Vitamin D

HOW MUCH VITAMIN D DO YOU NEED?

Vitamin D is a vitamin (a substance the body requires in small doses for proper nutrition and function) that is fat-soluble, meaning that it is dissolved and stored in the fat of your body. Vitamin D maintains proper levels of calcium and phosphorus in the blood and together with calcium builds strong bones. The November 9, 2005, issue of JAMA contains an article about sufficient levels of vitamin D for healthy bones.

HOW MUCH VITAMIN D DO YOU NEED?

SUNLIGHT EXPOSURE

Sun exposure for 10 to 15 minutes at least twice a week usually provides adequate amounts of vitamin D. Certain conditions such as cloud cover, northern climates, pollution, and the winter months may not provide adequate sunlight exposure. Excess sun exposure causes skin cancer, so you should limit exposure to sunlight, not use tanning beds, and wear protective clothing and a sunscreen with a sun protection factor (SPF) of at least 15 when outdoors for longer than 10 to 15 minutes twice a week. Infants should be kept out of direct sunlight all together.

VITAMIN D DEFICIENCY

When vitamin D levels are low, bones become weak and brittle. In children, vitamin D deficiency causes a disease called rickets, which results in poorly developed weak bones, delayed growth, immune deficiencies, and, when severe, seizures. In adults, vitamin D deficiency causes a disease called osteomalacia, which results in weak bones, fractures, bone pain, and weakness. Low levels of vitamin D may be a factor in osteoporosis (thin bones).

WHO IS AT RISK OF DEVELOPING VITAMIN D DEFICIENCY?

• Infants who are exclusively breast-fed or receiving less than about 2 cups a day of vitamin D fortified formula or milk
• People who have darker-pigmented skin
• People with very limited sunlight exposure
• People with fat malabsorption diseases, such as pancreatitis, cystic fibrosis, celiac disease, and surgical resection of the bowel
• People who have liver or kidney disease or enzyme deficiencies
• People in the northern hemisphere during winter

HOW MUCH VITAMIN D DO YOU NEED?

For infants to adults aged 50 years, the daily adequate intake is 200 international units (IU) of vitamin D. For adults aged 51 to 70 years, 400 IU is required, and for those older than 70 years, 600 IU is recommended. Discuss with your doctor the proper vitamin D intake and sun exposure for you and whether you should take a supplement, especially if you are at risk of developing a deficiency. Too much vitamin D can occur from taking excess vitamin D supplements and can cause serious problems, such as nausea, vomiting, and weakness or even confusion and heart rhythm abnormalities.

Reference Intakes of Vitamin D

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). 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, 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.

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.

Table 2: Adequate Intakes (AIs) for Vitamin D [4]

Age	Males	Females	Pregnancy	Lactation
0-12 months	5 mcg (200 IU)	5 mcg (200 IU)
1-13 years	5 mcg (200 IU)	5 mcg (200 IU)
14-18 years	5 mcg (200 IU)	5 mcg (200 IU)	5 mcg (200 IU)	5 mcg (200 IU)
19-50 years	5 mcg (200 IU)	5 mcg (200 IU)	5 mcg (200 IU)	5 mcg (200 IU)
51-70 years	10 mcg (400 IU)	10 mcg (400 IU)
71+ years	15 mcg (600 IU)	15 mcg (600 IU)

In 2008, the American Academy of Pediatrics (AAP) issued recommended intakes for vitamin D that exceed those of FNB. 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. (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.

The FNB established an expert committee in 2008 to review the DRIs for vitamin D (and calcium). The current DRIs for this nutrient were established in 1997, and since that time substantial new research has been published to justify a reevaluation of adequate vitamin D intakes for healthy populations. Determinations of DRIs are based on indicators of adequacy or hazard; dose-response curves; health outcomes; life-stage groups; and relations between intakes, biomarkers, and outcomes. For vitamin D, the FNB committee will focus on (1) effects of circulating concentrations of 25(OH)D on health outcomes, (2) effects of vitamin D intakes on circulating 25(OH)D and on health outcomes, and (3) levels of intake associated with adverse effects. The FNB expects to issue its report, updating as appropriate the DRIs for vitamin D and calcium, by May 2010.

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, which provides only about 25 IU/L. A recent review of reports of nutritional rickets found that a majority of cases occurred among young, breastfed African Americans. 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. As noted earlier, AAP recommends that exclusively and partially breastfed infants be supplemented with 400 IU of vitamin D per day.

Older adults
Americans aged 50 and older are at increased risk of developing vitamin D insufficiency. 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. 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).

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.

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. 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]. Fat malabsorption is associated with a variety of medical conditions including some forms of liver disease, cystic fibrosis, and Crohn's disease.

People who are obese or who have undergone gastric bypass surgery
Individuals with a BMI ≥30 typically have a low plasma concentration of 25(OH)D; this level decreases as obesity and body fat increase. 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. Obese individuals who have undergone gastric bypass surgery may become vitamin D deficient without a sufficient intake of this nutrient from food or supplements, since part of the upper small intestine where vitamin D is absorbed is bypassed.

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. 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. Some mushrooms provide vitamin D₂ (ergocalciferol) in variable amounts. Mushrooms with enhanced levels of vitamin D₂from being exposed to ultraviolet light under controlled conditions are also available.

Fortified foods provide most of the vitamin D in the American diet. 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. 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. Maximum levels of added vitamin D are specified by law.

Several food sources of vitamin D are listed in Table.

Table: Selected Food Sources of Vitamin D

Food	IUs per serving*	Percent DV**
Cod liver oil, 1 tablespoon	1,360	340
Salmon (sockeye), cooked, 3 ounces	794	199
Mushrooms that have been exposed to ultraviolet light to increase vitamin D, 3 ounces (not yet commonly available)	400	100
Mackerel, cooked, 3 ounces	388	97
Tuna fish, canned in water, drained, 3 ounces	154	39
Milk, nonfat, reduced fat, and whole, vitamin D-fortified, 1 cup	115-124	29-31
Orange juice fortified with vitamin D, 1 cup (check product labels, as amount of added vitamin D varies)	100	25
Yogurt, fortified with 20% of the DV for vitamin D, 6 ounces (more heavily fortified yogurts provide more of the DV)	80	20
Margarine, fortified, 1 tablespoon	60	15
Sardines, canned in oil, drained, 2 sardines	46	12
Liver, beef, cooked, 3.5 ounces	46	12
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)	40	10
Egg, 1 whole (vitamin D is found in yolk)	25	6
Cheese, Swiss, 1 ounce	6	2
*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.

Sun exposure

Most people meet their vitamin D needs through exposure to sunlight. 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. 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. 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; in far northern latitudes, this reduced intensity lasts for up to 6 months. In the United States, latitudes below 34 degrees north (a line between Los Angeles and Columbia, South Carolina) allow for cutaneous production of vitamin D throughout the year.

Complete cloud cover reduces UV energy by 50%; shade (including that produced by severe pollution) reduces it by 60%. UVB radiation does not penetrate glass, so exposure to sunshine indoors through a window does not produce vitamin D. 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. 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. 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 and UV radiation from tanning beds. 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. Lifetime cumulative UV damage to skin is also largely responsible for some age-associated 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.

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. 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. 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. Both forms (as well as vitamin D in foods and from cutaneous synthesis) effectively raise serum 25(OH)D levels.

Vitamin D May Treat Or Prevent Allergy To Common Mold

Research conducted by Dr. Jay Kolls, Professor and Chair of Genetics at LSU Health Sciences Center New Orleans, and colleagues, has found that vitamin D may be an effective therapeutic agent to treat or prevent allergy to a common mold that can complicate asthma and frequently affects patients with Cystic Fibrosis. The work was scheduled to be published online August 16, 2010, ahead of the print edition of the September 2010 issue of the Journal of Clinical Investigation. 

The environmental mold, Aspergillus fumigatus, is one of the most prevalent fungal organisms inhaled by people. In the vast majority, it is not associated with disease. However, in asthmatics and in patients with Cystic Fibrosis (CF), it can cause significant allergic symptoms. Up to 15% of CF patients develop a severe allergic response called Allergic Bronchopulmonary Aspergillosis (ABPA). Since the mold is so common, the researchers wanted to identify the factors that determine why only a subset of patients develop the allergy and what factors regulate tolerance or sensitization to the mold resulting in the development of ABPA. To gain insights, the group studied two groups of patients with CF. Both groups were colonized with A. Fumigatus, but only one had ABPA. 

The researchers focused on Th2 cells - the hormonal messengers of T-helper cells that produce an allergic response. They found that a protein called OX40L was critical in driving Th2 responses to A. fumigatus in the CD4+T cells isolated from patients with ABPA and that this group had a much greater Th2 responses to A. Fumigatus. The CD4+T cells from the group of patients that did not have ABPA had higher levels of the proteins, FoxP3 and TGF-ß, critical to the development of allergen tolerance. The researchers discovered that heightened Th2 reactivity in the ABPA group correlated with a lower average blood level of vitamin D. 

"We found that adding vitamin D not only substantially reduced the production of the protein driving an allergic response, but it also increased production of the proteins that promote tolerance," notes Dr. Jay Kolls, Professor and Chair of Genetics at LSU Health Sciences Center New Orleans. 

According to the National Institutes of Health, Cystic fibrosis (CF) is the most common, fatal genetic disease in the United States. About 30,000 people in the United States have the disease. CF causes the body to produce thick, sticky mucus that clogs the lungs, leads to infection, and blocks the pancreas, which stops digestive enzymes from reaching the intestine where they are required in order to digest food. It is estimated that about 70,000 people worldwide have the disease. 

Recent research has suggested that low levels of vitamin D may contribute to heart disease, a higher risk of diabetes, certain cancers, and depression as well as asthma, colds, and other respiratory disorders. 

"Our study provides further evidence that vitamin D appears to be broadly associated with human health," notes Dr. Jay Kolls, Professor and Chair of Genetics at LSU Health Sciences Center New Orleans. "The next step in our research is to conduct a clinical trial to see if vitamin D can be used to treat or prevent this complication of asthma and Cystic Fibrosis." 

Source: Louisiana State University Health Sciences Center 
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