presentation of vitamin d deficiency

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Vitamin D Deficiency

• Inadequate level of vitamin D in the body
• Symptoms include muscle pain, bone pain, tingly sensation in hands or feet, muscle weakness
• Treatment includes lifestyle changes, vitamin D supplements, medication
• Involves endocrinology, pediatric endocrinology & diabetes
Osteomalacia
Vitamin B12 Deficiency Anemia
Osteogenesis Imperfecta (brittle bone disease)

What is vitamin D deficiency?

What causes vitamin d deficiency, what are the symptoms of vitamin d deficiency, how is vitamin d deficiency diagnosed, how is vitamin d deficiency treated, what is the outlook for people with vitamin d deficiency, what makes yale unique in its treatment of vitamin d deficiency.

There has been debate recently about how much vitamin D people need to stay healthy—and how to tell whether we get enough of it—and, in truth, it’s complicated. But one thing experts agree on is that vitamin D is vital to our health. Without exposure to natural sunlight or eating foods rich in vitamin D, we may not maintain adequate amounts of the vitamin. That’s a problem because vitamin D deficiency can be harmful to bones and muscles.

Vitamin D deficiency affects people across the lifespan. Breastfed babies don’t get enough vitamin D from breast milk, so they need to take supplements. As people age, it’s harder for their skin to produce adequate amounts of vitamin D, which may lead to deficiency.

The actual prevalence of vitamin D deficiency depends on what is defined as a level of vitamin D in the blood that is considered sufficient to maintain musculoskeletal health. The Institute of Medicine has concluded that a level between 20-50 ng/mL of 25-hydroxyvitamin D will allow for this. This range of values is consistent with the prevailing view in Europe. However, there are professional societies in the United States that feel that a level of at least 30 ng/ml is required for optimal skeletal health.

“In our view, the preponderance of evidence supports the 20-50 ng/mL range, although it is also true that in some disease states a higher level may be required,” say Karl Insogna, MD , Ensign Professor of Medicine (endocrinology), and Thomas Carpenter, MD , professor of pediatrics (endocrinology) and of orthopaedics and rehabilitation at Yale School of Medicine . “Regardless of what level your physician decides constitutes vitamin D deficiency, therapy and prevention of vitamin D deficiency are straightforward, relatively inexpensive, and safe. We don’t feel that there is any measurable benefit when 25-hydroxyvitamin D levels exceed 50 ng/mL.”

Vitamin D deficiency is the state of having inadequate amounts of vitamin D in your body, which may cause health problems like brittle bones and muscle weakness. There may be no symptoms and doctors don’t routinely check vitamin D levels, so many people are deficient and don’t realize it.

Vitamin D helps the body absorb calcium and phosphorus, which are important to bone health. When a person is very vitamin D deficient, they cannot absorb dietary calcium well; having adequate levels is important to absorb adequate amounts of calcium from your diet. Healthy vitamin D levels also help to improve phosphorus absorption from your diet.

People typically get enough vitamin D from sun exposure: When sunlight hits the skin, the skin converts that ultraviolet radiation to vitamin D. People also get vitamin D from certain foods—including fish, egg yolks, and fortified milk and cereal—or dietary supplements.

When vitamin D levels are low and the body isn’t able to properly absorb calcium and phosphorus, there is an increased risk of bone pain, bone fractures, muscle pain and muscle weakness. In older adults, severe vitamin D deficiency (levels less than 10 ng/mL) may also contribute to an increased risk of falls.

People who don’t have adequate levels of vitamin D may be deficient for any of these reasons:

Not enough exposure to sunlight
Darker skin pigment
Malnutrition
Kidney or liver failure, which prevents the body from adequately processing vitamin D
Certain medications
Certain types of cancer, such as lymphoma
A family history of vitamin D deficiency or childhood rickets

“It is important to note that ‘normal’ vitamin D levels have largely been determined in Caucasian populations. African Americans tend to have lower levels of vitamin D. Much of vitamin D in the blood is bound to carrier proteins, but emerging evidence indicates that when the “free,” unbound fraction of vitamin D is measured, it tends to be lower as well,” say Drs. Insogna and Carpenter. “Therefore, defining vitamin D deficiency in this population requires a consideration of other factors, such as the levels of parathyroid hormone in the blood and the levels of calcium in blood and urine.”

Additionally, some people have health conditions that make it difficult for them to absorb vitamin D, including:

Inflammatory bowel disease (Crohn’s disease or ulcerative colitis)
Celiac disease
Cystic fibrosis
People who have had bariatric surgery for weight loss
People who have had sections of the small intestine removed (resection)
A condition affecting the pancreas, such as exocrine pancreatic insufficiency

It has been suggested that vitamin D deficiency may play a role in certain conditions, such as fibromyalgia , chronic fatigue syndrome, and multiple sclerosis . However, a firm causal link between vitamin D deficiency and these—and other—conditions, along with the therapeutic benefits of vitamin D supplementation, have yet to be established.

Most people with vitamin D deficiency don’t notice any symptoms. Others may notice vague symptoms that may be signs of any number of conditions.

Possible symptoms include:

Muscle pain
Increased sensitivity to pain
A tingly, “pins-and-needles” sensation in the hands or feet
Muscle weakness in body parts near the trunk of the body, such as the upper arms or thighs
Waddling while walking, due to muscle weakness in the hips or legs
A history of broken bones
Muscle twitches or tremors
Muscle spasms
Bowed legs (when the deficiency is severe)

Because there are often no symptoms, identifying vitamin D deficiency can be difficult. While a blood test that checks vitamin D levels can be used for diagnosis, it is not routinely ordered for all patients. Doctors typically order this test if a patient reports such symptoms as bone or muscle pain or has other health conditions that may indicate risk for vitamin D deficiency.

Doctors may ask about a personal or family history of rickets, osteoporosis, or bone fractures.

Eating more vitamin D-rich foods isn’t usually sufficient to correct vitamin D deficiency, so your doctor is likely to recommend treatment with supplements.

The dosage of vitamin D that doctors recommend may vary, depending on severity, age, weight and whether you’re pregnant or breastfeeding. Prescription-strength doses and dietary supplements are available. Some prescription doses are given weekly, rather than daily.

Types of vitamin D supplementation include:

Vitamin D₂ supplements (ergocalciferol), which are derived from a plant source; Drisdol, is a trade name for a vitamin D 2 product.
Vitamin D₃ supplements (cholecalciferol), which come from an animal source.
Calcidiol, a medication that’s a form of vitamin D₃, which may be prescribed when an individual has a health condition that leads to malabsorption, like cystic fibrosis or celiac disease

It’s also important to make sure you are consuming enough calcium. People who have adequate levels of both vitamin D and calcium are able to lower their risk of fractures, but this isn’t the case when people only have adequate levels of vitamin D and inadequate levels of calcium.

Depending on other health conditions, your doctor may also prescribe:

Medications to help strengthen bones and to lower the risk of osteoporosis and fractures

Ensuring a normal vitamin D level in patients with fat malabsorption issues, including cystic fibrosis and Crohn’s disease, can be challenging and may require very high doses of supplements.

You may also be encouraged to eat foods that are rich in vitamin D, including:

Certain fish, including tuna, salmon and sardines
Milk and other foods that have been fortified with vitamin D, such as breakfast cereals and orange juice

Some doctors also recommend exposing the skin on your arms, legs and/or face to natural sunlight for 15 minutes, three or more times per week, which helps your skin produce vitamin D. Other doctors discourage this, because direct exposure to sunlight without sunscreen may increase the risk of skin cancer.

Vitamin D deficiency is highly treatable. If you are diagnosed with the condition and follow treatment recommendations, you will likely be able to increase your intake to an acceptable level, which should eliminate any symptoms or long-term problems.

“Until recently there was no generally accepted “gold standard” for vitamin D that could be used to determine how accurate a given assay was for determining vitamin D levels,” says Dr. Insogna. “Such a standard is now available, and the Yale Mineral Metabolism laboratory that I direct adapted this standard in our assay very early on. We have a research interest in this area and also measure vitamin D levels for practitioners in our health system. Consequently, we pay particular attention to any new developments in the important area of vitamin D and musculoskeletal health.”

U.S. Department of Health & Human Services HHS
National Institutes of Health NIH
Division of Program Coordination, Planning, and Strategic Initiatives DPCPSI

The Office of Dietary Supplements (ODS) of the National Institutes of Health (NIH)

This is a fact sheet intended for health professionals. For a general overview, see our consumer fact sheet .

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, D 2 (ergocalciferol) and D 3 (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. In contrast, the Endocrine Society stated that, for clinical practice, a serum 25(OH)D concentration of more than 75 nmol/L (30 ng/mL) is necessary to maximize the effect of vitamin D on calcium, bone, and muscle metabolism [ 11 , 12 ]. 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).

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.

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 ]. The Endocrine Society states, for example, that to maintain serum 25(OH)D levels above 75 nmol/L (30 ng/mL), adults might need at least 37.5 to 50 mcg (1,500–2,000 IU)/day of supplemental vitamin D, and children and adolescents might need at least 25 mcg (1,000 IU)/day [ 11 ]. In contrast, the United Kingdom government recommends intakes of 10 mcg (400 IU)/day for its citizens age 4 years and older [ 16 ].

Sources of Vitamin D

Few foods naturally contain vitamin D. The flesh of fatty fish (such as trout, salmon, tuna, and mackerel) and fish liver 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 D 3 and its metabolite 25(OH)D 3 . Mushrooms provide variable amounts of vitamin D 2 [ 17 ]. Some mushrooms available on the market have been treated with UV light to increase their levels of vitamin D 2 . 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 D 2 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 D 3 . 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 D 3 [ 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.

* 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.

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 D 3 , which in turn becomes vitamin D 3 . 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 D 2 or D 3 . Vitamin D 2 is manufactured using UV irradiation of ergosterol in yeast, and vitamin D 3 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 D 2 and D 3 are identical. However, most evidence indicates that vitamin D 3 increases serum 25(OH)D levels to a greater extent and maintains these higher levels longer than vitamin D 2 , even though both forms are well absorbed in the gut [ 33-36 ].

Some studies have used dietary supplements containing the 25(OH)D 3 form of vitamin D. Per equivalent microgram dose, 25(OH)D 3 is three to five times as potent as vitamin D 3 [ 37 , 38 ]. However, no 25(OH)D 3 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 D 2 or D 3 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 D 3 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 D 3 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 D 3 , 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 D 3 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 D 3 . 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.

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 D 3 daily (six trials) or 500 mcg (20,000 IU)/week to 12,500 mcg (500,000 IU)/year boluses of vitamin D 3 (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 largest clinical trial, VITAL, to investigate the effects of vitamin D supplementation on the primary prevention of cancer in the general population gave 50 mcg (2,000 IU)/day vitamin D 3 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.

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 [ 94-97 ]. The Women's Health Initiative clinical trial randomized 36,282 postmenopausal women to receive 400 IU vitamin D 3 plus 1,000 mg calcium daily or a placebo for a mean of 7 years [ 98 ]. The vitamin D 3 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 [ 99 ].

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 [ 100 ]. 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 [ 101 ]. The results showed an association between 25(OH)D levels lower than 30 nmol/L (12 ng/mL) and a 31% higher colorectal cancer risk. Levels of 75 to less than 87.5 nmol/L (30 to less than 35 ng/mL) and 87.5 to less than 100 nmol/L (35 to less than 40 ng/mL) were associated with a 19% and 27% lower risk, respectively. The association was substantially stronger in women.

In the Women's Health Initiative clinical trial (described above), vitamin D 3 and calcium supplements had no effect on rates of colorectal cancer. In a subsequent investigation for 4.9 years after the study's end, women who had taken the vitamin D and calcium supplements (many of whom continued to take them) still had the same colorectal cancer risk as those who received placebo [ 100 ].

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 [ 102 ]. These participants were randomized to take 25 mcg (1,000 IU) vitamin D 3 , 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 [ 103 ].

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 [ 104 ].

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 [ 105 ]. 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]) [ 106 ]. 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 [ 107 ].

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 [ 108 ]. 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 [ 109 ]. 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 [ 110 ]. 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 [ 111 , 112 ]. 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 [ 113 ]. 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 [ 114 ]. 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 [ 115 ]. 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 [ 116 ].

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 [ 117 ]. 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 [ 118 ]. Vitamin D deficiency is associated with vascular dysfunction, arterial stiffening, left ventricular hypertrophy, and hyperlipidemia [ 119 ]. 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 [ 120 ]. 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 [ 121 ]. 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 [ 122 , 123 ].

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 D 3 followed by 2,500 mcg (100,000 IU) each month or a placebo for a median of 3.3 years [ 124 ]. 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 800 IU/day vitamin D 3 (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 [ 125 ].

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 [ 126 ].

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 [ 127 ]. 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 D 3 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 [ 128 ]. However, more than 20 mcg (800 IU)/day vitamin D 3 , 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 [ 129 ].

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 , 124 ].

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 [ 130 ].

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 [ 130 ].

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 [ 131 ]. 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 D 3 followed by 500 mcg (20,000 IU)/week or a placebo for 4 months [ 132 ]. 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 [ 133 , 134 ]. Participants were randomized to take either 30 mcg (1,200 IU)/day vitamin D 3 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 D 3 (with or without fish oil) or a placebo for a median of 5.3 years [ 135 ]. 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 [ 136 , 137 ]. 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 [ 137 ].

Many epidemiological and genetic studies have shown an association between MS and low 25(OH)D levels before and after the disease begins [ 137 ]. 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 [ 138 ]. 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 [ 139 ]. 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 [ 140 ] and the other with 576 individuals in northern Sweden [ 141 ]—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 [ 137 ]. 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 [ 142 ]. 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 [ 143 ]. 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 [ 1443 , 145 ].

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 [ 146 ].

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]) [ 147 ]. The investigators randomly assigned participants to receive either a bolus oral dose of 2,500 mcg (100,000 IU) vitamin D 3 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 [ 148 ]. 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 D 3 or a placebo each week for 5 years [ 149 ]. 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 D 3 or placebo for a median of 2.5 years [ 145 ]. 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 [ 145 , 150 ].

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 [ 143 ]. 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 [ 151 ]. 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 [ 152 ]. 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 [ 153 ]. 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 [ 154 ].

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]) [ 155 ]. 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, [ 155-157 ].

Experts do not believe that excessive sun exposure results in vitamin D toxicity because thermal activation of previtamin D 3 in the skin gives rise to various non-vitamin D forms that limit formation of vitamin D 3 . Some vitamin D 3 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) [ 158-160 ].

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 [ 161 ]. 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 [ 162 , 163 ].

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.

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.

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 [ 164-167 ].

Statin medications reduce cholesterol synthesis. Because endogenous vitamin D is derived from cholesterol, statins may also reduce vitamin D synthesis [ 167 ]. 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 [ 167-170 ].

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 [ 171-173 ]. 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%) [ 174 ].

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 [ 167 , 175 , 176 ].

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)."

The Dietary Guidelines for Americans describes a healthy dietary pattern as one that

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.
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.
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Vitamin D deficiency and fatigue: an unusual presentation

Kevin Johnson 1 &
Maryam Sattari 1

SpringerPlus volume 4 , Article number: 584 ( 2015 ) Cite this article

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Fatigue is a vague but common complaint that is poorly characterized by physicians as well as patients. While fatigue may result from a number of different etiologies, at the present time, a comprehensive approach to each patient with fatigue does not include routine measurement of serum vitamin D levels. A 61-year-old man was evaluated for excessive daytime fatigue. No features characteristic for depression, sleep apnea, or narcolepsy were present. A comprehensive work-up, including thyroid function tests and testosterone levels, did not reveal any abnormalities. However, serum 25-hydroxyvitamin D level was low, at 18.4 ng/mL. Vitamin D supplementation was initiated. At follow-up in 3 and 12 months, the patient reported complete resolution of daytime fatigue, corresponding to an increase in his vitamin D levels. Possible mechanisms for clinical improvement include effects of vitamin D on components of inflammatory cascades, including tumor necrosis factor-alpha and prostaglandin D2, which result in decrease in central nervous system homeostatic sleep pressure. While more research is needed to determine if patients presenting with fatigue should be routinely screened for vitamin D deficiency, clinicians should consider obtaining vitamin D levels in patients with unexplained fatigue, nonspecific musculoskeletal pain, and risk factors for vitamin D deficiency.

Fatigue is a vague but common complaint that is poorly characterized by physicians as well as patients. While fatigue may result from a number of different etiologies, at the present time, a comprehensive approach to each patient with fatigue does not include routine measurement of serum vitamin D levels. Vitamin D refers to a group of fat-soluble secosteroid hormones, and is typically ingested in dietary sources or manufactured in the skin after exposure to sunlight (Holick 2007 ). Increasing evidence suggests that vitamin D has many roles beyond its classically described effects on calcium homeostasis and bone health (Holick 2007 ). Research suggests possible associations between suboptimal levels of vitamin D and development of various diseases, including pulmonary disorders (Black and Scragg 2005 ; Sita-Lumsden et al. 2007 ; Camargo et al. 2007 ; Devereux et al. 2007 ; Litonjua and Weiss 2007 ) chronic rhinitis (Abuzeid et al. 2012 ), tonsillar hypertrophy, (Nunn et al. 1986 ; Reid et al. 2011 ), metabolic syndrome (Botella-Carretero et al. 2007 ), type 2 diabetes (Mattila et al. 2007 ), hypertension (Forman et al. 2007 ), cancers of the breast, colon, and prostate (Garland et al. 2006 ), poor stress resilience (Bracha et al. 2004 ), depression (Berk et al. 2007 ), and cognitive decline (Przybelski and Binkley 2007 ). Vitamin D appears to be necessary for skeletal muscle as well and its deficiency has been associated with nonspecific musculoskeletal pain (Plotnikoff and Quigley 2003 ), chronic pain (Turner et al. 2008 ), low back pain (Lotfi et al. 2007 ), and myopathy (Boltan et al. 2007 ; Goldstein 2007 ; Prabhala et al. 2000 ). Some researchers have even suggested a link between vitamin D deficiency and all-cause mortality (Giovannucci 2007 ).

Vitamin D also has immunomodulatory activities (Holick 2007 ). Deficiency of vitamin D might be associated with diseases of immune dysregulation, one manifestation of which could be excessive daytime sleepiness (Zitterman and Gummert 2010 ; Hoeck and Pall 2011 ). We present a case of daytime fatigue in an otherwise healthy male who was found to be vitamin D deficient.

Case presentation

A 61-year-old Caucasian man presented to primary care office with complaint of fatigue and daytime sleepiness, especially in the afternoons. His symptoms began gradually 2–3 months prior to presentation, insidiously worsening to the point that he began having functional difficulties with his normal tasks at work in the afternoons. He reported napping almost daily after work and even skipping some of his regular exercise sessions due to fatigue. He denied changes in his weight, new familial or occupational stressors, difficulty falling asleep, snoring, apnea, sleep disruptions, nocturnal awakenings, depression, or anxiety. In fact, his review of symptoms was only positive for chest pain that was worse in the afternoon when he felt tired. He reported good sleep hygiene and was able to get his customary 7–8 h of sleep each night. Before the onset of his symptoms, he had worked fulltime and exercised on an almost daily basis, without experiencing any difficulties. His past medical history was only significant for colon cancer, in remission since surgical resection and completion of systemic adjuvant chemotherapy in 2005 (7 years prior to presentation). He did not take any prescription medications and denied use of tobacco products, alcohol, or recreational drugs.

Physical exam revealed a pleasant male in no distress. Vital signs were within normal limits. His body mass index was 28. No significant abnormalities were detected on complete physical exam. Laboratory data, including thyroid stimulating hormone, liver function tests, and renal indices, were normal (Table 1 ). EKG and stress echocardiogram were normal. In absence of a common etiology explaining patient’s symptoms, serum 25-hydroxy vitamin D level was obtained and found to be low at 18.4 (normal range 30–80 ng/mL). Vitamin D replacement was initiated with ergocholecalciferol 50,000 international units (IU) weekly for 8 weeks, followed by vitamin D 1000 IU daily.

Patient reported improvement of his fatigue and daytime sleepiness within 2 weeks of initiation of vitamin D supplementation and complete resolution of his symptoms within 3 months of vitamin D initiation. In follow-up visit in 3 months, he reported being able to perform his previous daily routine without difficulty. In addition to working full-time, he had resumed his exercise routine (3 sessions of resistance training and at least 6 sessions of 30–60 min of cardiovascular training a week) without experiencing any limitations. He denied chest pain or daytime napping. He stated that—aside from initiating vitamin D supplementation—no other circumstances in his life had changed since his initial evaluation: there had been no interval changes in other medications, diet, social activities, caffeine use, stress level, or work. He continues to feel well and remains completely symptom-free to date. His repeat 25-hydroxy vitamin D levels were 27.2 ng/mL after 3 months of vitamin D supplementation and 32.2 ng/mL after 12 months (Table 2 ).

The exact mechanism for the improvement in this patient’s fatigue after identification and treatment of vitamin D deficiency is not known. To our knowledge, this is the second reported case of daytime fatigue and sleepiness resolving upon remediation of vitamin D deficiency. McCarty has previously reported a case of excessive daytime sleepiness and musculoskeletal pain in a 28-year-old African American female that improved with replacement of vitamin D (McCarty 2010 ). This patient underwent an overnight polysomnogram (PSG) before and after vitamin D repletion (McCarty 2010 ). While a full sleep evaluation before vitamin D repletion revealed the presence of heavy daytime napping and pervasive fatigue, the PSG did not show evidence of sleep disordered breathing or a sleep-related movement disorder (McCarty 2010 ). Post-replacement PSG did not show a decrease in episodes and duration of wake after sleep onset or an improvement in sleep continuity, but did reveal an interval decrease in stage N3 sleep, suggesting a reduction in homeostatic sleep pressure following vitamin D replacement (McCarty 2010 ).

McCarty postulated that vitamin D deficiency may contribute to symptoms of sleepiness via components of inflammatory cascades, including known sleep regulating substances (McCarty et al. 2012 ). For example, there is an inverse relationship between levels of tumor necrosis factor-alpha (TNF-α) and serum 25-hydroxyvitamin D (Fig. 1 ) (Peterson and Heffernan 2008 ). TNF-α has been implicated in the sleepiness associated with obstructive sleep apnea (Peterson and Heffernan 2008 ; Churchill et al. 2008 ). Vitamin D deficiency has also been associated with upregulation of nuclear factor kappa-B (NFĸB) (Jablonski et al. 2011 ), which is responsible for the regulation of numerous substances known to exert homeostatic sleep pressure, including prostaglandin D2 (Chen et al. 1999 ; Krueger et al. 2009 ). Prostaglandin D2 functions as a physiologic regulator of sleep and affects the central nervous system homeostatic sleep pressure (Fig. 1 ) (McCarty et al. 2012 ).

Proposed relationship between vitamin D and sleep regulation

Interestingly, the only identifiable potential risk factor our patient had for vitamin D deficiency was skin-protective behavior that consisted of sun avoidance and use of SPF protection. Though vitamin D deficiency is commonly understood to be disproportionately represented in underserved populations (Kakarala et al. 2007 ), patients residing in northern latitudes (Webb et al. 1988 ), individuals with darker skin tones (Matsuoka et al. 1991 , 1995 ), the elderly (Holick et al. 2005 ), the obese (Wortsman et al. 2000 ), and pregnant or lactating women (Lee et al. 2007 ), its prevalence among the general population is also increasing (Faiz et al. 2007 ; Zargar et al. 2007 ). In fact, vitamin D deficiency or insufficiency is estimated to affect over a billion persons worldwide (Holick 2007 ). Increased awareness of potential dangers of sun exposure, skin-protective behavior, and urbanization of the population are thought to be some of the factors underlying the increase in prevalence of vitamin D deficiency and insufficiency (Holick 2007 ). It is of note that this patient’s serum parathyroid hormone level was not checked and therefore, normocalcemic primary hyperparathyroidism cannot be ruled out as a contributing factor to his symptoms.

Conclusions

Our case lends support to the one presented by McCarty that vitamin D deficiency might be an unrecognized and easily reversible etiology of fatigue. Although a causal relationship cannot be confirmed by this case alone, the temporal relationship as well as biological plausibility makes this a possibility. While further study is needed to elucidate the possible mechanism for this association, and whether widespread screening for vitamin D deficiency among patients complaining of daytime sleepiness/fatigue is warranted, clinicians should consider obtaining serum vitamin D levels in patients who present with daytime sleepiness/fatigue, nonspecific musculoskeletal pain, and risk factors for vitamin D deficiency.

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KJ drafted the manuscript. MS revised the manuscript critically for important intellectual content. Both authors read and approved the final manuscript.

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Johnson, K., Sattari, M. Vitamin D deficiency and fatigue: an unusual presentation. SpringerPlus 4 , 584 (2015). https://doi.org/10.1186/s40064-015-1376-x

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Vitamin D plays a pivotal role in regulating calcium absorption, while also contributing to immune function and overall well-being. A daily intake of 15 µg is recommended for those aged 1–70 years old by the National Institutes of Health, which can be obtained through sun exposure, certain foods and supplementation.

Aging is a complex, multifaceted process that entails a gradual decline in organ function and an elevated risk of age-related ailments and mortality. Researchers investigating aging are concerned with how we can slow down this process and prevent age-related diseases, such as atherosclerosis, cardiovascular disease and Alzheimer's disease.

Aging is associated with a higher likelihood of vitamin D deficiency and dysregulated vitamin D function, which may result from a decrease in vitamin D receptor expression and altered expression of vitamin D metabolic enzymes. F actors such as nutrition and limited sunlight exposure may also elevate the risk of deficiency in elderly population. Consequently, many scientists are exploring whether vitamin D could help lead to healthier aging.

Vitamin D and the hallmarks of aging

A review article, recently published in Nutrients, looked at the effects of vitamin D on the hallmarks of aging, a set of biological mechanisms that are finely regulated and contribute to biological changes associated with several age-related diseases . 1 The researchers conducted a comprehensive search of PubMed and Embase using keywords related to vitamin D and the 12 hallmarks of aging from the past 10 years.

Ruggiero et al. found evidence that vitamin D may influence various aspects of aging, including DNA integrity, cellular senescence and immune modulation. While vitamin D supplementation showed promise in addressing certain hallmarks, such as dysbiosis and microbial balance, further research is needed to fully understand its effects and clinical implications on aging processes and age-related diseases.

The protective role of the vitamin D/vitamin D receptor pathway

A recent study published in Aging investigated the role of vitamin D in the aging process of intestinal epithelial cells – differentiated enterocytes (ECs) – in a Drosophila intestine model. 2 The researchers used fruit fly models with specific gene knockdowns for the vitamin D receptor (VDR), and applied immunostaining to study the role of VDR on the cell cycle, including PH3 – a specific biomarker for proliferating cells that stains cells in late G2 and mitosis.

Knockdown of VDR in ECs led to increased intestinal stem cell (ISC) proliferation and DNA damage accumulation, EC death, ISC aging and enteroendocrine cell differentiation. V itamin D treatment also reduced age- and oxidative stress-induced ISC proliferation.

Their findings suggest a direct anti-aging effect of the vitamin D/VDR pathway in protecting ECs during aging in Drosophila , providing insights into potential mechanisms underlying healthy aging.

Vitamin D deficiency and young-onset dementia

A study published in JAMA Neurology investigated several risk factors of young-onset dementia, affecting those under 65. 3 The study used data from over 350,000 participants in the UK, taken from the UK BioBank.

The researchers looked at 39 potential risk factors using the multivariable Cox proportional hazards regression model, which is a multivariate approach for analyzing survival time data in medical research, to assess the links between the risk factors and incidence of young-onset dementia. They Identified 15 risk factors that were associated with a high risk of young-onset dementia, including vitamin D deficiency.

"The cause is often assumed to be genetic, but for many people we don't actually know exactly what the cause is. This is why we also wanted to investigate other risk factors in this study," said lead author Dr. Stevie Hendriks , a researcher at Maastricht University.

While the protective effects of vitamin D on hallmarks of aging and age-related conditions are becoming increasingly evident, further investigation is crucial to fully comprehend its therapeutic potential.

References:

Ruggiero C, Tafaro L, Cianferotti L, et al. Targeting the hallmarks of aging with vitamin d: starting to decode the myth. Nutrients . 2024;16(6):906. doi: 10.3390/nu16060906
Park JS, Na HJ, Kim YJ. The anti-aging effect of vitamin D and vitamin D receptor in Drosophila midgut. Aging . 2024. doi: 10.18632/aging.205518
Hendriks S, Ranson JM, Peetoom K, et al. Risk factors for young-onset dementia in the UK Biobank. JAMA Neurol . 2024;81(2):134. doi: 10.1001/jamaneurol.2023.4929

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Vitamin D in the older population: a consensus statement

Andrea giustina.

1 Institute of Endocrine and Metabolic Sciences, San Raffaele Vita-Salute University and IRCCS Hospital, Milan, Italy

Roger Bouillon

2 Laboratory of Clinical and Experimental Endocrinology, Department of Chronic Diseases, Metabolism and Aging, Leuven, KU Belgium

Bess Dawson-Hughes

3 Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA USA

Peter R. Ebeling

4 Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC 3168 Australia

Marise Lazaretti-Castro

5 Division of Endocrinology, Bone and Mineral Diseases Unit, Department of Internal Medicine, Universidade Federal de Sao Paulo, Sao Paulo, Brazil

6 Department of Internal Medicine, Endocrine Section, Amsterdam University Medical Centre, Location VUMC, Amsterdam, The Netherlands

Claudio Marcocci

7 Department of Clinical and Internal Medicine, University of Pisa and Endocrine Unit 2, University Hospital of Pisa, Pisa, Italy

John P. Bilezikian

8 Department of Medicine, Vagelos College of Physicians and Surgeons, New York City, NY USA

This paper reports results from the 5th International Conference “Controversies in Vitamin D” that was held in Stresa, Italy, 15–18 September 2021. The conference is part of this series that started in 2017 and has been conducted annually since. The objective of these conferences is to identify timely and controversial topics related to Vitamin D. Dissemination of the results of the conference through publications in peer-reviewed journals is an important means by which the most up to date information can be shared with physicians, investigators, and other health care professionals. Vitamin D and aging, the subject of this paper was featured at the conference.

Participants were selected to review available literature on assigned topics related to vitamin D and aging and to present their findings with illustrative material, the intent of which was to stimulate discussion and to arrive at a consensus. The presentations were directed towards the following areas: impact of aging on vitamin D production and levels; skeletal effects of vitamin D deficiency in the older population; falls and vitamin D in the aging; potential extra skeletal effects of vitamin D; and strategies to prevent vitamin D deficiency. A final topic was related to how vitamin D might influence the efficacy of vaccines for Covid-19.

Hypovitaminosis D can lead to several skeletal and extra-skeletal outcomes. Older adults are at risk for vitamin D deficiency as both production and metabolism of vitamin D change with aging due to factors, such as reduced sun exposure and reduced production capacity of the skin. Skeletal consequences of these age-related changes can include reduced bone mineral density, osteomalacia and fractures. Potential extra-skeletal effects can include added risks for falls, reduced muscle strength, diabetes, cancer, and cardiovascular disease. Strategies to avoid these vitamin D deficiency-related negative outcomes include sun exposure, food fortification, and supplementation. While aging does not diminish sufficient reserve capacity for cutaneous vitamin D production, concerns about skin cancers and practical matters for the institutionalized elderly limit this option. Supplementation with vitamin D is the best option either pharmacologically or through food fortification. Regardless of treatment strategies, interventions to restore sufficient vitamin D status will show positive results only in those who are truly deficient. Thus, treatment goals should focus on avoiding 25(OH)D serum levels <30 nmol/l, with a goal to reach levels >50 nmol/l.

Conclusions

The results of this conference has led to consensus on several issues. Vitamin D supplementation should be combined with calcium to reduce fractures in the older population. The goal for adequate Vitamin D status should be to reach a serum level of 25(OH)D >50 nmol/l. It appears that daily low-dose vitamin D regimens reduce the risk of falling, especially in the elderly, compared with infrequent, large bolus doses that may increase it. The role of Vitamin D supplementation on muscle strength remains to be clarified. On the other hand, supplementation decreases the risk of progression to T2D from prediabetes among those who are Vitamin Ddeficient. Of three possible strategies to establish vitamin D sufficiency – sunshine exposure, food fortification, and supplementation – the latter seems to be the most effective and practical in the aging population.

Introduction

The 5th International Conference “Controversies in Vitamin D” was held in Stresa, Italy, 15–18 September 2021 as part of this series that started in 2017 [ 1 – 7 ]. The objective of this conference, which featured international experts and leaders, was to review and discuss controversial topics regarding vitamin D. Four sessions addressed different major aspects of vitamin D: aging, gastrointestinal system, guidelines, and COVID-19. Before the event, participants reviewed the available literature on their assigned topic and presented their findings at the time of the conference. After each presentation, open sessions enabled full discussion to reach a consensus. A separate document was prepared for each component of the conference.

This paper summarizes the deliberations of the experts on aging and Vitamin D. Regarding the literature review, there were no limitations in the types of articles that were included. Randomized clinical trials were given preference; when these were not available, observational, experimental, or opinion studies were also considered. Finally, although it is rather difficult to define the terms “older population” or “older subjects” as age cut-offs vary within the studies and can range from >65 years to >75 years, in general many studies define it as >65 years.

Impact of age on vitamin D production and levels

Both the production and metabolism of vitamin D change with aging. Causes include decreased sun exposure and reduced capacity of the skin to produce vitamin D. In the skin, 7-dehydrocholesterol is converted to previtamin D 3 by the sun’s ultraviolet (UV-B) light with a wavelength of 290–315 nm. As demonstrated in skin samples, the concentration of 7-dehydrocholesterol decreases by more than 50% from ages 20 to 80 years. Moreover, isolated, aged skin produces approximately 40% less vitamin D than younger skin [ 8 , 9 ]. A more recent study by Chalcraft and colleagues calculated an age-related reduction in vitamin D production of 13% per decade, demonstrating production at 70 years to be half of that at 20 years (Fig. (Fig.1) 1 ) [ 10 ].

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Vitamin D 3 production age continuum modeling. The simple linear regression model with decade as the independent variable and log D 3 production demonstrated the 13% decrease in D 3 production per decade of life. D 3 production at age 70 years is approximately half that produced at age 20 years. The graph also demonstrates that D 3 production occurs even in the later decades of life. Source: Chalcraft et al. 2020 [ 10 ]. Reproduced from MDPI under an open access Creative Common CC BY license

These issues are even more apparent in the housebound elderly and nursing home residents [ 11 ]. Additional factors accounting for the risk of vitamin D deficiency in the older population relate to relative vitamin D resistance to stimulating calcium absorption in the gastrointestinal tract and age-related renal function reduction. The aging kidney is also less able to produce 1,25-dihydroxyvitamin D from 25-hydroxyvitamin D (25[OH]D) [ 12 ].

Despite issues related to aging, a single 15-minute sun exposure (>40% body area) results in considerable vitamin D production in the skin, not only in younger volunteers but also in older ones [ 10 ]. The authors concluded that age accounts only for 20% of the variation in D 3 production. Thus, while aging may reduce cutaneous synthesis, sunlight exposure is still a significant source of vitamin D 3 [ 10 ]. Other studies in nursing home residents support this conclusion. It has been demonstrated that irradiation with artificial UV light with half the minimal erythematous dose three-times per week on a surface of 1000 cm 2 of the back increased mean serum 25(OH)D from 25 nmol/l to 60 nmol/l within 3 months, similar to daily oral vitamin D 3 400 IU supplementation [ 13 ]. This observation suggests that under those conditions, 1000 cm 2 exposure of skin every day may result in an increase of serum 25(OH)D comparable to daily supplementation of about 800 IU of vitamin D, such as daily recommendations for those >70 years. As the skin surface amounts to more than 15,000 cm 2 , the theoretical amount of vitamin D that could be produced in the skin is potentially high. For example, in another study from the same center, eight psychogeriatric vitamin D-deficient patients underwent half-body UV irradiation once a week with half of the minimal erythematous dose (2 min) for 8 weeks. The median serum 25(OH)D increased from 26.5 nmol/l (range 12–58) at baseline to 43.5 nmol/l (range 36–71) [ 14 ]. Thus, UV exposure effectively triggers cutaneous vitamin D synthesis even in older patients.

The potential of vitamin D production in the skin depends, of course, on a series of well-known factors that can facilitate or mitigate this process. Season, time of the day, latitude, altitude, cloudiness, air pollution [ 15 ], skin type, clothing, sunscreen [ 16 ], and lifestyle can all influence the ability of the sun’s UV-B energy to stimulate skin synthesis of vitamin D.

Beyond the skin, other factors influence vitamin D levels in the aging population. Smoking, for example, may decrease serum 25(OH)D concentrations [ 17 ], although the mechanism is unknown. A higher percentage of total body fat also results in lower circulating 25(OH)D levels. Fat content persists as a variable even after adjustment for age, season, and smoking in men and women. The two mechanisms appear to be reduced production and higher distribution volume of vitamin D [ 18 ]. As the aging population is experiencing a worldwide increase in BMI, especially in rural areas [ 19 ], obesity looms large as an increasingly important factor to account for reduced levels of 25(OH)D. Along with the increase in BMI, trends from the Longitudinal Aging Study Amsterdam (LASA) also show a secular decrease in physical activity in men and women, which may be another factor [ 20 ]. Indeed, physical activity is positively related to serum 25(OH)D levels [ 21 , 22 ]. With regard to gender, it is well known that vitamin D deficiency is more prevalent in men than in women in the general population. This is true also in older populations [ 23 – 25 ], although the difference between older men and women seems to become of smaller magnitude [ 23 ].

In summary, despite the reduction in vitamin D production with aging, cutaneous reserve capacity for production should be ample. It is, therefore, possible that most older people can produce sufficient vitamin D from the sun. Nonetheless, meeting vitamin D requirements for housebound and institutionalized people almost always requires vitamin D supplementation. Factors that might restrict the availability of vitamin D should be avoided, particularly in older individuals.

Skeletal effects of vitamin D deficiency in the older population

While it is undisputed that severe vitamin D deficiency has adverse skeletal effects (Fig. (Fig.2) 2 ) [ 4 ], including osteomalacia, high bone turnover and bone loss, and an increased risk of hip fractures in the elderly, skeletal effects of milder degrees of vitamin D deficiency have recently come under question. Milder degrees of vitamin D deficiency contribute to the development of osteoporosis, but supplementation with vitamin D alone does not appear to reduce fractures. In this regard, it is worth noting that vitamin D is a threshold nutrient. Skeletal benefits in the elderly will not likely be seen in those who are mildly vitamin D deficient and certainly not in those whose serum 25(OH)D is above the threshold value. On the other hand, in severely vitamin D-deficient individuals, the beneficial effects of vitamin D to reduce fracture risk are more likely to be appreciated. The best example of this expectation comes from the pivotal trial of Chapuy et al. [ 26 ]. Daily supplementation with vitamin D (800 IU) and calcium (1200 mg) of older, ambulatory French nursing home and apartment-dwelling women resulted in a reduction of hip and other non-vertebral fractures by 43% and 32%, respectively, over 18 months [ 26 ]. In this population, the mean baseline serum 25(OH)D concentration was only 36 nmol/L. However, tests were conducted with an old competitive protein binding assay with 80% higher values than high-performance liquid chromatography. Cross-calibration with high-performance liquid chromatography confirmed this and yielded even lower concentrations, mean value around 20 nmol/L, clearly indicating that most participants had moderate or severe vitamin D deficiency [ 27 ].

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Skeletal effects of vitamin D deficiency in the elderly and role of vitamin D in preventing them

Another contributory factor that places severely vitamin D-deficient individuals at risk is vitamin D deficiency-related increases in parathyroid hormone (PTH) levels. This secondary hyperparathyroidism could contribute, at least in part, to the pathophysiology of bone loss and fracture risk among severely vitamin D-deficient individuals.

Two older studies have provided insight into a possible threshold value for 25(OH)D below which PTH levels are likely to rise. In the MORE trial [ 28 ], serum PTH was higher in two groups of women with different degrees of vitamin D deficiency (serum 25(OH)D < 25 nmol/L and 25(OH)D 25–50 nmol/L; 4.8 ± 2.2 and 4.1 ± 1.8 pmol/L, respectively) compared with women whose serum 25(OH)D was >50 nmol/L (3.5 ± 1.5 pmol/L). Both groups showed a significant decrease in serum PTH after vitamin D treatment, while serum PTH did not decrease after vitamin D treatment in the group with serum 25(OH)D > 50 nmol/L. A study based on data collected within the LASA [ 29 ] found a 25(OH)D threshold value ranging from 40 to 60 nmol/l. In another study in osteoporotic postmenopausal women [ 30 ], the threshold for a secondary increase in PTH also appeared to be at a serum 25(OH)D concentration around 50 nmol/L.

Some controversy continues to exist about the precise 25(OH)D level below which PTH levels increase. If such a threshold could be clearly identified, one might define the extent of vitamin D deficiency by the extent of the secondary hyperparathyroidism induced by vitamin D deficiency. However, this threshold may also depend on other factors, such as calcium intake and physical activity.

Bone mineral density

Attempts to define a threshold have been recently published. A sub-study of the New Zealand Vitamin D Assessment (ViDA) study of older community-dwelling men and women showed that monthly dosing of 100,000 IU vitamin D for 2 years did not prevent bone loss from the femoral neck and hip [ 31 ]. However, mean baseline serum 25(OH)D levels were 55 nmol/L, indicating a non-deficient population. A pre-planned exploratory analysis showed clinically meaningful reductions in bone loss at the spine, femoral neck and total hip, which were statistically significant at the spine and femoral neck, in participants with a baseline serum 25(OH)D < 30 nmol/L. By contrast, smaller reductions in bone loss at the total hip alone were seen in those with baseline serum 25(OH)D > 30 nmol/L. PTH levels were not measured in this study. In the entire cohort of the ViDA study, with a mean baseline serum 25(OH)D concentration of 66 nmol/L and an adequate calcium intake, vitamin D 3 supplementation over 3.3 years did not reduce the incidence of fractures [ 32 ].

In the second study, the Aberdeen study [ 33 ], recruited 305 postmenopausal women in late winter and randomized them to receive vitamin D 400 IU/day or 1000 IU/day, or placebo over 1 year. A post-hoc analysis showed significant beneficial effects of vitamin D 1000 IU/day on both spine and hip BMD in those with baseline 25(OH)D ≤ 30 nmol/L, but no significant effects in those with baseline 25(OH)D above this level. These studies support the notion that adverse skeletal effects are most likely in older individuals with serum 25(OH)D levels <30 nmol/L, in whom supplementation with vitamin D would have the most definitive skeletal benefits.

Vitamin D and calcium

Dietary sources of vitamin D are scarce. Most frail older individuals following a western diet have a low dietary intake (i.e., around 150 IU) of vitamin D each day [ 34 – 36 ]. As noted above, they are limited in their sun exposure and capacity for cutaneous vitamin D synthesis [ 8 – 10 ]. They also may consume insufficient amounts of calcium-containing foods [ 37 ]. Older adults, thus, are likely to be at risk for both vitamin D deficiency and insufficient dietary calcium intake. Therefore, most older individuals should benefit from vitamin D and calcium supplementation. Meta-analyses of randomized controlled trials (RCTs) have shown that vitamin D, when combined with calcium and a compliance rate of >80%, decreases the incidence of hip fractures and other non-vertebral fractures by 16% and 14%, respectively. The effect on fractures is greater in 70- to >80-year-olds compared with 60–70-year-olds and in institutionalized rather than in the community-dwelling older population [ 38 , 39 ]. A more recent meta-analysis by Yao and colleagues resulted in a similar conclusion, with vitamin D showing a 6% reduction in risk of any fracture and a 16% reduction in risk of hip fracture, but only if taken with concomitant calcium supplementation [ 40 ].

Based upon our current knowledge, there is general agreement that serum 25(OH)D < 30 nmol/L in the older population should be avoided, as skeletal effects of vitamin D deficiency, such as a decrease in BMD, secondary hyperparathyroidism, and mineralization defects (osteomalacia) appear to be most evident, and are most likely to occur, below this threshold. Treatment goals should focus on avoiding 25(OH)D serum levels <30 nmol/l, with a goal to reach levels >50 nmol/ to ensure that the adverse effects of vitamin D deficiency are avoided. To reduce fractures in the elderly, vitamin D and calcium sufficiency are necessary (Fig. (Fig.2 2 ).

Many interventional studies have addressed the relationship between vitamin D and falls, but the results are variable and inconsistent. The large D-Health trial in Australia reported that supplementation with 60,000 IU of D 3 per month, when compared with placebo, had no significant effect on the risk of falling over a mean treatment period of 4.3 years in 15,416 men and women aged 60–84 years (OR 1.02; 95% CI: 0.95–1.10) [ 41 ]. It is worth noting that the intra-study mean serum 25(OH)D level in a subset of participants in the placebo group was 77.5 nmol/L, reflecting a vitamin D-sufficient state. The mean serum 25(OH)D was 114.8 nmol/L in a subset of treated participants. Among participants with a BMI < 25 kg/m 2 , there was a concern that vitamin D increased the risk of falling (OR 1.25; 95% CI: 1.09–1.43). This finding is consistent with an earlier observation that treatment with 60,000 IU of vitamin D 3 monthly increased the risk of falling compared with treatment with 24,000 IU per month [ 42 ].

Many meta-analyses have combined trials testing: (1) different doses; (2) some testing calcium + vitamin D and others vitamin D only (vs placebo); (3) different dose schedules (including daily and bolus dosing); (4) different intervention periods ranging from a few months to several years; and (5) study populations that differ in initial vitamin D status and differ in age and degree of mobility. These variables make it difficult to determine the relationship between vitamin D status and fall risk and which population segments may benefit from supplementation. Adding to the uncertainty is the recent meta-analysis by Bislev et al., finding no significant effect of vitamin D supplementation on a series of muscle performance measures, but the study did not include falls [ 43 ].

Thus, despite conflicting findings from meta-analyses, it appears that modest doses of vitamin D (700–1000 IU per day) may reduce the risk of falling in deficient older adults [ 44 ]. In contrast, infrequent larger bolus doses may increase fall risk [ 41 , 42 , 45 ]. A randomized prospective, placebo-controlled multi-dose vitamin D trial in postmenopausal women with baseline 25(OH)D levels <50 nmol/L found that treatment with low doses of vitamin D decreased the risk of falling whereas doses of 4000 and 4800 IU daily increased the risk of falling [ 46 ]. Since many regions of the world have widespread vitamin D deficiency, a large proportion of the world’s population would likely benefit from daily low- to medium-dose supplementation with vitamin D. High doses, given either daily or intermittently, should be avoided.

Extra-skeletal effects

Although vitamin D is metabolized into about 50 metabolites, it is the active form, 1,25(OH) 2 D, that serves as the ligand for the vitamin D receptor (VDR). The VDR is expressed in most tissues and its activation results in the altered expression of thousands of genes [ 4 ]. The ubiquity of the VDR is the basis for the hypothesis that vitamin D has many extra-skeletal effects, a topic that was reviewed in several recent publications generated from previous meetings of our group (Fig. (Fig.3) 3 ) [ 1 , 3 – 7 ].

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Extra skeletal effects of vitamin D deficiency in the elderly and possible role of vitamin D in preventing them. Continuous lines indicate a known effect. Dashed lines indicate a possible effect

Skeletal muscle

The relationship between skeletal muscle and vitamin D has been investigated experimentally utilizing global knock-out or muscle-specific VDR null mice. These mice develop a muscle phenotype, suggesting that the total absence of vitamin D negatively impacts skeletal muscle [ 47 ]. Previous meta-analyses suggested that vitamin D supplementation slightly improved muscle strength [ 48 ]. However, several intervention studies have been withdrawn [ 43 ]. A novel meta-analysis excluding such data and including more recent studies revealed that vitamin D supplementation did not have beneficial effects on various aspects of muscle strength and had a negative impact in some cases [ 43 ].

Muscle strength is important in the older population since it can influence falls (see above). While the relationship between falls and vitamin D deficiency has been explored above, adjunctive factors, like muscle strength, might be important. Classically, we consider vitamin D deficiency as affecting two distinct musculoskeletal pathways, one involving effects on neuromuscular tissue leading to falls and fractures and the other through decreased calcium absorption, leading to increased levels of PTH, increased bone resorption, and bone loss also leading to increased fracture risk. A related possibility is that the increased circulating PTH levels, seen in vitamin D and calcium deficiency, have a direct untoward dysfunctional effect on muscle. Preclinical and clinical evidence for a direct effect of PTH on muscle exists. Intact, bovine PTH and the synthetic 1–34 fragment of PTH increased muscle degradation and release of newly synthesized alanine and glutamine from skeletal muscle in rats [ 49 ]. Clinically, neuromuscular signs and symptoms and muscle weakness have been described in patients with advanced primary hyperparathyroidism, with muscle weakness reversing soon after successful parathyroid surgery [ 50 , 51 ]. Two groups of older women with similar clinical characteristics and low 25(OH)D levels but different PTH levels (above or within range) performed differently in several muscle strength and function tests. The group with higher PTH levels had lower knee flexion strength, lower maximal muscle force production and reduced postural stability. In contrast, several other muscle strength and balance measures did not differ in the two groups [ 52 ]. One small observational study examined the role of PTH in falls in 83 nursing home residents with a mean age of 84 years, a mean 25(OH)D level of 27 nmol/L and a median PTH level of 5.2 pmol/L (reference range 1–6.5 pmol/L), during which 33 participants fell at least once [ 53 ]. Those who fell had lower 25(OH)D levels and higher PTH levels, whereas the 1,25(OH)2D levels in the two groups did not differ significantly. Logistic regression analysis indicated that the PTH level was an independent determinant of falling [ 53 ]. Sambrook et al. performed a large observational study in 637 generally vitamin D-deficient older adults, mean age 86 years, who resided in intermediate- and full-care institutions in Australia [ 54 ]. Serum 25(OH)D levels in the fallers and non-fallers were 28.8 and 33.2 nmol/L, respectively, and PTH levels 64.8 were 57.0 pg/ml, respectively. Logistic regression revealed that PTH was an independent predictor of falls.

In conclusion, a low daily dose of vitamin D will likely reduce fall risk in deficient older adults. Further examination of the role of PTH as an independent predictor of falls is warranted.

Cardiovascular events

Preclinical data link poor vitamin D status to cardiovascular risks. Experimentally, lack of VDR causes high-renin hypertension, cardiac muscle hypertrophy and fibrosis. Thrombosis is enhanced [ 55 ]. Two large RCTs (VIDA and VITAL) clearly demonstrated that vitamin D supplementation did not decrease cardiovascular events [ 56 , 57 ]. A sub-study of the VIDA trial showed some minor beneficial effects on central blood pressure [ 58 ]. Mendelian randomization (MR) studies did not find a link between genetically low serum 25(OH)D concentrations and CV events, but the combined polymorphism in these studies did not permit any predictive value greater than 5% of the variation in serum 25(OH)D [ 59 – 62 ]. The overall results of a recent large MR study confirmed this conclusion, but by combining MR and serum 25(OH)D levels, this study showed that genetically low serum 25(OH)D in the group with severe vitamin D deficiency at the time of the study (<10 ng/ml) increased CV events and mortality [ 63 ].

Overall, it is unlikely that vitamin D status is a major contributor to the burden of CV diseases, but lifelong severe vitamin D deficiency may play a role.

Many genes regulated by the vitamin D endocrine system are involved in regulating cell cycle control and cell differentiation. Animal and preclinical data strongly suggest that the total absence of vitamin D action predispose to cancer when combined with other carcinogenic events and a preventive effect of vitamin D supplementation early during carcinogenesis. Poor vitamin D status is associated with many cancers, especially colon, breast and prostate. Two major, large RCTs (VITAL and VIDA) did not find an effect of long-term vitamin D supplementation on cancer incidence. However, cancer-related mortality is significantly lower in patients receiving daily supplements with 2000 IU of vitamin D, as suggested by a meta-analysis of the VITAL and four other similar studies. In the D-Health study, by contrast, there was an increased risk of death from cancer in those randomized to higher dose (60,000 IU) monthly vitamin D supplementation [ 64 ]. These findings are rather surprising as the preclinical data suggested a preventive effect early during carcinogenesis.

Many preclinical and observational studies suggest a link between low vitamin D status and type 2 diabetes (T2D). However, in the large Vitamin D and Type 2 Diabetes Study (D2d) RCT [ 65 ], vitamin D supplementation only showed a non-significant trend to slow the progression of prediabetes into T2D (0.88 CI of 0.75–1.04; p = 0.12). On the other hand, in a D2d post-hoc analysis, a significant effect was observed in subjects with either a baseline BMI below 30, severe vitamin D deficiency at baseline, perfect compliance during the study, or achieving serum 25(OH)D above 100 nmol/L throughout the study [ 66 ]. Moreover, two other trials [ 67 – 69 ], specifically designed to prevent diabetes, showed that vitamin D supplementation, compared with placebo, reduced the risk of developing diabetes by 10–13% in persons with prediabetes not selected for vitamin D deficiency [ 70 ]. This is in line with two recent meta-analyses concluding that vitamin D supplementation decreased the risk of progress to T2D by about 10%, especially when using doses above 1000 IU/day and in non-obese subjects [ 71 , 72 ]. Participant-level meta-analysis of these trials may better estimate risk reduction and identify patient populations likely to benefit the most from vitamin D supplementation to prevent diabetes.

Cognitive impairment

Data on cognitive impairment and vitamin D status are often conflicting and further studies are needed to clarify this relationship. It seems that older people with a sufficient vitamin D status have a lower prevalence of cognitive impairment [ 73 ]. Significant associations, however, were also found between vitamin D and Mini-Mental State Examination independently of the presence or absence of the cognitive impairment. These were confirmed also adjusting by age, sex, frailty, and diagnoses of cognitive impairment. Furthermore, patients affected by dementia show lower levels of vitamin D compared to those with only a mild cognitive impairment [ 74 ]. It should be noted that vitamin D exerts a variety of favorable effects on neural and endothelial dysfunctions, which could potentially explain a protective role against neurodegenerative processes [ 75 , 76 ]. Placebo controlled trials seem to confirm these findings. Vitamin D supplementation in older subjects with dementia or mild cognitive impairment was shown to improve cognitive functions measured with full scale intelligence quotient, and information, digit span, vocabulary, block design, and picture arrangement scores compared to placebo, even after adjustment for confounding factors [ 77 – 80 ]. Moreover, supplementation was able to reduce amyloid β-related biomarkers in patients with Alzheimer disease [ 78 ]. Finally, vitamin D seems to have differential effects on domain-specific cognitive measures and that a higher dose may negatively affect reaction time. Participants taking 2000 IU/day performed better in learning and memory tests compared to other regimens, yet dosages of 4000 IU/day resulted in slower reaction time compared to the 600 IU/d group [ 79 ]. Larger and longer trials taking into account various dosage regimens and the different cognitive domains will help clarify the role of vitamin D in tackling cognitive impairments.

To conclude, a very recent review summarized the results of RCTs and MR studies that took place between 2017 and 2020. The study concluded that supplementation of vitamin D-replete individuals does not provide demonstrable health benefits for global health or major diseases or medical events such as cancer, cardiovascular events, T2D, falls or fractures. However, it appears that supplementation with vitamin D might have some extra-skeletal benefits—namely reduced progression to T2D, decreased numbers of upper respiratory tract infections, increased lung function and decreased cancer or overall mortality—especially in severe deficient populations [ 81 ].

Strategies to prevent vitamin D deficiency

A timely topic among countries at this time is how public health policies can be implemented to prevent vitamin D deficiency in the elderly. Beyond an adequate diet, key strategies are sun exposure, food fortification and supplementation (Fig. (Fig.4 4 ).

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Strategies to avoid vitamin D deficiency in the elderly and related limitations

Sunshine exposure

Improving vitamin D status with higher UV exposure is controversial. The World Health Organization assumes that the health threats caused by UV exposure might outweigh the health risks induced by vitamin D deficiency. Non-melanoma skin cancer accounts for one-third of all cancers worldwide and is present mainly in the older population, with UV exposure being their main cause [ 82 ]. Although this strategy is debated, it should be recognized clearly that there is a worldwide seasonal variation of serum 25(OH)D levels, increasing after summer. Sunny countries have better vitamin D status, with a lower prevalence of rickets and osteomalacia. Therefore, the amount of local UV radiation is relevant to providing a greater supply of vitamin D from nature. Older skin is well capable of producing vitamin D, as already discussed [ 82 ].

Consistent with this, in a study performed in Sao Paulo, Brazil (latitude 23 o S), 110 adults older than 55 years (mean ± SD: 67.6 ± 5.4 years), and regularly registered in an outdoor physical activity program, had an average serum 25(OH)D levels of 78.9 ± 31 nmol/l during winter, which improved to 91.6 ± 32 nmol/l in summer, without supplementation [ 83 ]. Severe vitamin D deficiency (serum 25(OH)D < 25 nmol/L) was seen in less than 4% of subjects, and only during winter, but no summer improvement was seen in women, in those older than 70 years old and black individuals. On the other hand, at the same time and city, 177 Brazilians living in nursing homes had much lower serum levels of 25(OH)D even after summer (42.1 ± 26 nmol/l), with 50% of them with levels <25 nmol/l [ 83 ].

In a study performed in Sweden [ 84 ], at a higher latitude, only a slight but significant serum 25(OH)D increase (+11 nmol/l) was observed in the group assigned to stay outdoors 5 days/week for 20–30 min for 2 summer months. By contrast, investigators of a cluster RCT carried out in Australia with older persons living in a nursing home concluded that vitamin D supplementation appears to be a much more practical approach because of the low adherence to the sunlight exposure protocols (only 17% of all participants attended more than 50% of the UV sessions) [ 85 ]. Serum 25(OH)D slightly increased proportionally to the number of sessions, and a fall reduction was observed among those who attended more than 50% of the sessions [ 85 ].

Age and sunlight exposure are important factors that influence serum 25(OH)D levels. The outdoor activity could be considered a reasonable measure to prevent severe vitamin D deficiency and improve other health and well-being outcomes. However, the population must be educated about the risks of excessive sun exposure to avoid sunburn, about the use of sunscreen, and how to identify cancerous skin lesions early. Despite these considerations, a change in lifestyle as already known from other chronic conditions, such as obesity, is difficult to be persistently achieved and rarely finds adequate space in medical consultations.

Food and food fortification

The natural sources for vitamin D in food are scarce (around 150 IU/day in western diets) [ 86 , 87 ]. Therefore, food fortification with vitamin D can be a valid strategy to be applied to large populations to avoid severe deficiency, especially for countries with limited sun exposure.

In the last 3 years, two important statements have been published, one from the 2nd Rank Prize Funds Forum on vitamin D [ 36 ] and one from the European Calcified Tissue Society [ 88 ]. These highlighted the public health aim to decrease the risk of rickets and osteomalacia and avoid serum 25(OH)D levels below 25 nmol/L. These two documents concluded that fortification of foods is an urgent, to-be-implemented strategy, especially for groups at risk for severe vitamin D deficiency, such as children and adolescents, ethnic minority groups, and the institutionalized elderly. There are two very good examples supporting this strategy. In Finland, milk products were fortified with vitamin D from 2003 onwards. In 2000–2011, this public health policy increased serum 25(OH)D from 49.7 to 66.3 nmol/l in people aged 65–74 years, and similarly from 43.0 to 65.1 nmol/l in people of 75 years of age or older [ 89 , 90 ]. This improvement was uniform across seasons, educational status, smoking status and BMI [ 90 ]. In Canada, where milk fortification with vitamin D is mandatory, there is a lower prevalence of serum levels below 25 nmol/l, compared with the UK, US and Germany [ 89 ].

Biofortification of animal feed with vitamin D could improve its content in eggs or meat. Additionally, the increase in the vegan population will require an increase in the use of plant-based vitamin D.

However, the implementation of a food fortification program is challenging. The lack of standardization about the recommended intake, which varies between countries in Europe (from 200 to 800 IU/day according to age), the regulatory rules for food fortification, which is permitted in some countries (e.g., UK, Austria, Finland and Sweden) but not in others (e.g., Norway and Denmark), the implications for the industrial production and quality control (e.g., differences between content stated in the label and actual content), are examples of the many difficulties to be overcome [ 36 , 88 ].

Vitamin D supplementation

Considering these options, vitamin D supplementation seems to be the easiest way to achieve vitamin D sufficiency in an efficient manner, especially for older and institutionalized populations [ 7 ]. Most of the various regimens that have been tested demonstrate a dose-dependent increase in serum 25(OH)D levels, but there is great individual variability. As some studies using intermittent high-dose vitamin D supplementation have described an increased risk of falls and fractures, daily or weekly doses are preferred. However, the ViDA study that administered 100,000 IU of vitamin D monthly did not report an increase in fractures or falls [ 91 ].

To further shed light on vitamin D supplementation, Cashman and colleagues calculated the daily dose to reach the target serum 25(OH)D level in the blood, based on a meta-regression analysis of individual participants from seven winter-based RCTs, including 882 patients aged from 4 to 90 years [ 92 ]. They concluded that the daily dose to avoid severe deficiency (i.e., reaching 25 nmol/l in 97.5% of the individuals) is 400 IU. In comparison, 1000 IU daily is needed to reach the safer level of 50 nmol/l; however, 1000 IU daily is a higher dose than earlier recommended by the Institute of Medicine (IOM) and other regulatory agencies.

While vitamin D supplementation is the best option for the institutionalized (as they are likely to get it freely), in the general population, especially in the lower-income and culturally and linguistically diverse groups, including migrants and refugees, supplementation may be challenging, even with free distribution. In contrast, food fortification will increase vitamin D status over the population as a whole, preventing severe deficiency and avoiding rickets and osteomalacia in large populations, especially for high latitude countries or in groups at high risk. Ideally, a combination of fortification and supplementation is required to tackle vitamin D deficiency and raise serum 25(OH)D levels to 50 nmol/L throughout the entire population.

COVID-19 vaccination

Finally, no published evidence points to an improved immune response with vitamin D supplementation to COVID-19 vaccination. However, the label for the Pfizer vaccine does mention a possible positive role of concomitant immunomodulation [ 93 ]. Indeed, low vitamin D levels have been associated with increased susceptibility to SARS-CoV-2 infection and increased COVID-19 clinical impact (Fig. (Fig.3) 3 ) [ 94 , 95 ]. Moreover, vitamin D supplementation was shown to boost antigen-specific immunity in older adults with suboptimal vitamin D status [ 96 ], and to decrease the severity of COVID-19, as demonstrated by a reduced need for intensive care and decreased mortality risks [ 97 ]. To this point, vitamin D might be helpful, specifically in areas, such as southern Europe, where hypovitaminosis D is prevalent. If vitamin D is to be utilized to improve the host response to COVID-19 vaccination, this may present a unique opportunity to address the widespread prevalence of hypovitaminosis D. Repleting populations that are being immunized against COVID-19 with vitamin D may address the double pandemic of COVID-19 and vitamin D deficiency [ 98 ].

The Aging session of the Conference reviewed some of the most debated matters that center on vitamin D and the older population. In this manuscript, we report the findings emphasized during the meetings.

Vitamin D production decreases with age, but the aging skin can produce sufficient vitamin D when exposed to UV light. However, this remains a challenge, especially in the institutionalized. Vitamin D supplementation should be combined with calcium to reduce fractures in the older population. The goal for adequate vitamin D status should be to reach a serum level of 25(OH)D > 50 nmol/l. It appears that daily low-dose vitamin D regimens reduce the risk of falling, especially in the elderly, compared with infrequent, large bolus doses that may increase it. The role of vitamin D supplementation on muscle strength remains to be clarified. On the other hand, supplementation decreases the risk of progression to T2D from prediabetes among those who are vitamin D deficient. Finally, of the three possible strategies to gain vitamin D sufficiency—sunshine exposure, food fortification, and supplementation—the latter seems to be the most effective and practical. Better-designed clinical trials in the future especially targeted to those who are truly vitamin D deficient, may help us unravel the many controversies revolving around vitamin D and the aged population.

Acknowledgements

We would like to acknowledge the support of Fabio Perversi (Polistudium, Milan, Italy) in drafting the first version of the manuscript and Aashni Shah (Polistudium, Milan, Italy) for editorial assistance. We wish to acknowledge all participants in the Conference: Adrian Martineau, Neil Binkley, Anna Maria Formenti, Ghada El-Hajj Fuleihan, Angelo Fassio, Hector F. De Luca, Annemieke C. Heijboer, Daniel D. Bikle, Salvatore Minisola, Silvia Trasciatti, Nicola Napoli, Giulia Martina Cavestro, Giovanni Latella, David Feldman, Salvatore Minisola, Anastassios G. Pittas, René Rizzoli, and Fabio Massimo Ulivieri.

Author contributions

Study conception and design: J.P.B., A.G.; collection and interpretation of data from literature: J.P.B., P.R.E., R.B., B.D.H., M.L.-C., P.L., C.M.; manuscript drafting and editing: J.P.B., A.G., P.R.E., R.B., B.D.H., M.L.-C., P.L., C.M.; approval to submit: J.P.B., A.G., P.R.E., R.B., B.D.H., M.L.-C., P.L., C.M.

This work was supported, in part, by International Vitamin D Expert Association (IDEA). The conference and editorial assistance were supported by an unrestricted educational grant by Abiogen Pharma, Pisa, Italy. The sponsors had no role in the selection of discussion topics, speakers, or authors, preparation, or review of this paper.

Compliance with ethical standards

A.G. is consultant for Abiogen and Takeda and received research grant to Institution from Takeda, R.B. received lecture fees from Abiogen (Italy), FAES Farma (Spain) and Ceres (Belgium) outside of the submitted work. The other authors have no conflicts of interest to declare.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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What is Vitamin D3? Discover its benefits, sources and side effects

Vitamin D glass bottle on a beige background.

Vitamin D3 is a form of vitamin D that helps the body absorb calcium and other minerals which are important for healthy bones, immune function, and more.

It's also a popular dietary supplement and a staple in the drugstore vitamin aisle — which may feel overwhelming at times between all the ABCs and 123s. What is vitamin D3 exactly and how does it differ from vitamin D? Who should be taking a supplement?

We spoke to experts to get the DL on vitamin D3. Here's what to know about vitamin D3 benefits, sources, deficiencies, side effects and more.

What is vitamin D3?

Vitamin D (calciferol) is a fat-soluble vitamin that plays an important role in many bodily functions, including maintaining bone health, supporting immune function and more, Heather Hodson, clinical nutritionist at the Center for the Prevention of Cardiovascular Disease at NYU Langone Health, tells TODAY.com.

There are two main forms, vitamin D3 and vitamin D2.

Vitamin D3, also known as cholecalciferol, is a form of vitamin D that is synthesized in the skin upon exposure to sunlight, says Hodson. "It can also be consumed through dietary sources like fish and supplements," Hodson adds.

Once Vitamin D3 is synthesized in the skin or ingested, it gets converted to calcidiol n the liver, which is eventually converted to the active form of Vitamin D, calcitriol, says Hodson.

Vitamin D2, also known as ergocalciferol or "pre-vitamin D," is typically human-made and added to foods, per the National Institutes of Health .

Vitamin D3 benefits

Supports bone health
Strengthens the immune system
Promotes heart and brain health
Reduces inflammation

Vitamin D3 plays an important role in supporting and maintaining healthy bones, says Hodson. It does so by regulating calcium and phosphorus levels in the blood, and promoting the absorption of these minerals by the gut.

It is also essential for bone growth and remodeling, per the NIH. Vitamin D3 can help prevent bone disorders, such as osteoporosis, and bone loss.

"It really supports our bone integrity, so it's keeping your skeletal system nice and strong," Zelle Morefield, a transplant dietitian at the Mayo Clinic tells TODAY.com. Vitamin D3 supports healthy muscle and nerve function as well.

Vitamin D3 strengthens the immune system to help the body fight off bacteria and viruses, and it has neuroprotective properties which support brain cell activity, according to the Mayo Clinic.

"It has some different anti-inflammatory and antioxidant properties as well, and it's just good for just overall cellular functions and helps a lot of smaller cellular processes," says Morefield.

How much vitamin D3 do you need?

The recommended dietary allowance (RDA) of vitamin D is the daily intake sufficient to maintain bone health and normal calcium levels in healthy people, per the NIH . This varies by age:

Infants 0–12 months: 10 mcg (400 IU)
Children 1–18 years: 15 mcg (600 IU)
Adults 18–70 years: 15 mcg (600 IU)
Adults over 70 years: 20 mcg (800 IU)

What are the sources of vitamin D3?

Vitamin D3 can be obtained in three main ways: from your diet, sunlight or supplements.

Food sources of vitamin D3

Few foods are naturally rich in vitamin D3, but certain foods are fortified with vitamin D3, especially in the U.S., the experts note. Dietary sources of vitamin D3 include:

Fatty fish (salmon, tuna, sardines , trout)
Organ meats
Fish liver oil
Fortified milk
Fortified orange juice
Fortified cereals

The other form, vitamin D2, can be obtained from plant-based sources, including fortified plant milks, juices and mushrooms exposed to UV light, says Hodson.

Ultraviolet light

“The other way you get vitamin D would just be sunlight," says Morefield. Vitamin D is formed in the body when ultraviolet (UV) rays from sunlight hit uncovered skin, which triggers the synthesis of pre-vitaminD3, which is converted into vitamin D3, per the NIH.

"Typically after about 5-to-15 minutes of sun exposure, so a walk down the street, for example, your skin is able to synthesize vitamin D from the sunlight," says Morefield.

The amount of vitamin D the body makes will vary depending on several factors. These include location, season, time of day, cloud cover, air pollution, sunscreen, protective clothing, age and skin pigmentation or melanin content, according to the Mayo Clinic .

Suppl ements

Dietary supple ments can be used when a person does not get enough vitamin D from their diet or sunlight, or has a vitamin D deficiency caused by a medical condition or medication.

Vitamin D supplements may contain either vitamin D3, which is often derived from animals but can be sourced from lichen, or vitamin D2 which is plant-derived, per the NIH. Most standard multivitamins will contain vitamin D as well, says Morefield.

“Research demonstrates that compared to Vitamin D2, Vitamin D3 is more easily absorbed and may more effectively sustain desirable Vitamin D levels,” says Hodson.

Who should take vitamin D3?

While many people can get enough vitamin D from sunlight, food, or multivitamins, some may benefit from additional vitamin D3.

A vitamin D3 supplement may be recommended if you have an insufficiency or a deficiency. A healthcare provider can determine this through a test which measures levels of vitamin D in the blood, says Hodson.

A vitamin D deficiency typically occurs when people don't get enough vitamin D from their diet or sunlight; cannot synthesize or absorb vitamin D properly; or have certain medical conditions or take medications which affect vitamin D levels, the experts note.

Individuals with limited sun exposure, for example, those who spend very limited time outdoors or those living in cooler regions, may be at higher risk of vitamin D deficiency, says Hodson.

"In the colder months, we’re often bundled head-to-toe in winter gear. This leaves very little skin exposed to sunlight for vitamin D3 synthesis," Hodson adds.

People with dark skin, which has a higher melanin content, may not synthesize as much vitamin D, per the Cleveland Clinic . Older adults synthesize less vitamin D and often spend more time indoors, which increases the risk of a deficiency, Morefield adds.

Some medical conditions can impact the absorption or synthesis of active vitamin D, the experts note. These include:

Irritable bowel disease (Crohn's, ulcerative colitis)
Celiac disease
Cystic fibrosis
Liver or kidney disease

Individuals who've had a history of gastrointestinal surgery, such as bariatric weight loss surgery or small bowel resection surgery, may have difficulty absorbing vitamin D3, Hodson adds.

“Individuals with these conditions may benefit from additional vitamin D, though they should speak with their healthcare provider regarding what form would be most appropriate,” says Hodson.

Certain medications can also lower vitamin D levels. According to the Cleveland Clinic , these include, but are not limited to:

Steroids (prednisone)
Cholesterol-lowering drugs
Seizure drugs

Symptoms of vitamin D deficiency

"Vitamin D deficiency is not always characterized by noticeable symptoms," says Hodson. Some people have no signs or symptoms of a vitamin D deficiency at all, Hodson adds.

Potential symptoms of a vitamin D deficiency include:

Muscle pain
Mood changes

Over time, vitamin D deficiency can lead to complications including osteoporosis, which weakens the bones, and osteomalacia (a softening of the bones) and fractures, per the Cleveland Clinic.

“In older populations, deficiency may lead to increased fall risk,” says Hodson.

In severe pediatric cases, vitamin D deficiency can cause bowed legs or rickets, which can lead to skeletal deformities, Hodson adds.

The only way to know if you have a vitamin D deficiency is to get tested, the experts emphasize. Semi-regular monitoring of vitamin D levels (for example, with annual physical lab checks) may be helpful to treat or prevent deficiencies in a timely manner, Hodson adds.

Vitamin D3 dosage

“It’s always a good idea to consult with a healthcare professional and check your vitamin D levels before starting supplementation,” says Hodson.

The recommended daily allowance for vitamin D is between 400–600 IU for healthy children and adults. "That’s the standard amount that most of the population needs to support their basic functions, but if (you have) a deficiency, that number may be very different," says Morefield.

Most vitamin D3 supplements available over-the-counter are sold in dosages between 1000–5000 IU, but some are higher. “Ask for your provider’s recommendation as to what dosage, if any, is right for you and do not exceed this dosage,” Hodson adds.

Research has shown that healthy adults without a deficiency probably won’t benefit from consuming additional vitamin D3 through supplements, TODAY.com previously reported .

Vitamin D3 side effects and risks

When taken appropriately and as directed, vitamin D3 is generally safe. However, consuming too much vitamin D3 can lead to vitamin D toxicity, so it's important not to exceed your prescribed or recommended dosage, says Hodson.

"Because Vitamin D is a fat-soluble vitamin, any excess that is consumed is stored in the body rather than excreted through urine," says Hodson. If you are taking too much in a vitamin D3 supplement, it can built up in the body and reach toxic levels.

According to Hodson, vitamin D toxicity can lead to:

Constipation
Reduced appetite
Hypercalcemia

If you experience any side effects, talk to your doctor. “When selecting a supplement, choose brands that are reputable and third-party tested,” says Hodson.

Caroline Kee is a health reporter at TODAY based in New York City.

VITAMIN D DEFICIENCY

Mar 11, 2019

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VITAMIN D DEFICIENCY. Evolving Concepts And Importance In Overall Health Status. Silent epidemic. Vitamin D deficiency is a highly prevalent condition, present in approximately 30% to 50% of the general population. More prevalent in elderly, women of child bearing age and infants.

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VITAMIN D DEFICIENCY Evolving Concepts And Importance In Overall Health Status

Silent epidemic. • Vitamin D deficiency is a highly prevalent condition, presentin approximately 30% to 50% of the general population. • More prevalent in elderly, women of child bearing age and infants. • Often unrecognized by clinicians.

Case 1 • An elderly AA obese woman was readmitted to the hospital from a nursing home because of progressive weakness. She had been discharged two weeks earlier following a four-month hospitalization for severe chronic obstructive pulmonary disease. During her previous hospital stay, she required prolonged mechanical ventilation through a tracheostomy tube and total, or central, parenteral nutrition (CPN). She was discharged to the nursing home on low-flow oxygen therapy. On readmission, she had a weak cough and required vigorous tracheal suctioning through her tracheostomy tube. PMH is significant for seizure disorder, HTN, CRF. Depressed levels of serum calcium and phosphate resistant to vigorous oral and intravenous replacement were noted on both hospital admissions.

Question • Can you identify risk factors for Vitamin D deficiency in this patient?

Elderly • Dark skin • No sun exposure • Diet • Obesity • CPN-provides 200 IU/d. • Dilantin • CRF

For our patient, before she was to return to the nursing home, her 25-hydroxyvitamin D level was 7 ng per mL (17 nmol per L; normal: 8 to 38 ng per mL [20 to 95 nmol per L]), and her PTH level was 161 pg per mL (17 pmol per L; normal: 9.5 to 49.4 pg per mL [1.0 to 5.2 pmol per L]). Vitamin D and calcium supplementation was to begin in the nursing home.

Risk Factors • Individuals older than 65 years • Nursing home residents • Individuals with nonvertebral or hip fractures • Individuals with kidney disease • Individuals with low bone mass or osteoporosis • Individuals with a history of falls

Causes • Inadequate sun exposure • Sunscreen use SPF>=8 • Pigmented skin • Aging (older than 65 years) • Winter season • Northern latitudes above 40° • Decreased absorption • Bowel bypass surgery • Crohn’s disease • Celiac disease • Fat and cholesterol absorption inhibitors

Other Causes • Breastfeeding • Liver failure • Chronic renal disease • Medications; Steroids decrease half life of vitamin D. Dilantin, Phenobarbital, and Rifampin can induce hepatic p450 enzymes to accelerate the catabolism of vitamin D.

Metabolism Of Vitamin D

Metabolism • Source: Skin and diet • Stores: 25 OH Vitamin D3 (calcidiol) • Active form: 1,25(OH)2 Vitamin D (calcitriol) • MOA: Steroid hormone. Binds to VDR in nucleus to upregulate gene expression in target cells. • Functions: • Calcium absorption in the intestines and is required for the efficient utilization of dietary calcium.

Metabolism • Involved in cellular growth, differentiation and apoptosis • Simulates insulin secretion • Modulates the immune system. • Reduces inflammation • Muscle development • Telomere protective

Associated Clinical Conditions • Muscle Weakness and Falls • Proximal muscle weakness • Chronic muscle aches • Myopathy • Increase in falls • Recent studies suggest that vitamin D supplementation at doses between 700 and 800 IU/d in a vitamin D-deficient elderly population can significantly reduce the incidence of falls.

Bone Density and Fractures • Risk of osteoporosis may be reduced with adequate intake of vitamin D and calcium. • Studies support the concept that vitamin D at doses between 700 and 800 IU/d with calcium supplementation effectively increase hip bone density and reduced fracture risk, whereas lower vitamin D doses may have less effect.

Role in Cancer Prevention • Low intake of vitamin D and calcium has been associated with an increased risk of non-Hodgkin lymphomas, colon, ovarian, breast, prostate, and other cancers. • The anti-cancer activity of vitamin D is thought to result from its role as a nuclear transcription factor that regulates cell growth, differentiation, apoptosis and a wide range of cellular mechanisms central to the development of cancer. These effects may be mediated through vitamin D receptors expressed in cancer cells. • Vitamin D is not currently recommended for reducing cancer risk

Autoimmune Disease • Vitamin D supplementation is associated with a lower risk of autoimmune diseases. • In a Finnish birth cohort study of 10,821 children, supplementation with vitamin D at 2000 IU/d reduced the risk of type 1 diabetes by approximately 78%, whereas children who were at risk for rickets had a 3-fold higher risk for type 1 diabetes. • In a case-control study of 7 million US military personnel, high circulating levels of vitamin D were associated with a lower risk of multiple sclerosis. • Similar associations have also been described for vitamin D levels and rheumatoid arthritis.

Role in Cardiovascular Diseases • Vitamin D deficiencyactivates the renin-angiotensin-aldosterone system and can predisposeto hypertension and left ventricular hypertrophy. • Additionally,vitamin D deficiency causes an increase in parathyroid hormone,which increases insulin resistance secondary to down regulation of insulin receptors and is associated with diabetes,hypertension, inflammation, and increased cardiovascular risk.

Role in Reproductive Health • Vitamin D deficiency early in pregnancy is associated with a five-fold increased risk of preeclampsia. • Role in All Cause Mortality • Researchers concluded that having low levels of vitamin D (<17.8 ng/mL) was independently associated with an increase in all-cause mortality in the general population.

Diagnostic Tests • Measurement of 25(OH) vitamin D serum levels best reflects the vitamin D status of an individual. • Normal levels 25 (OH) vitamin D are in the range of 30 to 80 ng/mL (75 to 200 nmol/L). • Concentrations < 12 to 20 ng/mL (30 to 50 nmol/L) are considered deficient. • Levels > 150 ng/mL (374 nmol/L) are considered toxic.

Dietary Reference Intakes: Vitamin DEstablished in 1997

Dietary Sources • Natural sources of vitamin D include: • Fish liver oils, such as cod liver oil, 1 Tbs (15 mL) provides 1,360 IU • Fatty fish species, such as: • Herring, 85 g (3 ounces) provides 1383 IU • Catfish, 85 g (3 oz) provides 425 IU • Salmon, cooked, 100 g (3.5 oz]) provides 360 IU • Mackerel, cooked, 100 g (3.5 oz]), 345 IU • Sardines, canned in oil, drained, 50 g (1.75 oz), 250 IU • Tuna, canned in oil, 85 g (3 oz), 200 IU • Eel, cooked, 100 g (3.5 oz), 200 IU • A whole egg, provides 20 IU • Beef liver, cooked, 100 g (3.5 oz), provides 15 IU

Fortified Sources • Some of the dietary sources: • Fortified milk (100 IU/8 oz) • Cheeses and yogurt • Fortified cereals

Updated Recommendations In Process • Studies suggest that the daily vitamin D intakes should be much higher than 400 IU/d. • Daily intakes in the range of 800 to 1000 IU/d should be strongly considered. • Although there are concerns regarding vitamin D toxicity, side effects at intakes exceeding the current upper limit of 2000 IU/d have not been reported to date. • Assessment of vitamin D status with serum measurements of 25(OH) vitamin D levels for a broader range of patients should be encouraged.

Causes and Management of Vitamin D Deficiency • Lack of adequate sunlight or chronic sunscreen use; Ultraviolet lamp or increased sun exposure. In a Boston study, exposure of hands, face, and arms to sunlight for five to 15 minutes daily between 11 a.m. to 2 p.m. provided adequate vitamin D. • Total (central) parenteral nutrition; 400 to 800 IU of vitamin D orally per day, or 20 to 25 IU of vitamin D per kg intravenously per day.

Causes and Management of Vitamin D Deficiency • Vitamin D-deficient diet; Usually 1,500 to 5,000 IU of vitamin D2 orally per day, or 50,000 IU of vitamin D2 orally per week or 10,000 to 50,000 IU of vitamin D2 intramuscularly per month • Fat malabsorption; 25-hydroxyvitamin D, 20 to 30 mcg per day • Cirrhosis, nephrotic syndrome, renal failure, gastric or small bowel resection, rifampin, chronic corticosteroids, anticonvulsants; 1,25-dihydroxyvitamin D, 0.15 to 0.5 mcg daily.

Key clinical recommendation • Daily vitamin D supplementation of 800 to 1,000 IU is a reasonable dose for adults. Levels of 25-OH vitamin D should be maintained > 32 ng per mL (80 nmol per L) to maximize bone health. • The (AAP) has doubled the recommended intake of vitamin D to 400 IU per day for infants, children, and adolescents. • In patients with severe vitamin D deficiency, 50,000 IU of vitamin D should be given daily for one to three weeks, followed by weekly doses of 50,000 IU.

After repletion of body stores, 800 IU of vitamin D daily or 50,000 IU of vitamin D once or twice monthly is adequate maintenance therapy. • Patients with no sun exposure, malabsorption, or those taking antiepileptic drugs may require larger maintenance doses of vitamin D (i.e., up to 50,000 IU one to three times week. • In critically ill patients, albumin-adjusted calcium levels underestimate true or ionized hypocalcemia. Therefore, measured ionized calcium levels are recommended, particularly in patients who are being treated in an intensive care unit. • If calcium supplementation alone fails to maintain normal serum levels, the patient is vitamin D deficient or resistant and may benefit from a trial of calcitriol (Rocatrol). • Vitamin D toxicity is very uncommon, and there is a wide safety margin at these higher supplement doses.

References • Grant WB. An estimate of premature cancer mortality in the US due to inadequate doses of solar ultraviolet-B radiation. Cancer.2002;94:1867-1875. • 2. Holick MF. Calcium plus vitamin D and the risk of colorectal cancer. N Engl J Med. 2006;354:2287-2288. • 3. Giovannucci E, Liu Y, Rimm EB, et al. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J Natl Cancer Inst. 2006;98:451-459. • 4. Garland CF, Garland FC, Gorham ED, et al. The role of vitamin D in cancer prevention. Am J Public Health. 2006;96:252-261. • 5. Bodnar LM, Simhan HN, Powers RW, Frank MP, Cooperstein E, Roberts JM. High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates. J Nutr. 2007;137:447-452. • 6. Nesby-O’Dell S, Scanlon KS, Cogswell ME, et al. Hypovitaminosis D

prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988-1994. Am J Clin Nutr. 2002;76:187-192. • 7. Lips P, Chapuy MC, Dawson-Hughes B, Pols HA, Holick MF. An international comparison of serum 25-hydroxyvitamin D measurements.Osteoporos Int. 1999;9:394-397. • 8. Chen TC, Shao A, Heath H III, Holick MF. An update on the vitamin Dcontent of fortified milk from the United States and Canada. N EnglJ Med. 1993;329:1507. • 9. Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266-281

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Vitamin D deficiency

"Vitamins are needed your body for good health. Vitamin D is important for health and strong and healthy bones. For a number of reasons, many people aren’t getting enough vitamin D to stay healthy. This is called vitamin D deficiency. Nutrition consultation is available to you at OnlineNaturalHealth. We recommend balanced eating so you can feel and look your best. Onlinenaturalhealth recommend the best vitamin supplements. http://www.onlinenaturalhealth.ca/nutrition-consulation-and-vitamin-supplements.html"

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Pseudotumor cerebri with status epilepticus in a child: A rare presentation of vitamin D deficiency

Affiliations.

1 Nepalese Army Institute of Health Sciences- College of Medicine Kathmandu Nepal.
2 Patan Academy of Health Sciences Lalitpur Nepal.
3 Kathmandu Medical College Kathmandu Nepal.
PMID: 38550743
PMCID: PMC10965748
DOI: 10.1002/ccr3.8695

Pseudotumor cerebri (PTC) encompasses a constellation of symptoms caused by elevated intracranial pressure of unclear etiology. Various associations have been described, rarely hypovitaminosis D. Vitamin D deficiency should be considered as a potential etiology of neurological manifestations like PTC and seizures in children. Early diagnosis and correction of vitamin D deficiency is key to preventing morbidity and achieving good outcomes.

Keywords: case report; elevated intracranial pressure; pseudotumor cerebri; status epilepticus; vitamin D deficiency.

Publication types

Case Reports

Low Vitamin D Symptoms: How to Spot a Vitamin D Deficiency

V itamin D is considered a nutrient of public health concern, meaning that a staggering number of people don't get enough of this vitamin in their diet. If you think your diet may be low in vitamin D, learn about the signs and symptoms of a vitamin D deficiency and how you can easily increase your intake.

Known as the “sunshine vitamin” because our body can make its own vitamin D when sunlight hits our skin, vitamin D plays a critical role in keeping us healthy.

Vitamin D Benefits: Why This Nutrient Is Important

Vitamin D is a hard-working nutrient that has multiple functions, including:

Promotes calcium and phosphorus absorption to maintain bone strength and reduce the risk of osteoporosis.
Supports immune health and helps control infections.
Reduces inflammation .
Regulates blood sugar levels.
Supports muscles and nerves.
May reduce the risk of autoimmune diseases , such as rheumatoid arthritis and psoriasis.

How Much Vitamin D Do You Need?

The amount of vitamin D you need each day depends on your age. You’ll see vitamin D listed as international units (IU) and micrograms (mcg). The recommended dietary allowance, or RDA, for vitamin D is 600 IU or 15 mcg for children and young adults. After age 70, the RDA increases to 800 IU or 20 mcg per day.

Other experts suggest we need even more vitamin D. For example, the Endocrine Society recommends up to 1,500 to 2,000 IU of vitamin D daily for adults.

Incidence of Vitamin D Deficiency

Vitamin D deficiency has been called a global pandemic, impacting 1 billion people worldwide. An analysis of the National Health and Nutrition Examination Survey estimates that about 42% of the U.S. population is deficient in vitamin D.

However, it’s important to remember that a true vitamin deficiency means specific health problems result from the lack of a nutrient. An actual vitamin D deficiency results in rickets, which is the term for a bone-softening, leg-bowing disease that is more likely to impact children in developing countries. Rickets is rare in the U.S.

While many people in the U.S. fail to consume recommended levels of vitamin D, the concerns about severe deficiencies are overblown, says Clifford J. Rosen, MD, director of clinical and translational research and a senior scientist at the Maine Medical Center Research Institute in Scarborough, Maine, who is one of the country’s leading authorities on vitamin D.

The main source of controversy is the different definitions of “deficiency,” according to Rosen, who says various organizations have used different cutoff points for normal vitamin D levels, with some so high that it over-estimates the number of Americans who are truly deficient.

Vitamin D Deficiency Causes

What can lead to a vitamin D deficiency?

Dietary choices.
Environment.
Medical conditions.
Surgery or medication.

Dietary choices

Not getting enough vitamin D can be caused by your dietary choices. Few foods are naturally good sources of vitamin D, which makes it more difficult to consume adequate amounts.

Environment

Certain environmental factors could increase your risk of a vitamin D deficiency, including:

Lack of outdoor activity. If you spend most of the day indoors, you’ll miss out on opportunities to get vitamin D from the sun .
Sunblock. Using sunscreen to protect against harmful UV rays limits the skin’s ability to make vitamin D.
Geographic location. If you live farther away from the equator, you probably have less exposure to the type of sunlight that promotes vitamin D production in the skin.

Medical conditions

Certain medical conditions may interfere with vitamin D absorption, including:

Crohn’s disease .
Ulcerative colitis.
Celiac disease .
Cystic fibrosis.

Surgery or medication

Weight loss surgeries like gastric bypass surgery make it difficult to absorb sufficient quantities of vitamin D. Additionally, some medications can lower vitamin D levels, including:

Laxatives .
Cholesterol-lowering drugs.
Genetics. Some people have gene variants that make it hard for their bodies to produce vitamin D, even if their skin is exposed to ultraviolet light.

Who Is at Risk of Low Vitamin D?

Some people are more likely than others to have trouble getting enough vitamin D. Here are the factors that may determine your risk:

Age. The skin’s ability to make vitamin when exposed to sunlight declines as you age. This is one reason why higher vitamin D amounts are recommended for adults over age 70. Infants are also at risk of not getting enough vitamin D, especially breastfed babies since breast milk contains only a small about of vitamin D compared to infant formula, which is fortified with vitamin D.
Mobility. People who are homebound or rarely go outside, such as those who are hospitalized or in nursing homes , may not be able to use sun exposure as a source of vitamin D.
Skin color. The darker your skin, the less vitamin D you make from sunlight exposure. For example, African Americans and Hispanic people tend to have lower vitamin D levels.
Weight. A body mass index of 30 or greater is considered a risk factor. Some of the vitamin D can bind to body fat instead of getting into the bloodstream.
Restricted diets. People who are vegan or follow a 100% plant-based diet may struggle to get enough vitamin D because many of the best sources of vitamin D are from animals, such as dairy and fish.

Best Sources of Vitamin D

To increase daily vitamin D, there are four main sources:

Foods naturally rich in vitamin D. Fatty fish like salmon and tuna, egg yolks, beef liver, cod liver oil and mushrooms that have been exposed to UV light in the growing process are naturally rich in the vitamin.
Vitamin D fortified foods. Dairy and non-dairy milk, orange juice and breakfast cereals are sometimes fortified with additional vitamin D.
Supplements. Vitamin D supplements can help ensure you’re getting adequate amounts each day. Vitamin D3 or cholecalciferol is the preferred form.
Sunlight. About 20 minutes of unprotected sun exposure each day will help your body make adequate amounts of vitamin D.

Signs of Vitamin D Deficiency

You may not always have symptoms with a vitamin D deficiency. However, these are some of the early signs:

Mood changes.
More frequent infections and illnesses.
Muscle twitching, weakness or pain.
Joint stiffness or arthralgias.
Lower back pain .

Potential Complications of Low Vitamin D

If vitamin D deficiency continues for long periods, it may result in complications. Low blood levels of vitamin D have been associated with the following:

Bone fragility and osteoporosis .
Falls and fractures.
Increased risk of death from cardiovascular disease .
Cognitive impairment in older adults.
Depression .
Pregnancy complications.
Certain cancers, including breast, prostate and colon.

When to See a Doctor

If you have these signs and suspect they're linked to a vitamin D deficiency, talk to your healthcare provider about getting a blood test that can check for vitamin D levels.

The most accurate way to measure vitamin D levels is the 25-hydroxyvitamin D blood test. A vitamin D level less than 20 nanograms/milliliter (ng/mL) is generally accepted as deficient. However, some groups define vitamin D deficiency as less than 30 ng/mL

Even though there’s been increased attention on vitamin D deficiencies – and an estimated 10 million vitamin D blood tests are performed annually – the U.S. Preventive Services Task Force found insufficient evidence to recommend widespread vitamin D testing among healthy adults.

Only high-risk populations are recommended for vitamin D screening, including:

Nursing home residents.
Hospitalized patients.
Adults over 65.
Women with osteoporosis.
African American and Hispanic individuals.
People with chronic kidney disease, chronic liver disease and malabsorption syndromes .

What to Do If You're Vitamin D Deficient

If a lab test reveals low levels of vitamin D, your healthcare provider may recommend supplementation. The safe upper limit for vitamin D supplementation is 4,000 IU or 100 mcg per day, so it’s important not to go over that amount unless recommended by your doctor.

It’s also important not to expect miracles by taking more vitamin D. Even though vitamin D is an essential nutrient, more isn’t always better.

Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women’s Hospital in Harvard Medical School and leader of a large vitamin D randomized trial called VITAL, found that increasing vitamin D did not protect against fractures, heart disease or cancer.

“We only need small to moderate amounts of vitamin D, and among the healthy population, most people do not need screening tests or supplements,” she says. “Larger amounts do not confer greater benefits.”

High doses of vitamin D, however, may benefit the immune system and tamp down inflammation, Manson says. That may be why the VITAL trial found that vitamin D helped lower the risk of autoimmune conditions, such as rheumatoid arthritis and psoriasis, she says.

Vitamin D Supplement Side Effects

Unlike vitamins C and B, which are water-soluble vitamins, Vitamin D is a fat-soluble vitamin (along with vitamins A, E and K). This means that vitamin D can be stored in the body and could pose a risk for toxicity when consumed in large amounts.

With the growing consumer interest in vitamin D – and the articles and books extolling the benefits – there’s actually been an increase in vitamin D toxicity . Some of the cases are due to errors, yet much of the blame is due to the widespread availability of high-dose, over-the-counter supplements.

Taking 60,000 IU of vitamin D per day for several months has been shown to cause toxicity. The main consequence is a buildup of calcium in your blood, called hypercalcemia, which can cause several problems:

Nausea and vomiting.
Abdominal pain.
Poor appetite.
Dehydration.
Constipation.

Vitamin D toxicity could progress to kidney failure and irregular heartbeat or arrhythmias. As always, check with your doctor before taking vitamin D supplements.

young woman enjoying morning sun next to her window

Australian Journal of General Practice

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Malnutrition, nutritional deficiency and alcohol: A guide for general practice

Alcohol use has an effect on nutritional status, with nutritional deficiencies being a major contributor to morbidity, for example Wernicke’s encephalopathy. Currently, there is an absence of best-practice guidelines to support general practitioners (GPs) in the identification and management of malnutrition and nutritional risk factors in patients who drink at risky levels.

This article reviews some of the nutritional considerations in patients who drink at risky levels or who have alcohol dependence, with the aim of enhancing GPs’ awareness of the nutritional considerations in this patient group.

Nutritional risk factors extend beyond body mass index (BMI), and patients might present with a healthy BMI and be malnourished. Screening for risk of malnutrition and other nutritional deficiencies followed by supplementation and consideration of referral to multidisciplinary services, including a dietitian, is likely to improve patient outcomes.

Alcohol use causes a high disease burden and has significant social and economic consequences. 1,2 Although alcohol can be consumed in line with low-risk consumption guidelines, 3 excess consumption and other risk factors can lead to medical complications. 4 Alcohol dependence is characterised by a strong internal drive to use alcohol, manifested by an impaired ability to control use, with increasing priority given to use despite harm and negative consequences. 5 Alcohol consumption in excess is also known to negatively affect nutritional status, but this might be less recognisable in the early stages of risky drinking. 6 ‘Risky’ drinking is defined as more than 10 standard drinks a week and more than four standard drinks in one day. 3 General practitioners (GPs) play an important role in screening alcohol consumption and engaging patients in discussions about alcohol and nutrition. 7

Alcohol provides little beyond energy (29 kJ/g) to dietary intake and, when consumed in addition to other foods and fluids, promotes a positive energy balance. 8 A standard drink contains 10 g of alcohol; this equates to 290 kJ. However, this might translate to 435 kJ in a 150-mL glass of wine, and might further depend on the types of mixers used, such as soft drinks or juice. This is visually represented in Figure 1.

Figure 1. Comparison of the average energy content in kilojoules (kJ) of alcoholic beverages. Click here to enlarge

SD, standard drink.

However, alcohol’s influence on promoting weight gain and obesity is variable. 8 This can be related to other factors such as gender, sleeping habits and physical activity levels. Alcohol consumption also affects energy metabolism. Although risky drinkers more consistently gain weight and are more likely to have a body mass index (BMI) above the healthy range, paradoxically, those with high levels of alcohol intake lose weight. 8 In some instances, patients might prioritise alcohol consumption over other food or fluids, resulting in caloric intake without nutrient intake. Those with a hypermetabolic state (eg advanced liver disease or acute pancreatitis) might present with weight loss if oral intake is not sufficient to meet increased metabolic demands. Initially, patients might present with a healthy BMI but, over time, with insufficient oral intake and weight loss, present as underweight.

Malnutrition can involve a deficiency, excess or imbalance of nutrients, resulting in adverse effects on body composition, function and health outcomes. 9 Most commonly, this is through inadequate consumption of food and fluids. Malnutrition can occur at all body sizes, including in those who might have a healthy BMI. 10 In a cohort of patients admitted to hospital for alcohol withdrawal, 88% of patients presented with a BMI >20 kg/m 2 , but one in two patients were identified as being at a medium to high risk of malnutrition. 11 Alcohol increases the risk of malnutrition, with 20% of patients with well-compensated liver disease and more than 60% of patients with advanced cirrhosis being malnourished. 12 There is limited literature reporting on rates of malnutrition in patients in the absence of advanced liver disease. 11 This emphasises the need for routine screening for malnutrition in patients who drink at risky levels. 9,10

Alcohol has a significant effect on the digestion, absorption and metabolism of nutrients, which can lead to micronutrient deficiency and the development of chronic disease. 13 Micronutrients are vitamins and minerals needed by the body to maintain normal body function. Over half the patients admitted to hospital for substance use treatment, including alcohol, are deficient in vitamins, minerals or electrolytes. 14,15 This includes deficiencies in vitamin C, vitamin A and iron. Nutritional deficiencies are common and are major contributors to the morbidity related to alcohol use (eg thiamine deficiency causing Wernicke–Korsakoff syndrome). 16 There is an absence of best-practice guidelines to support GPs in the management of malnutrition and nutritional deficiency in this patient group.

This article reviews some of the nutritional considerations in patients who drink at risky levels or who have alcohol use disorder (AUD), with the aim of enhancing GPs’ awareness of the nutritional considerations in this patient group.

Alcohol use assessment

Screening for alcohol risk can be conducted opportunistically, during presentations for potentially alcohol-related conditions or during routine preventive health assessments. 17 Screening for alcohol risk using the Alcohol Use Disorders Identification Test–Concise (AUDIT-C) can help GPs identify patients who drink at risky levels or have AUD. AUDIT-C scores of ≥4 for men and ≥3 for women should trigger a more detailed review. 18 Following screening, GPs are able to deliver advice on lower-risk alcohol consumption levels, deliver brief interventions and consider referring to multidisciplinary team members as required.

Nutrition assessment and management

Nutrition risk screening is a simple and first step to identify patients at risk of malnutrition. 19 Measurement of BMI and/or waist circumference and a brief assessment of dietary intake are recommended for all Australians as part of routine preventive care every 6–24 months depending on risk level. 17 As part of taking a social history, GPs might be aware of other social and environmental conditions that could affect an individual’s health and nutrition. This might include issues such as their ability to access or store food, known as food insecurity, 20 and could be due to financial concerns, the prioritisation of purchasing alcohol over food or homelessness.

Malnutrition

GPs routinely record waist circumference, height and weight and calculate BMI. These tools can help identify whether a patient is within a healthy weight range or has lost weight between GP visits. The Malnutrition Universal Screening Tool (MUST), which includes measures of BMI and unplanned weight loss in the past three to six months, has been recommended for use in ambulatory settings. 21 For patients who are identified at high risk of malnutrition using MUST (ie a score of ≥2), GPs can consider referral to an Accredited Practising Dietitian (APD) for comprehensive nutrition assessment. 19,22 However, weight loss might not be obvious and might be masked by the presence of fluid retention, including oedema and ascites. Mid-upper arm circumference can be used as a substitute for assessing BMI in patients who are difficult to weigh or have other factors that might influence weight, such as fluid retention. 22 Table 1 summarises the variables and considerations when using MUST.

Pathology testing

The prevalence of micronutrient deficiencies increases with increasing alcohol consumption. 23 Existing guidelines have highlighted that there are several micronutrient deficiencies that are common to alcohol dependence. 23 Micronutrient concentrations should be interpreted in the context of the clinical assessment and the acute phase response. For example, ferritin is an acute phase protein and, when elevated, might mask underlying iron deficiency. 23 Therefore, micronutrient status should be assessed alongside C-reactive protein and albumin. 23 Investigations should be ‘chosen wisely’ according to clinical presentation to ensure testing is rational. 24 Table 2 provides suggested pathology testing, findings and associated physical signs, symptoms and outcomes.

Nutrient supplementation and education

There is variable literature on nutrient supplementation in the context of patients who drink at risky levels or have alcohol dependence. 26,27 However, vitamin and mineral supplementation should be commenced to treat confirmed or clinically suspected deficiency. 23 One nutrient of importance is thiamine, given the established evidence of its efficacy in the treatment and prevention of Wernicke encephalopathy. 1

Thiamine 100 mg orally should be considered for all patients who drink alcohol at risky levels. 1 In healthy patients who drink at risky levels but have a good dietary intake, oral thiamine 300 mg should be administered for three to five days. 1 However, in those patients with poor dietary intake and generally poor nutritional status, parenteral thiamine 300 mg (intravenous if hospitalised) should be administered for several days, with subsequent oral doses of thiamine 300 mg daily for several weeks. 1 Oral supplementation of thiamine 100 mg daily should continue indefinitely in an alcohol-dependent patient who continues to drink alcohol. 1

For all, a healthy, balanced diet is the priority (ie not replacing healthy food with alcohol). However, a multivitamin might be recommended for those unable to achieve a balanced diet. Specific nutritional deficiencies identified on pathology might also need replacement (eg magnesium). Other harm-minimisation strategies might be discussed with patients to address alcohol-related behaviours. 1 This can include strategies such as alternating alcohol with non-alcoholic drinks and eating before drinking. When drinking socially, it might also include ordering small serves and distracting yourself while drinking, such as by talking to friends or playing pool.

Some, but not all, nutritional supplements are available on the Pharmaceutical Benefits Scheme, including thiamine and magnesium for Aboriginal people at risk. 28 Those who are referred to an APD might be eligible for oral nutrition supplements (eg high-energy and high-protein ‘sip supplements’) through the home enteral nutrition program. Those with access to the National Disability Insurance Scheme (NDIS) might be eligible for nutritional supplements and the services of an APD.

Multidisciplinary team and nutritional care coordination

Multidisciplinary team collaboration is essential in supporting nutritional interventions. There is established evidence that multidisciplinary teams including dietitians contribute to improved patient outcomes for alcohol-related liver disease. 29 For example, patients identified at risk of malnutrition using MUST could be referred to an APD for a comprehensive nutrition assessment and intervention. Similarly, patients identified to have difficulty accessing food and fluids might be referred to non-governmental organisations that provide or facilitate access to food. The use of chronic disease management plans and team care arrangements, or mental health care plans, might facilitate referral and access to these services, promoting disease prevention and independence and improving quality of life. 30 Access to multidisciplinary team supports for eligible patients might also be achieved through the NDIS. Table 3 summarises potential multidisciplinary team members and their roles.

Case study: John

John, aged 45 years, presents to your general practice for a laceration following a fall on the weekend. The practice nurse has conducted screening for smoking and alcohol as part of quality improvement activities, and has completed a set of observations. John consumes three standard drinks five days a week and has a couple of ‘big nights’ with workmates each weekend, with an AUDIT-C score of 8. He has never had any seizures or tremors as symptoms of withdrawal. You discuss harm minimisation with John, discussing a reduction in alcohol intake, which is his preferred option, rather than immediate cessation, as well as the option of referral to a drug and alcohol counsellor.

As part of your routine consultation, you collect John’s height and weight to calculate his BMI. You ask John to remove his clothing, which appears to be loose fitting around his arms and legs, although John has a small belly. John weighs 60.0 kg and is 178.0 cm tall; his BMI is 18.9 kg/m 2 (normal 18.5–24.9 kg/m 2 ). You notice visual muscle wasting in his calf. John reports he has unintentionally lost 5 kg in the past four months (7.7%). On discussion, John reveals he has separated from his partner and moved out, and has been living off takeaway food. A symptom review and physical examination does not suggest cancer as a cause. You calculate John’s overall risk of malnutrition and identify him as high risk. You consider ordering blood tests, as well as urinalysis and faecal occult blood testing because of the weight loss. You recommend oral thiamine 300 mg for three to five days and then thiamine 100 mg thereafter.

John returns to the clinic following his blood test. The blood results show that John has macrocytosis on full blood count, raised gamma-glutamyl transferase and high triglycerides. You consider John’s eligibility for a chronic disease management plan and team care arrangement for enhanced primary care referral to an APD. You consider referral to a psychologist or other relevant healthcare professionals identified in Table 3.

The nutritional considerations in patients who drink at risky levels or who have alcohol dependence extend beyond the evaluation of BMI alone because patients who have a healthy BMI might also be malnourished. Consideration should be made around recent weight loss, signs of fat or muscle wasting and suspected or confirmed nutritional deficiency through pathology testing. Referral to members of the multidisciplinary team should be considered to support and address barriers related to nutrition and to provide treatment and support to patients and families, translating to improved health and nutrition outcomes.

Ask patients about alcohol use and screen for alcohol use using the AUDIT-C.
Ask patients about their dietary intake, routinely record weight and calculate BMI. Routinely assess risk of malnutrition and consider referral to members of the multidisciplinary team, such as an APD, to address nutritional concerns.
Encourage a balanced diet and a reduction in alcohol use, and supplement for confirmed or suspected micronutrient deficiency.
Thiamine supplementation should be provided to all patients undergoing alcohol withdrawal, with long-term supplementation considered for those who continue to drink.
For patients with alcohol dependence or AUD, consider referral to a multidisciplinary alcohol and other drugs team.

Did you know you can now log your CPD with a click of a button?

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Alcohol-related disorders Continuing Diet Education Medical education Nutrition Substance-related disorder

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7 risks of vitamin D deficiency [infographic]
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Signs and Symptoms of Vitamin D Deficiency
Signs and Symptoms that could mean you have Vitamin D Deficiency
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Vitamin D Deficiency: Signs, Symptoms and Treatment

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VITAMIN D DEFICIENCY SIGN & SYMPTOMS SAGAR T-V HAKEEM LUQMAN
Vitamin D Deficiency and how to overcome this problem
Vitamin D full detail l deficiency, treatment, dose, duration, Toxicity l Hindi
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PDF Vitamin D Deﬁciency
Severe and prolonged deficiency can cause bone mineralization diseases, such as rickets in children and osteomalacia in adults. Vitamin D deficiency has also been associated with fractures, falls, functional limitations, some types of cancer, diabetes, cardiovascular disease, and depression. However the U.S. Preventive Services Task Force notes ...
Vitamin D Deficiency
Vitamin D is a fat-soluble vitamin that plays an important role in calcium homeostasis and bone metabolism. Vitamin D deficiency can lead to osteomalacia and rickets in children and osteomalacia in adults. The fortification of milk with vitamin D in the 1930s was effective in eradicating rickets in the world. However, subclinical vitamin D deficiency is still widely prevalent in both developed ...
Vitamin D deficiency in adults: Definition, clinical ...
Overt vitamin D deficiency, characterized by hypocalcemia and/or hypophosphatemia and rickets and osteomalacia in children and osteomalacia in adults, is now uncommon in most developed countries (see "Epidemiology and etiology of osteomalacia" and "Clinical manifestations, diagnosis, and treatment of osteomalacia in adults").
Vitamin D Deficiency: Causes, Symptoms & Treatment
In general, the two main causes of vitamin D deficiency are: Not getting enough vitamin D in your diet and/or through sunlight. Your body isn't properly absorbing or using vitamin D. There are several specific causes of vitamin D deficiency, including: Certain medical conditions. Weight loss-surgeries.
Vitamin D Deficiency and Related Disorders
2000 IU/day of vitamin D 2 or D 3 for at least 6 weeks or. 50,000 IU of vitamin D 2 once weekly for at least 6 weeks. When the serum 25 (OH)D level exceeds 30 ng/mL, provide maintenance treatment of 600-1000 IU/day. Recommended treatment for vitamin D-deficient adults is as follows [ 2] : 50,000 IU of vitamin D 2 or D 3 once weekly for 8 ...
Vitamin D Deficiency > Fact Sheets > Yale Medicine
Vitamin D deficiency is the state of having inadequate amounts of vitamin D in your body, which may cause health problems like brittle bones and muscle weakness. There may be no symptoms and doctors don't routinely check vitamin D levels, so many people are deficient and don't realize it. Vitamin D helps the body absorb calcium and ...
Evaluation, Treatment, and Prevention of Vitamin D Deficiency
Treatment with either vitamin D2 or vitamin D3 was recommended for deficient patients. At the present time, there is not sufficient evidence to recommend screening individuals who are not at risk for deficiency or to prescribe vitamin D to attain the noncalcemic benefit for cardiovascular protection. Read the Full Guideline
Vitamin D
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 ...
Vitamin D deficiency: Causes, symptoms, and treatment
People need vitamin D for muscle and bone health. Limited sun exposure and low dietary intake can lead to brittle bones, mood changes, and chronic pain. Learn more about how to get enough vitamin D.
PDF Vitamin D Deficiency in Children and Its Management: Review of Current
The clinical presentation of vitamin D-deﬁciency rickets includes symptoms and signs of bone deformity and/or pain and may be associated with hypocalcemia and associated clinical features.20. The disease can be divided into 3 stages (Table 1). The ﬁrst stage is charac-
Presentation of vitamin D deficiency
Aims: To describe the various ways in which vitamin D deficiency presents in children in selected districts of London and to identify which factors, if any, determine the mode of presentation. Methods: Retrospective review of patients presenting to Newham General, Royal London, Great Ormond Street, and King's College Hospitals between 1996 and 2001with either hypocalcaemia or rickets caused by ...
Vitamin D deficiency and fatigue: an unusual presentation
Vitamin D also has immunomodulatory activities (Holick 2007 ). Deficiency of vitamin D might be associated with diseases of immune dysregulation, one manifestation of which could be excessive daytime sleepiness (Zitterman and Gummert 2010; Hoeck and Pall 2011 ). We present a case of daytime fatigue in an otherwise healthy male who was found to ...
Presentation of vitamin D deficiency
Aims: To describe the various ways in which vitamin D deficiency presents in children in selected districts of London and to identify which factors, if any, determine the mode of presentation. Methods: Retrospective review of patients presenting to Newham General, Royal London, Great Ormond Street, and King's College Hospitals between 1996 and 2001 with either hypocalcaemia or rickets caused ...
Vitamin D deficiency and fatigue: an unusual presentation
Deficiency of vitamin D might be associated with diseases of immune dysregulation, one manifestation of which could be excessive daytime sleepiness (Zitterman and Gummert 2010; Hoeck and Pall 2011 ). We present a case of daytime fatigue in an otherwise healthy male who was found to be vitamin D deficient.
Vitamin D Deficiency and Related Disorders Clinical Presentation
Vitamin D deficiency is often a silent disease. By definition, rickets occurs in children whose growth plates have not fused. These children are often found to have started walking late or prefer to sit down for prolonged periods. In adults, vitamin D deficiency results in osteomalacia, which presents as a poorly mineralized skeletal matrix.
Non-classical presentation of vitamin D deficiency: a case report
Background Vitamin D is a fat-soluble vitamin; vitamin D is essential to sustain health and it protects against osteoporosis. It is crucial to the human body's physiology in terms of muscular movement and neurological signal transmission, and to the immune system in defense against invading pathogens. Case presentation This was a case of a 26-year-old Sudanese woman who presented with a 2 ...
Scientists Reveal New Findings About Older Adults Who Take Vitamin D
Signs of vitamin D deficiency . We recommend speaking with your healthcare provider if you suspect a vitamin D deficiency, as they can take bloodwork and then recommend the appropriate ...
Signs of Vitamin D Deficiency and How to Get Enough of It
In the U.S., an estimated nearly 6 percent of adults have severe vitamin D deficiency (less than 30 nanomoles per liter, nmol/L), while 24 percent have vitamin D deficiency (less 50 nmol/L ...
Vitamin D and Aging: What's the Latest Research?
Vitamin D deficiency and young-onset dementia. A study published in JAMA Neurology investigated several risk factors of young-onset dementia, affecting those under 65. 3 The study used data from over 350,000 participants in the UK, taken from the UK BioBank.
Vitamin D deficiency: key signs that you're not getting enough
"Vitamin D plays a role in your energy levels," she explains. "You could have this combination of a low immune system, low mood and low energy, which leaves people feeling pretty rubbish."
Vitamin D in the older population: a consensus statement
After each presentation, open sessions enabled full discussion to reach a consensus. A separate document was prepared for each component of the conference. ... Severe vitamin D deficiency (serum 25(OH)D < 25 nmol/L) was seen in less than 4% of subjects, and only during winter, but no summer improvement was seen in women, in those older than 70 ...
Vitamin D3: Benefits, Sources And Side Effects
A vitamin D deficiency typically occurs when people don't get enough vitamin D from their diet or sunlight; cannot synthesize or absorb vitamin D properly; or have certain medical conditions or ...
7 Signs Of Vitamin D Deficiency
5. Overweight. Vitamin D is fat soluble and our fat cells love to soak it up leaving it less available for other functions in our body. Therefore, if you have extra fat cells in your body, you ...
VITAMIN D DEFICIENCY PowerPoint Presentation, free download
Presentation Transcript. VITAMIN D DEFICIENCY Evolving Concepts And Importance In Overall Health Status. Silent epidemic. • Vitamin D deficiency is a highly prevalent condition, presentin approximately 30% to 50% of the general population. • More prevalent in elderly, women of child bearing age and infants.
Pseudotumor cerebri with status epilepticus in a child: A rare ...
Pseudotumor cerebri (PTC) encompasses a constellation of symptoms caused by elevated intracranial pressure of unclear etiology. Various associations have been described, rarely hypovitaminosis D. Vitamin D deficiency should be considered as a potential etiology of neurological manifestations like PTC and seizures in children.
Low Vitamin D Symptoms: How to Spot a Vitamin D Deficiency
An actual vitamin D deficiency results in rickets, which is the term for a bone-softening, leg-bowing disease that is more likely to impact children in developing countries. Rickets is rare in the ...
RACGP
For example, ferritin is an acute phase protein and, when elevated, might mask underlying iron deficiency. 23 Therefore, micronutrient status should be assessed alongside C-reactive protein and albumin. 23 Investigations should be 'chosen wisely' according to clinical presentation to ensure testing is rational. 24 Table 2 provides suggested ...

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RELATED TOPICS

Vitamin D Deficiency

What is vitamin D deficiency?

Introduction

Serum concentrations of 25(OH)D and health

Recommended Intakes

Sources of Vitamin D

Sun exposure

Dietary supplements

Vitamin D Intakes and Status

Vitamin D Deficiency

Groups at Risk of Vitamin D Inadequacy

Breastfed infants

Older adults

People with limited sun exposure

People with dark skin

People with conditions that limit fat absorption

People with obesity or who have undergone gastric bypass surgery

Vitamin D and Health

Bone health and osteoporosis

Clinical trial evidence on older adults

Vitamin D supplements for bone health in minority populations

Vitamin D supplements and muscle function

Conclusions about vitamin D supplements and bone health

Total cancer incidence and mortality

Breast cancer

Colorectal cancer

Lung cancer

Pancreatic cancer

Prostate cancer

Conclusions about vitamin D and cancer

Cardiovascular disease

Multiple sclerosis

Type 2 diabetes

Weight loss

Health Risks from Excessive Vitamin D

Interactions with Medications

Thiazide diuretics

Vitamin D and Healthful Diets

Vitamin D deficiency and fatigue: an unusual presentation

Case presentation

Conclusions

Authors’ contributions

Competing interests

Author information

Corresponding author

Rights and permissions

About this article

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Proteomics & Metabolomics

Vitamin D and Aging: What’s the Latest Research?

Vitamin D and the hallmarks of aging

The protective role of the vitamin D/vitamin D receptor pathway

Vitamin D deficiency and young-onset dementia

Vitamin D in the older population: a consensus statement

Roger Bouillon

Bess Dawson-Hughes

Peter R. Ebeling

Marise Lazaretti-Castro

Claudio Marcocci

John P. Bilezikian

Conclusions

Introduction

Impact of age on vitamin D production and levels

Skeletal effects of vitamin D deficiency in the older population

Bone mineral density

Vitamin D and calcium

Extra-skeletal effects

Skeletal muscle

Cardiovascular events

Cognitive impairment

Strategies to prevent vitamin D deficiency

Sunshine exposure

Food and food fortification

Vitamin D supplementation

COVID-19 vaccination

Acknowledgements

Author contributions

Compliance with ethical standards