Office of Dietary Supplements – Vitamin D

Introduction A fat-soluble vitamin that is naturally present in very few foods, added to others, and available as a dietary supplement is known as Vitamin D. It is also developed endogenously when ultraviolet rays from sunlight affect the skin and trigger vitamin D synthesis. Vitamin D acquired from sun exposure, food, and supplements is biologically […]

Introduction

A fat-soluble vitamin that is naturally present in very few foods, added to others, and available as a dietary supplement is known as Vitamin D. It is also developed endogenously when ultraviolet rays from sunlight affect the skin and trigger vitamin D synthesis. Vitamin D acquired from sun exposure, food, and supplements is biologically motionless and must undergo two hydroxylations in the body in order to activate. The first happens in the liver and converts vitamin D to 25-hydroxyvitamin D [25(OH)D], also called as calcidiol. The second takes place primarily in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D [1,25(OH)2D], also called as calcitriol

Vitamin D helps in promoting calcium absorption in the gut and maintaining adequate serum calcium and phosphate concentrations for enabling normal mineralization of bone and for the prevention hypocalcemic tetany. For bone growth and bone remodeling it is also required. Bones can become thin, brittle, or misshapen if sufficient vitamin D is not present. Vitamin D sufficiency helps in preventing rickets in children and osteomalacia in adults. In combination with calcium, vitamin D also helps in protecting older adults from osteoporosis.

Other roles played by vitamin D in the body, including modulation of cell growth, neuromuscular and immune function, and reduction of inflammation.

The best indicator of vitamin D status is Serum concentration of 25(OH)D which reflects vitamin D that is produced cutaneously and that obtained from food and supplements 1and has a fairly long circulating half-life of 15 days. The amount of vitamin D stored in body tissues is not indicated by Serum 25(OH)D.

Sources – Vitamin D

Food

Vitamin D is contained in very few foods in nature. Foods such as flesh of fatty fish (such as salmon, tuna, and mackerel) and fish liver oils are among the best sources. Vitamin D is found in small amounts in beef liver, cheese, and egg yolks. In these foods vitamin D is primarily in the shape of vitamin D3 and its metabolite 25(OH)D3. Vitamin D2 is found some mushrooms in variable amounts. Mushrooms having enhanced levels of vitamin D2 from being exposed to ultraviolet light under conditions which are controlled are also available.

Other dairy products which are made from milk, such as cheese and ice cream, are generally not fortified. Ready-to-eat breakfast cereals often carry added vitamin D, which is done by some brands of orange juice, yogurt, margarine and other food products. Plant milk alternatives (such as beverages made from soy, almond, or oats) are often vitamin D fortified to the extent of amount found in fortified cow’s milk (about 100 IU/cup); the Nutrition Facts label will list the actual amount.

Several food sources of vitamin D are listed below.

Table 3: Selected Food Sources of Vitamin D [11]
Food* Micrograms
(mcg) per
serving
IUs* per
serving
Percent
DV**
Cod liver oil, 1 tablespoon 34.0 1,360 170
Trout (rainbow), farmed, cooked, 3 ounces 16.2 645 81
Salmon (sockeye), cooked, 3 ounces 14.2 570 71
Mushrooms, white, raw, sliced, exposed to UV light, 1/2 cup 9.2 366 46
Milk, 2% milkfat, vitamin D fortified, 1 cup 2.9 120 15
Sardines (Atlantic), canned in oil, drained, 2 sardines 1.2 46 6
Soy, almond, and oat milks, vitamin D fortified, various brands, 1 cup 2.5−3.6 100−144 13−18
Ready-to-eat cereal, fortified with 10% of the DV for vitamin D, 1 serving 2.0 80 10
Egg, 1 large, scrambled (vitamin D is in the yolk) 1.1 44 6
Liver, beef, braised, 3 ounces 1.0 42 5
Tuna fish (light), canned in water, drained, 3 ounces 1.0 40 5
Cheese, cheddar, 1 ounce 0.3 12 2
Mushrooms, portabella, raw, diced, 1/2 cup 0.1 4 1
Chicken breast, roasted, 3 ounces 0.1 4 1
Beef, ground, 90% lean, broiled, 3 ounces 0 1.7 0
Broccoli, raw, chopped, 1/2 cup 0 0 0
Carrots, raw, chopped, 1/2 cup 0 0 0
Almonds, dry roasted, 1 ounce 0 0 0
Apple, large 0 0 0
Banana, large 0 0 0
Rice, brown, long-grain, cooked, 1 cup 0 0 0
Whole wheat bread, 1 slice 0 0 0
Lentils, boiled, 1/2 cup 0 0 0
Sunflower seeds, roasted, 1/2 cup 0 0 0
Edamame, shelled, cooked, 1/2 cup 0 0 0

* IUs = International Units.
** DV = Daily Value.

The U.S. Department of Agriculture’s (USDA’s) has listed the content of nutrient of many foods and a comprehensive list of foods is provided carrying vitamin D arranged by nutrient content and by food name. A number of foods evolving are being examined for vitamin D content. Methods which are simpler and faster to measure vitamin D in foods are required, as are food standard reference materials with certified values for vitamin D to ensure accurate measurements

Some vitamin D can be provided in animal based foods 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.

Sun exposure

Through exposure to sunlight some of the vitamin D need is met for most people. Some factors affecting the UV radiation exposure and vitamin D synthesis are Season, time of day, length of day, cloud cover, smog, skin melanin content, and sunscreen. Perhaps surprisingly, average serum 25(OH)D levels in a population in geographic latitude cannot be predicted consistently. Forming vitamin D and storing it in the liver and fat will have abundant opportunities existing from exposure to sunlight during the spring, summer, and fall months even in the far north latitudes.

Clouds that are complete cover decreased UV energy by 50%; shade (including that produced by severe pollution) decreases it by 60%. Glass is not penetrated with UVB radiation, so exposure to sunshine indoors through a window does not produce vitamin D. Vitamin D-producing UV rays are blocked if sunscreens with a sun protection factor (SPF) of 8 or more are used, although in practice people usually do not apply sufficient amounts, cover all sun-exposed skin, or reapply sunscreen regularly. Therefore, some vitamin D likely synthesizes the skin even if it is protected by sunscreen as usually applied.

The factors that are affecting the UV radiation exposure and studies to date on the amount of sun exposure required for maintaining sufficient vitamin D levels make it hard to provide common guidelines. Some vitamin D researchers recommended, for example, that approximately 5–30 minutes of sun exposure between 10 AM and 3 PM at least 6-8 times in a month to the face, arms, legs, or back without sunscreen usually lead to enough vitamin D synthesis and that the moderate usage of commercial tanning beds that emit 2%–6% UVB radiation is also effective. Individuals getting sun exposure which is limited they are required to include good sources of vitamin D in their diet or take a supplement for achieving recommended levels of intake.

Besides the sun for vitamin D synthesis importance, it is advisable for limiting the exposure of skin to sunlight and UV radiation from tanning beds. A carcinogen which is responsible for most of the estimated 1.5 million skin cancers and around 7,000 deaths due to metastatic melanoma that occur annually in the United States is known as UV radiation. Cumulative UV damage for the whole life to skin is also mostly responsible for some dryness which is age related and other cosmetic changes. The American Academy of Dermatology advises that photoprotective precautions should be taken, including the usage of sunscreen, whenever being exposed to the sun. Vitamin D evaluation requirements cannot direct the sun exposure level because of public health concerns about skin cancer; studies to determine whether UVB-induced synthesis of vitamin D can occur without increased risk of skin cancer are not present.

Dietary supplements

Vitamin D is available in supplements and fortified foods in two forms, D2 (ergocalciferol) and D3 (cholecalciferol) that chemically varies only in their side-chain structure. Manufacturing of vitamin D2 is done by the UV irradiation of ergosterol found in yeast, and manufacturing of vitamin D3 is done by the irradiation of 7-dehydrocholesterol from lanolin and the cholesterol’s chemical conversion. The two forms have conventionally been considered as almost equal based on their ability to cure rickets and, in fact, most steps which are involved in the metabolism and actions of vitamin D2 and vitamin D3 are similar. Serum 25(OH)D levels are effectively raised in both forms. The different effects of firm conclusions of these two forms of vitamin D cannot be drawn. However, it appears that vitamins D2 and D3 are similar to each other at nutritional doses, but at high doses vitamin D2 is less powerful.

Vitamin D Intakes and Status

The National Health and Nutrition Examination Survey (NHANES), had estimated vitamin D consumptions from both food and dietary supplements. Average consumption levels for males from foods alone ranged from 204 to 288 IU/day depending on life stage group; for females the average consumption levels range was 144 to 276 IU/day. When considering the usage of dietary supplements, these mean values were significantly increased (37% of the U.S. population used a dietary supplement containing vitamin D.) The most noted increase was found in older women. For women who were aged around 51–70 years, average consumption of vitamin D from foods alone was 156 IU/day, but 404 IU/day with supplements. For women who are above 70 years, the equivalent figures were 180 IU/day to 400 IU/day

Comparison of vitamin D intake estimates from foods and dietary supplements to serum 25(OH)D concentrations is difficult. A reason can be that comparisons can only be done on group average rather than on data which is connected to individuals. Another fact is that vitamin D status is affected by sun exposure; serum 25(OH)D levels are usually higher than would be predicted on the basis of vitamin D consumption alone

Over many years, average serum 25(OH)D concentrations in the United States have slightly reduced among males but not females. This reduction is likely because of simultaneous increases in body weight, decreased milk consumption, and more use of sun protection when outside

Vitamin D Deficiency

The outcome of dietary inadequacy usually is due to nutrient deficiencies, impaired absorption and use, increased requirement, or increased excretion. When usual consumption is lower than suggested levels over time this results in the occurrence of Vitamin D deficiency, 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. Milk allergy, lactose intolerance, ovo-vegetarianism, and veganism are related to vitamin D deficient diets.

The classical vitamin D deficiency diseases are rickets and osteomalacia. Vitamin D deficiency causes rickets in children, a disease classified by a failure of bone tissue to properly mineralize, resulting in soft bones and skeletal deformities. The fortification of milk with vitamin D has made rickets a disease in the United States very rare, although it is still reported from time to time, particularly among African American infants and children.

Extended exclusive breastfeeding without the AAP-suggestion, a significant cause of rickets is the vitamin D supplementation, particularly in dark-skinned infants breastfed by mothers who are not vitamin D replete. Extensive use of sunscreens and placement of children in daycare programs are additional causes of rickets, where outdoor activity and sun exposure is often less. Rickets is also more frequent among immigrants from Asia, Africa, and the Middle East, maybe 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 [1,5]. 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

Vitamin D to be obtained abundant from natural food sources alone is hard. For many people, intakes of vitamin D-fortified foods and, arguably, being exposed to some sunlight are essential to maintain a healthy vitamin D status. In some groups, dietary supplements might be needed to meet the daily requirement for vitamin D.

Breastfed infants

Requirements of Vitamin D cannot typically be met by human milk alone, which gives <25 IU/L to 78 IU/L. content of the vitamin D of human milk is associated with the vitamin D status of mother, so mothers who are using supplements with intake of high doses of vitamin D may have correspondingly high levels of this nutrient in their milk.

Older adults

Risk of developing vitamin D deficiency is increased for adults who are older 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 consumption of the vitamin. 50 percent of older adults in the United States with hip fractures could have serum 25(OH)D levels <30 nmol/L (<12 ng/mL)

People with limited sun exposure

People who are unlikely to obtain sufficient vitamin D from sunlight can be homebound individuals, women who wear long robes and head coverings for religious reasons, and people with occupations that limit sun exposure. Because the magnitude and frequency of using the sunscreen are not known, the importance of the role that is played by the sunscreen in decreasing vitamin D synthesis is not clear. Absorbing RDA levels of vitamin D from foods and/or supplements will help in providing the above mentioned individuals with sufficient amounts of this nutrient.

People with dark skin

Darken skin and reduction in the ability of the skin to develop vitamin D from sunlight results in greater amounts of the pigment melanin in the epidermal layer. Identification of people as black or white has shown in various reports consistently the lower serum 25(OH)D levels in persons. It is not clear that lower levels of 25(OH)D for persons with dark skin have significant health consequences is unclear.

People with inflammatory bowel disease and other conditions causing fat malabsorption

Vitamin D being a fat-soluble vitamin, dietary fat absorption depends on the gut’s ability. Individuals who have a decreased ability for absorption of dietary fat might need supplement of vitamin D. A variety of medical conditions are related with fat malabsorption, 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. Additionally, people having some of these conditions might have lower consumption 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 related with lower serum 25(OH)D levels in comparison with individuals who are not obese; people who are obese may be required to consume larger than usual of vitamin D to achieve 25(OH)D levels comparing to those having normal weight. Skin’s capacity to synthesize vitamin D is not affected by obesity, but greater amounts of subcutaneous fat sequester more of the vitamin and alter its release into the circulation. Obese individuals may become vitamin D deficient over the period of time without a sufficient consumption of this nutrient from food or supplements if they have gone through gastric bypass surgery, 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

Vitamin D and Health

Optimal serum concentrations of 25(OH)D for bone and general health have not been established; they are likely to differ at every part of life, depending on the chosen physiological measures. Also, as mentioned before, while serum 25(OH)D functions as a biomarker of exposure to vitamin D that is from sun, food, and dietary supplements, the magnitude to which such levels serve as a biomarker of effect (i.e., health outcomes) is established unclearly

Moreover, while serum 25(OH)D levels increase in response to increased vitamin D consumption, the connection is non-linear for reasons that are unclear completely. The increase differs, for example, by baseline serum levels and time span of supplementation.

However, the FNB committee that incorporated DRIs for vitamin D extensively assessed a long list of potential health relationships on which suggestions for vitamin D consumptions might be based. These health connections included resistance to chronic diseases, physiological parameters, and functional measures. Exception of estimations which are associated to bone health, the health relationships evaluated were either not supported by sufficient evidence to establish cause and effect, or the disputing nature of the available evidence could not be used to relate health benefits to particular levels of consumption of vitamin D or serum estimates of 25(OH)D with any level of confidence.

Osteoporosis

Around 30 million adults in the United States are having or are at risk of developing osteoporosis, a disease classified by low bone mass and structural diminishing of bone tissue that increases bone fragility and the risk of bone fractures increases significantly. Osteoporosis is most often related with insufficient calcium consumption, but inadequate vitamin D contributes to osteoporosis by reducing calcium absorption. Examples of the effects of vitamin D deficiency are rickets and osteomalacia, osteoporosis is an example of a long-term effect of calcium and vitamin D deficiency. Sufficient storage levels of vitamin D help in maintaining bone strength and might help in the prevention of osteoporosis in older adults, non-ambulatory individuals who have problem in exercising, postmenopausal women, and individuals who are on chronic steroid therapy.

Normal bone is continuously being remodeled. The balance between these processes can change during the menopuase, resulting in more bone being resorbed than rebuilt. Estrogen and progesterone might be able to delay the onset of osteoporosis with the help of hormone therapy.

Calcium is included in most of the supplement trials of the effects of vitamin D on health of bone, so it is hard to isolate the effects of each nutrient. Among postmenopausal women and men who are older, both vitamin D and calcium supplements can give an outcome of small increases in bone mineral density throughout the skeleton. They also help in decreasing fractures in institutionalized older populations, although the advantage is not consistent in community-dwelling individuals. Supplements of Vitamin D alone materializes to have no effect on risk reduction for fractures nor does it appear to decrease falls among the elderly; one widely-cited meta-analysis recommending a protective benefit of supplemental vitamin D against falls has been severely evaluated. However, a large study of women who were aged about 69 years followed for an average of 4.5 years found both lower and higher 25(OH)D levels at baseline to be related with a greater risk of frailty. Healthcare providers should be consulted by women about their requirements 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 provide an indication that vitamin D plays a role for colon, prostate, and breast cancers prevention. Emerging epidemiologic data recommends that vitamin D may have a protective effect against colon cancer, but the data obtained might not be as powerful for a protective effect against prostate and breast cancer, and are variable for cancers at other sites. However, research does not continuously show a protective effect or no effect.

The largest clinical trial to evaluate the effects of vitamin D supplements on the initial prevention of cancer in the general population is the newly issued VITamin D and OmegA-3 TriaL (VITAL). This clinical trial evaluated the effects of supplements of vitamin D (2,000 IU/day), with or without marine omega-3 fatty acids (1,000 mg/day), in comparison to placebo for a median of 5.3 years in 25,871 men aged more than or equal to 50 and women aged more than or equal to 55 with no previous history of cancer, heart attacks, or strokes. Breast, prostate, and colorectal cancer figures did not vary significantly between the groups of vitamin D and placebo. However, candidates who have normal weight had recommended reductions in cancer incidence and mortality in comparison to those who are overweight or obese.

More research is required to determine whether vitamin D deficiency 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. When consumed together, however, research up to date does not support a powerful role for vitamin D, with or without calcium, in decreasing the risk of cancer.

Other conditions

A developing body of research recommends that vitamin D might play some role in the prevention and treatment of some conditions such as type 1 and type 2 diabetes, hypertension, glucose intolerance, multiple sclerosis, and other medical conditions. However, for these roles evidence mostly comes from in vitro, animal, and epidemiological researches, not the randomized clinical trials which are considered to be more definitive. Until such trials are undergone, the inference of the available evidence for public health and patient care will be debated. One meta-analysis found usage of supplements of vitamin D to be related with a statistically significant decrease in overall mortality from any cause, but an analysis of the data when reanalyzed found no association. A systematic evaluation of these and other health results associated to vitamin D and calcium consumption, both alone and in mixture was published in August 2009.

Health Risks from Excessive Vitamin D

Anorexia, weight loss, polyuria, and heart arrhythmias are non-specific symptoms caused in vitamin D toxicity. More seriously, blood levels of calcium can raise which may lead to vascular and tissue calcification, with future damage to the heart, blood vessels, and kidneys. The supplement usage of both calcium (1,000 mg/day) and vitamin D (400 IU) by postmenopausal women was associated with around 16% increase in the risk of kidney stones over the period of 7 years in the Women’s Health Initiative.

Vitamin D toxicity outcomes cannot be because of excessive sun exposure because the sustained heat on the skin is thought to photodegrade previtamin D3 and vitamin D3 as it is formed. Additionally, thermal activation of previtamin D3 in the skin gives rise to different non-vitamin D forms that restrict formation of vitamin D3 itself. Non-active forms can be a conversion of some vitamin D3. Vitamin D consumption is very unlikely from foods that are high enough to cause toxicity. Toxicity is much more likely to happen from high consumptions of dietary supplements having vitamin D.

Long-term consumptions above the UL increase the risk of adverse health effects as mentioned in the  table below

Table 4: Tolerable Upper Intake Levels (ULs) for Vitamin D [1]
Age Male Female Pregnancy Lactation
0–6 months 1,000 IU
(25 mcg)
1,000 IU
(25 mcg)
7–12 months 1,500 IU
(38 mcg)
1,500 IU
(38 mcg)
1–3 years 2,500 IU
(63 mcg)
2,500 IU
(63 mcg)
4–8 years 3,000 IU
(75 mcg)
3,000 IU
(75 mcg)
9–18 years 4,000 IU
(100 mcg)
4,000 IU
(100 mcg)
4,000 IU
(100 mcg)
4,000 IU
(100 mcg)
19+ years 4,000 IU
(100 mcg)
4,000 IU
(100 mcg)
4,000 IU
(100 mcg)
4,000 IU
(100 mcg)

Interactions with Medications

Supplementation of Vitamin D has the potential to interact with different types of medications. These medications taken by individuals on a daily basis should discuss vitamin D consumption with the healthcare providers.

Steroids

Corticosteroid medications such as prednisone often the specified medications to decrease the inflammation, can decrease calcium absorption and impair metabolism of vitamin D. These effects can help in contributing more to the bone loss and the development of osteoporosis related with the long-term use

Other medications

The weight-loss drug orlistat (brand names Xenical® and alliTM) and the cholesterol-lowering drug cholestyramine (brand names Questran®, LoCholest®, and Prevalite®) both can decrease the vitamin D absorption and other fat-soluble vitamins. Phenobarbital and phenytoin (brand name Dilantin®) both are used to prevent and control epileptic seizure and increase the hepatic metabolism of vitamin D to inactive compounds and decrease calcium absorption

Vitamin D and Healthful Diets

Foods should be the main requirement to meet the nutritional needs. Foods presented in nutrient-dense forms have essential vitamins and minerals and also dietary fiber and other substances which are occurring naturally which may have positive health effects. In some cases, fortified foods and dietary supplements may in some situations be useful in providing one or more nutrients that otherwise may be consumed in amounts which are lower than recommended.

A healthy eating pattern is described by Dietary guidelines for Americans is mentioned below:

  • Variety of vegetables, fruits, whole grains, fat-free or low-fat milk and milk products, and oils to be included.

Vitamin D fortified is milk as are many ready-to-eat cereals and some brands of yogurt and orange juice. Small amounts of vitamin D are contained in cheeses naturally.

  • Variation of protein foods, including seafood, lean meats and poultry, eggs, legumes (beans and peas), nuts, seeds, and soy products is included.

Salmon, tuna, and mackerel fatty fish are very good sources of vitamin D. Beef liver and egg yolks also contain small amounts of vitamin D.

  • Restricts saturated and Trans fats, added sugars, and sodium.

Some margarine has added vitamin D.

  • Staying within the daily calorie needs.

 

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