their calcium levels checked during the first few weeks. In practice, this is not usually done unless you have symptoms of high calcium .as described above

?What is the outcome with vitamin D deficiency The outcome is generally very good. Both the vitamin levels and the symptoms usually respond well to treatment. However, it can take time (months( for bones to recover. So, if you have symptoms such as bone .pain, this will also take time to improve There are some possible complications of severe deficiency (see below(. Most of these will improve or .recover with treatment Very severe, prolonged deficiency may cause bone problems (rickets or osteomalacia( which could lead to a .deformity if treated very late

?Are there any complications from vitamin D deficiency Mild or short-lived vitamin D deficiency usually causes no symptoms. With prolonged deficiency, the risk of getting osteoporosis (bone thinning and fractures in old age( is probably increased. The risk of getting other diseases might also be increased. This is uncertain, but it is possible that vitamin D helps to prevent .some conditions such as diabetes, heart disease and cancer :Prolonged, severe deficiency can cause medical problems, which are Softening of the bones. This leads to rickets in children and osteomalacia in adults.• .'See separate leaflets on 'Rickets' and 'Osteomalacia With severe deficiency, there may be low levels of calcium in the blood. If calcium• levels get very low, this can cause muscle spasms (cramps) or seizures. Babies may .get breathing difficulties. These symptoms need urgent treatment Very rarely, severe deficiency has been reported to cause heart muscle weakness,• .which was cured by vitamin D treatment

Follow up

Most people who are treated for vitamin D deficiency will need to be reviewed a few weeks or months after .starting treatment - depending how severe their symptoms are. A further review after one year is advised

Prevention Once you have been treated for vitamin D deficiency, prevention is needed to stop the deficiency from recurring again in the future. Diet change and sunshine can help (see below(. Many people find it hard to change their diets or to get more sunshine, and so will need to take long-term vitamin D supplements. :Supplements to prevent deficiency are Babies under one year: should have 200 units (5 micrograms) daily of vitamin D.• Breastfed babies should be given vitamin drops (see breastfeeding section above). Babies fed by formula milk do not need vitamin drops, as this milk already contains .vitamin D Children aged over one year: should have 280-400 units (7-10 micrograms) daily• of vitamin D. This is usually given as vitamin drops or tablets. Babies fed by formula milk do not need vitamin drops, as this milk already contains vitamin D. But when weaned on to ordinary milk they should have supplements, as ordinary milk in the UK contains little vitamin D. (Note: some countries outside of the UK do add (.vitamins to ordinary milk Adults: supplements of 400 units (10 micrograms) daily. However, people who get• no sunshine, and the elderly, probably need more - approximately 800 units (20 .micrograms) daily Higher preventative doses may be needed in certain situations. For• example, for people on certain medicines (carbamezepine, phenytoin, primidone .and barbiturates) and with other conditions such as liver or kidney disease

Cod liver oil can be taken instead of the usual vitamin D supplements (to give the same dose of vitamin D(. However, be careful about using cod liver oil if you are pregnant, as it also contains vitamin A, which may be harmful in large amounts (see pregnancy section(. Another option, instead of daily supplements, is to use the higher dose tablets, liquids or injections, taken at longer intervals. For example, this could be a weekly or monthly high dose tablet, or an injection every six to twelve months. You can discuss these options with .your doctor Diet and sunshine for vitamin D

Foods containing good amounts of vitamin D are: liver, some fish (mainly oily fish such as herring, sardines, pilchards, trout, salmon, tuna and mackerel(, egg yolk, and 'fortified' foods (which have vitamin D .added( such as some margarines and breakfast cereals Sunshine: 15 minutes three times weekly from April to September, with hands, arms and face uncovered, is said to be enough for fair-skinned people. Darker-skinned people will need more sunshine (we don't know how much more(. However, in winter in cold climates, there is not enough sunshine to maintain vitamin D .levels

A useful source of information Healthy Start Scheme

Web: www.healthystart.nhs.uk A government run scheme. With Healthy Start, you can get free vouchers every week which you swap for milk, fresh fruit, fresh vegetables and infant formula milk. You can also get free vitamins. You could qualify .if you're on benefits or you're pregnant and under 18

Vitamin D Deficiency Study Raises New Questions About Disease And Supplements ScienceDaily (Jan. 27, 2008( — Low blood levels of vitamin D have long been associated with disease, and the assumption has been that vitamin D supplements may protect against disease. However, this new

research demonstrates that ingested vitamin D is immunosuppressive and that low blood levels of vitamin D .may be actually a result of the disease process. Supplementation may make the disease worse :See also Health & Medicine Vitamin• Dietary Supplement• Cholesterol• Chronic Illness• Nutrition• Leukemia• Reference B vitamins• Essential nutrient• Vitamin D• Vitamin K•

In a new report Trevor Marshall, Ph.D., professor at Australia’s Murdoch University School of Biological Medicine and Biotechnology, explains how increased vitamin D intake affects much more than just nutrition or bone health. The paper explains how the Vitamin D Nuclear Receptor (VDR( acts in the repression or transcription of hundreds of genes, including genes associated with diseases ranging from cancers to .multiple sclerosis The VDR is at the heart of innate immunity, being responsible for expression of most of the antimicrobial" .peptides, which are the body’s ultimate response to infection," Marshall said Molecular biology is now forcing us to re-think the idea that a low measured value of vitamin D means we" simply must add more to our diet. Supplemental vitamin D has been used for decades, and yet the epidemics ".of chronic disease, such as heart disease and obesity, are just getting worse Our disease model has shown us why low levels of vitamin D are observed in association with major and" chronic illness," Marshall added. "Vitamin D is a secosteroid hormone, and the body regulates the production of all it needs. In fact, the use of supplements can be harmful, because they suppress the immune ".system so that the body cannot fight disease and infection effectively Marshall's research has demonstrated how ingested vitamin D can actually block VDR activation, the opposite effect to that of Sunshine. Instead of a positive effect on gene expression, Marshall reported that his own work, as well as the work of others, shows that quite nominal doses of ingested vitamin D can suppress the proper operation of the immune system. It is a different metabolite, a secosteroid hormone called 1,25-dihydroxyvitamin D, which activates the VDR to regulate the expression of the genes. Under conditions that exist in infection or inflammation, the body automatically regulates its production of all the vitamin D metabolites, including 25-hydroxyvitamin D, the metabolite which is usually measured to .indicate vitamin D status Vitamin D deficiency, long interpreted as a cause of disease, is more likely the result of the disease process, and increasing intake of vitamin D often makes the disease worse. "Dysregulation of vitamin D has been observed in many chronic diseases, including many thought to be autoimmune," said J.C. Waterhouse, .Ph.D., lead author of a book chapter on vitamin D and chronic disease We have found that vitamin D supplementation, even at levels many consider desirable, interferes with" ".recovery in these patients We need to discard the notion that vitamin D affects a disease state in a simple way," Marshall said." "Vitamin D affects the expression of over 1,000 genes, so we should not expect a simplistic cause and effect

between vitamin D supplementation and disease. The comprehensive studies are just not showing that ".supplementary vitamin D makes people healthier Journal reference: Marshall TG. Vitamin D discovery outpaces FDA decision making. Bioessays. 2008 Jan 15;30(2(:173-182 [Epub ahead of print] Online ISSN: 1521-1878 Print ISSN: 0265-9247 PMID: 18200565 .Adapted from materials provided by Autoimmunity Research Foundation, via AlphaGalileo :Email or share this story :Need to cite this story in your essay, paper, or report? Use one of the following formats

APA

MLA Autoimmunity Research Foundation (2008, January 27). Vitamin D Deficiency Study Raises New Questions About Disease And Supplements. ScienceDaily. Retrieved January 8, 2009, from http://www.sciencedaily.com/releases/2008/01/080125223302.htm

Vitamin D deficiency

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Definition Vitamin D deficiency exists when the concentration of 25-hydroxy-vitamin D (25-OH-D( in the blood serum occurs at 12 nanograms/milliliter (ng/ml( or less. This is one-half to one-fourth the amount normally present. When vitamin D deficiency continues for many months in growing children, the disease commonly .referred to as rickets occurs

Description Vitamin D is a fat-soluble vitamin, meaning it can be dissolved in fat. While some vitamin D is supplied by the diet, most of it is made in the body. To make vitamin D, cholesterol, a substance widely distributed in animal tissues, the yolk of eggs, and various oils and fats, is necessary. Once cholesterol enters the body, a slight alteration in the cholesterol molecule occurs, with one change taking place in the skin. This alteration requires ultraviolet light, a component of sunlight. Vitamin D deficiency and rickets tend to occur in .children who do not get enough sunlight and who do not eat foods that are rich in vitamin D

Once consumed or made in the body, vitamin D is further altered to produce a substance called 1,25dihydroxy-vitamin D (1,25-diOH-D(. The conversion of vitamin D to 1,25-diOH-D occurs in the liver and kidney. The role of 1,25-diOH-D in the body is to keep the concentration of calcium at a constant level in the bloodstream. Maintaining calcium at a constant level is absolutely required for human life, since dissolved calcium is required for nerves and muscles to work. One of the ways in which 1,25-diOH-D .accomplishes this is by stimulating the absorption of dietary calcium by the intestines The sequence of events that can lead to vitamin D deficiency and later to bone disease, is as follows: a lack of vitamin D in the body creates an inability to manufacture 1,25-diOH-D. This results in decreased absorption of dietary calcium and an increased loss of calcium in the feces. When this happens, the bones are affected. Vitamin D deficiency results in a lack of bone mineralization (calcification( in growing .children

Demographics Vitamin D deficiency is not common in the United States and other industrialized countries because of the wide availability of vitamin D fortified infant formulas and milks. It is somewhat more common in northern areas where there is not as much sunlight present during many parts of the year. Vitamin D deficiency is also slightly more common in inner city areas, because environmental factors, such as smog, can block the necessary ultraviolet (UV( component of sunlight. Children with darkly pigmented skin are more likely to be vitamin D deficient than light skinned children. Children who are exclusively breast-fed without vitamin D supplementation, particularly if they are not exposed to sunlight, are at higher risk of vitamin D .deficiency

Causes and symptoms Vitamin D deficiency can be caused by conditions that result in little exposure to sunlight. These conditions include: living in northern regions, having dark skin, and having little chance to go outside. Children whose faces and bodies remain covered when outside can develop vitamin D deficiency even while living in a sunny climate. In-born errors of vitamin D metabolism can also cause vitamin D deficiency and rickets; these children cannot convert inactive vitamin D to active vitamin D and suffer the same symptoms as .children with a nutritional deficiency Most foods contain little or no vitamin D. As a result, sunshine is often a deciding factor in whether vitamin D deficiency occurs. Although fortified milk and fortified infant formula contain high levels of vitamin D, human breast milk is rather low in the vitamin. (The term fortified means that vitamins are added to the (.food by the manufacturer The Recommended Dietary Allowance (RDA( of vitamin D for both children and adults is 200 International Units (IU( per day. Saltwater fish such as salmon, herring, and sardines are naturally rich in vitamin D. Vitamin D fortified milk contains 400 IU per quart (liter(, so half a quart (liter( of milk provides the RDA. .For comparison, human breast milk contains only 4 to 60 IU per quart No harm is likely to result from vitamin D deficiency that occurs only a few days a year. If the deficiency occurs for a period of many months or years, however, rickets may develop. The symptoms of rickets include bowed legs and bowed arms. The bowed appearance is due to the softening of bones, and their bending if the bones are weight-bearing. Bone growth occurs through the creation of new cartilage, a soft substance at the ends of bones. When the mineral calcium phosphate is deposited onto the cartilage, a hard structure is created. In vitamin D deficiency, though, calcium is not available to create hardened bone, and the result is soft bone. Other symptoms of rickets include bony bumps on the ribs called rachitic rosary (beadlike prominences at the junction of the ribs with their cartilages( and knock-knees. Seizures may also occasionally occur in a child with rickets, because of reduced levels of dissolved calcium in the .bloodstream When to call the doctor

The doctor should be called if the parent notices that the child has any signs of vitamin D deficiency or rickets. Such signs include skeletal pain, bowed limbs, and impaired growth. If there are lifestyle factors that make the child at risk for vitamin D deficiency, such as low milk or formula intake, a doctor should be .consulted about the possibility of using vitamin D supplements

Diagnosis

Vitamin D deficiency is diagnosed by measuring the level of 25-hydroxy-vitamin D in the blood serum. The

.X ray of a child's lower body affected by rickets, a result of a vitamin D deficiency (.Dr. LR/Photo Researchers, Inc ©) normal concentration of this form of vitamin D ranges from 25 to 50 ng/ml. Deficiency occurs .when this level decreases to about 12 ng/ml or less

Rickets is diagnosed by x-ray examination of the leg bones. A distinct pattern of irregularities, abnormalities, and a coarse appearance can be clearly seen if a child has rickets. Measurements of blood plasma 25-OH-D, blood plasma calcium, and blood plasma parathyroid hormone must also be obtained for the diagnosis of this disease. Parathyroid hormone and 1,25-diOH-D work together in the body to regulate .the levels of calcium in the blood

Treatment Rickets heals promptly with large doses vitamin D administered orally each day for approximately one month. During this treatment, the doctor should monitor the levels of 25-OH-D in the plasma to make sure that they are raised to a normal level. The bone abnormalities (visible by x ray( generally disappear gradually over a period of three to nine months. Parents are instructed to take their infants outdoors for approximately 20 minutes per day with their faces exposed. Children should be encouraged to play outside and to eat foods that are good sources of vitamin D. These foods include cod liver oil, egg yolks, butter, oily .fish and also foods, including milk and breakfast cereals, that are fortified with synthetic vitamin D Care must be taken in treating vitamin D deficiency, since high doses of vitamin D are toxic (poisonous( and can result in the permanent deposit of minerals in the heart, lungs, and kidneys. Symptoms of toxicity are nausea, vomiting, pain in the joints, and lack of interest in eating food. In adults, vitamin D toxicity occurs with eating 50,000 IU or more per day. In infants, toxicity occurs with 1,000 IU per day. The .continued intake of toxic doses results in death Rickets are usually treated with oral supplements of vitamin D, with the recommendation to acquire daily exposure to direct sunlight. An alternative to sunlight is the use of an ultraviolet lamp. When people use UV lamps, they need to cover their eyes to protect them against damage. Many types of sunglasses allow UV light to pass through, so only those that are opaque to UV light should be used. Attempts to acquire sunlight through glass windows fail to help the body make vitamin D because UV light does not pass through .window glass Rickets may also occur with calcium deficiency, even when a child is regularly exposed to sunshine. This type of rickets has been found in various parts of Africa. The bone deformities are similar to, or are the same as, those that occur in typical rickets; however, calcium deficiency rickets is treated by increasing the amount of calcium in the diet. No amount of vitamin D can cure the rickets of a child with a diet that is

extremely low in calcium. For this reason, it is recommended that calcium be given in conjunction with .vitamin D supplementation

Prognosis The prognosis for correcting vitamin D deficiency and rickets is excellent. Vitamin D treatment results in the return of bone mineralization to a normal rate, the correction of low plasma calcium levels, the prevention of seizures, and a recovery from bone pain. On the other hand, already established deformities .such as bowed legs and the rachitic rosary persist throughout adult life

Prevention Vitamin D deficiency is a very preventable. Eating foods that are high in vitamin D or foods that have been fortified with additional vitamins in combination with getting moderate amounts of exposure to direct .sunlight, are usually enough to prevent vitamin D deficiency

KEY TERMS .hydroxy-vitamin D—The form of vitamin D that is measured in order to assess vitamin D deficiency-25 Cholesterol—A steroid fat found in animal foods that is also produced in the human body from saturated fat. Cholesterol is used to form cell membranes and process hormones and vitamin D. High cholesterol .levels contribute to the development of atherosclerosis Fat-soluble vitamin—A vitamin that dissolves easily in fat or oil, but not in water. The fat-soluble vitamins .are vitamins D, E, A, and K International unit (IU)—A measurement of biological activity in which one IU is equal to one mg .((milligram Rachitic rosary—Beadlike bumps present at the junction of the ribs with their cartilages. It is often seen in .children with rickets Recommended Dietary Allowance (RDA)—The Recommended Dietary Allowances (RDAs( are quantities of nutrients in the diet that are required to maintain good health in people. RDAs are established by the Food and Nutrition Board of the National Academy of Sciences, and may be revised every few years. A separate RDA value exists for each nutrient. The RDA values refer to the amount of nutrient expected to maintain good health in people. The actual amounts of each nutrient required to maintain good health in .specific individuals differ from person to person Rickets—A condition caused by the dietary deficiency of vitamin D, calcium, and usually phosphorus, seen .primarily in infancy and childhood, and characterized by abnormal bone formation Some authorities still recommend exposure to sunshine as a way to prevent vitamin D deficiency, but early exposure to direct sunlight may be linked to a higher incidence of skin cancer later in life, so other experts recommend that infants not be taken into direct sunlight without protective coverings or sunscreen until at least six months of age. These experts recommend that supplemental drops or fortified formulas instead of direct sunlight provide infants' daily requirements of Vitamin D. Children playing in the sunlight with sunscreen on is not an effective way for them to get vitamin D because the sunscreen inhibits its production .in the skin Nutritional concerns

Vitamin D deficiency is caused by the child not getting enough vitamin D through nutrition and exposure to sunshine. Even after a case of vitamin D deficiency has successfully been resolved special care should be .taken with the child's diet, as vitamin D deficiency can reoccur

Parental concerns Vitamin D deficiency can cause rickets, which can lead to permanently stunted or irregular growth. Vitamin D deficiency can usually be easily corrected if it is noticed early, and if so the symptoms often resolve .themselves. However, negative effects such as short stature and pelvic deformations can be permanent Vitamin D Vitamin D has two main forms: D2 (ergocalciferol( and D3 (cholecalciferol(. Vitamin D3 is synthesized in skin by exposure to sunlight (ultraviolet radiation( and obtained in the diet chiefly in fish liver oils and egg

yolks. In some developed countries, milk and other foods are fortified with vitamin D. Human breast milk is low in vitamin D, containing an average of only 10% of the amount in fortified cow's milk. Requirements for vitamin D increase with aging. Vitamin D is a prohormone with several active metabolites that act as hormones. Vitamin D3 is metabolized by the liver to 25(OH(D, which is then converted by the kidneys to 1,25(OH(2D (1,25-dihydroxycholecalciferol, calcitriol, or active vitamin D hormone(. 25(OH(D, the major circulating form, has some metabolic activity, but 1,25(OH(2D is the most metabolically active. Inadequate exposure to sunlight may cause vitamin D deficiency. Deficiency impairs bone mineralization, causing .rickets in children and osteomalacia in adults and may contribute to osteoporosis

Cholecalciferol (Vitamin D3(

Vitamin D metabolism The current recommendations from the Institute of Medicine are 200 IU/day from birth through age 50, 400 IU for those aged 51 to 70, and 600 IU for those over 70 years. These recommendations were established by determining the level of Vitamin D that was enough to prevent bone demineralization or rickets. The safe .tolerable upper intake level for Vitamin D is 10,000 IU/day Randomized trials using the currently recommended intakes of 400 IU of Vitamin D/day have shown no appreciable reduction in fracture risk. In contrast, trials using 700–800 IU Vitamin D/day found less fracture incidence[8]. Adults should be consuming at least 1000 IU per day of Vitamin D to maintain blood serum .levels that are effective for strengthening the bones

Rickets Osteomalacia during enchondral bone growth• Age• months 4-18○ Histology• Zone of preparatory calcification does not form resulting in build-up of maturing○ cartilage cells Also occurs in shafts so that osteoid production elevates periosteum○ Clinical findings• Irritability○ Bone pain○

Tenderness○ Craniotabes○ Rachitic rosary○ Bowed legs○ Delayed dentition○ Swelling of wrists and ankles○ Location• Metaphyses of long bones subjected to stress are particularly involved○ Wrists Ankles Knees Imaging findings• Cupping and fraying of metaphysis○ Poorly mineralized epiphyseal centers with delayed appearance○ (Irregular widened epiphyseal plates (increased osteoid○ Increase in distance between end of shaft and epiphyseal center○ Cortical spurs projecting at right angles to metaphysis○ (Coarse trabeculation (not the ground-glass pattern found in scurvy○ Periosteal reaction may be present○ Deformities common○ Bowing of long bones Molding of epiphysis Fractures Frontal bossing

,Rickets of the knees demonstrates bowing of the femurs, metaphyseal cupping and fraying ,coarsening of the trabecular pattern, increase in distance between end of shaft and epiphyseal center poorly ossified epiphyseal centers Click here for this photo enlarged Causes Of Rickets• Abnormality In Vitamin D Metabolism○ Associated with hyperparathyroidism Vitamin D deficiency Dietary lack of vitamin D• Famine osteomalacia• Lack of sunshine exposure Malabsorption of vitamin D Pancreatitis and biliary tract disease• Steatorrhea, celiac disease, postgastrectomy•

Inflammatory bowel disease• Defective conversion of vitamin D to 25-OH-cholecalciferol in liver○ Liver disease Anticonvulsant drug therapy (= induction of hepatic enzymes that accelerate degradation of biologically active vitamin D (metabolites Defective conversion of 25-OH-D3 to 1,25-OH-D3 in kidney○ Chronic renal failure = renal osteodystrophy Vitamin D-dependent rickets = autosomal recessive enzyme defect of 1-OHase Abnormality In Phosphate Metabolism• Not associated with hyperparathyroidism secondary to normal serum calcium○ Phosphate deficiency○ Intestinal malabsorption of phosphates Ingestion of aluminum salts [Al(OH(2] forming insoluble complexes with phosphate Low phosphate feeding in prematurely born infants Severe malabsorption state Parenteral hyperalimentation Disorders of renal tubular reabsorption of phosphate (Renal tubular acidosis (renal loss of alkali• deToni-Debré-Fanconi syndrome =• hypophosphatemia, glucosuria, aminoaciduria Vitamin D-resistant rickets• Cystinosis• Tyrosinosis• Lowe syndrome• Hypophosphatemia with nonendocrine tumors○ Oncogenic rickets - elaboration of humeral substance which inhibits tubular reabsorption of phosphates Sclerosing hemangioma• Hemangiopericytoma• Ossifying mesenchymal tumor• Nonossifying fibroma• Hypophosphatasia○ Calcium Deficiency• (Dietary rickets = milk-free diet (extremely rare○ Malabsorption○ Consumption of substances forming chelates with calcium○ Classification Of Rickets• Primary vitamin D-deficiency rickets○

Gastrointestinal malabsorption○ Partial gastrectomy Small intestinal disease: gluten-sensitive enteropathy / regional enteritis Hepatobiliary disease: chronic biliary obstruction / biliary cirrhosis Pancreatic disease: chronic pancreatitis Primary hypophosphatemia; vitamin D-deficiency rickets○ Renal disease○ Chronic renal failure Renal tubular disorders: renal tubular acidosis Multiple renal defects Hypophosphatasia and pseudohypophosphatasia• Fibrogenesis imperfecta osseum○ Axial osteomalacia○ Miscellaneous• Hypoparathyroidism, hyperparathyroidism, thyrotoxicosis, osteoporosis, Paget○ ,disease, fluoride ingestion ureterosigmoidostomy, neurofibromatosis, osteopetrosis, macroglobulinemia,○ malignancy Vitamin D deficiency in pregnant New Zealand women Annie Judkins, Carl Eagleton Abstract Aim This aim of this study was to identify the prevalence of vitamin D deficiency in pregnant women of a Wellington general practice where 10 cases of childhood rickets had .been diagnosed over the past 3 years Methods Ninety pregnant women were screened for vitamin D deficiency by measuring 25-hydroxy vitamin D by DiaSorin radioimmunoassay. Recruitment into the study was over a 12-month period. A second appointment was arranged for clinical review and drawing of .blood for parathyroid hormone, adjusted calcium, and alkaline phosphatase Results 100% of women presenting to the general practice for antenatal care consented to the study. 87% of women had 25-hydroxy vitamin D levels below 50 nmol/L. 61.2% of women had a vitamin D level below 25 nmol/L consistent with severe vitamin D deficiency. 10 women had an elevated parathyroid hormone consistent with secondary hyperparathyroidism. Only 22% of our patients were veiled, and included a diverse ethnic .population, including African, Maori, European, Middle Eastern, and Polynesian women Conclusions Vitamin D deficiency is common in young pregnant women in this general practice, and it was not only confined to veiled women or women with dark skin. This highlights the magnitude of vitamin D deficiency in the pregnant population in a New Zealand setting; this vitamin D deficiency is responsible for the re-emergence of childhood .rickets

Vitamin D deficiency (and consequently rickets) is re-emerging as a major primary health care and public health issue throughout the world.1–5 Although there is no true international consensus on the best ways to treat vitamin D deficiency, it is acknowledged that the prevalence of vitamin D deficiency and its associated morbidities are higher than previously thought worldwide.6–11 Nozza and Rodda from their review of children with rickets in Melbourne, Australia have recommended pregnant women with dark skin pigment or “veiling” should have their vitamin D level checked. If vitamin D levels are low (<50 nmol/L) then supplementation should be given to the mother as well as supplements to the breast feed infants of deficient mothers.3 During pregnancy and lactation, the current consensus is that the vitamin D status of the infant is strongly influenced by the vitamin D status of the mother during pregnancy. During pregnancy, 80% of the fetal skeleton is mineralised in the third trimester, so maternal adaptations to fetal calcium demands are most important in the third trimester. The major adaptive process in humans is a two-fold increase in maternal intestinal calcium absorption, mediated by increases in 1-25 dihydroxy vitamin D. Therefore the level of 25-hydroxy vitamin D and the parathyroid hormone levels are felt to give the best indication of the body’s .balance of vitamin D during pregnancy Prompted by anecdotal reports of an increase in childhood rickets in South-East Wellington, we decided to examine the prevalence of vitamin D deficiency in a general practice population. Newtown Medical Health Services (NUHS) is part of a small Primary HealthCare Organisation (SECPHO) in South-East Wellington (latitude 41S) providing integrated medical and midwifery care for a population of approximately 7000 patients. Currently this includes a patient base of 437 children under the age of 5 years. Each year the number of births within .the practice is approximately 120 A review of their database for children under the age of 5 years identified 10 cases with a diagnosis of rickets over the last 3 years (Figure 1 and 2). Because of the re-emergence of childhood rickets in this practice, and in many countries around the world, a prospective clinical study was undertaken. We offered vitamin D screening for all pregnant women .presenting for antenatal care to this general practice Figure 1. Six-month-old child with rachitic changes showing expansion of the costochondral (junction (arrowed

Figure 2. Classic rachitic metaphyseal changes: cupping, fraying, widening, and fuzziness of (the zone of provisional calcification immediately under the growth plate (arrowed

The study aim was to identify the prevalence of vitamin D deficiency in pregnant women of this small, busy primary health organisation (PHO). With an intention to treat vitamin D deficiency in order to prevent neonatal or childhood rickets in this population. We aimed to recruit 120 women to the study and replace vitamin D with ergocalciferol (vitamin D2) in those who were deficient from as early as 13 weeks gestation and continue this treatment .throughout pregnancy and up to 6 months postpartum

Methods In addition to the first antenatal bloods done routinely at commencement of maternity services, a 25-hydroxy vitamin D level was performed after consent was obtained. Each woman was asked to complete a simple dietary and sun exposure questionnaire. At the same time, an information sheet about vitamin D was provided and was available in several .languages OH vitamin D was measured by acetonitrile extraction followed by DiaSorin-25 radioimmunoassay (Stillwater, MN, USA). Patients with values less than 50 nmol/L were bought back for a further consultation and were considered to be significantly vitamin D .deficient and offered replacement treatment At the second appointment, additional blood tests for parathyroid hormone (PTH), adjusted calcium, alkaline phosphatase, and phosphate were taken. Parathyroid hormone was

measured by a Roche immunoassay (Basel, Switzerland). In pregnant women of 13 weeks gestation and over, with a vitamin D level of less than 50 nmol/L, ergocalciferol (vitamin D2) was prescribed as one 1,000 IU tablet per day. Follow up of the women later in pregnancy and in the postpartum period is the focus of the continuing prospective study. Daily supplementation of 400–1000 IU/day in pregnancy is felt to be safe.1,12–16 The study received ethics approval from the Wellington Ethics Committee. Vitamin D in the form of ergocalciferol (vitamin D2) was purchased from New Hope Nutrition Ltd (Browns Bay, Auckland, New Zealand). The only active ingredient was vitamin D as ergocalciferol (vitamin .(D2) 1,000 IU (release limits 900–1650 IU

Results To date, of the 90 pregnant women that have been seen at Newtown Union Health, 100% consented to be study participants. The community of this general practice is multicultural and was reflected in the diverse ethnic groups included in the study. Of the 90 pregnant women, 78 (87%) were vitamin D deficient—with 25-hydroxy vitamin D levels below 50 (.nmol/L. (See Table 1 below Table 1. Pregnant women (n=90) screened at Newtown Union Health (Wellington) for vitamin D deficiency Ethnicity Number screened Vitamin D deficient Middle Eastern 15 (100%) 15 Indian 2 (100%) 2 African 21 (86%) 18 European 12 (67%) 8 New Zealand 10 (90%) 9 Maori 18 (94%) 17 Samoan 1 1 Tokelauan 3 2 Chinese 5 4 Other 2 2 Cook Islander Two patients with vitamin D levels above 50 nmol/L had had previous children with rickets and had been treated with vitamin D replacement before pregnancy. 25-OH vitamin D levels ranged from <7.5 to 112 nmol/L in the study group; 61.2% of women had a 25-hydroxy vitamin D level less than 25 nmol/L, 24.4% between 25 and 50 nmol/L, and only 14.4% had a level of 50 nmol/L or greater. Seventeen of 39 women who returned for their repeat blood .testing had an adjusted calcium below the normal range of 2.25 mmol/L Amongst the 78 vitamin D deficient women, 10 had secondary hyperparathyroidism with a parathyroid hormone (PTH) of greater than 6.0 pmol/L (1.5–6.0 pmol/L). All those with a PTH .of greater than 9.5 pmol/L had a 25-hydroxy vitamin D level less than 12 nmol/L

Conclusions Deficiency of vitamin D is common in this general practice’s (Newtown Union Health’s) population of pregnant women. This practice does serve a diverse population and will not be the same for all other New Zealand general practices. However some of the significant findings include the high incidence of vitamin D deficiency (in our study group) in New .Zealand Maori, Samoans, and other Pacific Islanders

The African, Middle Eastern, and Asian groups showed a very high incidence of vitamin D deficiency, which was perhaps not unexpected. Secondary hyperparathyroidism and hypocalcaemia due to the vitamin D deficiency were also common, reflecting the severity of .the deficiency Previously described risk factors for vitamin D deficiency include veiling with traditional dress. This only contributed to a minority of cases in our series with only 22% wearing veils. Sunlight exposure may also be related to the ability to sit outside for periods of time but only 33 of the .90 women were living in apartments In a general practice with a re-emergence of rickets in children, this study highlights the potential magnitude of this preventable disease. All these women have gone onto receive treatment where they have elected to continue with the pregnancy. Further follow up on the .efficacy of treatment is planned Because of the high incidence of vitamin D deficiency in this group of pregnant women we seriously believe that further population studies are needed. It is also important to make midwives, general practitioners, endocrinologists, and obstetric medicine physicians aware .that vitamin D deficiency is common in the pregnant patient Indeed, in our study population, vitamin D deficiency was not only common in the veiled and .dark-skinned patients but among all ethnicities in our pregnant general practice population Author information: Annie Judkins, General Practitioner, Newtown Union Health Services; Carl Eagleton, Endocrinologist, Department of Endocrinology, Wellington Hospital; Newtown, Wellington :Acknowledgements: We gratefully acknowledge ;The Wellington Endocrine Foundation• ;Newtown Union Health Services• Newtown Union Health Service Midwives; and• .South-East City Primary Health Care Organisation• Correspondence: Dr Carl Eagleton, Department of Endocrinology, Wellington Hospital, Private Bag 7902, Wellington. Email: [email protected] or [email protected]

Rickets and Osteomalacia Author: Rick Alan (En Español (Spanish Version Definition

Rickets (in children( and osteomalacia (in adults( are two forms of a metabolic bone disease resulting from vitamin D deficiency. Both cause softening and weakening of bones because of defective or inadequate .bone mineralization

Rickets

.Nucleus Medical Art, Inc 2008 © Causes

:Rickets and osteomalacia result when there is a vitamin D deficiency in the body. This may occur when .The supply of vitamin D from the diet or sun exposure is inadequate• .The metabolism of vitamin D is abnormal• .Tissue is resistant to the action of vitamin D•

Vitamin D regulates calcium absorption in the body. It also controls levels of calcium and phosphate in bone. Vitamin D is absorbed in the intestines from food. Vitamin D is also produced by the skin during .exposure to sunlight :Most often, rickets and osteomalacia are caused by a deficiency of vitamin D. This can result from :Insufficient vitamin D in the diet. In children, this may be related to• Insufficient consumption of vitamin D-fortified milk○ Insufficient intake of vitamin D supplements to children being○ breastfed or to children who are lactose intolerant .Lack of exposure to sunlight•

Less often, rickets and osteomalacia can be caused by other disorders that affect vitamin D absorption, :metabolism, or action in the body such as :Kidney problems• A hereditary disorder of the kidney called vitamin D-resistant rickets○ Renal tubular acidosis—a nonhereditary kidney disorder which causes○ bone calcium to dissolve Chronic kidney failure○ Long-term kidney dialysis○ Diseases of the small intestines with malabsorption• Disorders of the liver or pancreas disease• Cancer• :Certain drugs, such as• Certain seizure medications, such as phenytoin or phenobarbital○ Acetazolamide○ Ammonium chloride○ Disodium etidronate○

Fluoride treatment○ :Toxicity or poisoning from• Cadmium○ Lead○ Aluminum○ Outdated tetracycline○ Risk Factors

A risk factor is something that increases your chance of getting a disease or condition. Risk factors for :rickets/osteomalacia include Age in children: 6 to 24 months old• Either the child is consuming breast milk (from a mother who is○ .deficient in vitamin D) or milk not fortified with vitamin D Age in adults: 50-80 years• Lactose intolerance with inadequate intake of vitamin D-fortified milk• Family history of rickets• Race: Black, especially in association with breastfeeding• Symptoms

:Symptoms may include Bone pain and tenderness• Skeletal and/or skull deformities• Bow legs or knock knees• Deformity or curvature of the spine• (Pigeon chest (forward protrusion of the chest bone• Impaired growth, resulting in short stature• Susceptibility to bone fractures• Dental deformities• Delayed tooth formation• Defects in teeth• Increased cavities• Loss of appetite or weight loss• Difficulty sleeping• Poor muscle development and tone• Muscle weakness• Delay of learning to walk in children• Diagnosis

The doctor will ask about your symptoms and medical history, and perform a physical exam. Tests to :confirm the diagnosis may include Blood and urine tests• Bone x-rays• Bone biopsy, when other tests are not conclusive•

Treatment

:Treatment attempts to Correct the underlying cause• Relieve or reverse symptoms• Treating the Underlying Cause

:Treatment of the underlying cause may include :Adding the following to your diet• Vitamin D-fortified dairy products○ Foods high in vitamin D (such as fatty fish, egg yolk, and green○ (vegetables Supplements of vitamin D, calcium, and other minerals○ Biologically active vitamin D○ Adequate but not excessive exposure to sunlight• Treating Symptoms

:Treatment to relieve or correct symptoms may include Wearing braces to reduce or prevent bony deformities• In severe cases, surgery to correct bony deformities• Prevention

:To help prevent rickets or osteomalacia .Drink vitamin D-fortified milk• Consume sufficient vitamin D, calcium, and other minerals. If you think your diet• may be deficient, talk with your doctor about alternate sources of vitamins and .minerals Get sufficient, but not excessive, exposure to sunlight. Fifteen minutes a day is• usually considered sufficient. Any longer than that requires sun protection with clothing or sunscreens, especially in fair-skinned infants or children. Children with dark skin and their mothers are at increased risk for rickets and may need more sun .exposure and dietary supplementation with vitamin D Breastfed, dark-skinned babies should receive 400 International Units per day (IU/d)• .of supplementation with vitamin D starting at no later than two months of age

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