For data on vitamin D and COVID-19, see dietary Supplements in the Time of COVID-19 .
Vitamin D ( besides referred to as “ vitamin d ” ) is a fat-soluble vitamin that is naturally present in a few foods, added to others, and available as a dietary supplement. It is besides produced endogenously when ultraviolet ( UV ) rays from sunlight hit the skin and trigger vitamin D deduction .
Vitamin D obtained from sun exposure, foods, and supplements is biologically inert and must undergo two hydroxylations in the consistency for activation. The first base hydroxylation, which occurs in the liver, converts vitamin D to 25-hydroxyvitamin D [ 25 ( OH ) D ], besides known as “ calcidiol. ” The second hydroxylation occurs primarily in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D [ 1,25 ( OH ) 2D ], besides known as “ calcitriol ” [ 1 ].
Vitamin D promotes calcium absorption in the catgut and maintains adequate serum calcium and phosphate concentrations to enable normal bone mineralization and to prevent hypocalcemic tetany ( involuntary contraction of muscles, leading to cramps and spasms ). It is besides needed for bone increase and bone remodel by osteoblasts and osteoclasts [ 1-3 ]. Without sufficient vitamin D, bones can become thin, brittle, or misshapen. Vitamin D sufficiency prevents rickets in children and osteomalacia in adults. together with calcium, vitamin D besides helps protect older adults from osteoporosis .
Vitamin D has other roles in the body, including reduction of ignition ampere well as intonation of such processes as cell increase, neuromuscular and immune function, and glucose metamorphosis [ 1-3 ]. many genes encoding proteins that regulate cell proliferation, specialization, and apoptosis are modulated in part by vitamin D. Many tissues have vitamin D receptors, and some convert 25 ( OH ) D to 1,25 ( OH ) 2D .
In foods and dietary supplements, vitamin D has two main forms, D2 ( vitamin d ) and D3 ( vitamin d ), that differ chemically lone in their side-chain structures. Both forms are well absorbed in the small intestine. Absorption occurs by elementary passive diffusion and by a mechanism that involves intestinal membrane carrier proteins [ 4 ]. The coincident presence of fatten in the gut enhances vitamin D concentration, but some vitamin D is absorbed even without dietary fat. Neither aging nor fleshiness alters vitamin D absorption from the intestine [ 4 ] .
Serum assiduity of 25 ( OH ) D is presently the main index of vitamin D condition. It reflects vitamin D produced endogenously and that obtained from foods and supplements [ 1 ]. In serum, 25 ( OH ) D has a fairly long circulating half life of 15 days [ 1 ]. Serum concentrations of 25 ( OH ) D are reported in both nanomoles per liter ( nmol/L ) and nanograms per milliliter ( ng/mL ). One nmol/L is equal to 0.4 ng/mL, and 1 ng/mL is equal to 2.5 nmol/L .
Assessing vitamin D condition by measuring serum 25 ( OH ) D concentrations is complicated by the considerable variability of the available assays ( the two most park ones involve antibodies or chromatography ) used by laboratories that conduct the analyses [ 5, 6 ]. As a result, a find can be falsely low or falsely high, depending on the assay used and the lab. The international Vitamin D Standardization Program has developed procedures for standardizing the testing ground measurement of 25 ( OH ) D to improve clinical and public health exercise [ 5, 7-10 ] .
In contrast to 25 ( OH ) D, circulating 1,25 ( OH ) 2D is generally not a commodity indicator of vitamin D status because it has a short circuit half life measured in hours, and serum levels are tightly regulated by parathyroid gland hormone, calcium, and phosphate [ 1 ]. Levels of 1,25 ( OH ) 2D do not typically decrease until vitamin D insufficiency is austere [ 2 ] .
Serum concentrations of 25 ( OH ) D and health
Although 25 ( OH ) D functions as a biomarker of exposure, the extent to which 25 ( OH ) D levels besides serve as a biomarker of consequence on the body ( i, relating to health condition or outcomes ) is not clear [ 1, 3 ] .
Researchers have not definitively identified serum concentrations of 25 ( OH ) D associated with insufficiency ( for example, rickets ), sufficiency for cram health, and overall health. After reviewing data on vitamin D needs, an expert committee of the Food and Nutrition Board ( FNB ) at the National Academies of Sciences, Engineering, and Medicine ( NASEM ) concluded that people are at hazard of vitamin D insufficiency at serum 25 ( OH ) D concentrations less than 30 nmol/L ( 12 ng/mL ; see board 1 for definitions of “ lack ” and “ insufficiency ” ) [ 1 ]. Some people are potentially at gamble of inadequacy at 30 to 50 nmol/L ( 12–20 ng/mL ). Levels of 50 nmol/L ( 20 ng/mL ) or more are sufficient for most people. In contrast, the Endocrine Society stated that, for clinical drill, a serum 25 ( OH ) D assiduity of more than 75 nmol/L ( 30 ng/mL ) is necessary to maximize the effect of vitamin D on calcium, bone, and brawn metabolism [ 11, 12 ]. The FNB committee besides noted that serum concentrations greater than 125 nmol/L ( 50 ng/mL ) can be associated with adverse effects [ 1 ] ( Table 1 ) .
|<30||<12||Associated with vitamin D deficiency, which can lead to rickets in infants and children and osteomalacia in adults|
|30 to <50||12 to <20||Generally considered inadequate for bone and overall health in healthy individuals|
|≥50||≥20||Generally considered adequate for bone and overall health in healthy individuals|
|>125||>50||Linked to potential adverse effects, particularly at >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). One nmol/L = 0.4 ng/mL, and 1 ng/mL = 2.5 nmol/L.
*Serum concentrations of 25 ( OH ) D are reported in both nanomoles per liter ( nmol/L ) and nanograms per milliliter ( ng/mL ). One nmol/L = 0.4 ng/mL, and 1 ng/mL = 2.5 nmol/L. Optimal serum concentrations of 25 ( OH ) D for bone and general health have not been established because they are probable to vary by stage of life, by race and ethnicity, and with each physiologic meter used [ 1, 13, 14 ]. In addition, although 25 ( OH ) D levels emanation in response to increased vitamin D intake, the relationship is nonlinear [ 1 ]. The total of addition varies, for case, by service line serum levels and duration of supplement .
Intake recommendations for vitamin D and other nutrients are provided in the Dietary Reference Intakes ( DRIs ) developed by technical committees of NASEM [ 1 ]. DRI is the general term for a set of mention values used for plan and assessing alimentary intakes of healthy people. These values, which vary by old age and sex, include :
- Recommended Dietary Allowance (RDA): Average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy individuals; often used to plan nutritionally adequate diets for individuals.
- Adequate Intake (AI): Intake at this level is assumed to ensure nutritional adequacy; established when evidence is insufficient to develop an RDA.
- Estimated Average Requirement (EAR): Average daily level of intake estimated to meet the requirements of 50% of healthy individuals; usually used to assess the nutrient intakes of groups of people and to plan nutritionally adequate diets for them; can also be used to assess the nutrient intakes of individuals.
- Tolerable Upper Intake Level (UL): Maximum daily intake unlikely to cause adverse health effects.
An FNB committee established RDAs for vitamin D to indicate casual intakes sufficient to maintain bone health and normal calcium metamorphosis in healthy people. RDAs for vitamin D are listed in both micrograms ( microgram ) and external units ( IU ) ; 1 microgram vitamin D is equal to 40 IU ( Table 2 ). even though sunlight is a major generator of vitamin D for some people, the FNB based the vitamin D RDAs on the assumption that people receive minimal sun exposure [ 1 ]. For infants, the FNB committee developed AIs based on the amount of vitamin D that maintains serum 25 ( OH ) D levels above 20 ng/mL ( 50 nmol/L ) and supports bone development .
|0-12 months*||10 mcg
|1–13 years||15 mcg
|14–18 years||15 mcg
|19–50 years||15 mcg
|51–70 years||15 mcg
|>70 years||20 mcg
*Adequate Intake (AI)
*Adequate Intake ( AI ) many other countries around the worldly concern and some professional societies have somewhat different guidelines for vitamin D intakes [ 15 ]. These differences are a leave of an incomplete sympathy of the biology and clinical implications of vitamin D, different purposes for the guidelines ( for example, for public health in a healthy population or for clinical practice ), and/or the use in some guidelines of experimental studies in addition to randomized clinical trials to establish recommendations [ 9, 15 ]. The Endocrine Society states, for example, that to maintain serum 25 ( OH ) D levels above 75 nmol/L ( 30 ng/mL ), adults might need at least 37.5 to 50 microgram ( 1,500–2,000 IU ) /day of supplementary vitamin D, and children and adolescents might need at least 25 microgram ( 1,000 IU ) /day [ 11 ]. In contrast, the United Kingdom politics recommends intakes of 10 microgram ( 400 IU ) /day for its citizens aged 4 years and older [ 16 ] .
Sources of Vitamin D
Few foods naturally contain vitamin D. The flesh of fatty fish ( such as trout, salmon, tuna, and mackerel ) and fish liver-colored oils are among the best sources [ 17, 1 ]. An animal ’ mho diet affects the amount of vitamin D in its tissues. Beef liver-colored, egg yolks, and cheese have modest amounts of vitamin D, chiefly in the form of vitamin D3 and its metabolite 25 ( OH ) D3. Mushrooms provide variable amounts of vitamin D2 [ 17 ]. Some mushrooms available on the market have been treated with UV light to increase their levels of vitamin D2. In addition, the Food and Drug Administration ( FDA ) has approved UV-treated mushroom powder as a food linear for use as a source of vitamin D2 in food products [ 18 ]. very limited tell suggests no solid differences in the bioavailability of vitamin D from respective foods [ 19 ] .
Animal-based foods typically provide some vitamin D in the form of 25 ( OH ) D in addition to vitamin D3. The affect of this form on vitamin D condition is an emerging area of research. Studies show that 25 ( OH ) D appears to be approximately five times more potent than the parent vitamin for raising serum 25 ( OH ) D concentrations [ 17, 20, 21 ]. One report found that when the 25 ( OH ) D subject of gripe, pork barrel, chicken, turkey, and eggs is taken into report, the sum sum of vitamin D in the food is 2 to 18 times higher than the sum in the parent vitamin entirely, depending on the food [ 20 ] .
Fortified foods provide most of the vitamin D in American diets [ 1, 22 ]. For example, about all of the U.S. milk add is voluntarily fortified with about 3 mcg/cup ( 120 IU ), normally in the form of vitamin D3 [ 23 ]. In Canada, milk must be fortified with 0.88–1.0 mcg/100 milliliter ( 35–40 IU ), and the needed come for margarine is at least 13.25 mcg/100 gigabyte ( 530 IU ). other dairy products made from milk, such as cheese and ice cream, are not normally fortified in the United States or Canada. Plant milk alternatives ( such as beverages made from soy, almond, or oats ) are frequently fortified with similar amounts of vitamin D to those in bastioned cow ‘s milk ( about 3 mcg [ 120 IU ] /cup ) ; the Nutrition Facts label lists the actual sum [ 24 ]. ready-to-eat breakfast cereals much contain total vitamin D, as do some brands of orange juice, yogurt, margarine, and early food products .
The United States mandates the fortification of baby convention with 1–2.5 mcg/100 kcal ( 40–100 IU ) vitamin D ; 1–2 mcg/100 kcal ( 40–80 IU ) is the ask come in Canada [ 1 ] .
A variety show of foods and their vitamin D levels per serving are listed in postpone 3 .
|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, ½ cup||9.2||366||46|
|Milk, 2% milkfat, vitamin D fortified, 1 cup||2.9||120||15|
|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|
|Sardines (Atlantic), canned in oil, drained, 2 sardines||1.2||46||6|
|Egg, 1 large, scrambled**||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, 1.5 ounce||0.4||17||2|
|Mushrooms, portabella, raw, diced, ½ 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, ½ cup||0||0||0|
|Carrots, raw, chopped, ½ cup||0||0||0|
|Almonds, dry roasted, 1 ounce||0||0||0|
|Rice, brown, long-grain, cooked, 1 cup||0||0||0|
|Whole wheat bread, 1 slice||0||0||0|
|Lentils, boiled, ½ cup||0||0||0|
|Sunflower seeds, roasted, ½ cup||0||0||0|
|Edamame, shelled, cooked, ½ cup||0||0||0|
* DV = Daily Value. The FDA developed DVs to help consumers compare the nutrient contents of foods and dietary supplements within the context of a total diet. The DV for vitamin D is 20 mcg (800 IU) for adults and children aged 4 years and older [
** Vitamin D is in the yolk.
* DV = Daily Value. The FDA developed DVs to help consumers compare the nutrient contents of foods and dietary supplements within the context of a sum diet. The DV for vitamin D is 20 microgram ( 800 IU ) for adults and children aged 4 years and older [ 26 ]. The labels must list vitamin D content in microgram per serving and have the choice of besides listing the amount in IUs in parentheses. Foods providing 20 % or more of the DV are considered to be gamey sources of a nutrient, but foods providing lower percentages of the DV besides contribute to a sanitary diet. ** Vitamin D is in the yolk. The U.S. Department of Agriculture ’ mho ( USDA ’ sulfur ) FoodData Central lists the alimentary message of many foods and provides a comprehensive list of foods containing vitamin D arranged by nutrient content and by food mention. however, FoodData Central does not include the amounts of 25 ( OH ) D in foods .
Most people in the earth meet at least some of their vitamin D needs through exposure to sunlight [ 1 ]. type B UV ( UVB ) radiation with a wavelength of approximately 290–320 nanometers penetrates uncovered hide and converts cutaneous 7-dehydrocholesterol to previtamin D3, which in become becomes vitamin D3. Season, time of day, duration of day, cloud cover, smog, skin melanin subject, and sunscreen are among the factors that affect UV radiation photograph and vitamin D deduction. Older people and people with colored hide are less able to produce vitamin D from sunlight [ 1 ]. UVB radiation sickness does not penetrate glass, therefore exposure to sunshine indoors through a window does not produce vitamin D [ 27 ] .
The factors that affect UV radiation exposure, individual responsiveness, and uncertainties about the amount of sunday exposure needed to maintain adequate vitamin D levels make it unmanageable to provide guidelines on how much sun exposure is required for sufficient vitamin D deduction [ 15, 28 ]. Some adept bodies and vitamin D researchers suggest, for case, that approximately 5–30 minutes of sun exposure, peculiarly between 10 ante meridiem and 4 post meridiem, either daily or at least twice a workweek to the face, arms, hands, and legs without sunscreen normally leads to sufficient vitamin D deduction [ 13, 15, 28 ]. Moderate manipulation of commercial tanning beds that emit 2 % to 6 % UVB radiation sickness is besides effective [ 13, 29 ] .
But despite the importance of the sun for vitamin D synthesis, limiting skin exposure to sunlight and UV radiation from tanning beds is prudent [ 28 ]. UV radiation sickness is a carcinogen, and UV exposure is the most preventable lawsuit of skin cancer. Federal agencies and home organizations advise taking photoprotective measures to reduce the gamble of skin cancer, including using sunscreen with a sun security factor ( SPF ) of 15 or higher, whenever people are exposed to the sun [ 28, 30 ]. Sunscreens with an SPF of 8 or more appear to block vitamin D-producing UV rays. In practice, however, people normally do not apply sufficient amounts of sunscreen, cover all sun-exposed clamber, or reapply sunscreen regularly. Their hide credibly synthesizes some vitamin D, even with typically applied sunscreen amounts [ 1, 28 ] .
dietary supplements can contain vitamins D2 or D3. Vitamin D2 is manufactured using UV radiotherapy of ergosterol in yeast, and vitamin D3 is typically produced with radiotherapy of 7-dehydrocholesterol from lanolin obtained from the wool of sheep [ 13, 31 ]. An animal-free interpretation of vitamin D3 sourced from lichen is besides available [ 32 ]. People who avoid all animal-sourced products can contact dietary supplement manufacturers to ask about their source and serve techniques .
Both vitamins D2 and D3 raise serum 25 ( OH ) D levels, and they seem to have equivalent ability to cure rickets [ 4 ]. In addition, most steps in the metabolism and actions of vitamins D2 and D3 are identical. however, most testify indicates that vitamin D3 increases serum 25 ( OH ) D levels to a greater extent and maintains these higher levels longer than vitamin D2, even though both forms are well absorbed in the gut [ 33-36 ] .
Some studies have used dietary supplements containing the 25 ( OH ) D3 form of vitamin D. Per equivalent microgram venereal disease, 25 ( OH ) D3 is three to five times angstrom potent as vitamin D3 [ 37, 38 ]. however, no 25 ( OH ) D3 dietary supplements appear to be available to consumers on the U.S. marketplace at this time [ 32 ] .
Vitamin D Intakes and Status
Most people in the United States consume less than recommended amounts of vitamin D. An analysis of data from the 2015–2016 National Health and Nutrition Examination Survey ( NHANES ) found that average daily vitamin D intakes from foods and beverages were 5.1 microgram ( 204 IU ) in men, 4.2 microgram ( 168 IU ) in women, and 4.9 microgram ( 196 IU ) in children aged 2–19 years [ 39 ]. In fact, 2013–2016 NHANES data showed that 92 % of men, more than 97 % of women, and 94 % of people aged 1 class and older ingested less than the EAR of 10 microgram ( 400 IU ) of vitamin D from food and beverages [ 40 ] .
The analysis of 2015–2016 data besides showed that 28 % of all individuals aged 2 years and older in the United States took a dietary addendum containing vitamin D [ 39 ]. In summation, 26 % of participants aged 2–5 years and 14 % of those aged 6–11 years took supplements ; rates increased with age from 10 % of those aged 12–19 years to 49 % of men and 59 % of women aged 60 and older. total vitamin D intakes were three times higher with append practice than with diet alone ; the mean inhalation from foods and beverages alone for individuals aged 2 and older was 4.8 microgram ( 192 IU ) but increased to 19.9 microgram ( 796 IU ) when dietary supplements were included .
Some people take identical high doses of vitamin D supplements. In 2013–2014, an estimated 3.2 % of the U.S. pornographic population took supplements containing 100 microgram ( 4,000 IU ) or more vitamin D [ 41 ] .
One might expect a big proportion of the U.S. population to have vitamin D insufficiency on the basis of vitamin D intakes from foods, beverages, and flush dietary supplements. however, comparing vitamin D intakes to serum 25 ( OH ) D levels is debatable. One reason is that sun exposure affects vitamin D condition, so serum 25 ( OH ) D levels are normally higher than would be predicted on the basis of vitamin D dietary intakes entirely [ 1 ]. Another argue is that animal foods contain some 25 ( OH ) D. This form of vitamin D is not included in inhalation surveys and is well more potent than vitamins D2 or D3 at raising serum 25 ( OH ) D levels [ 42 ] .
An analysis of NHANES 2011–2014 data on serum 25 ( OH ) D levels found that most people in the United States aged 1 year and older had sufficient vitamin D intakes according to the FNB thresholds [ 43 ]. however, 18 % were at risk of insufficiency ( levels of 30–49 nmol/L [ 12–19.6 ng/mL ] ), and 5 % were at hazard of insufficiency ( levels below 30 nmol/L [ 12 ng/mL ] ). Four percentage had levels higher than 125 nmol/L ( 50 ng/mL ). Proportions at risk of insufficiency were lowest among children aged 1–5 years ( 0.5 % ), peaked at 7.6 % in adults aged 20–39 years, and fell to 2.9 % among adults aged 60 years and older ; patterns were like for risks of insufficiency. Rates of insufficiency varied by race and ethnicity : 17.5 % of non-Hispanic Blacks were at gamble of vitamin D insufficiency, as were 7.6 % of non-Hispanic Asians, 5.9 % of Hispanics, and 2.1 % of non-Hispanic White people. Again, the convention was similar for the gamble of insufficiency. Vitamin D condition in the United States remained stable in the decade between 2003–2004 and 2013–2014 .
Vitamin D Deficiency
People can develop vitamin D insufficiency when common intakes are lower over prison term than recommend levels, exposure to sunlight is limited, the kidneys can not convert 25 ( OH ) D to its active form, or assimilation of vitamin D from the digestive tract is inadequate. Diets low in vitamin D are more common in people who have milk allergy or lactose intolerance and those who consume an ovo-vegetarian or vegan diet [ 1 ] .
In children, vitamin D insufficiency is manifested as rickets, a disease characterized by a failure of bone tissue to become by rights mineralized, resulting in soft bones and bony deformities [ 44 ]. In addition to bone deformities and annoyance, hard rickets can cause failure to thrive, developmental delay, hypocalcemic seizures, tetanic spasms, cardiomyopathy, and dental abnormalities [ 45, 46 ] .
Prolonged exclusive breastfeed without vitamin D supplementation can cause rickets in infants, and, in the United States, rickets is most common among breastfed Black infants and children [ 47 ]. In one Minnesota county, the incidence rate of rickets in children younger than 3 years in the decade begin in 2000 was 24.1 per 100,000 [ 48 ]. Rickets occurred chiefly in Black children who were breastfed longer, were born with depleted birthweight, weighed less, and were shorter than other children. The incidence pace of rickets in the infants and children ( younger than 7 ) seen by 2,325 pediatricians throughout Canada was 2.9 per 100,000 in 2002–2004, and about all patients with rickets had been breastfed [ 49 ] .
The fortification of milk ( a effective source of calcium ) and other staples, such as breakfast cereals and margarine, with vitamin D beginning in the 1930s along with the use of cod liver anoint made rickets rare in the United States [ 28, 50 ]. however, the incidence of rickets is increasing globally, even in the United States and Europe, specially among immigrants from african, Middle-Eastern, and asian countries [ 51 ]. possible explanations for this increase include genetic differences in vitamin D metabolism, dietary preferences, and behaviors that lead to less sun photograph [ 45, 46 ] .
In adults and adolescents, vitamin D lack can lead to osteomalacia, in which existing bone is incompletely or defectively mineralized during the remodeling process, resulting in weak bones [ 46 ]. Signs and symptoms of osteomalacia are similar to those of rickets and include bone deformities and trouble, hypocalcemic seizures, tetanic spasm, and dental abnormalities [ 45 ] .
Screening for vitamin D status is becoming a more coarse part of the act lab bloodwork ordered by primary-care physicians, regardless of any indications for this practice [ 6, 52-54 ]. No studies have examined whether such screening for vitamin D insufficiency results in better health outcomes [ 55 ]. The U.S. Preventive Services Task Force ( USPSTF ) found insufficient evidence to assess the benefits and harms of screening for vitamin D insufficiency in asymptomatic adults [ 6 ]. It added that no national professional constitution recommends population screening for vitamin D lack .
Groups at Risk of Vitamin D Inadequacy
Obtaining sufficient vitamin D from natural ( nonfortified ) food sources alone is unmanageable. For many people, consuming vitamin D-fortified foods and exposing themselves to some sunlight are essential for maintaining a goodly vitamin D status. however, some groups might need dietary supplements to meet their vitamin D requirements. The following groups are among those most probably to have inadequate vitamin D condition .
Consumption of human milk alone does not normally enable infants to meet vitamin D requirements, because it provides less than 0.6 to 2.0 mcg/L ( 25 to 78 IU/L ) [ 1, 56, 57 ]. The vitamin D subject of homo milk is related to the mother ’ sulfur vitamin D condition ; studies suggest that the breastmilk of mothers who take daily supplements containing at least 50 microgram ( 2,000 IU ) vitamin D3 have higher levels of the alimentary [ 57, 58 ] .
Although UVB vulnerability can produce vitamin D in infants, the american english Academy of Pediatrics ( AAP ) advises parents to keep infants younger than 6 months out of direct sunlight, dress them in protective clothing and hats, and apply sunscreen on small areas of expose skin when sunlight photograph is ineluctable [ 59 ]. The AAP recommends 10 microgram ( 400 IU ) /day vitamin D supplements for entirely and partially breastfed infants starting shortly after parturition and lasting until they are weaned and consume at least 1,000 mL/day vitamin D-fortified formula or wholly milk [ 57 ]. The AAP besides recommends 10 microgram ( 400 IU ) /day supplementary vitamin D for all infants who are not breastfed and ingest less than 1,000 mL/day vitamin D-fortified formula or milk. An analysis of NHANES 2009–2016 data found that only 20.5 % of breastfed infants and 31.1 % of infants who were not breastfed ingested these recommended amounts of supplements [ 60 ] .
Older adults are at increased gamble of developing vitamin D insufficiency, partially because the skin ‘s ability to synthesize vitamin D declines with age [ 1, 61 ]. In summation, older adults are probably to spend more clock than younger people indoors, and they might have inadequate dietary intakes of the vitamin [ 1 ] .
People with limited sun vulnerability
Homebound individuals ; people who wear long robes, dresses, or drumhead coverings for religious reasons ; and people with occupations that limit sun exposure are among the groups that are unlikely to obtain adequate amounts of vitamin D from sunlight [ 62 ]. The use of sunscreen besides limits vitamin D deduction from sunlight. however, because the extent and frequency of sunscreen use are unknown, the character that sunscreen may play in reducing vitamin D synthesis is indecipherable [ 1 ] .
People with blue clamber
Greater amounts of the pigment melanin in the cuticular layer of the clamber result in dark skin and reduce the skin ’ s ability to produce vitamin D from sunlight [ 1 ]. Black Americans, for example, typically have lower serum 25 ( OH ) D levels than White Americans. however, whether these lower levels in persons with blue clamber have meaning health consequences is not net [ 14 ]. Those of african american lineage, for case, have lower rates of cram fracture and osteoporosis than do Whites ( see the segment below on bone health and osteoporosis ) .
People with conditions that limit fatty concentration
Because vitamin D is fat soluble, its concentration depends on the gut ’ s ability to absorb dietary fat [ 4 ]. Fat malabsorption is associated with medical conditions that include some forms of liver disease, cystic fibrosis, coeliac disease, Crohn ’ sulfur disease, and ulcerative colitis [ 1, 63 ]. In addition to having an increased gamble of vitamin D insufficiency, people with these conditions might not eat sealed foods, such as dairy products ( many of which are fortified with vitamin D ), or consume only small amounts of these foods. Individuals who have difficulty absorbing dietary fat might therefore ask vitamin D supplementation [ 63 ] .
People who are corpulent or have undergone gastric bypass surgery
Individuals with a body mass index ( BMI ) of 30 or more have lower serum 25 ( OH ) D levels than nonobese individuals. fleshiness does not affect the skin ’ randomness capacity to synthesize vitamin D. however, greater amounts of hypodermic adipose tissue seclude more of the vitamin [ 1 ]. corpulent people might need greater intakes of vitamin D to achieve 25 ( OH ) D levels similar to those of people with normal system of weights [ 1, 64, 65 ] .
corpulent individuals who have undergone gastric beltway surgery can besides become vitamin D insufficient. In this routine, region of the upper berth small intestine, where vitamin D is absorbed, is bypassed, and vitamin D that is mobilized into the bloodstream from fatty stores might not raise 25 ( OH ) D to adequate levels over clock [ 66, 67 ]. Various adept groups—including the American Association of Metabolic and Bariatric Surgery, The Obesity Society, and the british Obesity and Metabolic Surgery Society—have developed guidelines on vitamin D screen, monitoring, and replacement before and after bariatric surgery [ 66, 68 ]
Vitamin D and Health
The FNB committee that established DRIs for vitamin D found that the evidence was inadequate or besides contradictory to conclude that the vitamin had any effect on a long list of potential health outcomes ( for example, on immunity to chronic diseases or functional measures ), except for measures related to bone health. similarly, in a review of data from about 250 studies published between 2009 and 2013, the Agency for Healthcare Research and Quality concluded that no kinship could be firm established between vitamin D and health outcomes other than bone health [ 69 ]. however, because research has been conducted on vitamin D and numerous health outcomes, this section focuses on seven diseases, conditions, and interventions in which vitamin D might be involved : bone health and osteoporosis, cancer, cardiovascular disease ( CVD ), depression, multiple sclerosis ( MS ), type 2 diabetes, and weight loss .
Most of the studies described in this segment measured serum 25 ( OH ) D levels using versatile methods that were not standardized by comparing them to the best methods. Use of unstandardized 25 ( OH ) D measures can raise questions about the accuracy of the results and about the cogency of conclusions drawn from studies that use such measures and, specially, from meta-analyses that pool data from many studies that use different unstandardized measures [ 5, 9, 70 ]. More information about assay standardization is available from the Vitamin D Standardization Program web page .
Bone health and osteoporosis
Bone is constantly being remodeled. however, as people age—and particularly in women during menopause—bone breakdown rates overtake rates of bone construction. Over time, bone concentration can decline, and osteoporosis can finally develop [ 71 ] .
More than 53 million adults in the United States have or are at risk of developing osteoporosis, which is characterized by low bone batch and structural deterioration of bone weave that increases bone fragility and the gamble of bone fractures [ 72 ]. About 2.3 million osteoporotic fractures occurred in the United States in 2015 [ 73 ]. osteoporosis is, in part, a long-run effect of calcium and/or vitamin D insufficiency, in contrast to rickets and osteomalacia, which result from vitamin D insufficiency. osteoporosis is most frequently associated with inadequate calcium intakes, but insufficient vitamin D intakes contribute to osteoporosis by reducing calcium absorption [ 1 ] .
Bone health besides depends on digest from the surrounding muscles to assist with balance and postural sway and thereby reduce the risk of falling. Vitamin D is besides needed for the normal growth and emergence of muscleman fibers. In addition, inadequate vitamin D levels can adversely affect brawn strength and contribute to muscle helplessness and annoyance ( myopathy ) [ 1 ] .
Most trials of the effects of vitamin D supplements on bone health besides included calcium supplements, so isolating the effects of each nutrient is difficult. In addition, studies provided unlike amounts of nutrients and used different drug schedules .
clinical trial evidence on older adults
Among postmenopausal women and older men, many clinical trials have shown that supplements of both vitamin D and calcium leave in little increases in bone mineral concentration throughout the skeleton [ 1, 74 ]. They besides help reduce fracture rates in commit older people. however, the testify on the affect of vitamin D and calcium supplements on fractures in community-dwelling individuals is inconsistent .
The USPSTF evaluated 11 randomize clinical trials of vitamin D and/or calcium supplement in a entire of 51,419 goodly, community-dwelling adults aged 50 years and older who did not have osteoporosis, vitamin D lack, or prior fractures [ 75, 76 ]. It concluded that the stream tell was insufficient to evaluate the benefits and harms of supplementation to prevent fractures. In addition, the USPSTF recommended against supplementation with 10 mcg ( 400 IU ) or less of vitamin D and 1,000 milligram or less of calcium to prevent fractures in this population, but it could not determine the symmetry of benefits and harms from higher doses .
The USPSTF besides reviewed the seven published studies on the effects of vitamin D supplementation ( two of them besides included calcium supplement ) on the risk of falls in community-dwelling adults aged 65 years or older who did not have osteoporosis or vitamin D insufficiency. It concluded “ with moderate certainty ” that vitamin D supplement does not reduce the numbers of falls or injuries, such as fractures, resulting from falls [ 77, 78 ]. Another holocene taxonomic reappraisal besides found that vitamin D and calcium supplements had no beneficial effects on fractures, falls, or bone mineral concentration [ 79, 80 ]. In contrast, a meta-analysis of 6 trials in 49,282 older adults found that daily vitamin D ( 10 or 20 mcg [ 400 IU or 800 IU ] /day ) and calcium ( 800 or 1,200 mg/day ) supplementation for a intend of 5.9 years reduced the risk of any fracture by 6 % and of hip fracture by 16 % [ 81 ] .
One systematic review and meta-analysis of 11 randomized, controlled trials published through 2018 of vitamin D supplementation alone ( 10–20 microgram [ 400–800 IU ] /day or more at least every workweek or adenine rarely as once a class ) for 9 months to 5 years found that the supplements provided no protection from fractures in 34,243 older adults [ 81 ] .
Vitamin D supplements for bone health in minority populations
Bone mineral concentration, bone mass, and fracture risk are correlated with serum 25 ( OH ) D levels in White Americans and Mexican Americans, but not in Black Americans [ 14, 82 ]. Factors such as adiposity, skin pigmentation, vitamin D binding protein polymorphisms, and genetics contribute to differences in 25 ( OH ) D levels between Black and White Americans.
One clinical test randomized 260 Black women aged 60 years and older ( hateful age 68.2 years ) to receive 60 to 120 microgram ( 2,400 to 4,800 IU ) per day vitamin D3 supplement to maintain serum 25 ( OH ) D levels above 75 nmol/L ( 30 ng/mL ) for 3 years [ 83 ]. The results showed no association between 25 ( OH ) D levels or vitamin D drug and the gamble of falling in the 184 participants who completed the study. In fact, Black Americans might have a greater risk than White Americans of falls and fractures with day by day vitamin D intakes of 50 microgram ( 2,000 IU ) or more [ 14 ]. furthermore, the bone health of older Black american women does not appear to benefit from raising serum 25 ( OH ) D levels beyond 50 nmol/L ( 20 ng/mL ) [ 83 ] .
Vitamin D supplements and muscleman function
Studies examining the effects of supplementary vitamin D on muscleman persuasiveness and on rate of decline in brawn function have had inconsistent results [ 55 ]. One holocene clinical trial, for example, randomized 78 frail and near-frail adults aged 65 years and older to receive 20 microgram ( 800 IU ) vitamin D3, 10 microgram 25 ( OH ) D, or placebo casual for 6 months. The groups showed no significant differences in measures of muscle force or operation [ 84 ]. Another study randomized 100 community-dwelling men and women aged 60 years and older ( most were White ) with serum 25 ( OH ) D levels of 50 nmol/L ( 20 ng/ml ) or less to 800 IU vitamin D3 or placebo for 1 year [ 85 ]. Participants in the discussion group whose serum 25 ( OH ) D level was less than 70 nmol/L ( 28 ng/ml ) after 4 months received an extra 800 IU/day vitamin D3. Despite increasing serum 25 ( OH ) D levels to an average of more than 80 nmol/L ( 32 ng/ml ), vitamin D supplement did not affect lower-extremity exponent, force, or lean mass .
Conclusions about vitamin D supplements and bone health
All adults should consume recommended amounts of vitamin D and calcium from foods and supplements if needed. Older women and men should consult their healthcare providers about their needs for both nutrients as separate of an overall plan to maintain bone health and to prevent or treat osteoporosis .
Laboratory and animal studies suggest that vitamin D might inhibit carcinogenesis and slowly tumor progress by, for exemplar, promoting cell differentiation and inhibit metastasis. Vitamin D might besides have anti-inflammatory, immunomodulatory, proapoptotic, and antiangiogenic effects [ 1, 86 ]. experimental studies and clinical trials provide shuffle attest on whether vitamin D intakes or serum levels affect cancer incidence, progression, or deathrate gamble .
sum cancer incidence and mortality
Some experimental studies show associations between first gear serum levels of 25 ( OH ) D and increased risks of cancer incidence and death. In a meta-analysis of 16 prospective age group studies in a sum of 137,567 participants who had 8,345 diagnoses of cancer, 5,755 participants died from cancer [ 87 ]. A 50 nmol/L ( 20 ng/mL ) increase in 25 ( OH ) D levels was associated with an 11 % decrease in sum cancer incidence rates and, in women but not men, a 24 % decrease in cancer deathrate rates. A meta-analysis of prospective studies that evaluated the affiliation between serum 25 ( OH ) D levels and cancer incidence ( 8 studies ) or cancer deathrate ( 16 studies ) found that cancer risk decreased by 7 % and cancer deathrate rates decreased by 2 % with each 20 nmol/L ( 8 ng/mL ) increase in serum 25 ( OH ) D levels [ 88 ]. importantly, not all experimental studies found higher vitamin D status to be beneficial, and the studies varied well in study populations, baseline comorbidities, and measurement of vitamin D levels .
clinical trial attest provides some support for the experimental findings. For example, three meta-analyses of clinical trial evidence found that vitamin D supplement does not affect cancer incidence but does significantly reduce sum cancer deathrate rates by 12–13 % [ 89-91 ]. In the most holocene meta-analysis, 10 randomized clinical trials ( including the Vitamin D and Omega-3 Trial [ VITAL ] trial described below ) that included 6,537 cancer cases provided 10 to 50 microgram ( 400 to 2,000 IU ) vitamin D3 daily ( six trials ) or 500 microgram ( 20,000 IU ) /week to 12,500 microgram ( 500,000 IU ) /year boluses of vitamin D3 ( four trials ) [ 90 ]. The study reports included 3–10 years of follow-up data. The vitamin D supplements were associated with serum 25 ( OH ) D levels of 54 to 135 nmol/L ( 21.6 to 54 ng/mL ). Vitamin D supplementation reduced cancer mortality rates by 13 %, and most of the benefit occurred with daily supplementation .
The largest clinical trial, VITAL, to investigate the effects of vitamin D supplementation on the basal prevention of cancer in the general population gave 50 microgram ( 2,000 IU ) /day vitamin D3 supplements with or without 1,000 mg/day marine omega-3 fatty acid fatso acids or a placebo for a median of 5.3 years [ 92 ]. The sketch included 25,871 men aged 50 years and older and women aged 55 years and older who had no history of cancer, and most had adequate serum 25 ( OH ) D levels at baseline. Rates of summit, prostate, and colorectal cancer did not differ significantly between the vitamin D and placebo groups. however, normal-weight participants had greater reductions in cancer incidence and mortality rates than those who were corpulence or corpulent .
A few studies have examined the impression of vitamin D supplementation on specific cancers. Below are brief descriptions of studies of vitamin D and its affiliation with, or effect on, breast, colorectal, lung, pancreatic, and prostate cancers .
Some experimental studies support an inverse association between 25 ( OH ) D levels and breast cancer risk and deathrate, but others do not [ 93-96 ]. The Women ‘s Health Initiative clinical trial randomized 36,282 postmenopausal women to receive 400 IU vitamin D3 plus 1,000 milligram calcium day by day or a placebo for a base of 7 years [ 97 ]. The vitamin D3 and calcium supplements did not reduce breast cancer incidence, and 25 ( OH ) D levels at the start of the survey were not associated with summit cancer gamble [ 98 ] .
In a subsequent investigation for 4.9 years after the study ‘s end, women who had taken the vitamin D and calcium supplements ( many of whom continued to take them ) had an 18 % lower hazard of in situ ( noninvasive ) breast cancer [ 99 ]. however, women with vitamin D intakes higher than 15 microgram ( 600 IU ) /day at the start of the test and who received the supplements experienced a 28 % increased gamble of invasive ( but not in situ ) breast cancer .
A large case-control study included 5,706 individuals who developed colorectal cancer and whose 25 ( OH ) D levels were assessed a medial of 5.5 years from blood draw to cancer diagnosis and 7,105 matched controls [ 100 ]. The results showed an association between 25 ( OH ) D levels lower than 30 nmol/L ( 12 ng/mL ) and a 31 % higher colorectal cancer risk. Levels of 75 to less than 87.5 nmol/L ( 30 to less than 35 ng/mL ) and 87.5 to less than 100 nmol/L ( 35 to less than 40 ng/mL ) were associated with a 19 % and 27 % lower risk, respectively. The association was substantially stronger in women .
In the Women ‘s Health Initiative clinical trial ( described above ), vitamin D3 and calcium supplements had no effect on rates of colorectal cancer. In a subsequent investigation for 4.9 years after the study ‘s end, women who had taken the vitamin D and calcium supplements ( many of whom continued to take them ) even had the same colorectal cancer hazard as those who received placebo [ 99 ] .
Another study included 2,259 goodly individuals aged 45 to 75 years who had had one or more serrate polyps ( harbinger lesions to colorectal cancer ) that had been removed [ 101 ]. These participants were randomized to take 25 mcg ( 1,000 IU ) vitamin D3, 1,200 magnesium calcium, both supplements, or a placebo casual for 3–5 years, followed by an extra 3–5 years of notice after participants stopped the treatment. Vitamin D alone did not importantly affect the development of new serrate polyps, but the combination of vitamin D with calcium increased the hazard about fourfold. The VITAL trial found no affiliation between vitamin D supplementation and the hazard of colorectal adenoma or serrated polyps [ 102 ] .
A discipline of cohorts that included 5,313 participants who developed lung cancer and 5,313 matched controls found no association between serum 25 ( OH ) D levels and gamble of subsequent lung cancer, even when the investigators analyzed the data by sex, age, race and ethnicity, and smoking condition [ 103 ] .
One study comparing 738 men who developed pancreatic cancer to 738 matched controls found no relationship between serum 25 ( OH ) D levels and risk of pancreatic cancer [ 104 ]. Another study that compared 200 male smokers in Finland with pancreatic cancer to 400 matched controls found that participants in the highest quintile of 25 ( OH ) D levels ( more than 65.5 nmol/L [ 26.2 ng/mL ] ) had a threefold greater gamble of developing pancreatic cancer over 16.7 years than those in the lowest quintile ( less than 32 nmol/L [ 12.8 ng/mL ] ) [ 105 ]. An probe that pooled data from 10 studies of cancer in 12,205 men and women found that concentrations of 25 ( OH ) D greater than 75 nmol/L ( 30 ng/mL ) but less than 100 nmol/L ( 40 ng/mL ) did not reduce the risk of pancreatic cancer. however, the results did show an increased risk of pancreatic cancer with 25 ( OH ) D levels of 100 nmol/L ( 40 ng/mL ) or above [ 106 ] .
Research to date provides blend evidence on whether levels of 25 ( OH ) D are associated with the exploitation of prostate gland cancer. several studies published in 2014 suggested that senior high school levels of 25 ( OH ) D might increase the risk of prostate gland cancer. For exemplar, a meta-analysis of 21 studies that included 11,941 men with prostate cancer and 13,870 controls found a 17 % higher risk of prostate gland cancer for participants with higher levels of 25 ( OH ) D [ 107 ]. What constituted a “ higher ” level varied by study but was typically at least 75 nmol/L ( 30 ng/mL ). In a cohort of 4,733 men, of which 1,731 had prostate cancer, those with 25 ( OH ) D levels of 45–70 nmol/L ( 18–28 ng/mL ) had a significantly lower hazard of the disease than men with either lower or higher values [ 108 ]. This u-shaped affiliation was most pronounce for men with the most aggressive forms of prostate cancer. A case-control analysis of 1,695 cases of prostate gland cancer and 1,682 controls found no associations between 25 ( OH ) D levels and prostate cancer gamble [ 109 ]. however, higher serum 25 ( OH ) D levels ( at a cut steer of 75 nmol/L [ 30 ng/mL ] ) were linked to a modestly higher hazard of slow-growth prostate gland cancer and a more hearty lower risk of aggressive disease .
Since 2014, however, several published studies and meta-analyses have found no kinship between 25 ( OH ) D levels and prostate cancer risk [ 110, 111 ]. For model, an analysis was conducted of 19 prospective studies that provided data on prediagnostic levels of 25 ( OH ) D for 13,462 men who developed prostate gland cancer and 20,261 control participants [ 112 ]. Vitamin D lack or insufficiency did not increase the risk of prostate gland cancer, and higher 25 ( OH ) D concentrations were not associated with a lower risk .
several studies have examined whether levels of 25 ( OH ) D in men with prostate cancer are associated with a lower risk of end from the disease or from any campaign. One study included 1,119 men treated for prostate gland cancer whose plasma 25 ( OH ) D levels were measured 4.9 to 8.6 years after their diagnosis. Among the 198 participants who died ( 41 deaths were due to prostate cancer ), 25 ( OH ) D levels were not associated with risk of death from prostate cancer or any lawsuit [ 113 ]. however, a meta-analysis of 7 cohort studies that included 7,808 men with prostate gland cancer found higher 25 ( OH ) D levels to be significantly associated with lower deathrate rates from prostate gland cancer or any early lawsuit [ 114 ]. A dose-response analysis found that each 20 nmol/L [ 8 ng/mL ] increase in 25 ( OH ) D was associated with a 9 % lower risk of both all-cause and prostate cancer-specific deathrate .
For men with prostate cancer, whether vitamin D supplementation lengthens cancer-related survival is not clear. A meta-analysis of 3 randomized controlled trials in 1,273 men with prostate gland cancer found no meaning differences in total mortality rates between those receiving vitamin D supplement ( from 10 mcg [ 400 IU ] /day for 28 days to 45 mcg [ 1,800 IU ] given in three doses total at 2-week intervals ) and those receiving a placebo [ 115 ] .
Conclusions about vitamin D and cancer
The USPSTF stated that, due to insufficient evidence, it was unable to assess the proportion of benefits and harms of supplementary vitamin D to prevent cancer [ 116 ]. Taken together, studies to date do not indicate that vitamin D with or without calcium supplement reduces the incidence of cancer, but adequate or higher 25 ( OH ) D levels might reduce cancer deathrate rates. Further research is needed to determine whether vitamin D insufficiency increases cancer gamble, whether greater exposure to the nutrient can prevent cancer, and whether some individuals could have an increased hazard of cancer because of their vitamin D status over time .
Vitamin D helps regulate the renin-angiotensin-aldosterone system ( and thereby blood blackmail ), vascular cell growth, and incendiary and fibrotic pathways [ 117 ]. Vitamin D lack is associated with vascular dysfunction, arterial stiffen, left ventricular hypertrophy, and lipemia [ 118 ]. For these reasons, vitamin D has been linked to heart health and risk of CVD .
experimental studies support an association between higher serum 25 ( OH ) D levels and a lower gamble of CVD incidence and deathrate. For exemplar, a meta-analysis included 34 experimental studies that followed 180,667 participants ( mean age greater than 50 years ) for 1.3 to more than 32 years. The results showed that service line serum 25 ( OH ) D levels were inversely associated with entire phone number of CVD events ( including myocardial infarct, ischemic heart disease, heart failure, and stroke ) and deathrate gamble [ 119 ]. Overall, the hazard of CVD events was 10 % lower for each 25 nmol/L ( 10 ng/mL ) increase in serum 25 ( OH ) D .
Another large experimental study that followed 247,574 adults from Denmark for 0–7 years found that levels of 25 ( OH ) D that were low ( about 12.5 nmol/L [ 5 ng/mL ] ) and high ( about 125 nmol/L [ 50 ng/mL ] ) were associated with a greater risk of mortality from CVD, stroke, and acute accent myocardial infarct [ 120 ]. early meta-analyses of prospective studies have found associations between lower vitamin D status measured by serum 25 ( OH ) D levels or vitamin D intakes and an increased hazard of ischemic stroke, ischemic heart disease, myocardial infarct, and early death [ 121, 122 ] .
In contrast to the experimental studies, clinical trials have provided little support for the hypothesis that auxiliary vitamin D reduces the risk of CVD or CVD mortality. For exemplar, a 3-year trial in New Zealand randomized 5,110 adults ( hateful old age 65.9 years ) to a single dose of 5,000 microgram ( 200,000 IU ) vitamin D3 followed by 2,500 mcg ( 100,000 IU ) each calendar month or a placebo for a medial of 3.3 years [ 123 ]. Vitamin D supplement had no effect on the incidence rate of myocardial infarct, angina pectoris, heart failure, cardiac arrhythmia, arteriosclerosis, stroke, venous thrombosis, or death from CVD. similarly, the VITAL clinical trial described above witness that vitamin D supplements did not importantly decrease rates of affection attacks, strokes, coronary revascularization, or deaths from cardiovascular causes [ 92 ]. furthermore, the effects did not vary by baseline serum 25 ( OH ) D levels or whether participants took the test ’ s omega-3 fatty acid append in addition to vitamin D .
however, another clinical trial designed to investigate bone fracture hazard found that 800 IU/day vitamin D3 ( with or without calcium ) or a placebo in 5,292 adults aged 70 years and older for a median of 6.2 years offered auspices from cardiac failure, but not myocardial infarct or stroke [ 124 ] .
eminent serum cholesterol levels and high blood pressure are two of the chief risk factors for CVD. The data on supplementary vitamin D and cholesterol levels are mix, as shown in one meta-analysis of 41 clinical trials in a entire of 3,434 participants ( base age 55 years ). The results of this psychoanalysis showed that 0.5 microgram ( 20 IU ) to 214 microgram ( 8,570 IU ) /day vitamin D supplement ( average of 2,795 IU ) for 6 weeks to 3 years reduced serum sum cholesterol, low-density lipoprotein cholesterol, and triglyceride levels, but not high-density lipoprotein cholesterol levels [ 125 ] .
Studies of the effects of vitamin D supplements on high blood pressure have besides had mixed findings. In one meta-analysis of 46 clinical trials that included 4,541 participants, vitamin D supplements ( typically 40 mcg [ 1,600 IU ] /day or less ) for a minimum of 4 weeks had no significant effects on systolic or diastolic lineage pressure [ 126 ]. In contrast, another meta-analysis of 30 clinical trials in 4,744 participants ( mean age 54.5 years ) that administered 5 microgram ( 200 IU ) to 300 microgram ( 12,000 IU ) /day vitamin D3 for a mean of 5.6 months showed that more than 20 microgram ( 800 IU ) /day importantly reduced systolic and diastolic blood atmospheric pressure in normal-weight participants who had high blood pressure [ 127 ]. however, more than 20 microgram ( 800 IU ) /day vitamin D3, when taken with calcium supplements, importantly increased blood pressure in fleshy and corpulent participants. Another meta-analysis of genic studies in 146,581 participants ( chiefly adults ) found that a low vitamin D condition increased lineage press and high blood pressure hazard in people with familial variants associated with low endogenous production of 25 ( OH ) D [ 128 ] .
overall, clinical trials show that vitamin D supplement does not reduce CVD hazard, even for people with depleted 25 ( OH ) D status ( below 20 nmol/L [ 12 ng/mL ] ) at baseline [ 92, 123 ] .
Vitamin D is involved in respective brain processes, and vitamin D receptors are present on neurons and glia in areas of the genius thought to be involved in the pathophysiology of depression [ 129 ] .
A taxonomic review and meta-analysis of 14 experimental studies that included a sum of 31,424 adults ( hateful old age ranging from 27.5 to 77 years ) found an affiliation between insufficient or low levels of 25 ( OH ) D and depression [ 129 ] .
clinical trials, however, do not support these findings. For exercise, a meta-analysis of 9 trials with a entire of 4,923 pornographic participants diagnosed with depression or depressive symptoms found no significant decrease in symptoms after supplementation with vitamin D [ 130 ]. The trials administered different amounts of vitamin D ( ranging from 10 mcg [ 400 IU ] /day to 1,000 mcg [ 40,000 IU ] /week ). They besides had different study durations ( 5 days to 5 years ), beggarly participant ages ( compass, 22 years to 75 years ), and baseline 25 ( OH ) D levels ; furthermore, some but not all studies administered coincident antidepressant medications .
Three trials conducted since that meta-analysis besides found no effect of vitamin D supplementation on depressive symptoms. One trial included 206 adults ( beggarly historic period 52 years ) who were randomized to take a bolus dose of 2,500 microgram ( 100,000 IU ) vitamin D3 followed by 500 mcg ( 20,000 IU ) /week or a placebo for 4 months [ 131 ]. Most participants had minimal or balmy depression, had a gloomy base baseline 25 ( OH ) floor of 33.8 nmol/L ( 13.5 ng/mL ), and were not taking antidepressants. The second gear test included 155 adults aged 60–80 years who had clinically relevant depressive symptoms, no major depressive disorder, and serum 25 ( OH ) D levels less than 50 to 70 nmol/L ( 20 to 28 ng/mL ) depending on the season ; in accession, they were not taking antidepressants [ 132, 133 ]. Participants were randomized to take either 30 microgram ( 1,200 IU ) /day vitamin D3 or a placebo for 1 year. In the VITAL trial described above, 16,657 men and women 50 years of age and older with no history of depressive disorder and 1,696 with an increased risk of perennial natural depression ( that had not been medically treated for the past 2 years ) were randomized to take 50 mcg ( 2,000 IU ) /day vitamin D3 ( with or without fish anoint ) or a placebo for a medial of 5.3 years [ 134 ]. The groups showed no significant differences in the incidence and perennial rates of depression, clinically relevant depressive symptoms, or changes in temper scores .
overall, clinical trials did not find that vitamin D supplements helped prevent or cover depressive symptoms or meek depressive disorder, specially in middle-aged to older adults who were not taking prescription drug antidepressants. No studies have evaluated whether vitamin D supplements may benefit individuals under medical worry for clinical depression who have low or deficient 25 ( OH ) D levels and are taking antidepressant medicine .
MS is an autoimmune disease of the central aflutter arrangement that damages the myelin sheath surrounding and protecting nerve cells in the brain and spinal anesthesia cord. This wrong hinders or blocks messages between the brain and body, leading to clinical features, such as imagination loss, motor helplessness, spasticity, ataxia, tremor, sensational passing, and cognitive stultification [ 135, 136 ]. Some people with MS finally lose the ability to write, speak, or walk .
The geographic distribution of MS around the world is inadequate. few people near the equator develop the disease, whereas the preponderance is higher promote north and south. This spotty distribution has led to guess that lower vitamin D levels in people who have less sunlight exposure might predispose them to the disease [ 136 ] .
many epidemiologic and familial studies have shown an association between MS and humble 25 ( OH ) D levels before and after the disease begins [ 136 ]. Observational studies suggest that adequate vitamin D levels might reduce the risk of contracting MS and, once MS is award, decrease the risk of relapse and slow the disease ‘s progress [ 137 ]. One survey, for example, tested 25 ( OH ) D levels in 1,092 women in Finland an median of 9 years before their MS diagnosis and compared their outcomes with those of 2,123 similar women who did not develop MS [ 138 ]. More than half the women who developed MS had insufficient or insufficient vitamin D levels. Women with 25 ( OH ) D levels of less than 30 nmol/L ( 12 ng/mL ) had a 43 % higher MS risk than women with levels of 50 nmol/L ( 20 ng/mL ) or higher. Among the women with two or more serum 25 ( OH ) D samples taken before diagnosis ( which reduced random measurement variation ), a 50 nmol/L increase in 25 ( OH ) D was associated with a 41 % reduced risk of MS, and 25 ( OH ) D levels less than 30 nmol/L were associated with an MS risk that was twice deoxyadenosine monophosphate high as levels of 50 nmol/L or higher .
Two earlier prospective studies of like design—one in the United States with 444 non-Hispanic White individuals [ 139 ] and the early with 576 individuals in northerly Sweden [ 140 ] —found that levels of 25 ( OH ) D greater than 99.1 nmol/L ( 39.6 ng/mL ) and at least 75 nmol/L ( 30 ng/mL ), respectively, were associated with a 61–62 % lower risk of MS .
No clinical trials have examined whether vitamin D supplementation can prevent the onset of MS, but several have investigated whether supplementary vitamin D can help manage the disease. A 2018 Cochrane review analyzed 12 such trials that had a total of 933 participants with MS ; the reviewers judged all of these trials to be of moo choice [ 136 ]. overall, vitamin D supplementation, when compared with placebo administration, had no effect on relevant clinical outcomes, such as perennial get worse or worsened disability .
Experts have reached no firm consensus on whether vitamin D can help prevent MS given the lack of clinical trial testify [ 141 ]. In addition, studies have not systematically shown that vitamin D supplement tempers the signs and symptoms of active MS or reduces rates of backsliding .
Type 2 diabetes
Vitamin D plays a function in glucose metamorphosis. It stimulates insulin secretion via the vitamin D receptor on pancreatic beta cells and reduces peripheral insulin resistance through vitamin D receptors in the muscles and liver [ 142 ]. Vitamin D might be involved in the pathophysiology of type 2 diabetes through its effects on glucose metabolism and insulin bespeak deoxyadenosine monophosphate well as its ability to reduce ignition and improve pancreatic beta-cell function [ 143, 144 ] .
experimental studies have linked lower serum 25 ( OH ) D levels to an increased risk of diabetes, but their results might have been confounded by the fact that many participants were corpulence or corpulent and were therefore more predisposed to developing diabetes and having lower 25 ( OH ) D levels [ 1 ]. A inspection of 71 experimental studies in adults with and without type 2 diabetes from 16 countries found a significant inverse relationship between vitamin D condition and blood boodle levels in participants who did and did not have diabetes [ 145 ] .
In contrast to experimental studies, clinical trials provide small confirm for the benefits of vitamin D supplement for glucose homeostasis. One trial included 65 fleshy or corpulent adult men and women ( beggarly age 32 years ) who were otherwise healthy, did not have diabetes, and had low serum vitamin D levels ( at or below 50 nmol/L [ 20 ng/mL ] ) [ 146 ]. The investigators randomly assigned participants to receive either a bolus oral dose of 2,500 microgram ( 100,000 IU ) vitamin D3 followed by 100 mcg ( 4,000 IU ) /day or a placebo for 16 weeks. In the 54 participants who completed the report, vitamin D supplementation did not improve insulin sensitivity or insulin secretion in comparison with placebo .
One taxonomic review and meta-analysis evaluated 35 clinical trials that included 43,407 adults with convention glucose allowance, prediabetes, or type 2 diabetes who received a median of 83 microgram ( 3,332 IU ) /day vitamin D supplements or placebo for a median of 16 weeks [ 147 ]. Vitamin D had no significant effects on glucose homeostasis, insulin secretion or resistance, or hemoglobin A1c levels ( a meter of average lineage sugar levels over the previous 2–3 months ), regardless of the survey population, vitamin D dose, or trial quality .
several trials have investigated whether vitamin D supplementation can prevent the transition from prediabetes to diabetes in patients with adequate 25 ( OH ) D levels, and all have had negative results. In a test in Norway, 511 men and women aged 25–80 years ( beggarly historic period 62 years ) with prediabetes received 500 microgram ( 20,000 IU ) vitamin D3 or a placebo each workweek for 5 years [ 148 ]. The results showed no significant differences in rates of progression to type 2 diabetes ; in serum glucose, insulin, or hemoglobin A1c levels ; or in measures of insulin underground. At baseline, participants had an adequate beggarly serum 25 ( OH ) D level of 60 nmol/L ( 24 ng/mL ) .
The largest test to date of vitamin D supplements for diabetes prevention randomized 2,423 men and women aged 25 years and older ( bastardly historic period 60 years ) with prediabetes who were corpulence or corpulent ( entail BMI of 32.1 ) to 100 microgram ( 4,000 IU ) /day vitamin D3 or placebo for a median of 2.5 years [ 144 ]. Most participants ( 78 % ) had adequate serum levels of vitamin D at baseline ( at least 50 nmol/L [ 20 ng/mL ] ). Vitamin D did not significantly prevent the development of diabetes in comparison with placebo. however, a post hoc analysis showed a 62 % lower incidence of diabetes among participants with low baseline serum 25 ( OH ) D levels ( less than 30 nmol/L [ 12 ng/mL ] ) who took the vitamin D supplement than among those who took the placebo [ 144, 149 ] .
Studies have besides assessed the value of vitamin D supplementation for managing diabetes, and they have found that the vitamin offers limit benefits. One meta-analysis of 20 clinical trials compared the effects of 0.5 microgram ( 20 IU ) /day to 1,250 microgram ( 50,000 IU ) /week vitamin D supplement for 2–6 months with those of placebo on glycemic control in 2,703 adults from around the world who had diabetes [ 142 ]. The vitamin D reduced insulin resistor to a small but significant degree, particularly in people taking more than 50 microgram ( 2,000 IU ) /day who were vitamin D deficient at baseline, had thoroughly glycemic manipulate, were not corpulent, and were of Middle Eastern ethnicity. however, the supplementation had no meaning effects on fasting blood glucose, hemoglobin A1c, or fasting insulin levels .
clinical trials to date provide little evidence that vitamin D supplement helps maintain glucose homeostasis, reduces the risk of progress from prediabetes to type 2 diabetes, or helps manage the disease, particularly in vitamin D-replete individuals .
Observational studies indicate that greater body weights are associated with lower vitamin D condition, and corpulent individuals frequently have bare or deficient circulating 25 ( OH ) D levels [ 150 ]. however, clinical trials do not support a cause-and-effect kinship between vitamin D and weight loss .
A taxonomic follow-up and meta-analysis of 15 weight-loss interposition studies that used thermal restriction, drill, or both, but not necessarily vitamin D supplement or other treatments, found that people who lost weight had significantly greater increases in serum 25 ( OH ) D levels than those who maintained their burden [ 151 ]. In another learn, 10 microgram ( 400 IU ) /day vitamin D and 1,000 mg/day calcium supplement slenderly, but significantly, reduced weight gain amounts in comparison with placebo in postmenopausal women, specially those with a baseline entire calcium inhalation of less than 1,200 mg/day [ 152 ]. however, a meta-analysis of 12 vitamin D supplement trials ( including 5 in which body typography measurements were primary outcomes ) found that vitamin D supplements without calorie restriction did not affect body weight or adipose tissue batch when the results were compared with those of placebo [ 153 ] .
overall, the available research suggests that consuming higher amounts of vitamin D or taking vitamin D supplements does not promote slant loss .
Health Risks from Excessive Vitamin D
excess amounts of vitamin D are toxic. Because vitamin D increases calcium assimilation in the gastrointestinal tract, vitamin D perniciousness results in check hypercalcemia ( total calcium greater than 11.1 mg/dL, beyond the normal range of 8.4 to 10.2 mg/dL ), hypercalciuria, and high gear serum 25 ( OH ) D levels ( typically greater than 375 nmol/l [ 150 ng/mL ] ) [ 154 ]. Hypercalcemia, in plow, can lead to nausea, vomiting, muscle weakness, neuropsychiatric disturbances, pain, loss of appetite, dehydration, polyuria, excessive crave, and kidney stones .
In extreme cases, vitamin D toxicity causes nephritic failure, calcification of easy tissues throughout the body ( including in coronary thrombosis vessels and heart valves ), cardiac cardiac arrhythmia, and even death. Vitamin D toxicity has been caused by consumption of dietary supplements that contained excessive vitamin D amounts because of fabricate errors, that were taken inappropriately or in excessive amounts, or that were falsely prescribed by physicians, [ 154-156 ] .
Experts do not believe that excessive sunday exposure results in vitamin D toxicity because thermal energizing of previtamin D3 in the skin gives rebel to assorted non-vitamin D forms that limit formation of vitamin D3. Some vitamin D3 is besides converted to nonactive forms [ 1 ]. however, frequent use of tanning beds, which provide artificial UV radiation, can lead to 25 ( OH ) D levels well above 375–500 nmol/L ( 150–200 ng/mL ) [ 157-159 ] .
The combination of high intakes of calcium ( about 2,100 mg/day from food and supplements ) with tone down amounts of vitamin D ( about 19 mcg [ 765 IU ] /day from food and supplements ) increased the hazard of kidney stones by 17 % over 7 years among 36,282 postmenopausal women who were randomly assigned to take 1,000 mg/day calcium and 10 microgram ( 400 IU ) /day vitamin D or a placebo [ 160 ]. however, other, shorter ( from 24 weeks to 5 years ) clinical trials of vitamin D supplementation entirely or with calcium in adults found greater risks of hypercalcemia and hypercalciuria, but not of kidney stones [ 161, 162 ] .
The FNB established ULs for vitamin D in 2010 ( Table 4 ) [ 1 ]. While acknowledging that signs and symptoms of toxicity are improbable at daily intakes below 250 microgram ( 10,000 IU ), the FNB noted that even vitamin D intakes lower than the ULs might have adverse health effects over time. The FNB recommended avoiding serum 25 ( OH ) D levels above approximately 125–150 nmol/L ( 50–60 ng/mL ), and it found that tied lower serum levels ( approximately 75–120 nmol/L [ 30–48 ng/mL ] ) are associated with increases in rates of all-cause deathrate, risk of cancer at some sites ( for example, pancreas ), hazard of cardiovascular events, and count of falls and fractures among older adults .
|0-6 months||25 mcg (1,000 IU)||25 mcg (1,000 IU)|
|7–12 months||38 mcg (1,500 IU)||38 mcg (1,500 IU)|
|1–3 years||63 mcg (2,500 IU)||63 mcg (2,500 IU)|
|4–8 years||75 mcg (3,000 IU)||75 mcg (3,000 IU)|
|9–18 years||100 mcg (4,000 IU)||100 mcg (4,000 IU)||100 mcg (4,000 IU)||100 mcg (4,000 IU)|
|19+ years||100 mcg (4,000 IU)||100 mcg (4,000 IU)||100 mcg (4,000 IU)||100 mcg (4,000 IU)|
Interactions with Medications
Vitamin D supplements may interact with several types of medications. A few examples are provided below. Individuals taking these and other medications on a regular basis should discuss their vitamin D intakes and status with their healthcare providers .
The weight-loss drug orlistat ( Xenical® and alli® ), together with a reduced-fat diet, can reduce the absorption of vitamin D from food and supplements, leading to lower 25 ( OH ) D levels [ 163-166 ] .
Statin medications reduce cholesterol synthesis. Because endogenous vitamin D is derived from cholesterol, statins may besides reduce vitamin D synthesis [ 166 ]. In addition, high intakes of vitamin D, particularly from supplements, might reduce the potential of atorvastatin ( Lipitor® ), lovastatin ( Altoprev® and Mevacor® ), and simvastatin ( FloLipid™ and Zocor® ), because these statins and vitamin D appear to compete for the same metabolize enzyme [ 166-169 ] .
Corticosteroid medications, such as prednisone ( Deltasone®, Rayos®, and Sterapred® ), are frequently prescribed to reduce inflammation. These medications can reduce calcium absorption and impair vitamin D metabolism [ 170-172 ]. In the NHANES 2001–2006 survey, 25 ( OH ) D lack ( less than 25 nmol/L [ 10 ng/mL ] ) was more than twice as common among children and adults who reported oral steroid hormone use ( 11 % ) than in nonusers ( 5 % ) [ 173 ] .
Thiazide diuretics ( for example, Hygroton®, Lozol®, and Microzide® ) decrease urinary calcium elimination. The combination of these diuretics with vitamin D supplements ( which increase intestinal calcium absorption ) might lead to hypercalcemia, particularly among older adults and individuals with compromise nephritic function or hyperparathyroidism [ 166, 174, 175 ] .
Vitamin D and Healthful Diets
The federal government ‘s 2020-2025 Dietary Guidelines for Americans notes that “ Because foods provide an align of nutrients and other components that have benefits for health, nutritional needs should be met chiefly through foods. … In some cases, fortified foods and dietary supplements are utilitarian when it is not possible otherwise to meet needs for one or more nutrients ( for example, during specific life stages such as pregnancy ). ”
For more information about building a healthy dietary traffic pattern, refer to the Dietary Guidelines for Americans and the U.S. Department of Agriculture ‘s MyPlate.
The Dietary Guidelines for Americans describes a healthy dietary blueprint as one that :
- Includes a variety of vegetables; fruits; grains (at least half whole grains); fat-free and low-fat milk, yogurt, and cheese; and oils.
- Milk, many ready-to-eat cereals, and some brands of yogurt and orange juice are fortified with vitamin D. Cheese naturally contains small amounts of vitamin D. Vitamin D is added to some margarines.
- Includes a variety of protein foods such as lean meats; poultry; eggs; seafood; beans, peas, and lentils; nuts and seeds; and soy products.
- Fatty fish, such as salmon, tuna, and mackerel, are very good sources of vitamin D. Beef liver and egg yolks have small amounts of vitamin D.
- Limits foods and beverages higher in added sugars, saturated fat, and sodium.
- Limits alcoholic beverages.
- Stays within your daily calorie needs.
This fact sheet by the National Institutes of Health ( NIH ) Office of Dietary Supplements ( ODS ) provides information that should not take the home of medical advice. We encourage you to talk to your healthcare providers ( repair, registered dietician, pharmacist, etc. ) about your pastime in, questions about, or practice of dietary supplements and what may be best for your overall health. Any mention in this publication of a specific intersection or service, or recommendation from an organization or professional society, does not represent an endorsement by ODS of that product, service, or technical advice .