Vitamin D

Fact Sheet for Health Professionals

For information on vitamin D and COVID-19, see Dietary Supplements in the Time of COVID-19.

Introduction
Vitamin D (also referred to as calciferol) is a fat-soluble vitamin that is naturally present in a few foods,
added to others, and available as a dietary supplement. It is also produced endogenously when
ultraviolet (UV) rays from sunlight strike the skin and trigger vitamin D synthesis.

Vitamin D obtained from sun exposure, foods, and supplements is biologically inert and must undergo
two hydroxylations in the body for activation. The first hydroxylation, which occurs in the liver, converts
vitamin D to 25-hydroxyvitamin D [25(OH)D], also known as calcidiol. The second hydroxylation occurs
primarily in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D [1,25(OH)2D], also
known as calcitriol [1].

Vitamin D promotes calcium absorption in the gut 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 also needed for bone growth
and bone remodeling 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 also helps protect older adults from osteoporosis.

Vitamin D has other roles in the body, including reduction of inflammation as well as modulation of
such processes as cell growth, neuromuscular and immune function, and glucose metabolism [1-3].
Many genes encoding proteins that regulate cell proliferation, differentiation, 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 (ergocalciferol) and D3
(cholecalciferol), that differ chemically only in their side-chain structures. Both forms are well absorbed
in the small intestine. Absorption occurs by simple passive diffusion and by a mechanism that involves
intestinal membrane carrier proteins [4]. The concurrent presence of fat in the gut enhances vitamin D
absorption, but some vitamin D is absorbed even without dietary fat. Neither aging nor obesity alters
vitamin D absorption from the gut [4].

Serum concentration of 25(OH)D is currently the main indicator of vitamin D status. 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 status by measuring serum 25(OH)D concentrations is complicated by the

considerable variability of the available assays (the two most common ones involve antibodies or
chromatography) used by laboratories that conduct the analyses [5,6]. As a result, a finding can be
falsely low or falsely high, depending on the assay used and the laboratory. The international Vitamin D
Standardization Program has developed procedures for standardizing the laboratory measurement of
25(OH)D to improve clinical and public health practice [5,7-10].

In contrast to 25(OH)D, circulating 1,25(OH)2D is generally not a good indicator of vitamin D status
because it has a short half-life measured in hours, and serum levels are tightly regulated by parathyroid
hormone, calcium, and phosphate [1]. Levels of 1,25(OH)2D do not typically decrease until vitamin D
deficiency is severe [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 also serve
as a biomarker of effect on the body (i.e., relating to health status or outcomes) is not clear [1,3].

Researchers have not definitively identified serum concentrations of 25(OH)D associated with
deficiency (e.g., rickets), adequacy for bone 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 risk of vitamin D deficiency
at serum 25(OH)D concentrations less than 30 nmol/L (12 ng/mL; see Table 1 for definitions of
deficiency and inadequacy) [1]. Some people are potentially at risk 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. The FNB
committee also noted that serum concentrations greater than 125 nmol/L (50 ng/mL) can be
associated with adverse effects [1] (Table 1). The Endocrine Society has not identified 25(OH)D
concentrations associated with vitamin D sufficiency, insufficiency, and deficiency and does not
recommend routine testing of 25(OH)D concentrations in healthy individuals [11,12].

Table 1: Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health [1]

nmol/L* ng/mL* Health status
<30 <12 Associated with vitamin D deficiency, which can lead to rickets in infants and
children and osteomalacia in adults
30 to 12 to Generally considered inadequate for bone and overall health in healthy individuals
<50 <20
≥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.
Optimal serum concentrations of 25(OH)D for bone and general health have not been established
because they are likely to vary by stage of life, by race and ethnicity, and with each physiological
measure used [1,13,14]. In addition, although 25(OH)D levels rise in response to increased vitamin D
intake, the relationship is nonlinear [1]. The amount of increase varies, for example, by baseline serum
levels and duration of supplementation.

Recommended Intakes
Intake recommendations for vitamin D and other nutrients are provided in the Dietary Reference
Intakes (DRIs) developed by expert committees of NASEM [1]. DRI is the general term for a set of
reference values used for planning and assessing nutrient intakes of healthy people. These values,
which vary by age and sex, include the following:

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 daily intakes sufficient to maintain bone
health and normal calcium metabolism in healthy people. RDAs for vitamin D are listed in both
micrograms (mcg) and International Units (IU); 1 mcg vitamin D is equal to 40 IU (Table 2). Even though
sunlight is a major source 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.

Table 2: Recommended Dietary Allowances (RDAs) for Vitamin

D [1]
Age Male Female Pregnancy Lactation
0-12 months* 10 mcg 10 mcg
(400 IU) (400 IU)
1–13 years 15 mcg 15 mcg
(600 IU) (600 IU)
14–18 years 15 mcg 15 mcg 15 mcg 15 mcg
(600 IU) (600 IU) (600 IU) (600 IU)
19–50 years 15 mcg 15 mcg 15 mcg 15 mcg
(600 IU) (600 IU) (600 IU) (600 IU)
Age Male Female Pregnancy Lactation
51–70 years 15 mcg 15 mcg
(600 IU) (600 IU)
>70 years 20 mcg 20 mcg
(800 IU) (800 IU)

*Adequate Intake (AI)

Many other countries around the world and some professional societies have somewhat different
guidelines for vitamin D intakes [15]. These differences are a result of an incomplete understanding of
the biology and clinical implications of vitamin D, different purposes for the guidelines (e.g., for public
health in a healthy population or for clinical practice), and/or the use in some guidelines of
observational studies in addition to randomized clinical trials to establish recommendations [9,15]. For
example, the United Kingdom Scientific Advisory Committee on Nutrition recommends intakes of 10
mcg (400 IU)/day for individuals age 4 years and older [16]. The Endocrine Society recommends
routine vitamin D supplementation for children and teens age 1 to 18 years, people who are pregnant,
adults with pre-diabetes, and adults age 75 years and older, but not for healthy adults age 19 to 74
[11,12]. The Endocrine Society does not recommend specific doses but notes that all individuals
should adhere to the RDA.

Sources of Vitamin D
Food
Few foods naturally contain vitamin D. The flesh of fatty fish (such as trout, salmon, tuna, and
mackerel) and fish liver oils are among the best sources [17,1]. An animal’s diet affects the amount of
vitamin D in its tissues. Beef liver, egg yolks, and cheese have small amounts of vitamin D, primarily 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 additive for use as a source of vitamin D2 in food products [18]. Very
limited evidence suggests no substantial differences in the bioavailability of vitamin D from various
foods [19].

Animal-based foods typically provide some vitamin D in the form of 25(OH)D in addition to vitamin D3.
The impact of this form on vitamin D status 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 study found that when the 25(OH)D content of beef, pork,
chicken, turkey, and eggs is taken into account, the total amount of vitamin D in the food is 2 to 18
times higher than the amount in the parent vitamin alone, depending on the food [20].

Fortified foods provide most of the vitamin D in American diets [1,22]. For example, almost all of the
U.S. milk supply is voluntarily fortified with about 3 mcg/cup (120 IU), usually in the form of vitamin D3
[23]. In Canada, milk must be fortified with 0.88–1.0 mcg/100 mL (35–40 IU), and the required amount
for margarine is at least 13.25 mcg/100 g (530 IU). Other dairy products made from milk, such as
cheese and ice cream, are not usually fortified in the United States or Canada. Plant milk alternatives
(such as beverages made from soy, almond, or oats) are often fortified with similar amounts of vitamin
D to those in fortified cow’s milk (about 3 mcg [120 IU]/cup); the Nutrition Facts label lists the actual
amount [24]. Ready-to-eat breakfast cereals often contain added vitamin D, as do some brands of
orange juice, yogurt, margarine, and other food products.

The United States mandates the fortification of infant formula with 1–2.5 mcg/100 kcal (40–100 IU)
vitamin D; 1–2 mcg/100 kcal (40–80 IU) is the required amount in Canada [1].

A variety of foods and their vitamin D levels per serving are listed in Table 3.

Table 3: Vitamin D Content of Selected Foods [25]

Micrograms International
(mcg) per Units (IU) Percent
Food serving per serving 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, 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, 2.5–3.6 100–144 13–18
1 cup
Ready-to-eat cereal, fortified with 10% of the DV for vitamin D, 2.0 80 10
1 serving
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
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, ½ cup 0 0 0
Sunflower seeds, roasted, ½ cup 0 0 0
 Micrograms International
(mcg) per Units (IU) Percent
Food serving per serving DV*
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 age 4 years and older [26]. The labels must list vitamin D content in mcg per
serving and have the option of also listing the amount in IUs in parentheses. Foods providing 20% or
more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages
of the DV also contribute to a healthful diet.
** Vitamin D is in the yolk.

The U.S. Department of Agriculture’s (USDA’s) FoodData Central (https://fdc.nal.usda.gov/) lists the
nutrient content of many foods and provides a comprehensive list of foods containing vitamin D
arranged by nutrient content (https://ods.od.nih.gov/pubs/usdandb/VitaminD-Content.pdf) and by food name
(https://ods.od.nih.gov/pubs/usdandb/VitaminD-Food.pdf). However, FoodData Central does not include the
amounts of 25(OH)D in foods.

Sun exposure
Most people in the world 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 skin and converts cutaneous 7-dehydrocholesterol to previtamin D3, which in turn becomes
vitamin D3. Season, time of day, length of day, cloud cover, smog, skin melanin content, and sunscreen
are among the factors that affect UV radiation exposure and vitamin D synthesis. Older people and
people with dark skin are less able to produce vitamin D from sunlight [1]. UVB radiation does not
penetrate glass, so 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 sun exposure needed to maintain adequate vitamin D levels make it difficult to provide
guidelines on how much sun exposure is required for sufficient vitamin D synthesis [15,28]. Some
expert bodies and vitamin D researchers suggest, for example, that approximately 5–30 minutes of sun
exposure, particularly between 10 a.m. and 4 p.m., either daily or at least twice a week to the face,
arms, hands, and legs without sunscreen usually leads to sufficient vitamin D synthesis [13,15,28].
Moderate use of commercial tanning beds that emit 2% to 6% UVB radiation is also effective [13,29].

However, 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 is a carcinogen, and UV exposure is
the most preventable cause of skin cancer. Federal agencies and national organizations advise taking
photoprotective measures to reduce the risk of skin cancer, including using sunscreen with a sun
protection 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
usually do not apply sufficient amounts of sunscreen, cover all sun-exposed skin, or reapply sunscreen
regularly. Their skin probably synthesizes some vitamin D, even with typically applied sunscreen
amounts [1,28].

Dietary supplements
Dietary supplements can contain vitamins D2 or D3. Vitamin D2 is manufactured using UV irradiation of
ergosterol in yeast, and vitamin D3 is typically produced with irradiation of 7-dehydrocholesterol from
lanolin obtained from the wool of sheep [13,31]. An animal-free version of vitamin D3 sourced from
lichen is also available [32]. People who avoid all animal-sourced products can contact dietary
supplement manufacturers to ask about their sourcing and processing 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 evidence 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 dose, 25(OH)D3 is three to five times as potent as vitamin D3 [37,38]. However,
no 25(OH)D3 dietary supplements appear to be available to consumers on the U.S. market 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 mcg (204 IU) in men, 4.2 mcg (168
IU) in women, and 4.9 mcg (196 IU) in children age 2–19 years [39]. In fact, 2013–2016 NHANES data
showed that 92% of men, more than 97% of women, and 94% of people age 1 year and older ingested
less than the EAR of 10 mcg (400 IU) of vitamin D from food and beverages [40].

The analysis of 2015–2016 data also showed that 28% of all individuals age 2 years and older in the
United States took a dietary supplement containing vitamin D [39]. In addition, 26% of participants age
2–5 years and 14% of those age 6–11 years took supplements; rates increased with age from 10% of
those age 12–19 years to 49% of men and 59% of women age 60 and older. Total vitamin D intakes
were three times higher with supplement use than with diet alone; the mean intake from foods and
beverages alone for individuals age 2 and older was 4.8 mcg (192 IU) but increased to 19.9 mcg (796
IU) when dietary supplements were included.

Some people take very high doses of vitamin D supplements. In 2013–2014, an estimated 3.2% of the
U.S. adult population took supplements containing 100 mcg (4,000 IU) or more vitamin D [41].

One might expect a large proportion of the U.S. population to have vitamin D inadequacy on the basis
of vitamin D intakes from foods, beverages, and even dietary supplements. However, comparing
vitamin D intakes to serum 25(OH)D levels is problematic. One reason is that sun exposure affects
vitamin D status, so serum 25(OH)D levels are usually higher than would be predicted on the basis of
vitamin D dietary intakes alone [1]. Another reason is that animal foods contain some 25(OH)D. This
form of vitamin D is not included in intake surveys and is considerably 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 age 1 year and older had sufficient vitamin D intakes according to the FNB thresholds
[43]. However, 18% were at risk of inadequacy (levels of 30–49 nmol/L [12–19.6 ng/mL]), and 5% were
at risk of deficiency (levels below 30 nmol/L [12 ng/mL]). Four percent had levels higher than 125
nmol/L (50 ng/mL). Proportions at risk of deficiency were lowest among children age 1–5 years (0.5%),
peaked at 7.6% in adults age 20–39 years, and fell to 2.9% among adults age 60 years and older;
patterns were similar for risks of inadequacy. Rates of deficiency varied by race and ethnicity: 17.5% of
non-Hispanic Blacks were at risk of vitamin D deficiency, as were 7.6% of non-Hispanic Asians, 5.9% of
Hispanics, and 2.1% of non-Hispanic White people. Again, the pattern was similar for the risk of
inadequacy. Vitamin D status in the United States remained stable in the decade between 2003–2004
and 2013–2014.

Vitamin D Deficiency
People can develop vitamin D deficiency when usual intakes are lower over time than recommended
levels, 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. 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 deficiency is manifested as rickets, a disease characterized by a failure of bone

tissue to become properly mineralized, resulting in soft bones and skeletal deformities [44]. In addition
to bone deformities and pain, severe rickets can cause failure to thrive, developmental delay,
hypocalcemic seizures, tetanic spasms, cardiomyopathy, and dental abnormalities [45,46].

Prolonged exclusive breastfeeding 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
beginning in 2000 was 24.1 per 100,000 [48]. Rickets occurred mainly in Black children who were
breastfed longer, were born with low birthweight, weighed less, and were shorter than other children.
The incidence rate 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 almost all patients with rickets had been
breastfed [49].

The fortification of milk (a good 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 oil made rickets rare in
the United States [28,50]. However, the incidence of rickets is increasing globally, even in the United
States and Europe, especially 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 exposure [45,46].
In adults and adolescents, vitamin D deficiency 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
pain, hypocalcemic seizures, tetanic spasms, and dental abnormalities [45].

Screening for vitamin D status is becoming a more common part of the routine laboratory bloodwork
ordered by primary-care physicians, irrespective of any indications for this practice [6,52-54]. No
studies have examined whether such screening for vitamin D deficiency results in improved 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 deficiency in asymptomatic adults [6]. It
added that no national professional organization recommends population screening for vitamin D
deficiency.

Groups at Risk of Vitamin D Inadequacy

Obtaining sufficient vitamin D from natural (nonfortified) food sources alone is difficult. For many
people, consuming vitamin D-fortified foods and exposing themselves to some sunlight are essential
for maintaining a healthy vitamin D status. However, some groups might need dietary supplements to
meet their vitamin D requirements. The following groups are among those most likely to have
inadequate vitamin D status.

Breastfed infants
Consumption of human milk alone does not ordinarily 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 content of
human milk is related to the mother’s vitamin D status; studies suggest that the breastmilk of mothers
who take daily supplements containing at least 50 mcg (2,000 IU) vitamin D3 have higher levels of the
nutrient [57,58].

Although UVB exposure can produce vitamin D in infants, the American 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 exposed skin when sun exposure is
unavoidable [59]. The AAP recommends 10 mcg (400 IU)/day vitamin D supplements for exclusively
and partially breastfed infants starting shortly after birth and lasting until they are weaned and
consume at least 1,000 mL/day vitamin D-fortified formula or whole milk [57]. The AAP also
recommends 10 mcg (400 IU)/day supplemental 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
Older adults are at increased risk of developing vitamin D insufficiency, partly because the skin’s ability
to synthesize vitamin D declines with age [1,61]. In addition, older adults are likely to spend more time
than younger people indoors, and they might have inadequate dietary intakes of the vitamin [1].
People with limited sun exposure
Homebound individuals; people who wear long robes, dresses, or head 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 also limits vitamin D
synthesis from sunlight. However, because the extent and frequency of sunscreen use are unknown,
the role that sunscreen may play in reducing vitamin D synthesis is unclear [1].

People with dark skin

Greater amounts of the pigment melanin in the epidermal layer of the skin result in darker 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 dark skin have significant health consequences is not clear [14]. Those of African
American ancestry, for example, have lower rates of bone fracture and osteoporosis than do Whites
(see the section below on bone health and osteoporosis).

People with conditions that limit fat absorption

Because vitamin D is fat soluble, its absorption 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, celiac disease, Crohn’s disease, and ulcerative colitis [1,63]. In addition to having an increased
risk of vitamin D deficiency, people with these conditions might not eat certain foods, such as dairy
products (many of which are fortified with vitamin D), or eat only small amounts of these foods.
Individuals who have difficulty absorbing dietary fat might therefore require vitamin D supplementation
[63].

People with obesity or who have undergone gastric bypass surgery

Individuals with a body mass index (BMI) of 30 or more have lower serum 25(OH)D levels than
individuals without obesity. Obesity does not affect the skin’s capacity to synthesize vitamin D.
However, greater amounts of subcutaneous fat sequester more of the vitamin [1]. People with obesity
might need greater intakes of vitamin D to achieve 25(OH)D levels similar to those of people with
normal weight [1,64,65].

Individuals with obesity who have undergone gastric bypass surgery can also become vitamin D
deficient. In this procedure, part of the upper small intestine, where vitamin D is absorbed, is bypassed,
and vitamin D that is mobilized into the bloodstream from fat stores might not raise 25(OH)D to
adequate levels over time [66,67]. Various expert 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 screening, 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 too
contradictory to conclude that the vitamin had any effect on a long list of potential health outcomes
(e.g., on resistance to chronic diseases or functional measures), except for measures related to bone
health. Similarly, in a review of data from nearly 250 studies published between 2009 and 2013, the
Agency for Healthcare Research and Quality concluded that no relationship could be firmly 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 section measured serum 25(OH)D levels using various 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 validity of conclusions
drawn from studies that use such measures and, especially, 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 webpage.

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 building. Over time, bone density can
decline, and osteoporosis can eventually 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 mass and structural deterioration of bone tissue that increases bone
fragility and the risk of bone fractures [72]. About 2.3 million osteoporotic fractures occurred in the
United States in 2015 [73]. Osteoporosis is, in part, a long-term effect of calcium and/or vitamin D
insufficiency, in contrast to rickets and osteomalacia, which result from vitamin D deficiency.
Osteoporosis is most often associated with inadequate calcium intakes, but insufficient vitamin D
intakes contribute to osteoporosis by reducing calcium absorption [1].

Bone health also depends on support from the surrounding muscles to assist with balance and
postural sway and thereby reduce the risk of falling. Vitamin D is also needed for the normal
development and growth of muscle fibers. In addition, inadequate vitamin D levels can adversely affect
muscle strength and lead to muscle weakness and pain (myopathy) [1].

Most trials of the effects of vitamin D supplements on bone health also included calcium supplements,
so isolating the effects of each nutrient is difficult. In addition, studies provided different amounts of
nutrients and used different dosing 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 result in small increases in bone mineral density throughout the skeleton
[1,74]. They also help reduce fracture rates in institutionalized older people. However, the evidence on
the impact of vitamin D and calcium supplements on fractures in community-dwelling individuals is
inconsistent.

The USPSTF evaluated 11 randomized clinical trials of vitamin D and/or calcium supplementation in a
total of 51,419 healthy, community-dwelling adults age 50 years and older who did not have
osteoporosis, vitamin D deficiency, or prior fractures [75,76]. It concluded that the current evidence 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
mg or less of calcium to prevent fractures in this population, but it could not determine the balance of
benefits and harms from higher doses.

The USPSTF also reviewed the seven published studies on the effects of vitamin D supplementation
(two of them also included calcium supplementation) on the risk of falls in community-dwelling adults
age 65 years or older who did not have osteoporosis or vitamin D deficiency. It concluded with
moderate certainty that vitamin D supplementation does not reduce the numbers of falls or injuries,
such as fractures, resulting from falls [77,78]. Another recent systematic review also found that vitamin
D and calcium supplements had no beneficial effects on fractures, falls, or bone mineral density
[79,80]. In contrast, a meta-analysis of six 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 mean 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 mcg [400–800 IU]/day or more at least every week or as
rarely as once a year) for 9 months to 5 years found that the supplements provided no protection from
fractures in 34,243 older adults [81].

More recently, a 2022 ancillary study of the Vitamin D and Omega-3 Trial (VITAL; described in the
Cancer section below) investigated whether supplemental vitamin D3 (50 mcg [2,000 IU]/day) would
lower the risk of fractures in 25,871 generally healthy men age 50 years and older and women age 55
years and older over a median follow-up of 5.3 years [82]. The mean age of all participants was 67.1
years; 50.6% were women and 20.2% were Black. Most participants were vitamin D sufficient; at
baseline, only 2.4% had serum 25(OH)D levels less than 30 nmol/L (12 ng/mL), and 12.9% less than 50
nmol/L (20 ng/mL). Vitamin D supplementation did not lower the risk of total fractures, hip fractures, or
nonvertebral fractures as compared with placebo. No substantial between-group differences in fracture
incidence were found by race, ethnic group, BMI, age, baseline 25(OH)D levels, or whether participants
took supplemental calcium, were at high fracture risk, or had a history of fragility fractures.

Vitamin D supplements for bone health in minority populations

Bone mineral density, bone mass, and fracture risk are correlated with serum 25(OH)D levels in White
Americans and Mexican Americans, but not in Black Americans [14,83]. 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 trial randomized 260 Black women age 60 years and older (mean age 68.2 years) to
receive 60 to 120 mcg (2,400 to 4,800 IU) per day vitamin D3 supplementation to maintain serum
25(OH)D levels above 75 nmol/L (30 ng/mL) for 3 years [84]. The results showed no association
between 25(OH)D levels or vitamin D dose and the risk 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 daily vitamin D intakes of 50 mcg (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) [84].

Vitamin D supplements and muscle function

Studies examining the effects of supplemental vitamin D on muscle strength and on rate of decline in
muscle function have had inconsistent results [55]. One recent clinical trial, for example, randomized
78 frail and near-frail adults age 65 years and older to receive 20 mcg (800 IU) vitamin D3, 10 mcg
25(OH)D, or placebo daily for 6 months. The groups showed no significant differences in measures of
muscle strength or performance [85]. Another study randomized 100 community-dwelling men and
women age 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 [86]. Participants in the treatment group whose serum
25(OH)D level was less than 70 nmol/L (28 ng/ml) after 4 months received an additional 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 supplementation did not affect lower-extremity power, strength, 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 health care providers about their
needs for both nutrients as part of an overall plan to maintain bone health and to prevent or treat
osteoporosis.

Cancer
Laboratory and animal studies suggest that vitamin D might inhibit carcinogenesis and slow tumor
progression by, for example, promoting cell differentiation and inhibiting metastasis. Vitamin D might
also have anti-inflammatory, immunomodulatory, proapoptotic, and antiangiogenic effects [1,87].
Observational studies and clinical trials provide mixed evidence on whether vitamin D intakes or serum
levels affect cancer incidence, progression, or mortality risk.

Total cancer incidence and mortality

Some observational studies show associations between low serum levels of 25(OH)D and increased
risks of cancer incidence and death. In a meta-analysis of 16 prospective cohort studies in a total of
137,567 participants who had 8,345 diagnoses of cancer, 5,755 participants died from cancer [88]. A
50 nmol/L (20 ng/mL) increase in 25(OH)D levels was associated with an 11% reduction in total cancer
incidence rates and, in women but not men, a 24% reduction in cancer mortality rates. A meta-analysis
of prospective studies that evaluated the association between serum 25(OH)D levels and cancer
incidence (8 studies) or cancer mortality (16 studies) found that cancer risk decreased by 7% and
cancer mortality rates decreased by 2% with each 20 nmol/L (8 ng/mL) increase in serum 25(OH)D
levels [89]. Importantly, not all observational studies found higher vitamin D status to be beneficial, and
the studies varied considerably in study populations, baseline comorbidities, and measurement of
vitamin D levels.

Clinical trial evidence provides some support for the observational findings. For example, three meta-
analyses of clinical trial evidence found that vitamin D supplementation does not affect cancer
incidence but does significantly reduce total cancer mortality rates by 12%–13% [90-92]. In the most
recent meta-analysis, 10 randomized clinical trials (including the VITAL trial described below) that
included 6,537 cancer cases provided 10 to 50 mcg (400 to 2,000 IU) vitamin D3 daily (six trials) or 500
mcg (20,000 IU)/week to 12,500 mcg (500,000 IU)/year boluses of vitamin D3 (four trials) [91]. 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 VITAL clinical trial that investigated the effects of vitamin D supplementation on the primary
prevention of cancer in the general population gave 50 mcg (2,000 IU)/day vitamin D3 supplements
with or without 1,000 mg/day marine omega-3 fatty acids or a placebo for a median of 5.3 years [93].
The study included 25,871 men age 50 years and older and women age 55 years and older who had no
history of cancer, and most had adequate serum 25(OH)D levels at baseline. Rates of breast, 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
with overweight or obesity.

The Women’s Health Initiative (WHI) clinical trial randomized 36,282 postmenopausal women to
receive 10 mcg (400 IU) vitamin D3 plus 1,000 mg calcium daily or a placebo for a mean of 7 years [94].
Results showed no effect of supplemental vitamin D and calcium on cancer incidence or mortality
during the 7-year trial. Similarly, the supplements did not affect cancer incidence over a long-term
median follow-up of 22.3 years, but they did reduce cancer mortality by 7% over this period of time [95].

A few studies have examined the effect of vitamin D supplementation on specific cancers. Below are
brief descriptions of studies of vitamin D and its association with, or effect on, breast, colorectal, lung,
pancreatic, and prostate cancers.

Breast cancer
Some observational studies support an inverse association between 25(OH)D levels and breast cancer
risk and mortality, but others do not [96-99]. In the WHI clinical trial described above, vitamin D3 and
calcium supplements did not reduce breast cancer incidence, and 25(OH)D levels at the start of the
study were not associated with breast cancer risk [100].

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 risk of in situ
(noninvasive) breast cancer [101]. However, women with vitamin D intakes higher than 15 mcg (600
IU)/day at the start of the trial and who received the supplements experienced a 28% increased risk of
invasive (but not in situ) breast cancer.
Colorectal cancer
A large case-control study included 5,706 individuals who developed colorectal cancer and whose
25(OH)D levels were assessed a median of 5.5 years from blood draw to cancer diagnosis and 7,105
matched controls [102]. 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 WHI clinical trial described above, vitamin D3 and calcium supplements had no effect on rates of
colorectal cancer [103]. 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) still had the
same colorectal cancer risk as those who received placebo [101].

Another study included 2,259 healthy individuals age 45 to 75 years who had had one or more serrated
polyps (precursor lesions to colorectal cancer) that had been removed [104]. These participants were
randomized to take 25 mcg (1,000 IU) vitamin D3, 1,200 mg calcium, both supplements, or a placebo
daily for 3–5 years, followed by an additional 3–5 years of observation after participants stopped the
treatment. Vitamin D alone did not significantly affect the development of new serrated polyps, but the
combination of vitamin D with calcium increased the risk almost fourfold. The VITAL trial found no
association between vitamin D supplementation and the risk of colorectal adenomas or serrated
polyps [105].

Lung cancer
A study 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 risk of subsequent lung cancer, even
when the investigators analyzed the data by sex, age, race and ethnicity, and smoking status [106].

Pancreatic cancer
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 [107]. 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 risk of developing pancreatic cancer over 16.7 years than those in the lowest quintile
(less than 32 nmol/L [12.8 ng/mL]) [108]. An investigation 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 [109].

Prostate cancer
Research to date provides mixed evidence on whether levels of 25(OH)D are associated with the
development of prostate cancer. Several studies published in 2014 suggested that high levels of
25(OH)D might increase the risk of prostate cancer. For example, 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
cancer for participants with higher levels of 25(OH)D [110]. 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
risk of the disease than men with either lower or higher values [111]. This U-shaped association was
most pronounced for men with the most aggressive forms of prostate cancer. A case-control analysis
of 1,695 cases of prostate cancer and 1,682 controls found no associations between 25(OH)D levels
and prostate cancer risk [112]. However, higher serum 25(OH)D levels (at a cut point of 75 nmol/L [30
ng/mL]) were linked to a modestly higher risk of slow-growth prostate cancer and a more substantial
lower risk of aggressive disease.

Since 2014, however, several published studies and meta-analyses have found no relationship between
25(OH)D levels and prostate cancer risk [113,114]. For example, 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 cancer and 20,261 control participants [115]. Vitamin D deficiency or insufficiency
did not increase the risk of prostate 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 death from the disease or from any cause. One study included 1,119 men treated
for prostate 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 cause [116]. However, a meta-analysis of
seven cohort studies that included 7,808 men with prostate cancer found higher 25(OH)D levels to be
significantly associated with lower mortality rates from prostate cancer or any other cause [117]. 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 mortality.

For men with prostate cancer, whether vitamin D supplementation lengthens cancer-related survival is
not clear. A meta-analysis of three randomized controlled trials in 1,273 men with prostate cancer
found no significant differences in total mortality rates between those receiving vitamin D
supplementation (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 [118].

Conclusions about vitamin D and cancer

The USPSTF stated that, due to insufficient evidence, it was unable to assess the balance of benefits
and harms of supplemental vitamin D to prevent cancer [119]. Taken together, studies to date do not
indicate that vitamin D with or without calcium supplementation reduces the incidence of cancer, but
adequate or higher 25(OH)D levels might reduce cancer mortality rates. Further research is needed to
determine whether vitamin D inadequacy increases cancer risk, whether greater exposure to the
nutrient can prevent cancer, and whether some individuals could have an increased risk of cancer
because of their vitamin D status over time.

Cardiovascular disease
Vitamin D helps regulate the renin-angiotensin-aldosterone system (and thereby blood pressure),
vascular cell growth, and inflammatory and fibrotic pathways [120]. Vitamin D deficiency is associated
with vascular dysfunction, arterial stiffening, left ventricular hypertrophy, and hyperlipidemia [121]. For
these reasons, vitamin D has been linked to heart health and risk of CVD.

Observational studies support an association between higher serum 25(OH)D levels and a lower risk of
CVD incidence and mortality. For example, a meta-analysis included 34 observational studies that
followed 180,667 participants (mean age greater than 50 years) for 1.3 to more than 32 years. The
results showed that baseline serum 25(OH)D levels were inversely associated with total number of
CVD events (including myocardial infarction, ischemic heart disease, heart failure, and stroke) and
mortality risk [122]. Overall, the risk of CVD events was 10% lower for each 25 nmol/L (10 ng/mL)
increase in serum 25(OH)D.

Another large observational 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 myocardial
infarction [123]. Other 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 risk of
ischemic stroke, ischemic heart disease, myocardial infarction, and early death [124,125].

In contrast to the observational studies, clinical trials have provided little support for the hypothesis
that supplemental vitamin D reduces the risk of CVD or CVD mortality. For example, a 3-year trial in
New Zealand randomized 5,110 adults (mean age 65.9 years) to a single dose of 5,000 mcg (200,000
IU) vitamin D3 followed by 2,500 mcg (100,000 IU) each month or a placebo for a median of 3.3 years
[126]. Vitamin D supplementation had no effect on the incidence rate of myocardial infarction, angina,
heart failure, arrhythmia, arteriosclerosis, stroke, venous thrombosis, or death from CVD. Similarly, the
VITAL clinical trial described above found that vitamin D supplements did not significantly decrease
rates of heart attacks, strokes, coronary revascularization, or deaths from cardiovascular causes [93].
Moreover, the effects did not vary by baseline serum 25(OH)D levels or whether participants took the
trial’s omega-3 supplement in addition to vitamin D.

However, another clinical trial designed to investigate bone fracture risk found that 20 mcg (800
IU)/day vitamin D3 (with or without calcium) or a placebo in 5,292 adults age 70 years and older for a
median of 6.2 years offered protection from cardiac failure, but not myocardial infarction or stroke
[127]. In the WHI clinical trial described above, daily supplementation with 10 mcg (400 IU) vitamin D3
and 1,000 mg calcium did not affect cardiovascular disease risk during the 7-year trial [128] or during a
long-term median follow-up of 22.3 years [95]. However, during this long-term follow-up period, women
who received the supplements had a 6% higher risk of death from cardiovascular disease than those
who received placebo [95].

High serum cholesterol levels and hypertension are two of the main risk factors for CVD. The data on
supplemental vitamin D and cholesterol levels are mixed, as shown in one meta-analysis of 41 clinical
trials in a total of 3,434 participants (mean age 55 years). The results of this analysis showed that 0.5
mcg (20 IU) to 214 mcg (8,570 IU)/day vitamin D supplementation (mean of 2,795 IU) for 6 weeks to 3
years reduced serum total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels, but
not high-density lipoprotein cholesterol levels [129].

Studies of the effects of vitamin D supplements on hypertension have also 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
blood pressure [130]. In contrast, another meta-analysis of 30 clinical trials in 4,744 participants (mean
age 54.5 years) that administered 5 mcg (200 IU) to 300 mcg (12,000 IU)/day vitamin D3 for a mean of
5.6 months showed that more than 20 mcg (800 IU)/day significantly reduced systolic and diastolic
blood pressure in normal-weight participants who had hypertension [131]. However, more than 20 mcg
(800 IU)/day vitamin D3, when taken with calcium supplements, significantly increased blood pressure
in participants with overweight and obesity. Another meta-analysis of genetic studies in 146,581
participants (primarily adults) found that a low vitamin D status increased blood pressure and
hypertension risk in people with genetic variants associated with low endogenous production of
25(OH)D [132].

Overall, clinical trials show that vitamin D supplementation does not reduce CVD risk, even for people
with low 25(OH)D status (below 20 nmol/L [12 ng/mL]) at baseline [93,126].

Depression
Vitamin D is involved in various brain processes, and vitamin D receptors are present on neurons and
glia in areas of the brain thought to be involved in the pathophysiology of depression [133].

A systematic review and meta-analysis of 14 observational studies that included a total of 31,424
adults (mean age ranging from 27.5 to 77 years) found an association between deficient or low levels
of 25(OH)D and depression [133].

Clinical trials, however, do not support these findings. For example, a meta-analysis of nine trials with a
total of 4,923 adult participants diagnosed with depression or depressive symptoms found no
significant reduction in symptoms after supplementation with vitamin D [134]. The trials administered
different amounts of vitamin D (ranging from 10 mcg [400 IU]/day to 1,000 mcg [40,000 IU]/week).
They also had different study durations (5 days to 5 years), mean participant ages (range, 22 years to
75 years), and baseline 25(OH)D levels; furthermore, some but not all studies administered concurrent
antidepressant medications.

Three trials conducted since that meta-analysis also found no effect of vitamin D supplementation on
depressive symptoms. One trial included 206 adults (mean age 52 years) who were randomized to take
a bolus dose of 2,500 mcg (100,000 IU) vitamin D3 followed by 500 mcg (20,000 IU)/week or a placebo
for 4 months [135]. Most participants had minimal or mild depression, had a low mean baseline 25(OH)
level of 33.8 nmol/L (13.5 ng/mL), and were not taking antidepressants. The second trial included 155
adults age 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 addition, they were not taking antidepressants [136,137]. Participants were randomized to
take either 30 mcg (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 depression and 1,696 with an
increased risk of recurrent 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 oil) or a placebo for a
median of 5.3 years [138]. The groups showed no significant differences in the incidence and recurrent
rates of depression, clinically relevant depressive symptoms, or changes in mood scores.

Overall, clinical trials did not find that vitamin D supplements helped prevent or treat depressive
symptoms or mild depression, especially in middle-age to older adults who were not taking prescription
antidepressants. No studies have evaluated whether vitamin D supplements may benefit individuals
under medical care for clinical depression who have low or deficient 25(OH)D levels and are taking
antidepressant medication.

Multiple sclerosis
MS is an autoimmune disease of the central nervous system that damages the myelin sheath
surrounding and protecting nerve cells in the brain and spinal cord. This damage hinders or blocks
messages between the brain and body, leading to clinical features, such as vision loss, motor
weakness, spasticity, ataxia, tremor, sensory loss, and cognitive impairment [139,140]. Some people
with MS eventually lose the ability to write, speak, or walk.

The geographical distribution of MS around the world is unequal. Few people near the equator develop
the disease, whereas the prevalence is higher further north and south. This uneven distribution has led
to speculation that lower vitamin D levels in people who have less sunlight exposure might predispose
them to the disease [140].

Many epidemiological and genetic studies have shown an association between MS and low 25(OH)D
levels before and after the disease begins [140]. Observational studies suggest that adequate vitamin
D levels might reduce the risk of contracting MS and, once MS is present, decrease the risk of relapse
and slow the disease’s progression [141]. One study, for example, tested 25(OH)D levels in 1,092
women in Finland an average of 9 years before their MS diagnosis and compared their outcomes with
those of 2,123 similar women who did not develop MS [142]. More than half the women who developed
MS had deficient 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 as
high as levels of 50 nmol/L or higher.

Two earlier prospective studies of similar design—one in the United States with 444 non-Hispanic
White individuals [143] and the other with 576 individuals in northern Sweden [144]—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 supplemental 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 low quality [140]. Overall, vitamin D supplementation, when compared
with placebo administration, had no effect on relevant clinical outcomes, such as recurrent relapse or
worsened disability.

Experts have reached no firm consensus on whether vitamin D can help prevent MS given the lack of
clinical trial evidence [145]. In addition, studies have not consistently shown that vitamin D
supplementation tempers the signs and symptoms of active MS or reduces rates of relapse.

Type 2 diabetes
Vitamin D plays a role in glucose metabolism. 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 [146]. Vitamin D might be involved in the pathophysiology of type 2 diabetes through
its effects on glucose metabolism and insulin signaling as well as its ability to reduce inflammation
and improve pancreatic beta-cell function [147,148].

Observational 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 overweight or had
obesity and were therefore more predisposed to developing diabetes and having lower 25(OH)D levels
[1]. A review of 71 observational studies in adults with and without type 2 diabetes from 16 countries
found a significant inverse relationship between vitamin D status and blood sugar levels in participants
who did and did not have diabetes [149].

In contrast to observational studies, clinical trials provide little support for the benefits of vitamin D
supplementation for glucose homeostasis. One trial included 65 adult men and women (mean age 32
years) with overweight or obesity who were otherwise healthy, did not have diabetes, and had low
serum vitamin D levels (at or below 50 nmol/L [20 ng/mL]) [150]. The investigators randomly assigned
participants to receive either a bolus oral dose of 2,500 mcg (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 study, vitamin
D supplementation did not improve insulin sensitivity or insulin secretion in comparison with placebo.

One systematic review and meta-analysis evaluated 35 clinical trials that included 43,407 adults with
normal glucose tolerance, prediabetes, or type 2 diabetes who received a median of 83 mcg (3,332
IU)/day vitamin D supplements or placebo for a median of 16 weeks [151]. Vitamin D had no significant
effects on glucose homeostasis, insulin secretion or resistance, or hemoglobin A1c levels (a measure
of average blood sugar levels over the previous 2–3 months), irrespective of the study 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 trial in Norway, 511 men and women age 25–80 years (mean age 62 years) with prediabetes received
500 mcg (20,000 IU) vitamin D3 or a placebo each week for 5 years [152]. 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 resistance. At baseline, participants had an adequate
mean serum 25(OH)D level of 60 nmol/L (24 ng/mL).

The largest trial to date of vitamin D supplements for diabetes prevention randomized 2,423 men and
women age 25 years and older (mean age 60 years) with prediabetes and overweight or obesity (mean
BMI of 32.1) to 100 mcg (4,000 IU)/day vitamin D3 or placebo for a median of 2.5 years [148]. 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 [148,153].

Studies have also assessed the value of vitamin D supplementation for managing diabetes, and they
have found that the vitamin offers limited benefits. One meta-analysis of 20 clinical trials compared the
effects of 0.5 mcg (20 IU)/day to 1,250 mcg (50,000 IU)/week vitamin D supplementation for 2–6
months with those of placebo on glycemic control in 2,703 adults from around the world who had
diabetes [146]. The vitamin D reduced insulin resistance to a small but significant degree, especially in
people taking more than 50 mcg (2,000 IU)/day who were vitamin D deficient at baseline, had good
glycemic control, did not have obesity, and were of Middle Eastern ethnicity. However, the
supplementation had no significant effects on fasting blood glucose, hemoglobin A1c, or fasting
insulin levels.

Clinical trials to date provide little evidence that vitamin D supplementation helps maintain glucose
homeostasis, reduces the risk of progression from prediabetes to type 2 diabetes, or helps manage the
disease, particularly in vitamin D-replete individuals.

Weight loss
Observational studies indicate that greater body weights are associated with lower vitamin D status,
and individuals with obesity frequently have marginal or deficient circulating 25(OH)D levels [154].
However, clinical trials do not support a cause-and-effect relationship between vitamin D and weight
loss.

A systematic review and meta-analysis of 15 weight-loss intervention studies that used caloric
restriction, exercise, or both, but not necessarily vitamin D supplementation or other treatments, found
that people who lost weight had significantly greater increases in serum 25(OH)D levels than those
who maintained their weight [155]. In another study, 10 mcg (400 IU)/day vitamin D and 1,000 mg/day
calcium supplementation slightly, but significantly, reduced weight gain amounts in comparison with
placebo in postmenopausal women, especially those with a baseline total calcium intake of less than
1,200 mg/day [156]. However, a meta-analysis of 12 vitamin D supplementation trials (including 5 in
which body composition measurements were primary outcomes) found that vitamin D supplements
without calorie restriction did not affect body weight or fat mass when the results were compared with
those of placebo [157].
Overall, the available research suggests that consuming higher amounts of vitamin D or taking vitamin
D supplements does not promote weight loss.

Health Risks from Excessive Vitamin D

Excess amounts of vitamin D are toxic. Because vitamin D increases calcium absorption in the
gastrointestinal tract, vitamin D toxicity results in marked hypercalcemia (total calcium greater than
11.1 mg/dL, beyond the normal range of 8.4 to 10.2 mg/dL), hypercalciuria, and high serum 25(OH)D
levels (typically greater than 375 nmol/l [150 ng/mL]) [158]. Hypercalcemia, in turn, can lead to nausea,
vomiting, muscle weakness, neuropsychiatric disturbances, pain, loss of appetite, dehydration, polyuria,
excessive thirst, and kidney stones.

In extreme cases, vitamin D toxicity causes renal failure, calcification of soft tissues throughout the
body (including in coronary vessels and heart valves), cardiac arrhythmias, and even death. Vitamin D
toxicity has been caused by consumption of dietary supplements that contained excessive vitamin D
amounts because of manufacturing errors, that were taken inappropriately or in excessive amounts, or
that were incorrectly prescribed by physicians, [158-160].

Experts do not believe that excessive sun exposure results in vitamin D toxicity because thermal
activation of previtamin D3 in the skin gives rise to various non-vitamin D forms that limit formation of
vitamin D3. Some vitamin D3 is also 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) [161-163].

The combination of high intakes of calcium (about 2,100 mg/day from food and supplements) with
moderate amounts of vitamin D (about 19 mcg [765 IU]/day from food and supplements) increased the
risk 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 mcg (400 IU)/day vitamin D or a placebo [164].
However, other, shorter (from 24 weeks to 5 years) clinical trials of vitamin D supplementation alone or
with calcium in adults found greater risks of hypercalcemia and hypercalciuria, but not of kidney stones
[165,166].

The FNB established ULs for vitamin D in 2010 (Table 4) [1]. While acknowledging that signs and
symptoms of toxicity are unlikely at daily intakes below 250 mcg (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 even lower serum levels (approximately 75–120 nmol/L [30–48 ng/mL]) are
associated with increases in rates of all-cause mortality, risk of cancer at some sites (e.g., pancreas),
risk of cardiovascular events, and number of falls and fractures among older adults.

Table 4: Tolerable Upper Intake Levels (ULs) for Vitamin D [1]

Age Male Female Pregnancy Lactation
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)
Age Male Female Pregnancy Lactation
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 health care providers.

Orlistat
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 [167-170].

Statins
Statin medications reduce cholesterol synthesis. Because endogenous vitamin D is derived from
cholesterol, statins may also reduce vitamin D synthesis [170]. In addition, high intakes of vitamin D,
especially from supplements, might reduce the potency of atorvastatin (Lipitor), lovastatin (Altoprev
and Mevacor), and simvastatin (FloLipid and Zocor), because these statins and vitamin D appear to
compete for the same metabolizing enzyme [170-173].

Steroids
Corticosteroid medications, such as prednisone (Deltasone, Rayos, and Sterapred), are often
prescribed to reduce inflammation. These medications can reduce calcium absorption and impair
vitamin D metabolism [174-176]. In the NHANES 2001–2006 survey, 25(OH)D deficiency (less than 25
nmol/L [10 ng/mL]) was more than twice as common among children and adults who reported oral
steroid use (11%) than in nonusers (5%) [177].

Thiazide diuretics
Thiazide diuretics (e.g., Hygroton, Lozol, and Microzide) decrease urinary calcium excretion. The
combination of these diuretics with vitamin D supplements (which increase intestinal calcium
absorption) might lead to hypercalcemia, especially among older adults and individuals with
compromised renal function or hyperparathyroidism [170,178,179].

Vitamin D and Healthful Diets

The federal government’s 2020–2025 Dietary Guidelines for Americans notes that “Because foods
provide an array of nutrients and other components that have benefits for health, nutritional needs
should be met primarily through foods. … In some cases, fortified foods and dietary supplements are
useful when it is not possible otherwise to meet needs for one or more nutrients (e.g., during specific
life stages such as pregnancy).”

For more information about building a healthy dietary pattern, refer to the Dietary Guidelines for
Americans (https://www.dietaryguidelines.gov) and the USDA’s MyPlate. (https://www.choosemyplate.gov/)

The Dietary Guidelines for Americans describes a healthy dietary pattern 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.

References
1. Institute of Medicine, Food and Nutrition Board. Dietary Reference Intakes for Calcium and
Vitamin D. Washington, DC: National Academy Press, 2010.
2. Norman AW, Henry HH. Vitamin D. In: Erdman JW, Macdonald IA, Zeisel SH, eds. Present
Knowledge in Nutrition, 10th ed. Washington DC: Wiley-Blackwell, 2012.
3. Jones G. Vitamin D. In: Ross AC, Caballero B, Cousins RJ, Tucker KL, Ziegler TR, eds. Modern
Nutrition in Health and Disease, 11th ed. Philadelphia: Lippincott Williams & Wilkins, 2014.
4. Silva MC, Furlanetto TW. Intestinal absorption of vitamin D: A systematic review. Nutr Rev
2018;76:60-76. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/29025082/)]
5. Sempos CT, Heijboer AC, Bikle DD, Bollerslev J, Bouillon R, Brannon PM, et al. Vitamin D assays
and the definition of hypovitaminosis D. Results from the First International Conference on
Controversies in Vitamin D. Br J Clin Pharmacol 2018;84:2194-207. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/29851137/)]
6. LeFevre ML. Screening for vitamin deficiency in adults: U.S. Preventive Services Task Force
recommendation statement. Ann Intern Med 2015;162:133-40. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/25419853/)]
7. Brooks SPJ, Sempos CT. The importance of 25-hydroxyvitamin D assay standardization and the
Vitamin D Standardization Program. Journal of AOAC International 2017;100:1223-4.
8. Taylor CL, Sempos CT, Davis CD, Brannon PM. Vitamin D: moving forward to address emerging
science. Nutrients 2017, 9, 1308; doi:10.3390/mu9121308. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/29194368/)]
 9. Sempos CT, Binkley N. 25-hydroxyvitamin D assay standardisation and vitamin D guidelines
paralysis. Public Health Nutrition 2020;23:1153-64. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/32301688/)]
10. Office of Dietary Supplements, National Institutes of Health. Vitamin D Standardization Program
(VDSP).
11. Demay MB, Pittas AG, Bikle DD, Diab DL, Kiely ME, et al. Vitamin D for the Prevention of Disease:
An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2024 Jul
12;109(8):1907-1947. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/38828931/)]
12. Shah VP, Nayfeh T, Alsawaf Y, Saadi S, Farah M, et al. A Systematic Review Supporting the
Endocrine Society Clinical Practice Guidelines on Vitamin D. J Clin Endocrinol Metab. 2024 Jul
12;109(8):1961-1974. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/38828942/)]
13. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266-81. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/17634462/)]
14. Brown LL, Cohen B, Tabor D, Zappala G, Maruvada P, Coates PM. The vitamin D paradox in Black
Americans: A systems-based approach to investigating clinical practice, research, and public
health—expert panel meeting report. BMC Proceedings, 2018;12(Suppl 6):6. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/30044889/)]
15. Bouillon R. Comparative analysis of nutritional guidelines for vitamin D. Nat Rev Endocrinol
2017;13:466-79. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/28387318/)]
16. Scientific Advisory Committee on Nutrition. Vitamin D and Health
(https://www.gov.uk/government/publications/sacn-vitamin-d-and-health-report). 2016.
17. Roseland JM, Phillips KM, Patterson KY, Pehrsson PR, Taylor CL. Vitamin D in foods: An evolution
of knowledge. Pages 41-78 in Feldman D, Pike JW, Bouillon R, Giovannucci E, Goltzman D,
Hewison M, eds. Vitamin D, Volume 2: Health, Disease and Therapeutics, Fourth Edition. Elsevier,
2018.
18. U.S. Food and Drug Administration. Food additives permitted for direct addition to food for
human consumption; vitamin D2 mushroom powder. Federal Register 2020;85:41916-20.
19. Borel P, Caillaud D, Cano NJ. Vitamin D bioavailability: State of the art. Crit Rev Food Sci Nutr
2015;55:1193-205. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/24915331/)]
20. Taylor CL, Patterson KY, Roseland JM, Wise SA, Merkel JM, Pehrsson PR, Yetley EA. Including
food 25-hydroxyvitamin D in intake estimates may reduce the discrepancy between dietary and
serum measures of vitamin D status. J Nutr 2014;144:654-9. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/24623845/)]
21. Cashman KD, Seamans KM, Lucey AJ, Stocklin E, Weber P, Kiely M, Hill TR. Relative effectiveness
of oral 25-hydroxyvitamin D3 and vitamin D3 in raising wintertime serum 25-hydroxyvitamin D in
older adults. Am J Clin Nutr 2012;95:1350-6. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/22552038/)]
22. Calvo MS, Whiting SJ, Barton CN. Vitamin D fortification in the United States and Canada: Current
status and data needs. Am J Clin Nutr 2004;80:1710S-6S. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/15585792/)]
23. Yetley EA. Assessing the vitamin D status of the US population. Am J Clin Nutr 2008;88:558S-
64S. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/18689402/)]
24. U.S. Food and Drug Administration. Vitamin D for milk and milk alternatives
(https://www.fda.gov/food/food-additives-petitions/vitamin-d-milk-and-milk-alternatives). January 4,
2018.
25. U.S. Department of Agriculture, Agricultural Research Service. FoodData Central
(https://fdc.nal.usda.gov/index.html).
26. U.S. Food and Drug Administration. Food labeling: Revision of the Nutrition and Supplement Facts
labels (https://www.federalregister.gov/documents/2016/05/27/2016-11867/food-labeling-revision-of-the-
nutrition-and-supplement-facts-labels). Federal Register 81(103):33742-33999. 2016.
27. Hossein-nezhad A, Holick MF. Vitamin D for health: A global perspective. Mayo Clin Proc
2013;88:720-55. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/23790560/)]
28. U.S. Department of Health and Human Services. The Surgeon General’s Call to Action to Prevent
Skin Cancer (https://www.surgeongeneral.gov/library/calls/prevent-skin-cancer/call-to-action-prevent-skin-
cancer.pdf). Washington, DC: U.S. Dept of Health and Human Services, Office of the Surgeon
General; 2014.
29. Holick MF. Vitamin D: the underappreciated D-lightful hormone that is important for skeletal and
cellular health. Curr Opin Endocrinol Diabetes 2002;9:87-98.
30. Weisberg P, Scanlon KS, Li R, Cogswell ME. Nutritional rickets among children in the United
States: review of cases reported between 1986 and 2003. Am J Clin Nutr 2004;80:1697S-705S.
[PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/15585790/)]
31. Hirsch AL. Industrial Aspects of Vitamin D
(https://www.sciencedirect.com/science/article/pii/B978012381978910006X). In: Feldman D, Pike JW,
Adams JS, eds. Vitamin D. 3rd ed. Academic Press; 2011:73-93.
32. National Institutes of Health. Dietary Supplement Label Database. (https://dsld.nlm.nih.gov/dsld/)
2020.
33. Tripkovic L, Lambert H, Hart K, Smith CP, Bucca G, Penson S, et al. Comparison of vitamin D2 and
vitamin D3 supplementation in raising serum 25-hydroxyvitamin D status: A systematic review
and meta-analysis. Am J Clin Nutr 2012;95:1357-64. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/22552031/)]
34. Lehmann U, Hirche F, Stangl GI, Hinz K, Westphal S, Dierkes J. Bioavailability of vitamin D2 and D3
in healthy volunteers, a randomised placebo-controlled trial. J Clin Endocrin Metab 2013;98:4339-
45. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/24001747/)]
35. Logan VF, Gray AR, Peddie MC, Harper MJ, Houghton LA. Long-term vitamin D3 supplementation
is more effective than vitamin D2 in maintaining serum 25-hydroxyvitamin D status over the
winter months. Br J Nutr 2013;109:1082-8. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/23168298/)]
36. Tripkovic L, Wilson LR, Hart K, Johnsen S, de Lusignan S, Smith CP, et al. Daily supplementation
with 15 µg vitamin D2 compared with vitamin D3 to increase wintertime 25-hydroxyvitamin D
status in healthy South Asian and white European women: A 12-wk randomized, placebo-
controlled food-fortification trial. Am J Clin Nutr 2017;106:481-90. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/28679555/)]
37. Graeff-Armas LA, Bendik I, Kunz I, Schoop R, Hull S, Beck M. Supplemental 25-
hydroxycholecalciferol is more effective than cholecalciferol in raising serum 25-hydroxyvitamin
 D concentrations in older adults. J Nutr 2020;150:73-81. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/31518424/)]
38. Quesada-Gomez JM, Bouillon R. Is calcifediol better than cholecalciferol for vitamin D
supplementation? Osteoporos Int 2018;29:1697-1711. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/29713796/)]
39. Percent reporting and mean amounts of selected vitamins and minerals food and beverages and
dietary supplements by gender and age, in the United States, 2015-2016
(https://www.ars.usda.gov/ARSUserFiles/80400530/pdf/1516/Table_37_SUP_GEN_15.pdf). What We Eat
in America, NHANES 2015-2016. 2019.
40. Usual nutrient intake from foods and beverages, by gender and age
(https://www.ars.usda.gov/ARSUserFiles/80400530/pdf/usual/Usual_Intake_gender_WWEIA_2013_2016.pd
f). What We Eat in America, NHANES 2013-2016. 2019.
41. Rooney MR, Harnack L, Michos ED, Ogilvie RP, Sempos CT, Lutsey PL. Trends in use of high-dose
vitamin D supplements exceeding 1000 or 4000 International Units daily, 1999-2014. JAMA
2017;317:2448-50. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/28632857/)]
42. Taylor CL, Roseland JM, Coates PM, Pehrsson PR. The emerging issue of 25-hydroxyvitamin D in
foods. J Nutr 2016;146:855-6. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/27037407/)]
43. Herrick KA, Storandt RJ, Afful J, Pfeiffer CM, Schleicher RL, Gahche JJ, Potischman N. Vitamin D
status in the United States, 2011-2014. Am J Clin Nutr 2019;110:150-7. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/31076739/)]
44. Elder CJ, Bishop NJ. Rickets. Lancet 2014;383:1665-76. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/24412049/)]
45. Munns CF, Shaw N, Kiely M, Specker BL, Thacher TD, Ozono K, et al. Global consensus
recommendations on prevention and management of nutritional rickets. J Clin Endocrinol Metab
2016;101:394-415. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/26745253/)]
46. Uday S, Hogler W. Nutritional rickets and osteomalacia in the twenty-first century: Revised
concepts, public health, and prevention strategies. Curr Osteoporos Rep 2017;15:293-302.
[PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/28612338/)]
47. Weisberg P, Scanlon KS, Li R, Cogswell ME. Nutritional rickets among children in the United
States: Review of cases reported between 1986 and 2003. Am J Clin Nutr 2004;80:1697S-705S.
[PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/15585790/)]
48. Thacher TM, Fischer PR, Tebben PJ, Singh RJ, Cha SS, Maxson JA, Yawn BP. Increasing incidence
of nutritional rickets: A population-based study in Olmsted County, Minnesota. Mayo Clin Proc
2013;88:176-83. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/23374621/)]
49. Ward LM, Gaboury I, Ladhani M, Zlotkin S. Vitamin D-deficiency rickets among children in Canada.
CMAJ 2007;177:161-6. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/17600035/)]
50. Rajakumar K. Vitamin D, cod-liver oil, sunlight, and rickets: A historical perspective. Pediatrics
2003;112:e132-5. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/12897318/)]
51. Creo AL, Thacher TD, Pettifor JM, Strand MA, Ficsher PR. Nutritional rickets around the world: An
update. Paediatr Int Child Health 2017;37:84-98. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/27922335/)]
52. Rockwell M, Kraak V, Hulver M, Epling J. Clinical management of low vitamin D: A scoping review
of physicians’ practices. Nutrients 2018 Apr 16;10(4). pii: E493. doi: 10.3390/nu10040493.
[PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/29659534/)]
53. Taylor CL, Thomas PR, Aloia JF, Millard PS. Questions about vitamin D for primary care practice:
Input from an NIH conference. Am J Med 2015;128:1167-70. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/26071820/)]
54. Taylor CL, Rosen CJ, Dwyer JT. Considerations in dietetic counseling for vitamin D. J Acad Nutr
Diet 2019;119:901-9. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/30005822/)]
55. Agency for Healthcare Research and Quality. Screening for vitamin D deficiency: Systematic
review for the U.S. Preventive Services Task Force recommendation. Evidence Synthesis Number
118. AHRQ-Pub No. 13-05183-EF-1. June 2014.
56. Picciano MF. Nutrient composition of human milk. Pediatr Clin North Am 2001;48:53-67. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/11236733/)]
57. Wagner CL, Greer FR, American Academy of Pediatrics Section on Breastfeeding, American
Academy of Pediatrics Committee on Nutrition. Prevention of rickets and vitamin D deficiency in
infants, children, and adolescents. Pediatrics 2008;122:1142-52. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/18977996/)]
58. Dawodu A, Tsang RC. Maternal vitamin D status: Effect on milk vitamin D content and vitamin D
status of breastfeeding infants. Adv Nutr 2012;3:353-61. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/22585912/)]
59. Davis CD, Dwyer JT. The ‘sunshine vitamin’: benefits beyond bone? J Natl Cancer Inst
2007;99:1563-5. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/17971523/)]
60. Simon AE, Ahrens KA. Adherence to vitamin D intake guidelines in the United States. Pediatrics
2020;145:e20193574. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/32424077/)]
61. Chalcraft JR, Cardinal LM, Wechsler PJ, Hollis BW, Gerow KG, Alexander BM, et al. Vitamin D
synthesis following a single bout of sun exposure in older and younger men and women.
Nutrients 2020; 12, 2237; doi:10.3390/nu12082237. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/32727044/)]
62. Sowah D, Fan X, Dennett L, Hagtvedt R, Straube S. Vitamin D levels and deficiency with different
occupations: A systematic review. BMC Public Health 2017;17:519. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/28637448/)]
63. Pappa HM, Bern E, Kamin D, Grand RJ. Vitamin D status in gastrointestinal and liver disease. Curr
Opin Gastroenterol 2008;24:176-83. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/18301268/)]
64. Drincic A, Fuller E, Heaney RP, Armas LAG. 25-hydroxyvitamin D response to graded vitamin D3
supplementation among obese adults. J Clin Endocrinol Metab 2013;98:4845-51. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/24037880/)]
65. Ekwaru JP, Zwicker JD, Holick MF, Giovannucci E, Veugelers PJ. The importance of body weight
for the dose response relationship of oral vitamin D supplementation and serum 25-
hydroxyvitamin D in healthy volunteers. PLOS ONE 2014;9:e111265. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/25372709/)]
66. Chakhtoura M, Rahme M, Fuleihan E-H. Vitamin D metabolism in bariatric surgery. Endocrinol
Metab Clin North Am 2017;46:947-82. [PubMed abstract
 (https://pubmed.ncbi.nlm.nih.gov/29080645/)]
67. Peterson L, Zeng X, Caufield-Noll CP, Schweitzer MA, Magnuson TH, Steele KE. Vitamin D status
and supplementation before and after bariatric surgery: A comprehensive literature review. Surg
Obes Relat Dis 2016;12:693-702. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/27036669/)]
68. Chakhtoura MT, Nakhoul N, Akl EA, Mantzoros CS, El Hajj Guleihan GA. Guidelines on vitamin D
replacement in bariatric surgery? Identification and systematic appraisal. Metabolism
2016;65:586-97. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/26833101/)]
69. Newberry SJ, Chung M, Shekelle PG, Booth MS, Liu JL, Maher AR, et al. Vitamin D and calcium: A
systematic review of health outcomes (update) (https://www.ncbi.nlm.nih.gov/books/NBK253540/).
Evidence Report/Technology Assessment No. 217. (Prepared by the Southern California
Evidence-based Practice Center under Contract No. 290- 2012-00006-I.) AHRQ Publication No.
14-E004-EF. Rockville, MD: Agency for Healthcare Research and Quality. September 2014.
70. Sempos CT, Carter GD, Binkley NC. 25-hydroxyvitamin D assays: Standardization, guidelines,
problems, and interpretation. Pages 939-57 in Feldman D, Pike JW, Bouillon R, Giovannucci E,
Goltzman D, Hewison M, eds. Vitamin D, Volume 1: Biochemistry, Physiology and Diagnostics,
Fourth Edition. Elsevier, 2018.
71. Jin, J. Vitamin D and calcium supplements for preventing fractures. JAMA 2018;319:1630.
[PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/29677304/)]
72. National Institutes of Health Osteoporosis and Related Bone Diseases National Resource Center.
Osteoporosis Overview (https://www.bones.nih.gov/health-info/bone/osteoporosis/overview).
73. Hansen D, Bazell C, Pelizzari P, Pyenson B. Medicare cost of osteoporotic fractures
(https://static1.squarespace.com/static/5c0860aff793924efe2230f3/t/5d76b949deb7e9086ee3d7dd/1568
061771769/Medicare+Cost+of+Osteoporotic+Fractures+20190827.pdf). Milliman research report,
August 2019.
74. Chung M, Balk EM, Brendel M, Ip S, Lau J, Lee J, et al. Vitamin D and calcium: A systematic review
of health outcomes. Evidence Report/Technology Assessment No. 183 prepared by the Tufts
Evidence-based Practice Center under Contract No. 290-2007-10055-I. AHRQ Publication No. 09-
E015. Rockville, MD: Agency for Healthcare Research and Quality, 2009.
75. U.S. Preventive Services Task Force. Vitamin D, calcium, or combined supplementation for the
primary prevention of fractures in community-dwelling adults. US Preventive Services Task Force
recommendation statement. JAMA 2018;319:1592-9. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/29677309/)]
76. Kahwati LC, Weber RP, Pan H, Gourlay M, LeBlanc E, Coker-Schwimmer M, Viswanathan M.
Vitamin D, calcium, or combined supplementation for the primary prevention of fractures in
community-dwelling adults: Evidence report and systematic review for the US Preventive Services
Task Force. JAMA 2018;319:1600-12. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/29677308/)]
77. Guirguis-Blake JM, Michael YL, Perdue LA, Coppola EL, Beil TL. Interventions to prevent falls in
older adults: Updated evidence report and systematic review for the US Preventive Services Task
Force. JAMA 2018;319:1705-16. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/29710140/)]
78. U.S. Preventive Services Task Force. Interventions to prevent falls in community-dwelling older
adults. US Preventive Services Task Force recommendation statement. JAMA 2018;319:1696-
 1704. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/29710141/)]
79. Bolland MJ, Grey A, Avenell A. Effects of vitamin D supplementation on musculoskeletal health: A
systematic review, meta-analysis, and trial sequential analysis. Lancet Diabetes Endocrinol
2018;6:847-58. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/30293909/)]
80. Gallagher JC. Vitamin D and bone density, fractures, and falls: The end of the story? Lancet
Diabetes Endocrinol 2018;6:834-5. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/30293910/)]
81. Yao P, Bennett D, Mafham M, Lin X, Chen Z, Armitage J, Clarke R. Vitamin D and calcium for the
prevention of fracture: A systematic review and meta-analysis. JAMA Network Open
2019;2(12):e1917789. doi: 10.1001/jamanetworkopen.2019.17789.
82. LeBoff MS, Chou SH, Ratliff KA, Cook NR, Khurana B, Kim E, et al. Supplemental vitamin D and
incident fractures in midlife and older adults. N Eng J Med 2022;387:299-309. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/35939577/)]
83. Aloia JF, Talwar SA, Pollack S, Yeh J. A randomized controlled trial of vitamin D3 supplementation
in African American women. Arch Intern Med 2005;165:1618-23. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/16043680/)]
84. Aloia JF, Rubinova R, Fazzari M, Islam S, Mikhail M, Ragolia L. Vitamin D and falls in older African
American women: The PODA randomized clinical trial. J Am Geriatr Soc 2019;67:1043-49.
[PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/30698279/)]
85. Vaes AMM, Tieland M, Toussaint N, Nilwik R, Verdijk LB, van Loon LJC, de Groot CPGM.
Cholecalciferol or 25-hydroxycholecalciferol supplementation does not affect muscle strength
and physical performance in prefrail and frail older adults. J Nutr 2018;148:712-20. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/30053278/)]
86. Shea MK, Fielding RA, Dawson-Hughes B. The effect of vitamin D supplementation on lower-
extremity power and function in older adults: a randomized controlled trial. Am J Clin Nutr
2019;109:369-79. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/30715090/)]
87. Manson JE, Bassuk SS, Buring JE. Vitamin D, calcium, and cancer: Approaching daylight? JAMA
2017;317:1217-8. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/28350909/)]
88. Yin L, Ordonez-Mena JM, Chen T, Schottker B, Arndt V, Brenner H. Circulating 25-hydroxyvitamin D
serum concentration and total cancer incidence and mortality: A systematic review and meta-
analysis. Preventive Medicine 2013;57:753-64. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/24036014/)]
89. Han J, Guo X, Yu X, Liu S, Cui X, Zhang B, Liang H. 25-hydroxyvitamin D and total cancer incidence
and mortality: A meta-analysis of prospective cohort studies. Nutrients 2019;11,2295;
doi:10.3390/nu11102295. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/31561503/)]
90. Keum N, Giovannucci E. Vitamin D supplements and cancer incidence and mortality: A meta-
analysis. British Journal of Cancer 2014;111:976-80. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/24918818/)]
91. Keum N, Lee DH, Greenwood DC, Manson JE, Giovannucci E. Vitamin D supplementation and total
cancer incidence and mortality: A meta-analysis of randomized controlled trials. Ann Oncol
2019;30:733-43. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/30796437/)]
92. Bjelakovic G, Gluud LL, Nikolova D, Whitfield K, Krstic G, Wetterslev J, Gluud C. Vitamin D
supplementation for prevention of cancer in adults. Cochrane Database Syst Rev 2014;
 23(6):CD007469. doi: 10.1002/14651858.CD007469.pub2. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/24953955/)]
93. Manson JE, Cook NR, Lee I-M, Christen W, Bassuk S, Mora S, et al. Vitamin D supplements and
prevention of cancer and cardiovascular disease. N Engl J Med 2019:380:33-44. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/30415629/)]
94. Brunner RL, Wactawski-Wende J, Caan BJ, Cochrane BB, Chlebowski RT, et al. The effect of
calcium plus vitamin D on risk for invasive cancer: results of the Women’s Health Initiative (WHI)
calcium plus vitamin D randomized clinical trial. Nutr Cancer. 2011;63(6):827-41. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/21774589/)]
95. Thomson CA, Aragaki AK, Prentice RL, Stefanick ML, Manson JE, et al. Long-Term Effect of
Randomization to Calcium and Vitamin D Supplementation on Health in Older Women :
Postintervention Follow-up of a Randomized Clinical Trial. Ann Intern Med. 2024 Apr;177(4):428-
438. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/38467003/)]
96. McNamara M, Rosenberger KD. The significance of vitamin D status in breast cancer: A state of
the science review. J Midwifery Womens Health 2019;64:276-88. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/30977263/)]
97. O’Brien KM, Sandler DP, Taylor JA, Weinberg CR. Serum vitamin D and risk of breast cancer within
five years. Environ Health Perspect 2017;125(7):077004. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/28728134/)]
98. Skaaby T, Husemoen LLN, Thuesen BH, Pisinger C, Jorgensen T, Roswall N, et al. Prospective
population-based study of the association between serum 25-hydroxyvitamin-D levels and the
incidence of specific types of cancer. Cancer Epidemiol Biomarkers Prev 2014;23:1220-9.
[PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/24789846/)]
99. Yao S, Kwan ML, Ergas IJ, Roh JM, Cheng T-YD, Hong C-C, et al. Association of serum level of
vitamin D at diagnosis with breast cancer survival: A case-cohort analysis in the Pathways Study.
JAMA Oncol 2017;3:351-7. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/27832250/)]
100. Chlebowski RT, Johnson KC, Kooperberg C, Pettinger M, Wactawski-Wende J, Rohan T, et al.
Calcium plus vitamin D supplementation and the risk of breast cancer. J Natl Cancer Inst
2007;100:1581-91. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/19001601/)]
101. Cauley JA, Chlebowski RT, Wactawski-Wende J, Robbins JA, Rodabough RJ, Chen Z, et al.
Calcium plus vitamin D supplementation and health outcomes five years after active intervention
ended: The Women’s Health Initiative. J Womens Health 2013:22,915-29. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/24131320/)]
102. McCullough ML, Zoltick ES, Weinstein SJ, Fedirko V, Wang M, Cook NR, et al. Circulating vitamin D
and colorectal cancer risk: An international pooling project of 17 cohorts. J Natl Cancer Inst
2019;111:158-69. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/29912394/)]
103. Wactawski-Wende J, Kotchen JM, Anderson GL, Assaf AR, Brunner RL, O’Sullivan MJ, et al.
Calcium plus vitamin D supplementation and the risk of colorectal cancer. N Engl J Med
2006;354:684-96. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/16481636/)]
104. Crockett SD, Barry EL, Mott LA, Ahnen DJ, Robertson DJ, Anderson JC, et al. Calcium and vitamin
D supplementation and increased risk of serrated polyps: Results from a randomised clinical trial.
Gut. 2019 Mar;68(3):475-486. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/29496722/)]
105. Song M, Lee IM, Manson JE, Buring JE, Dushkes R, Gordon D, et al. No association between
vitamin D supplementation and risk of colorectal adenomas or serrated polyps in a randomized
trial. Clin Gastroeterol Hepatol 2020. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/32062040/)]
106. Muller DC, Hodge AM, Fanidi A, Albanes D, Mai XM, Shu XO, et al. No association between
circulating concentrations of vitamin D and risk of lung cancer: An analysis in 20 prospective
studies in the Lung Cancer Cohort Consortium (LC3). Ann Oncol 2018;29:1468-75. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/29617726/)]
107. van Duijnhoven FJB, Jenab M, Hveem K, Siersema PD, Fedirko V, Duell EJ, et al. Circulating
concentrations of vitamin D in relation to pancreatic cancer risk in European populations. Int J
Cancer 2018;142:1189-201. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/29114875/)]
108. Stolzenberg-Solomon RZ, Vieth R, Azad A, Pietinen P, Taylor PR, Virtamo J, et al. A prospective
nested case-control study of vitamin D status and pancreatic cancer risk in male smokers.
Cancer Res 2006;66:10213-9. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/17047087/)]
109. Helzlsouer KJ for the VDPP Steering Committee. Overview of the Cohort Consortium Vitamin D
Pooling Project of Rarer Cancers. Am J Epidemiol 2010;172:4-9. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/20562193/)]
110. Xu Y, Shao X, Yao Y, Xu L, Chang L, Jiang Z, Lin Z. Positive association between circulating 25-
hydroxyvitamin D levels and prostate cancer risk: New findings from an updated meta-analysis. J
Cancer Res Clin Oncol 2014;140:1465-77. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/24838848/)]
111. Kristal AR, Till C, Song X, Tangen CM, Goodman PJ, Neuhauser ML, et al. Plasma vitamin D and
prostate cancer risk: Results from the Selenium and Vitamin E Cancer Prevention Trial. Cancer
Epidemiol Biomarkers Prev 2014;23:1494-504. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/24732629/)]
112. Schenk JM, Till CA, Tangen CM, Goodman PJ, Song X, Torkko KC, et al. Serum 25-hydroxyvitamin
D concentrations and risk of prostate cancer: Results from the Prostate Cancer Prevention Trial.
Cancer Epidemiol Biomarkers Prev 2014;23:1484-93. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/25085836/)]
113. Heath AK, Hodge AM, Ebeling PR, Eyles DW, Kvaskoff D, Buchanan DD, et al. Circulating 25-
hydroxyvitamin D concentration and risk of breast, prostate, and colorectal cancers: The
Melbourne Collaborative Cohort Study. Cancer Epidemiol Biomarkers Prev 2019;28:900-8.
[PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/30842127/)]
114. Jiang X, Dimou NL, Al-Dabhani K, Lewis SJ, Martin RM, Haycock PC, et al. Circulating vitamin D
concentrations and risk of breast and prostate cancer: A Mendelian randomization study.
International Journal of Epidemiology 2019;48:1416-24. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/30597039/)]
115. Travis RC, Perez-Cornago A, Appleby PN, Albanes D, Joshu CE, Lutsey PL, et al. A collaborative
analysis of individual participant data from 19 prospective studies assesses circulating vitamin D
and prostate cancer risk. Cancer Res 2019;79:274-85. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/30425058/)]
116. Nair-Shalliker V, Bang A, Egger S, Clements M, Gardiner RA, Kricker A, et al. Post-treatment levels
of plasma 25- and 1,25-dihydroxy vitamin D and mortality in men with aggressive prostate cancer.
Scientific Reports 2020;10:7736. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/32385370/)]
117. Song Z-y, Yao Q, Zhuo Z, Ma Z, Chen G. Circulating vitamin D level and mortality in prostate
cancer patients: A dose-response meta-analysis. Endocrine Connections 2018;7:R294-303.
[PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/30352424/)]
118. Shahvazi S, Soltani S, Ahmadi SM, de Souza RJ, Salehi-Abargouei A. The effect of vitamin D
supplementation on prostate cancer: A systematic review and meta-analysis of clinical trials.
Horm Metab Res 2019;51:11-21. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/30522147/)]
119. US Preventive Services Task Force; Mangione CM, Barry MJ, Nicholson WK, Cabana M, et al.
Vitamin, Mineral, and Multivitamin Supplementation to Prevent Cardiovascular Disease and
Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2022 Jun
21;327(23):2326-2333. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/35727271/)]
120. Kassi E, Adamopoulos C, Basdra EK, Papavassiliou AG. Role of vitamin D in atherosclerosis.
Circulation 2013;128:2517-31. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/24297817/)]
121. Mheid IA, Quyyumi AA. Vitamin D and cardiovascular disease: Controversy unresolved. J Am Coll
Cardiol 2017;70:89-100. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/28662812/)]
122. Zhang R, Li B, Gao X, Tian R, Pan Y, Jiang Y, et al. Serum 25-hydroxyvitamin D and the risk of
cardiovascular disease: Dose-response meta-analysis of prospective studies. Am J Clin Nutr
2017;105:810-9. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/28251933/)]
123. Durup D, Jorgensen HL, Christensen J, Tjonnland A, Olsen A, Halkjaer J, et al. A reverse J-shaped
association between serum 25-hydroxyvitamin D and cardiovascular disease mortality: The CopD
study. J Clin Endorcinol Metab 2015;100:2339-46. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/25710567/)]
124. Brondum-Jacobsen P, Benn M, Jensen GB, Nordestgaard BG. 25-hydroxyvitamin D levels and risk
of ischemic heart disease, myocardial infarction, and early death: Population-based study and
meta-analyses of 18 and 17 studies. Arterioscler Thromb Vasc Biol 2012;32:2794-802. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/22936341/)]
125. Zhou R, Wang M, Huang H, Li W, Hu Y, Wu T. Lower vitamin D status is associated with an
increased risk of ischemic stroke: A systematic review and meta-analysis. Nutrients 2018; 10,
277;doi:10.3390/nu10030277. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/29495586/)]
126. Scragg R, Stewart AW, Waayer D, Lawes CMM, Toop L, Sluyter J, et al. Effect of monthly high-dose
vitamin D supplementation on cardiovascular disease in the Vitamin D Assessment Study: A
randomized clinical trial. JAMA Cardiol 2017;2:608-16. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/28384800/)]
127. Ford JA, MacLennan GS, Avenell A, Bolland M, Grey A, Witham M. Cardiovascular disease and
vitamin D supplementation: Trial analysis, systematic review, and meta-analysis. Am J Clin Nutr
2014;100:746-55. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/25057156/)]
128. Hsia J, Heiss G, Ren H, Allison M, Dolan NC, et al. Calcium/vitamin D supplementation and
cardiovascular events. Circulation. 2007 Feb 20;115(7):846-54. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/17309935/)]
129. Dibaba DT. Effect of vitamin D supplementation on serum lipid profiles: A systematic review and
meta-analysis. Nutr Rev 2019;77:890-902. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/31407792/)]
130. Beveridge LA, Struthers AD, Khan F, Jorde R, Scragg R, Macdonald HM, et al. Effect of vitamin D
supplementation on blood pressure: A systematic review and meta-analysis incorporating
individual patient data. JAMA Intern Med 2015;175:745-54. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/25775274/)]
131. Golzarand M, Shab-Bidar S, Koochakpoor G, Speakman JR, Djafarian K. Effect of vitamin D3
supplementation on blood pressure in adults: An updated meta-analysis. Nutr Metab Cardiovasc
Dis 2016;26:663-73. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/27287826/)]
132. Vimaleswaran KS, Cavadino A, Berry DJ, Jorde R, Dieffenbach AK, Lu C, et al. Association of
vitamin D status with arterial blood pressure and hypertension risk: A mendelian randomisation
study. Lancet Diabetes-Endocrinol 2014;2:719-29. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/24974252/)]
133. Anglin RES, Samaan Z, Walter SD, McDonald SD. Vitamin D deficiency and depression in adults:
Systematic review and meta-analysis. The British Journal of Psychiatry 2013;202:100-7. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/23377209/)]
134. Gowda U, Mutowo MP, Smith BJ, Wluka AE, Renzaho AMN. Vitamin D supplementation to reduce
depression in adults: Meta-analysis of randomized controlled trials. Nutrition 2015;31:421-9.
[PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/25701329/)]
135. Jorde R, Kubiak J. No improvement in depressive symptoms by vitamin D supplementation:
Results from a randomised controlled trial. Journal of Nutrition Science 2018;7:1-7. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/30510695/)]
136. de Koning EJ, Lips P, Penninx BWJH, Elders PJM, Heijboer AC, den Heijer M, et al. Vitamin D
supplementation for the prevention of depression and poor physical function in older persons:
The D-Vitaal study, a randomized clinical trial. Am J Clin Nutr 2019;110:1119-30. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/31340012/)]
137. Jorde R, Grimnes G. Vitamin D: No cure for depression. Am J Clin Nutr 2019;110:1043-4. PMID:
31504098 [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/31504098/)]
138. Okereke OI, Reynolds III CF, Mischoulon D, Chang G, Vyas CM, Cook NR, et al. Effect of long-term
vitamin D3 supplementation vs placebo on risk of depression or clinically relevant depressive
symptoms and on change in mood scores: A randomized clinical trial. JAMA 2020;324:471-80.
[PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/32749491/)]
139. MedLinePlus. Multiple sclerosis. (https://vsearch.nlm.nih.gov/vivisimo/cgi-bin/query-meta?
v%3Aproject=medlineplus&v%3Asources=medlineplus-
bundle&query=ms&_ga=2.37114720.1394485401.1566930319-1661442768.1566930319) 2020.
140. Jagannath VA, Filippini G, Di Pietrantonj C, Asokan GV, Robak EW, Whamond L, Robinson SA.
Vitamin D for the management of multiple sclerosis (review). Cochrane Database of Systematic
Reviews 2018, issue 9, Art. No.: CD008422. DOI: 10.1002/14651858.CD008422.pub3. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/30246874/)]
141. Sintzel MB, Rametta M, Reder AT. Vitamin D and multiple sclerosis: A comprehensive review.
Neurol Ther 2018;7:59-85. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/29243029/)]
142. Munger K, Hongell K, Aivo J, Soilu-Hanninen M, Surcel H-M, Ascherio A. 25-hydroxyvitamin D
deficiency and risk of MS among women in the Finnish Maternity Cohort. Neurology 2017;89:
1578-83. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/28904091/)]
143. Munger KL, Levin LI, Hollis BW, Howard NS, Ascherio A. Serum 25-hydroxyvitamin D levels and
risk of multiple sclerosis. JAMA 2006;296:2832-8. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/17179460/)]
144. Salzer J, Hallmans G, Nystrom M, Stenlund H. Wadell G, Sundstrom P. Vitamin D as a protective
factor in multiple sclerosis. Neurology 2012;79:2140-5. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/23170011/)]
145. Marrie RA, Beck CA. Preventing multiple sclerosis: To (take) vitamin D or not to (take) vitamin D?
Neurology 2017;89:1538-9. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/28904085/)]
146. Li X, Liu Y, Zheng Y, Wang P, Zhang Y. The effect of vitamin D supplementation on glycemic control
in type 2 diabetes patients: A systematic review and meta-analysis. Nutrients 2018; 10, 375;
doi:10.3390/nu10030375 [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/29562681/)]
147. Mousa A, Naderpoor N, Teede H, Scragg R, de Courten, B. Vitamin D supplementation for
improvement of chronic low-grade inflammation in patients with type 2 diabetes: A systematic
review and meta-analysis of randomized controlled trials. Nutr Rev 2018;76:380-94. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/29490085/)]
148. Pittas A, Dawson-Hughes B, Sheehan P, Ware JH, Knowler WC, Aroda VR, et al. Vitamin D
supplementation and prevention of type 2 diabetes. N Engl J Med 2019;381:520-30. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/31173679/)]
149. Rafiq S, Jeppesen PB. Is hypovitaminosis D related to incidence of type 2 diabetes and high
fasting glucose level in healthy subjects: A systematic review and meta-analysis of observational
studies. Nutrients 2018, 10, 59; doi:10.3390/nu10010059. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/29320437/)]
150. Mousa A, Naderpoor N, de Courten MPJ, Teede H, Kellow N, Walker K, et al. Vitamin D
supplementation has no effect on insulin sensitivity or secretion in vitamin D-deficient,
overweight or obese adults: A randomized placebo-controlled trial. Am J Clin Nutr
2017;105:1372-81. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/28490514/)]
151. Seida JC, Mitri J, Colmers IN, Majumdar SR, Davidson MB, Edwards AL, et al. Effect of vitamin D3
supplementation on improving glucose homeostasis and preventing diabetes: A systematic
review and meta-analysis. J Clin Endocrinol Metab 2014;99:3551-60. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/25062463/)]
152. Jorde R, Sollid ST, Svartberg J, Schirmer H, Joakimsen RM, Njolstad I, et al. Vitamin D 20 000 IU
per week for five years does not prevent progression from prediabetes to diabetes. J Clin
Endocrinol Metab 2016;101:1647-55. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/26829443/)]
153. Pittas A, Dawson-Hughes B, Staten M. The authors reply: Vitamin D supplementation and
prevention of type 2 diabetes. N Engl J Med 2019;381:1785-6. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/31665590/)]
154. Earthman CP, Beckman LM, Masodkar K, Sibley SD. The link between obesity and low circulating
25-hydroxyvitamin D concentrations: considerations and implications. Int J Obes (Lond)
 2012;36:387-96. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/21694701/)]
155. Mallard SR, Howe AS, Houghton LA. Vitamin D status and weight loss: A systematic review and
meta-analysis of randomized and nonrandomized controlled weight-loss trials. Am J Clin Nutr
2016;104:1151-9. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/27604772/)]
156. Caan B, Neuhouser M, Aragaki A, Lewis CB, Jackson R, LeBoff MS, et al. Calcium plus vitamin D
supplementation and the risk of postmenopausal weight gain. Arch Intern Med 2007;167:893-
902. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/17502530/)]
157. Pathak K, Soares MJ, Calton EK, Zhao Y, Hallett J. Vitamin D supplementation and body weight
status: A systematic review and meta-analysis of randomized controlled trials. Obes Rev
2014;15:528-37. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/24528624/)]
158. Galior K, Grebe S, Singh R. Development of vitamin D toxicity from overcorrection of vitamin D
deficiency: A review of case reports. Nutrients 2018, 10, 953. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/30042334/)]
159. Auguste BL, Avila-Casado C, Bargman JM. Use of vitamin D drops leading to kidney failure in a
54-year-old man. CMAJ 2019;191:E390-4. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/30962197/)]
160. Vogiatzi MG, Jacobson-Dickman E, DeBoer MD. Vitamin D supplementation and risk of toxicity in
pediatrics: A review of current literature. J Clin Endocrinol Metab 2014;99:1132-41. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/24456284/)]
161. Singh P, Trivedi N. Tanning beds and hypervitaminosis D: A case report. Ann Intern Med
2014;160:810-1. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/24887628/)]
162. Laurent MR, Gielen E, Pauwels S, Vanderschueren D, Bouillon R. Hypervitaminosis D associated
with tanning bed use: A case report. Ann Intern Med 2017;166:155-6. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/28114469/)]
163. Perez-Castrillon JL, Vega G, Abad L, Sanz A, Chaves J, Hernandez G, Duenas A. Effects of
atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Am J Cardiol
2007;99:903-5. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/17398180/)]
164. Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, et al. Calcium plus vitamin D
supplementation and the risk of fractures. N Engl J Med 2006;354:669-82. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/16481635/)]
165. Malihi Z, Lawes CMM, Wu Z, Huang Y, Waayer D, Toop L, et al. Monthly high-dose vitamin D
supplementation does not increase kidney stone risk or serum calcium: Results from a
randomized controlled trial. Am J Clin Nutr 2019;109:1578-87. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/31005969/)]
166. Malihi Z, Wu Z, Stewart AW, Lawes CMM, Scragg R. Hypercalcemia, hypercalciuria, and kidney
stones in long-term studies of vitamin D supplementation: A systematic review and meta-
analysis. Am J Clin Nutr 2016;104:1039-51. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/27604776/)]
167. Gotfredsen A, Westergren Hendel H, Andersen T. Influence of orlistat on bone turnover and body
composition. Int J Obes Relat Metab Disord 2001;25:1154-60. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/11486790/)]
168. James WP, Avenell A, Broom J, Whitehead J. A one-year trial to assess the value of orlistat in the
management of obesity. Int J Obes Relat Metab Disord 1997;21:S24-30. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/9225173/)]
169. McDuffie JR, Calis KA, Booth SL, Uwaifo GI, Yanovski JA. Effects of orlistat on fat-soluble
vitamins in obese adolescents. Pharmacotherapy 2002;22:814-22. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/12126214/)]
170. Robien K, Oppeneer SJ, Kelly JA, Hamilton-Reeves JM. Drug-vitamin D interactions: A systematic
review of the literature. Nutr Clin Pract 2013;28:194-208. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/23307906/)]
171. Schwartz JB. Effects of vitamin D supplementation in atorvastatin-treated patients: A new drug
interaction with an unexpected consequence. Clin Pharmacol Ther 2009;85:198-203. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/18754003/)]
172. Perez-Castrillon JL, Vega G, Abad L, Sanz A, Chaves J, Hernandez G, Duenas A. Effects of
atorvastatin on vitamin D levels in patients with acute ischemic heart disease. Am J Cardiol
2007;99:903-5. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/17398180/)]
173. Aloia JF, Li-Ng M, Pollack S. Statins and vitamin D. Am J Cardiol 2007;100:1329. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/17920383/)]
174. Buckley LM, Leib ES, Cartularo KS, Vacek PM, Cooper SM. Calcium and vitamin D3
supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in
patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial. Ann Intern
Med 1996;125:961-8. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/8967706/)]
175. de Sevaux RGL, Hoitsma AJ, Corstens FHM, Wetzels JFM. Treatment with vitamin D and calcium
reduces bone loss after renal transplantation: a randomized study. J Am Soc Nephrol
2002;13:1608-14. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/12039990/)]
176. Lukert BP, Raisz LG. Glucocorticoid-induced osteoporosis: pathogenesis and management. Ann
Intern Med 1990;112:352-64. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/2407167/)]
177. Skversky AL, Kumar J, Abramowitz MK, Kaskel FJ, Melamed ML. Association of glucocorticoid
use and low 25-hydroxyvitamin D levels: Results from the National Health and Nutrition
Examination Survey (NHANES): 2001-2006. J Clin Endocrinol Metab 2011;96:3838-45. [PubMed
abstract (https://pubmed.ncbi.nlm.nih.gov/21956424/)]
178. Drinka PJ, Nolten WE. Hazards of treating osteoporosis and hypertension concurrently with
calcium, vitamin D, and distal diuretics. J Am Geriatr Soc 1984;32:405-7. [PubMed abstract
(https://pubmed.ncbi.nlm.nih.gov/6715769/)]
179. Crowe M, Wollner L, Griffiths RA. Hypercalcaemia following vitamin D and thiazide therapy in the
elderly. Practitioner 1984;228:312-3. [PubMed abstract (https://pubmed.ncbi.nlm.nih.gov/6709583/)]

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