Vitamin D

Vitamin D
Vitamin D

What is Vitamin D

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. Vitamin D obtained from sun exposure, food, and supplements is biologically inert and must undergo two hydroxylations in the body for activation 4). The first occurs in the liver and converts vitamin D to 25-hydroxyvitamin 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 5).

Vitamin D is a nutrient found in some foods that is needed for health and to maintain strong bones. It does so by helping the body absorb calcium (one of bone’s main building blocks) from food and supplements. People who get too little vitamin D may develop soft, thin, and brittle bones, a condition known as rickets in children and osteomalacia in adults.

Vitamin D is important to the body in many other ways as well. Muscles need it to move, for example, nerves need it to carry messages between the brain and every body part, and the immune system needs vitamin D to fight off invading bacteria and viruses. Together with calcium, vitamin D also helps protect older adults from osteoporosis. Vitamin D is found in cells throughout the body.

Vitamin D promotes calcium absorption in the gut and maintains adequate serum calcium and phosphate concentrations to enable normal mineralization of bone and to prevent hypocalcemic tetany. It is also needed for bone growth and bone remodeling by osteoblasts and osteoclasts 6), 7). Without sufficient vitamin D, bones can become thin, brittle, or misshapen. Vitamin D sufficiency prevents rickets in children and osteomalacia in adults 8). Together with calcium, vitamin D also helps protect older adults from osteoporosis.

vitamin D functions

Vitamin D has other roles in the body, including modulation of cell growth, neuromuscular and immune function, and reduction of inflammation 9), 10), 11). Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D 12). Many cells have vitamin D receptors, and some convert 25(OH)D to 1,25(OH)2D.

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 13) and has a fairly long circulating half-life of 15 days 14). 25(OH)D functions as a biomarker of exposure, but it is not clear to what extent 25(OH)D levels also serve as a biomarker of effect (i.e., relating to health status or outcomes) 15). Serum 25(OH)D levels do not indicate the amount of vitamin D stored in body tissues.

In contrast to 25(OH)D, 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 16). Levels of 1,25(OH)2D do not typically decrease until vitamin D deficiency is severe 17), 18).

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, and cut points have not been developed by a scientific consensus process. Based on its review of data of vitamin D needs, a committee of the Institute of Medicine concluded that persons are at risk of vitamin D deficiency at serum 25(OH)D concentrations <30 nmol/L (<12 ng/mL). Some are potentially at risk for inadequacy at levels ranging from 30–50 nmol/L (12–20 ng/mL). Practically all people are sufficient at levels ≥50 nmol/L (≥20 ng/mL); the committee stated that 50 nmol/L is the serum 25(OH)D level that covers the needs of 97.5% of the population. Serum concentrations >125 nmol/L (>50 ng/mL) are associated with potential adverse effects 19) (Table 1).

Table 1: Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health* 20)
nmol/L**ng/mL*Health status
<30<12Associated with vitamin D deficiency, leading to rickets
in infants and children and osteomalacia in adults
30 to <5012 to <20Generally considered inadequate for bone and overall health
in healthy individuals
≥50≥20Generally considered adequate for bone and overall health
in healthy individuals
>125>50Emerging evidence links potential adverse effects to such
high levels, particularly >150 nmol/L (>60 ng/mL)

* Serum concentrations of 25(OH)D are reported in both nanomoles per liter (nmol/L) and nanograms per milliliter (ng/mL).
** 1 nmol/L = 0.4 ng/mL

An additional complication in assessing vitamin D status is in the actual measurement of serum 25(OH)D concentrations. Considerable variability exists among the various assays available (the two most common methods being antibody based and liquid chromatography based) and among laboratories that conduct the analyses 21), 22), 23). This means that compared with the actual concentration of 25(OH)D in a sample of blood serum, a falsely low or falsely high value may be obtained depending on the assay or laboratory used 24). A standard reference material for 25(OH)D became available in July 2009 that permits standardization of values across laboratories and may improve method-related variability 25), 26).

vitamin D production

How much vitamin D do you need ?

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) 27). 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 28).

The FNB established an RDA for vitamin D representing a daily intake that is sufficient to maintain bone health and normal calcium metabolism in healthy people. RDAs for vitamin D are listed in both International Units (IUs) and micrograms (mcg); the biological activity of 40 IU is equal to 1 mcg (Table 2). Even though sunlight may be a major source of vitamin D for some, the vitamin D RDAs are set on the basis of minimal sun exposure 29).

Table 2 : The amount of vitamin D you need each day depends on your age. Average daily recommended amounts from the Food and Nutrition Board (a national group of experts) for different ages are listed below in International Units (IU):

Life StageRecommended Amount
Birth to 12 months400 IU
Children 1–13 years600 IU
Teens 14–18 years600 IU
Adults 19–70 years600 IU
Adults 71 years and older800 IU
Pregnant and breastfeeding women600 IU

What foods provide vitamin D ?

Very few foods naturally have vitamin D.

The flesh of fatty fish (such as salmon, tuna, and mackerel) and fish liver oils are among the best sources 30), 31). 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 and its metabolite 25(OH)D3 32). Some mushrooms provide vitamin D2 in variable amounts 33), 34). Mushrooms with enhanced levels of vitamin D2 from being exposed to ultraviolet light under controlled conditions are also available.

The U.S. Department of Agriculture’s (USDA’s) Nutrient Database website 35) lists the nutrient content of many foods with vitamin D arranged by nutrient content 36) and by food name 37). A growing number of foods are being analyzed for vitamin D content. Simpler and faster methods to measure vitamin D in foods are needed, as are food standard reference materials with certified values for vitamin D to ensure accurate measurements 38).

Fortified foods provide most of the vitamin D in the American diet 39), 40). For example, almost all of the U.S. milk supply is voluntarily fortified with 100 IU/cup 41). (In Canada, milk is fortified by law with 35–40 IU/100 mL, as is margarine at ≥530 IU/100 g.) In the 1930s, a milk fortification program was implemented in the United States to combat rickets, then a major public health problem 42). 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, margarine and other food products.

Both the United States and Canada mandate the fortification of infant formula with vitamin D: 40–100 IU/100 kcal in the United States and 40–80 IU/100 kcal in Canada 43).

Fortified foods provide most of the vitamin D in American diets.

  • Fatty fish such as salmon, tuna, and mackerel are among the best sources.
  • Beef liver, cheese, and egg yolks provide small amounts.
  • Mushrooms provide some vitamin D. In some mushrooms that are newly available in stores, the vitamin D content is being boosted by exposing these mushrooms to ultraviolet light.
  • Almost all of the U.S. milk supply is fortified with 400 IU of vitamin D per quart. But foods made from milk, like cheese and ice cream, are usually not fortified.
  • Vitamin D is added to many breakfast cereals and to some brands of orange juice, yogurt, margarine, and soy beverages; check the labels.

Table 3: Selected Food Sources of Vitamin D

FoodIUs per serving*Percent DV**
Cod liver oil, 1 tablespoon1,360340
Swordfish, cooked, 3 ounces566142
Salmon (sockeye), cooked, 3 ounces447112
Tuna fish, canned in water, drained, 3 ounces15439
Orange juice fortified with vitamin D, 1 cup (check product labels, as amount of added vitamin D varies)13734
Milk, nonfat, reduced fat, and whole, vitamin D-fortified, 1 cup115-12429-31
Yogurt, fortified with 20% of the DV for vitamin D, 6 ounces (more heavily fortified yogurts provide more of the DV)8020
Margarine, fortified, 1 tablespoon6015
Sardines, canned in oil, drained, 2 sardines4612
Liver, beef, cooked, 3 ounces4211
Egg, 1 large (vitamin D is found in yolk)4110
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)4010
Cheese, Swiss, 1 ounce62

* IUs = International Units.
** DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration to help consumers compare the nutrient contents among products within the context of a total daily diet. The DV for vitamin D is currently set at 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, but foods providing lower percentages of the DV also contribute to a healthful diet.

[Source 44)]

Animal-based foods can provide some vitamin D in the form of 25(OH)D, which appears to be approximately five times more potent than the parent vitamin in raising serum 25(OH)D concentrations 45). One study finds that taking into account the serum 25(OH)D content of beef, pork, chicken, turkey, and eggs can increase the estimated levels of vitamin D in the food from two to 18 times, depending upon the food 46). At the present time, the USDA’s Nutrient Database does not include 25(OH)D when reporting the vitamin D content of foods. Actual vitamin D intakes in the U.S. population may be underestimated for this reason.

Can you get vitamin D from the sun ?

Most people meet at least some of their vitamin D needs through exposure to sunlight 47), 48). Ultraviolet (UV) B radiation with a wavelength of 290–320 nanometers penetrates uncovered skin and converts cutaneous 7-dehydrocholesterol to previtamin D3, which in turn becomes vitamin D3 49). Season, time of day, length of day, cloud cover, smog, skin melanin content, and sunscreen are among the factors that affect UV radiation exposure and vitamin D synthesis 50). Perhaps surprisingly, geographic latitude does not consistently predict average serum 25(OH)D levels in a population. Ample opportunities exist to form vitamin D (and store it in the liver and fat) from exposure to sunlight during the spring, summer, and fall months even in the far north latitudes 51).

Complete cloud cover reduces UV energy by 50%; shade (including that produced by severe pollution) reduces it by 60% 52). UVB radiation does not penetrate glass, so exposure to sunshine indoors through a window does not produce vitamin D 53). Sunscreens with a sun protection factor (SPF) 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 54), 55). Therefore, 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 56), 57). Individuals with limited sun exposure need to include good sources of vitamin D in their diet or take a supplement to achieve recommended levels of intake.

Despite the importance of the sun for vitamin D synthesis, it is prudent to limit exposure of skin to sunlight 58) and UV radiation from tanning beds 59). 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 60). Lifetime cumulative UV damage to skin is also largely responsible for some age-associated dryness and other cosmetic changes. The American Academy of Dermatology advises that photoprotective measures be taken, including the use of sunscreen, whenever one is exposed to the sun 61). Assessment of vitamin D requirements cannot address the level of sun exposure because of these public health concerns about skin cancer, and there are no studies to determine whether UVB-induced synthesis of vitamin D can occur without increased risk of skin cancer 62).

The body makes vitamin D when skin is directly exposed to the sun, and most people meet at least some of their vitamin D needs this way. Skin exposed to sunshine indoors through a window will not produce vitamin D. Cloudy days, shade, and having dark-colored skin also cut down on the amount of vitamin D the skin makes.

However, despite the importance of the sun to vitamin D synthesis, it is prudent to limit exposure of skin to sunlight in order to lower the risk for skin cancer. When out in the sun for more than a few minutes, wear protective clothing and apply sunscreen with an SPF (sun protection factor) of 15 or more. Tanning beds also cause the skin to make vitamin D, but pose similar risks for skin cancer.

People who avoid the sun or who cover their bodies with sunscreen or clothing should include good sources of vitamin D in their diets or take a supplement. Recommended intakes of vitamin D are set on the assumption of little sun exposure.

What kinds of vitamin D dietary supplements are available ?

Vitamin D is found in supplements (and fortified foods) in two different forms: D2 (ergocalciferol) and D3 (cholecalciferol). Both increase vitamin D in the blood.

In supplements and fortified foods, vitamin D is available in two forms, D2 (ergocalciferol) and D3 (cholecalciferol) that differ chemically only in their side-chain structure. 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 63). The two forms have traditionally been regarded as equivalent based on their ability to cure rickets and, indeed, most steps involved in the metabolism and actions of vitamin D2 and vitamin D3 are identical. Both forms (as well as vitamin D in foods and from cutaneous synthesis) effectively raise serum 25(OH)D levels 64). Firm conclusions about any different effects of these two forms of vitamin D cannot be drawn. However, it appears that at nutritional doses vitamins D2 and D3 are equivalent, but at high doses vitamin D2 is less potent.

The American Academy of Pediatrics (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 65). 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 66). 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. However, this latter recommendation (issued November 2008) needs to be reevaluated in light of the Food and Nutrition Board’s vitamin D RDA of 600 IU/day for children and adolescents (issued November 2010 and which previously was an AI of 200 IU/day).

Are you getting enough vitamin D ?

Because vitamin D can come from sun, food, and supplements, the best measure of one’s vitamin D status is blood levels of a form known as 25-hydroxyvitamin D. Levels are described in either nanomoles per liter (nmol/L) or nanograms per milliliter (ng/mL), where 1 nmol/L = 0.4 ng/mL.

In general, levels below 30 nmol/L (12 ng/mL) are too low for bone or overall health, and levels above 125 nmol/L (50 ng/mL) are probably too high. Levels of 50 nmol/L or above (20 ng/mL or above) are sufficient for most people.

By these measures, some Americans are vitamin D deficient and almost no one has levels that are too high. In general, young people have higher blood levels of 25-hydroxyvitamin D than older people and males have higher levels than females. By race, non-Hispanic blacks tend to have the lowest levels and non-Hispanic whites the highest. The majority of Americans have blood levels lower than 75 nmol/L (30 ng/mL).

Certain other groups may not get enough vitamin D:

  • Breastfed infants, because human milk is a poor source of the nutrient. Breastfed infants should be given a supplement of 400 IU of vitamin D each day.
  • Older adults, because their skin doesn’t make vitamin D when exposed to sunlight as efficiently as when they were young, and their kidneys are less able to convert vitamin D to its active form.
  • People with dark skin, because their skin has less ability to produce vitamin D from the sun.
  • People with disorders such as Crohn’s disease or celiac disease who don’t handle fat properly, because vitamin D needs fat to be absorbed.
  • Obese people, because their body fat binds to some vitamin D and prevents it from getting into the blood.

What happens if you don’t get enough vitamin D ?

People can become deficient in vitamin D because they don’t consume enough or absorb enough from food, their exposure to sunlight is limited, or their kidneys cannot convert vitamin D to its active form in the body. In children, vitamin D deficiency causes rickets, where the bones become soft and bend. It’s a rare disease but still occurs, especially among African American infants and children. In adults, vitamin D deficiency leads to osteomalacia, causing bone pain and muscle weakness.

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 25(OH)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, ovo-vegetarianism, and veganism 67).

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 68). In the late 19th and early 20th centuries, German physicians noted that consuming 1–3 teaspoons/day of cod liver oil could reverse rickets 69). The fortification of milk with vitamin D beginning in the 1930s has made rickets a rare disease in the United States, although it is still reported periodically, particularly among African American infants and children 70), 71), 72).

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 73). 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 74), 75). 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.

In adults, vitamin D deficiency can lead to osteomalacia, resulting in weak bones 76), 77). 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 is difficult. For many people, consuming vitamin D-fortified foods and, arguably, being exposed to some 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 ordinarily be met by human milk alone 78), 79), which provides <25 IU/L to 78 IU/L 80). (The vitamin D content of human milk is related to the mother’s vitamin D status, so mothers who supplement with high doses of vitamin D may have correspondingly high levels of this nutrient in their milk 81).) A review of reports of nutritional rickets found that a majority of cases occurred among young, breastfed African Americans 82). A survey of Canadian pediatricians found the incidence of rickets in their patients to be 2.9 per 100,000; almost all those with rickets had been breast fed 83). While the sun is a potential source of vitamin D, the AAP advises keeping infants out of direct sunlight and having them wear protective clothing and sunscreen 84). As noted earlier, the AAP recommends that exclusively and partially breastfed infants be supplemented with 400 IU of vitamin D per day 85), the RDA for this nutrient during infancy.

  • Older adults

Older adults are at increased risk of developing vitamin D insufficiency in part because, as they age, skin cannot synthesize vitamin D as efficiently, they are likely to spend more time indoors, and they may have inadequate intakes of the vitamin 86). As many as half of older adults in the United States with hip fractures could have serum 25(OH)D levels <30 nmol/L (<12 ng/mL) 87).

  • People with limited sun exposure

Homebound individuals, women who wear long robes and head coverings for religious reasons, and people with occupations that limit sun exposure are unlikely to obtain adequate vitamin D from sunlight 88), 89). Because the extent and frequency of use of sunscreen are unknown, the significance of the role that sunscreen may play in reducing vitamin D synthesis is unclear 90). Ingesting RDA levels of vitamin D from foods and/or supplements will provide these individuals with adequate amounts of this nutrient.

  • People with dark skin

Greater amounts of the pigment melanin in the epidermal layer result in darker skin and reduce the skin’s ability to produce vitamin D from sunlight 91). Various reports consistently show lower serum 25(OH)D levels in persons identified as black compared with those identified as white. It is not clear that lower levels of 25(OH)D for persons with dark skin have significant health consequences. Those of African American ancestry, for example, have reduced rates of fracture and osteoporosis compared with Caucasians (see section below on osteoporosis). Ingesting RDA levels of vitamin D from foods and/or supplements will provide these individuals with adequate amounts of this nutrient.

  • People with inflammatory bowel disease and other conditions causing fat malabsorption

Because vitamin D is a fat-soluble vitamin, its absorption depends on the gut’s ability to absorb dietary fat. Individuals who have a reduced ability to absorb dietary fat might require vitamin D supplementation 92). Fat malabsorption is associated with a variety of medical conditions, including some forms of liver disease, cystic fibrosis, celiac disease, and Crohn’s disease, as well as ulcerative colitis when the terminal ileum is inflamed 93), 94), 95). In addition, people with some of these conditions might have lower intakes of certain foods, such as dairy products fortified with vitamin D.

  • People who are obese or who have undergone gastric bypass surgery

A body mass index ≥30 is associated with lower serum 25(OH)D levels compared with non-obese individuals; people who are obese may need larger than usual intakes of vitamin D to achieve 25(OH)D levels comparable to those of normal weight 96). 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. Obese individuals who have undergone gastric bypass surgery may become vitamin D deficient over time 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 and vitamin D mobilized into the serum from fat stores may not compensate over time 97), 98).

What are some effects of vitamin D on health ?

Vitamin D is being studied for its possible connections to several diseases and medical problems, including diabetes, hypertension, and autoimmune conditions such as multiple sclerosis. Two of them discussed below are bone disorders and some types of cancer.

  • Osteoporosis & Bone disorders

More than 40 million adults in the United States have or are at risk of developing osteoporosis, a disease characterized by low bone mass and structural deterioration of bone tissue that increases bone fragility and significantly increases the risk of bone fractures 99). Osteoporosis is most often associated with inadequate calcium intakes, but insufficient vitamin D contributes to osteoporosis by reducing calcium absorption 100). 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. Adequate storage levels of vitamin D maintain bone strength and might help prevent osteoporosis in older adults, non-ambulatory individuals who have difficulty exercising, postmenopausal women, and individuals on chronic steroid therapy 101).

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. Several medical groups and professional societies support the use of HRT as an option for women who are at increased risk of osteoporosis or fractures 102), 103), 104). Such women should discuss this matter with their health care providers.

Most supplementation trials of the effects of vitamin D on bone health also include calcium, so it is difficult to isolate the effects of each nutrient. Among postmenopausal women and older men, supplements of both vitamin D and calcium result in small increases in bone mineral density throughout the skeleton. They also help to reduce fractures in institutionalized older populations, although the benefit is inconsistent in community-dwelling individuals 105), 106), 107). Vitamin D supplementation alone appears to have no effect on risk reduction for fractures nor does it appear to reduce falls among the elderly 108), 109), 110); one widely-cited meta-analysis suggesting a protective benefit of supplemental vitamin D against falls 111) has been severely critiqued 112). However, a large study of women aged ≥69 years followed for an average of 4.5 years found both lower (<50 nmol/L [<20 ng/mL]) and higher(≥75 nmol/L [≥30 ng/mL]) 25(OH)D levels at baseline to be associated with a greater risk of frailty 113). 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.

As they get older, millions of people (mostly women, but men too) develop, or are at risk of, osteoporosis, where bones become fragile and may fracture if one falls. It is one consequence of not getting enough calcium and vitamin D over the long term. Supplements of both vitamin D3 (at 700–800 IU/day) and calcium (500–1,200 mg/day) have been shown to reduce the risk of bone loss and fractures in elderly people aged 62–85 years. Men and women should talk with their health care providers about their needs for vitamin D (and calcium) as part of an overall plan to prevent or treat osteoporosis.

  • 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 may have 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 114), 115), 116). Studies do not consistently show a protective or no effect, however. One study of Finnish smokers, for example, found that subjects in the highest quintile of baseline vitamin D status had a threefold higher risk of developing pancreatic cancer 117). A recent review found an increased risk of pancreatic cancer associated with high levels of serum 25(OH)D (≥100 nmol/L or ≥40 ng/mL) 118).

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 119). 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 120). 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 with women taking a placebo 121). The small number of cancers (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 (1988–1994), in which total cancer mortality was found to be unrelated to baseline vitamin D status 122). However, colorectal cancer mortality was inversely related to serum 25(OH)D concentrations. A large observational study with participants from 10 western European countries also found a strong inverse association between prediagnostic 25(OH)D concentrations and risk of colorectal cancer 123).

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 124), 125). Taken together, however, studies to date do not support a role for vitamin D, with or without calcium, in reducing the risk of cancer 126).

Can vitamin D reduce your risk of prostate cancer ? It’s too early to say, but it’s a possibility that requires additional study 127).. Vitamin D has an important role in regulating cell growth. Laboratory experiments suggest that it helps prevent the unrestrained cell multiplication that characterizes cancer by reducing cell division, restricting tumor blood supply (angiogenesis), increasing the death of cancer cells (apoptosis), and limiting the spread of cancer cells (metastasis). Like many human tissues, the prostate has an abundant supply of vitamin D receptors. And, like some other tissues, it also contains enzymes that convert biologically inactive 25(OH)D into the active form of the vitamin, 1,25(OH)2D. These enzymes are much more active in normal prostate cells than in prostate cancer cells.

  • Other conditions

A growing body of research suggests that vitamin D might play some role in the prevention and treatment of type 1 128) and type 2 diabetes 129), hypertension 130), glucose intolerance 131), multiple sclerosis 132), and other medical conditions 133), 134). However, most evidence for these roles comes from in vitro, animal, and epidemiological studies, not the randomized clinical trials considered to be more definitive 135). Until such trials are conducted, the implications of the available evidence for public health and patient care will be debated. One meta-analysis found use of vitamin D supplements to be associated with a statistically significant reduction in overall mortality from any cause 136), 137), but a reanalysis of the data found no association 138). A systematic review of these and other health outcomes related to vitamin D and calcium intakes, both alone and in combination, was published in August 2009 139).

Vitamin D and Cardiovascular Disease

Vitamin D may play an important role in vascular health. Osteoporosis is associated with an increased risk of coronary artery disease, and low blood levels of vitamin D have been linked to increased coronary artery calcification. Although animal studies suggest that vitamin D has a role in regulating blood pressure, a 2005 Harvard analysis found no link between the consumption of vitamin D and human hypertension. Still, low levels of the vitamin appear related to an increased risk of stroke and congestive heart failure; and a study found that supplements reduce inflammation in patients with congestive heart failure 140). The role vitamin D may play in developing high blood pressure and heart disease is less clear 141). Vitamin D deficiency may be linked to heart disease and a higher risk of high blood pressure (hypertension). However, more research is needed. It’s too early to say whether too little vitamin D causes high blood pressure — or whether vitamin D supplements may have any role in the treatment of high blood pressure 142), 143).


Vitamin D and Multiple Sclerosis 144)

A study conducted by researchers at the University of Oxford and another conducted at the New Jersey Medical School have suggested that maintaining adequate levels of vitamin D may have a protective effect and lower the risk of developing multiple sclerosis (MS).

Another study conducted at Maastricht University in the Netherlands and others suggest that for people who already have MS, vitamin D may lessen the frequency and severity of their symptoms. More research is needed to assess these findings.

When a person has MS, his or her immune system attacks the coating that protects the nerve cells. Research suggests that a connection between vitamin D and MS could be tied to the positive effects vitamin D has on the immune system.

The link between vitamin D and MS is strengthened by the association between sunlight and the risk of MS. The farther away from the equator a person lives, the higher the risk of MS. Sunlight is the body’s most efficient source for vitamin D — suggesting that exposure to sunlight may offer protection from MS. In addition, in studies of a group of nurses, the risk of developing MS was substantially less for women taking 400 international units (IUs) or more of vitamin D a day.

Screening for vitamin D deficiency is important for African-Americans and other ethnic groups with dark skin, due to decreased natural production of vitamin D from sun exposure.

The Institute of Medicine recommends 600 IUs of vitamin D a day for adults ages 19 to 70. The recommendation increases to 800 IUs a day for adults age 71 and older.

Some doctors question whether these levels are adequate and think that getting more vitamin D would benefit many people. However, the Institute of Medicine recommends that adults avoid taking more than 4,000 IUs a day.

If you are diagnosed with vitamin D deficiency, it may be appropriate to use up to 50,000 IUs weekly for up to three months until your vitamin D levels become normal, and then switch to a maintenance dose

Very large doses of vitamin D over an extended period can result in toxicity. Signs and symptoms include nausea, vomiting, constipation, poor appetite, weakness and weight loss. In addition, vitamin D toxicity can lead to elevated levels of calcium in your blood, which can result in kidney stones.

Can Vitamin D prevent Alzheimer’s & Dementia ? 145)

Maybe. But it’s too soon to say for certain. New research suggests people with very low levels of vitamin D in their blood, known as vitamin D deficiency, are more likely to develop Alzheimer’s disease and other forms of dementia.

For example, a large 2014 study published in Neurology showed people with extremely low blood levels of vitamin D were more than twice as likely to develop Alzheimer’s disease or other types of dementia than those with normal vitamin D levels. But it’s important to point out that the association between vitamin D deficiency and dementia risk is only observational at this point. More research is needed to show cause and effect.

Vitamin D is vital to bone metabolism, calcium absorption and other metabolic processes in the body. Its role in brain function, cognition and the aging process is still unclear. Some studies suggest vitamin D may be involved in a variety of processes related to cognition, but more research is needed to better understand this relationship.

Most of our vitamin D is produced within the body in response to sunlight exposure. Vitamin D occurs naturally in only a few foods, including fatty fish and fish liver oils. The biggest dietary sources of vitamin D are fortified foods, such as milk, breakfast cereals and orange juice. Vitamin D supplements are also widely available.

Vitamin D deficiency is common among older adults, partially because the skin’s ability to synthesize vitamin D from the sun decreases with age.

It’s too early to recommend increasing your daily dose of vitamin D in hopes of preventing dementia or Alzheimer’s disease. But maintaining healthy vitamin D levels can’t hurt and may pay off in other ways, such as reducing the risk of osteoporosis. According to the Institute of Medicine, the recommended daily dose of Vitamin D is 600 International Units (IU) per day for adults under age 70 and 800 IU per day for adults over 70.

More studies are needed to determine if vitamin D deficiency is indeed a risk factor for Alzheimer’s disease and dementia, and if treatment with vitamin D supplements or sun exposure can prevent or treat these conditions.

Can Excessive Vitamin D be harmful ?

Yes, when amounts in the blood become too high. Signs of toxicity include nausea, vomiting, poor appetite, constipation, weakness, and weight loss. And by raising blood levels of calcium, too much vitamin D can cause confusion, disorientation, and problems with heart rhythm. Excess vitamin D can also damage the kidneys.

Vitamin D toxicity can cause non-specific symptoms such as anorexia, weight loss, polyuria, and heart arrhythmias. More seriously, it can also raise blood levels of calcium which leads to vascular and tissue calcification, with subsequent damage to the heart, blood vessels, and kidneys 146). The use of supplements of both calcium (1,000 mg/day) and vitamin D (400 IU) by postmenopausal women was associated with a 17% increase in the risk of kidney stones over 7 years in the Women’s Health Initiative 147). A serum 25(OH)D concentration consistently >500 nmol/L (>200 ng/mL) is considered to be potentially toxic 148).

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 149). In addition, thermal activation of previtamin D3 in the skin gives rise to various non-vitamin D forms that limit formation of vitamin D3 itself. Some vitamin D3 is also converted to nonactive forms 150). Intakes of vitamin D from food that are high enough to cause toxicity are very unlikely. Toxicity is much more likely to occur from high intakes of dietary supplements containing vitamin D.

Long-term intakes above the UL increase the risk of adverse health effects 151) (Table 4). Most reports suggest a toxicity threshold for vitamin D of 10,000 to 40,000 IU/day and serum 25(OH)D levels of 500–600 nmol/L (200–240 ng/mL). While symptoms of toxicity are unlikely at daily intakes below 10,000 IU/day, the FNB pointed to emerging science from national survey data, observational studies, and clinical trials suggesting that even lower vitamin D intakes and serum 25(OH)D levels might have adverse health effects over time. The FNB concluded that serum 25(OH)D levels above approximately 125–150 nmol/L (50–60 ng/mL) should be avoided, as even lower serum levels (approximately 75–120 nmol/L or 30–48 ng/mL) are associated with increases in all-cause mortality, greater risk of cancer at some sites like the pancreas, greater risk of cardiovascular events, and more falls and fractures among the elderly. The FNB committee cited research which found that vitamin D intakes of 5,000 IU/day achieved serum 25(OH)D concentrations between 100–150 nmol/L (40–60 ng/mL), but no greater. Applying an uncertainty factor of 20% to this intake value gave a UL of 4,000 IU which the FNB applied to children aged 9 and older and adults, with corresponding lower amounts for younger children.

Table 4: Tolerable Upper Intake Levels (ULs) for Vitamin D 152)
0–6 months1,000 IU
(25 mcg)
1,000 IU
(25 mcg)
7–12 months1,500 IU
(38 mcg)
1,500 IU
(38 mcg)
1–3 years2,500 IU
(63 mcg)
2,500 IU
(63 mcg)
4–8 years3,000 IU
(75 mcg)
3,000 IU
(75 mcg)
9–18 years4,000 IU
(100 mcg)
4,000 IU
(100 mcg)
4,000 IU
(100 mcg)
4,000 IU
(100 mcg)
19+ years4,000 IU
(100 mcg)
4,000 IU
(100 mcg)
4,000 IU
(100 mcg)
4,000 IU
(100 mcg)

The upper limit for vitamin D is 1,000 to 1,500 IU/day for infants, 2,500 to 3,000 IU/day for children 1-8 years, and 4,000 IU/day for children 9 years and older, adults, and pregnant and lactating teens and women. Vitamin D toxicity almost always occurs from overuse of supplements. Excessive sun exposure doesn’t cause vitamin D poisoning because the body limits the amount of this vitamin it produces.

Vitamin D Side Effects and Warnings 153)

Vitamin D is likely safe when taken by mouth in doses of 100 micrograms of vitamin D3 daily (4,000 IU) and when applied to the skin alone or in combination with corticosteroids for up to three months.

Vitamin D is possibly safe when taken by mouth or injected into the muscle in doses of 300,000 IU three times a year for vitamin D deficiency.

Vitamin D may cause allergic skin reactions (inflammation, irritation, rash, and thinning), build-up of calcium in the arteries, changes in cholesterol levels, daytime sleepiness, excessive vitamin D levels, hardening of the arteries, headaches, increased calcium excretion or levels, increased risk of falls and fractures, increased risk of heart attack and stroke, increased risk of high blood pressure during pregnancy, increased risk of urinary tract infection, kidney or urinary stones, muscle pain, respiratory tract infection, and stomach problems (constipation, cramps, diarrhea, upset stomach, and vomiting).

Vitamin D may affect blood sugar levels. Caution is advised in people with diabetes or low blood sugar, and in those taking drugs, herbs, or supplements that affect blood sugar. Blood sugar levels may need to be monitored by a qualified healthcare professional, including a pharmacist, and medication adjustments may be necessary.

Vitamin D may affect blood pressure. Caution is advised in people with blood pressure disorders or those taking drugs or herbs and supplements that affect blood pressure.

Use cautiously in people with headaches, heart disease, immune disorders (including lymph cancer and tuberculosis), kidney disease, liver disease, lung disorders, musculoskeletal disorders, skin disorders, stomach disorders, and thyroid disorders.

Use cautiously in pregnant women at risk of high blood pressure associated with pregnancy.

Use cautiously in breastfeeding women.

Avoid in people with known allergy or sensitivity to vitamin D, any similar compounds, or any part of the formula.

Avoid in people with abnormal calcium excretion or levels.

Pregnancy and Breastfeeding

Use cautiously in pregnant women at risk of high blood pressure associated with pregnancy. The recommended adequate intake for pregnant women is the same as for non-pregnant adults. Most prenatal vitamins provide 400 IU of vitamin D daily as cholecalciferol, while high-risk populations may benefit from higher amounts (2,000-4,000 IU daily).

Use cautiously in breastfeeding women. The daily recommended intake for vitamin D during breastfeeding is 400 IU (10 micrograms) daily. Vitamin D2 in doses of 2,000 IU daily or 60,000 IU monthly for three months has been found to be safe and effective. Exclusively breastfed babies may be supplemented with 400-2,000 IU daily.

References   [ + ]