vitamin d foods

What is Vitamin D

Vitamin D also called calciferol, is a fat-soluble vitamin that is naturally present in very few foods, added to others, and available as a dietary supplement. In foods and dietary supplements, vitamin D has two main forms, vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol), that differ chemically only in their side-chain structures. Vitamin D2 (ergocalciferol) is synthesized from ergosterol and found in yeast, sun dried and ultraviolet irradiated mushrooms, and plants 1. Vitamin D3 (cholecalciferol) is synthesized endogenously from 7-dehydrocholesterol in the skin and found naturally in cod liver oil and oily fish 1. Both forms are well absorbed in the small intestine and raise serum 25-hydroxyvitamin D [25(OH)D or calcidiol] levels, and they seem to have equivalent ability to cure rickets 2. However, most evidence indicates that vitamin D3 (cholecalciferol) increases serum 25-hydroxyvitamin D [25(OH)D or calcidiol] levels to a greater extent and maintains these higher levels longer than vitamin D2 (ergocalciferol), even though both forms are well absorbed in the gut 3.

  • Vitamin D2 (ergocalciferol): Vitamin D2 is created in plants, such as yeast or mushrooms. Vitamin D2 is also available as a supplement and in fortified foods like breakfast cereals, milk, and other dairy items.
  • Vitamin D3 (cholecalciferol): Vitamin D3 is generated in the skin when it is exposed to sunlight. Vitamin D3 is also found in some animal-based foods (eggs and fatty fish, such as salmon, tuna, and mackerel) and may be consumed in certain fortified foods or dietary supplements.

The main function of vitamin D is to help your body absorb calcium from the gut and maintains adequate serum calcium and phosphate concentrations to enable normal mineralization of bone and to prevent hypocalcemic tetany. Vitamin D also helps maintain proper levels of calcium, phosphate, and parathyroid hormone in your blood. Calcium is one of the main building blocks of bones and teeth. Vitamin D is needed for bone growth and bone remodeling by osteoblasts and osteoclasts 4. Maintaining adequate levels of vitamin D supports healthy bones. Vitamin D deficiency can lead to bone diseases such as osteoporosis, rickets and osteomalacia 5. In addition, vitamin D has other roles in the body, including anti-inflammatory and other properties that play a role in maintaining normal muscle, immune, and nervous system functions and glucose metabolism 6. Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D 7. The major source of vitamin D is sunlight (exposure to ultraviolet B radiation). Vitamin D deficiency is typically due to limited sunlight exposure. However, too much sun exposure can lead to skin aging and skin cancer. So many people try to get their vitamin D from other sources. Vitamin D-rich foods include egg yolks, saltwater fish, and liver. Some other foods, like milk and cereal, often have added vitamin D. You can also take vitamin D supplements. Check with your health care provider to see how much vitamin D you should take.

You can get vitamin D in three ways: through your skin, from your diet, and from supplements. Vitamin D obtained from sun exposure, food, and supplements is biologically inert and must undergo two hydroxylations in the body for activation before being able to be used by your body (see Figure 1 below) 8. Both vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) need to go through chemical changes in your liver and kidneys before being able to be used by your body. The first occurs in your liver where vitamin D is converted by vitamin D-25-hydroxylase (CYP2R1) enzyme into measurable substance called 25-hydroxyvitamin D [25(OH)D], also known as “calcidiol” 9. The second hydroxylation occurs primarily in your kidneys where the enzyme 25-hydroxyvitamin D-1-alpha-hydroxylase (CYP27B1) convert 25-hydroxyvitamin D [25(OH)D] into a hormone called active vitamin D or 1,25-dihydroxyvitamin D [1,25(OH)2D], also known as “calcitriol” (active vitamin D) 10. The enzyme 25-hydroxyvitamin D-1-alpha-hydroxylase (CYP27B1) is also expressed by many other tissues including activated macrophages, parathyroid glands, microglia, breast, colon, and keratinocytes where 1,25-dihydroxyvitamin D [calcitriol or 1,25(OH)2D] is produced and exerts its autocrine and paracrine functions 11. 1,25-dihydroxyvitamin D [1,25(OH)2D or calcitriol] exerts its physiologic functions in the target tissue by binding to the vitamin D receptor in the nucleus where it leads to up- or down-regulation of a multitude of genes 12. A manufactured calcitriol (1,25-dihydroxyvitamin D3) is used to treat kidney disease with low blood calcium, hyperparathyroidism due to kidney disease, low blood calcium due to hypoparathyroidism, osteoporosis, osteomalacia, and familial hypophosphatemia. It is taken by mouth or by injection into a vein.

Vitamin D absorption occurs by simple passive diffusion and by a mechanism that involves intestinal membrane carrier proteins 2. 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 2.

Vitamin D (calciferol) is also produced in your body when ultraviolet (UV) rays from sunlight strike your skin and trigger vitamin D synthesis (see Figure 1). Sunlight exposure is the primary source of vitamin D for most people. Solar ultraviolet-B radiation (UVB; wavelengths of 290 to 315 nanometers) stimulates the production of vitamin D3 (cholecalciferol) from 7-dehydrocholesterol in the epidermis of your skin. Hence, vitamin D is actually more like a hormone than a vitamin, a substance that is required from the diet.

Vitamin D enters the circulation and is transported to the liver, where it is hydroxylated to form 25-hydroxyvitamin D (calcidiol; the major circulating form of vitamin D). In the kidneys, the 1-alpha-hydroxylase enzyme catalyzes a second hydroxylation of 25-hydroxyvitamin D, resulting in the formation of 1,25-dihydroxyvitamin D [calcitriol or 1,25(OH)2D] — the most potent form of vitamin D 13. Most of the physiological effects of vitamin D in the body are related to the activity of 1,25-dihydroxyvitamin D (calcitriol or 1,25(OH)2D).

Most of the time, vitamin D levels will be tested by measuring blood levels of 25-hydroxyvitamin D [25(OH)D or calcidiol]. Testing 25-hydroxyvitamin D [25(OH)D or calcidiol] is considered the most accurate way to measure how much vitamin D is in your body because 25-hydroxyvitamin D [25(OH)D or calcidiol] is the major form of vitamin D circulating in your bloodstream. Sometimes, doctors may check your blood level of 1,25 dihydroxyvitamin D (active vitamin D), which is also called calcitriol. However, 1,25 dihydroxyvitamin D (calcitriol) is generally not used to detect inadequate vitamin D levels, but it may be measured in patients with abnormal calcium levels or kidney problems 14.

Vitamin D testing measures the level of this essential substance in your blood. Vitamin D blood testing is used to diagnose vitamin D deficiencies or to monitor treatment for a known vitamin D deficiency. Less commonly, vitamin D testing may be used to detect vitamin D toxicity, a condition in which there is an excess of vitamin D in the body.

There is a bit of controversy regarding what is considered a low vitamin D level between different expert organizations. A vitamin D level measures levels of 25-hydroxyvitamin D (25(OH)D) also known as calcidiol, in the blood.

Most experts recommend:

  • Levels of 20-50 nanograms/milliliter (ng/ml) of 25-hydroxyvitamin D (calcidiol): Sufficient (good)
  • Levels of 12-19 ng/ml of 25-hydroxyvitamin D (calcidiol): Borderline
  • Levels of less than 12 ng/ml of 25-hydroxyvitamin D (calcidiol): Deficient (low)

However, not everybody agrees, and some organizations suggest different cut-off values.

The Institute of Medicine states:

  • Levels above 20 ng/ml of 25-hydroxyvitamin D (calcidiol): Sufficient
  • Levels below 20 ng/ml of 25-hydroxyvitamin D (calcidiol): Deficient

Note that several members of the Institute of Medicine committee publicly stated that over screening for vitamin D deficiency was a problem which typically resulted in unnecessary treatment. They were not in agreement with a cut-off level of 20 ng/ml for deficiency and recommended a lower level of 12.5 ng/ml.

The Endocrine Society states:

  • Levels above 30 ng/ml of 25-hydroxyvitamin D (calcidiol): Sufficient; however, some assays are inaccurate and levels of 40-60 ng/ml better guarantee sufficiency
  • Levels of 21-29 ng/ml of 25-hydroxyvitamin D (calcidiol): Insufficient
  • Levels below 20 ng/ml pf 25-hydroxyvitamin D (calcidiol): Deficient

Other medical institution states 15:

  • Levels below 20 ng/mL of 25-hydroxyvitamin D (calcidiol): Mild deficiency
  • Levels below 10 ng/mL of 25-hydroxyvitamin D (calcidiol): Moderate deficiency
  • Levels below 5 ng/mL of 25-hydroxyvitamin D (calcidiol): Severe deficiency

Talk to your doctor about what he/she considers to be a low vitamin D level. Abnormal levels of vitamin D can indicate bone disorders, nutrition problems, organ damage, or other medical conditions.

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 16. No studies have examined whether such screening for vitamin D deficiency results in improved health outcomes 17. 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 18. It added that no national professional organization recommends population screening for vitamin D deficiency.

Figure 1. Production of vitamin D3 in the skin

vitamin D production in the skin
vitamin D functions
vitamin D metabolism

The plasma calcitriol (1,25-dihydroxyvitamin D or 1,25(OH)2D) or vitamin D concentration depends on the availability of calcidiol (25-hydroxyvitamin D or 25(OH)D) and the activities of the renal enzymes 1-α-hydroxylase and 24-α-hydroxylase 19. The renal 1-alpha-hydroxylase enzyme (CYP27B1) is primarily regulated by parathyroid hormone (PTH), serum calcium and phosphate concentrations, and fibroblast growth factor 23 (FGF23) 20. Increased parathyroid hormone (PTH), calcitonin, and hypophosphatemia (low blood phosphate) stimulate the renal enzymes 25-hydroxyvitamin D-1-alpha-hydroxylase (CYP27B1) and enhance calcitriol [1,25-dihydroxyvitamin D or 1,25(OH)2D] production, while high calcium, hyperphosphatemia (high blood phosphate) and calcitriol [1,25(OH)2D] inhibit the renal enzymes 1-alpha-hydroxylase (CYP27B1) 21. Calcitriol [1,25-dihydroxyvitamin D or 1,25(OH)2D] inhibits the synthesis and secretion of parathyroid hormone (PTH), providing negative feedback regulation of calcitriol production. Calcitriol [1,25-dihydroxyvitamin D or 1,25(OH)2D] synthesis may also be modulated by vitamin D receptors on the cell surface; downregulation of these receptors may play an important role in regulating vitamin D activation 22. Fibroblast growth factor 23 (FGF23), a newly described phosphaturic hormone, inhibits renal production of calcitriol [1,25-dihydroxyvitamin D or 1,25(OH)2D] by inhibiting 1-α-hydroxylase in the renal proximal tubule and by simultaneously increasing the expression of 24-α-hydroxylase and production of 24,25(OH)2D (an inactive metabolite) 23. Calcitriol [1,25-dihydroxyvitamin D or 1,25(OH)2D] stimulates fibroblast growth factor 23 (FGF23), creating a feedback loop. Fibroblast growth factor 23 (FGF23) decreases renal reabsorption of phosphate, and thereby counteracts the increased gastrointestinal phosphate reabsorption induced by Calcitriol, maintaining phosphate homeostasis 24.

When hypocalcemia (low blood calcium) occurs, serum parathyroid hormone (PTH) concentration increases and enhances renal tubular reabsorption of calcium, as well as the activity of 1-α-hydroxylase in the kidney. This results in increased Calcitriol [1,25-dihydroxyvitamin D or 1,25(OH)2D] production, and in turn, intestinal calcium absorption. Parathyroid hormone (PTH) also stimulates bone osteoclast activity to mobilize bone calcium stores, thereby increasing serum calcium. Both Calcitriol [1,25-dihydroxyvitamin D or 1,25(OH)2D] and Calcidiol [25-hydroxyvitamin D or 25(OH)D] are degraded in part by being hydroxylated at the 24 position by a 24-hydroxylase. The activity of the 24-hydroxylase gene is increased by calcitriol (which therefore promotes its own inactivation) and reduced by parathyroid hormone (thereby allowing more active hormone to be formed) 20. Estrogen, placental growth hormone, and prolactin may also regulate vitamin D metabolism, playing a role during pregnancy to meet increased calcium demands. Calcitriol is also formed in some other tissues, but is used only within the tissues and not circulated. Parathyroid hormone (PTH)- independent extrarenal production of Calcitriol from Calcidiol is by activated macrophages in the lung and lymph nodes. The 1-α-hydroxylase enzyme is also expressed at other extrarenal sites, including the gastrointestinal tract, skin, vasculature, mammary epithelial cells, and in osteoblasts and osteoclasts 25.

People can become deficient in vitamin D because they don’t consume enough or absorb enough from food, their exposure to sunlight is limited, or their kidneys cannot convert vitamin D to its active form in the body. In children, vitamin D deficiency causes rickets, a disease where the bones become soft and bend due to a failure of bone tissue to properly mineralize 26. The fortification of milk and other staples, such as breakfast cereals and margarine, with vitamin D beginning in the 1930s has made rickets a rare disease in the United States, although it is still reported periodically, particularly among African American infants and children, immigrants from African, Middle-Eastern, and Asian countries 27, 28, 29. Rickets is also more prevalent among immigrants from Asia, Africa, and the Middle East, possibly because of genetic differences in vitamin D metabolism, dietary preferences, and behavioral differences that lead to less sun exposure 30.

Prolonged exclusive breastfeeding without the American Academy of Pediatrics-recommended vitamin D supplementation is a significant cause of rickets, particularly in dark-skinned infants breastfed by mothers who are not vitamin D replete 31. Additional causes of rickets include extensive use of sunscreens and placement of children in daycare programs, where they often have less outdoor activity and sun exposure 26, 32.

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 causing bone pain and muscle weakness 33. Signs and symptoms of osteomalacia are similar to those of rickets and include bone deformities and pain, hypocalcemic seizures, tetanic spasms, and dental abnormalities 34.

A lack of vitamin D has been associated with:

  • An impairment in memory and thinking skills in older adults
  • Bone, back, or muscle pain
  • Cancer (particularly colon cancer)
  • Cardiovascular disease, and an increased risk of dying from a stroke or a heart attack
  • Constant fatigue and tiredness
  • Frequent infections (such as colds and flu)
  • Hair loss
  • Kidney disease
  • Low mood or depression
  • Osteomalacia
  • Osteoporosis
  • Poor dental health
  • Rickets
  • Severe asthma in children
  • Skin wounds that take a long time to heal.

Research also suggests low vitamin D may be a factor in several other conditions such as type 2 diabetes, high blood pressure, and multiple sclerosis.

vitamin Dcalcitriol_function

Vitamin D has other roles in the body, including modulation of cell growth, neuromuscular and immune function, and reduction of inflammation 5, 27, 35. Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D 5. Many cells have vitamin D receptors, and some convert 25-hydroxyvitamin D (25(OH)D or calcidiol) to calcitriol [1,25-dihydroxyvitamin D or 1,25(OH)2D].

Serum concentration of 25-hydroxyvitamin D (25(OH)D or calcidiol) is the best indicator of vitamin D status. It reflects vitamin D produced cutaneously and that obtained from food and supplements 5 and has a fairly long circulating half-life of 15 days 36. 25-hydroxyvitamin D (25(OH)D or calcidiol) functions as a biomarker of exposure, but it is not clear to what extent 25-hydroxyvitamin D (25(OH)D or calcidiol) levels also serve as a biomarker of effect (i.e., relating to health status or outcomes) 5. Serum 25-hydroxyvitamin D (25(OH)D or calcidiol) levels do not indicate the amount of vitamin D stored in body tissues.

In contrast to 25-hydroxyvitamin D [25(OH)D or calcidiol], circulating Calcitriol [1,25-dihydroxyvitamin D or 1,25(OH)2D] is generally not a good indicator of vitamin D status because it has a short half-life of 15 hours and serum concentrations are closely regulated by parathyroid hormone, calcium, and phosphate 36. Levels of 1,25(OH)2D do not typically decrease until vitamin D deficiency is severe 37, 38.

Researchers have not definitively identified serum concentrations of 25-hydroxyvitamin D [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 at the National Academies of Sciences, Engineering, and Medicine concluded that people are at risk of vitamin D deficiency at serum 25-hydroxyvitamin D [25(OH)D] concentrations less than 30 nmol/L (12 ng/mL; see Table 1 for definitions of “deficiency” and “inadequacy”) 10. 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 39. The Food and Nutrition Board committee also noted that serum concentrations greater than 125 nmol/L (50 ng/mL) can be associated with adverse effects (Table 1).

Optimal serum concentrations of 25-hydroxyvitamin D [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 40. In addition, although 25-hydroxyvitamin D [25(OH)D] levels rise in response to increased vitamin D intake, the relationship is nonlinear 5. The amount of increase varies, for example, by baseline serum levels and duration of supplementation.

An additional complication in assessing vitamin D status is in the actual measurement of 25-hydroxyvitamin D (25(OH)D or calcidiol) concentrations. Considerable variability exists among the various assays available (the two most common methods being antibody based and liquid chromatography based) and among laboratories that conduct the analyses 5, 41, 42. This means that compared with the actual concentration of 25-hydroxyvitamin D (25(OH)D or calcidiol) in a sample of blood serum, a falsely low or falsely high value may be obtained depending on the assay or laboratory used 43. A standard reference material for 25-hydroxyvitamin D (25(OH)D or calcidiol) became available in July 2009 that permits standardization of values across laboratories and may improve method-related variability 5, 44.

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

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

Footnotes:

* Serum concentrations of 25(OH)D are reported in both nanomoles per liter (nmol/L) and nanograms per milliliter (ng/mL).
** 1 nmol/L = 0.4 ng/mL and 1 ng/mL = 2.5 nmol/L.

[Source 5 ]

Is vitamin D water soluble?

No, vitamin D is fat soluble. This means it is stored within your adipose (fat) tissue and small amounts can be mobilized if your daily intake temporarily falters. Other fat-soluble vitamins are vitamin A, vitamin E and vitamin K. Because it is fat soluble, vitamin D toxicity can occur if too much is taken.

Vitamin D deficiency is prevalent among obese people, because greater amounts of vitamin D are locked up in their adipose tissue (fat stores), rather than in the blood where it can be used. Obese people are also less likely to eat foods naturally high in vitamin D or expose their skin to sunlight.

What is a healthy vitamin D level?

It is still controversial how much vitamin D is needed, how it should be given, i.e., daily versus weekly or monthly (bolus doses), and what level of serum 25-hydroxyvitamin D [25(OH)D or calcidiol] is optimal for immune health and overall health benefits 45. It is also unknown whether maintenance of serum vitamin D itself has its own effect on modulating immune function. However, historical evidence suggests that our hunter gatherer forefathers maintained their circulating vitamin D levels in the range of 10–50 ng/mL (25–125 nmol/L). Indigenous populations such as Maasai herders and Hadza tribesmen were found to have serum 25-hydroxyvitamin D [25(OH)D or calcidiol] levels in the range of 40–60 ng/mL (100–150 nmol/L) 46. These levels are consistent with those reported in populational studies to be associated with the lowest risk of several types of cancers, cardiovascular diseases, autoimmune diseases, and all-cause mortality 47. To maintain these blood levels with minimal sunlight exposure, a person would require ingestion of 4000–6000 IUs of vitamin D daily, which would maintain serum vitamin D levels in the range of 20–40 ng/mL (50–100 nmol/L) and serum 25-hydroxyvitamin D [25(OH)D or calcidiol] levels in the range of 40–60 ng/mL (50–100 nmol/L) 39. The recommended dosage for vitamin D intake by the Endocrine Society Guidelines on Vitamin D for treatment and prevention for vitamin D deficiency is shown in Table 2.

Table 2. The recommended dosage for vitamin D intake in individuals who are at risk for vitamin D deficiency and dosage of vitamin therapy treatment for patients with vitamin D deficiency.

recommended dosage for vitamin D intake in individuals who are at risk for vitamin D deficiency
[Source 39 ]

What is a low vitamin D level?

There is a bit of controversy regarding what is considered a low vitamin D level between different expert organizations. A vitamin D level measures levels of 25-hydroxyvitamin D [25(OH)D] also known as calcidiol, in the blood.

Most experts recommend:

  • Levels of 20-50 nanograms/milliliter (ng/ml) of 25-hydroxyvitamin D (calcidiol): Sufficient (good)
  • Levels of 12-19 ng/ml of 25-hydroxyvitamin D (calcidiol): Borderline
  • Levels of less than 12 ng/ml 25-hydroxyvitamin D (calcidiol): Deficient (low)

However, not everybody agrees, and some organizations suggest different cut-off values.

The Institute of Medicine states:

  • Levels above 20 ng/ml 25-hydroxyvitamin D (calcidiol): Sufficient
  • Levels below 20 ng/ml 25-hydroxyvitamin D (calcidiol): Deficient

Note that several members of the Institute of Medicine committee publicly stated that over screening for vitamin D deficiency was a problem which typically resulted in unnecessary treatment. They were not in agreement with a cut-off level of 20 ng/ml for deficiency and recommended a lower level of 12.5 ng/ml.

The Endocrine Society states:

  • Levels above 30 ng/ml 25-hydroxyvitamin D (calcidiol): Sufficient; however, some assays are inaccurate and levels of 40-60 ng/ml better guarantee sufficiency
  • Levels of 21-29 ng/ml 25-hydroxyvitamin D (calcidiol): Insufficient
  • Levels below 20 ng/ml 25-hydroxyvitamin D (calcidiol): Deficient

Other medical institution states 15:

  • Levels below 20 ng/mL of 25-hydroxyvitamin D (calcidiol): Mild deficiency
  • Levels below 10 ng/mL of 25-hydroxyvitamin D (calcidiol): Moderate deficiency
  • Levels below 5 ng/mL of 25-hydroxyvitamin D (calcidiol): Severe deficiency

Talk to your doctor about what he/she considers to be a low vitamin D level. Abnormal levels of vitamin D can indicate bone disorders, nutrition problems, organ damage, or other medical conditions.

Is vitamin D vegan?

Vitamin D3 (cholecalciferol) has historically been made from lanolin extracted from sheep wool, but recently, a vegan/vegetarian form has become available. This version is extracted from lichen (a type of plant usually found on rocks, walls, or trees) and it is called Vitashine. This product is also sugar, wheat, gluten, and dairy-free.

Vitamin D2 (ergocalciferol) supplements, made by irradiating mushrooms, are also vegan/vegetarian-friendly.

Studies have shown that vitamin D3 (cholecalciferol) increases blood levels of vitamin D more significantly than vitamin D2 (ergocalciferol).

How much vitamin D do you need?

Intake reference values for vitamin D and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of The National Academies (formerly National Academy of Sciences) 5. DRI is the general term for a set of reference values used to plan and assess nutrient intakes of healthy people. These values, which vary by age and gender, include:

  • Recommended Dietary Allowance (RDA): average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy people.
  • Adequate Intake (AI): established when evidence is insufficient to develop an RDA and is set at a level assumed to ensure nutritional adequacy.
  • Tolerable Upper Intake Level (UL): maximum daily intake unlikely to cause adverse health effects 5.

The Food and Nutrition Board (FNB) established an RDA for vitamin D representing a daily intake that is sufficient to maintain bone health and normal calcium metabolism in healthy people. RDAs for vitamin D are listed in both International Units (IUs) and micrograms (mcg); the biological activity of 40 IU is equal to 1 mcg (Table 2). Even though sunlight may be a major source of vitamin D for some, the vitamin D RDAs are set on the basis of minimal sun exposure 5.

Table 3. The amount of vitamin D you need each day depends on your age. Average daily recommended amounts from the Food and Nutrition Board (a national group of experts) for different ages are listed below in International Units (IU):

Life StageRecommended Amount
Birth to 12 months400 IU (10 mcg)
Children 1–13 years600 IU (15 mcg)
Teens 14–18 years600 IU (15 mcg)
Adults 19–70 years600 IU (15 mcg)
Adults 71 years and older800 IU (20 mcg)
Pregnant and breastfeeding women600 IU (15 mcg)

Footnote: The amount of vitamin D contained in supplements is sometimes expressed in international units (IU) where 40 IU is equal to one microgram (1 mcg) of vitamin D.

[Source 48 ]

What foods provide vitamin D?

Very few foods naturally have vitamin D. The flesh of fatty fish (such as salmon, tuna, and mackerel) and fish liver oils are among the best sources 5, 49. An animal’s diet affects the amount of vitamin D in its tissues. Small amounts of vitamin D are found in beef liver, cheese, and egg yolks. Vitamin D in these foods is primarily in the form of vitamin D3 and its metabolite 25(OH)D3 50. Mushrooms provide variable amounts of vitamin D2 51. Some mushrooms available on the market have been treated with UV light to increase their levels of vitamin D2. In addition, the Food and Drug Administration (FDA) has approved UV-treated mushroom powder as a food additive for use as a source of vitamin D2 in food products 52. Very limited evidence suggests no substantial differences in the bioavailability of vitamin D from various foods 53.

The U.S. Department of Agriculture’s (USDA’s) FoodData Central (https://fdc.nal.usda.gov) lists the nutrient content of many foods and provides a comprehensive list of foods containing vitamin D arranged by nutrient content (https://ods.od.nih.gov/pubs/usdandb/VitaminD-Content.pdf) and by food name (https://ods.od.nih.gov/pubs/usdandb/VitaminD-Food.pdf). However, FoodData Central does not include the amounts of 25(OH)D in foods. A variety of foods and their vitamin D levels per serving are listed in Table 3.

Animal-based foods typically provide some vitamin D in the form of 25-hydroxyvitamin D (25(OH)D or calcidiol) in addition to vitamin D3 (cholecalciferol). The impact of this form on vitamin D status is an emerging area of research. Studies show that 25-hydroxyvitamin D (25(OH)D or calcidiol) appears to be approximately five times more potent than the parent vitamin D for raising serum 25(OH)D concentrations 51. One study found that when the 25-hydroxyvitamin D (25(OH)D or calcidiol) 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 D alone, depending on the food 54.

Fortified foods provide most of the vitamin D in the American diet 5, 55. For example, almost all of the U.S. milk supply is voluntarily fortified with about 3 mcg/cup (120 IU), usually in the form of vitamin D3 56. In the 1930s, a milk fortification program was implemented in the United States to combat rickets, then a major public health problem 5. 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 57. Ready-to-eat breakfast cereals often contain added vitamin D, as do some brands of orange juice, yogurt, margarine, and other food products.

Both the United States and Canada mandate the fortification of infant formula with vitamin D: 1–2.5 mcg/100 kcal (40–100 IU) vitamin D in the United States and 1–2 mcg/100 kcal (40–80 IU) in Canada 5.

Fortified foods provide most of the vitamin D in American diets 5:

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

A variety of foods and their vitamin D levels per serving are listed in Table 4.

Table 4. Vitamin D content of selected foods

FoodMicrograms (mcg) per servingInternational Units (IU) per servingPercent DV*
Cod liver oil, 1 tablespoon341360170
Trout (rainbow), farmed, cooked, 3 ounces16.264581
Salmon (sockeye), cooked, 3 ounces14.257071
Mushrooms, white, raw, sliced, exposed to UV light, ½ cup9.236646
Milk, 2% milkfat, vitamin D fortified, 1 cup2.912015
Soy, almond, and oat milks, vitamin D fortified, various brands, 1 cup2.5-3.6100-14413-18
Ready-to-eat cereal, fortified with 10% of the DV for vitamin D, 1 serving28010
Sardines (Atlantic), canned in oil, drained, 2 sardines1.2466
Egg, 1 large, scrambled**1.1446
Liver, beef, braised, 3 ounces1425
Tuna fish (light), canned in water, drained, 3 ounces1405
Cheese, cheddar, 1.5 ounce0.4172
Mushrooms, portabella, raw, diced, ½ cup0.141
Chicken breast, roasted, 3 ounces0.141
Beef, ground, 90% lean, broiled, 3 ounces01.70
Broccoli, raw, chopped, ½ cup000
Carrots, raw, chopped, ½ cup000
Almonds, dry roasted, 1 ounce000
Apple, large000
Banana, large000
Rice, brown, long-grain, cooked, 1 cup000
Whole wheat bread, 1 slice000
Lentils, boiled, ½ cup000
Sunflower seeds, roasted, ½ cup000
Edamame, shelled, cooked, ½ cup000

Footnotes:

* DV = Daily Value. The FDA developed DVs to help consumers compare the nutrient contents of foods and dietary supplements within the context of a total diet. The DV for vitamin D is 20 mcg (800 IU) for adults and children aged 4 years and older 58. 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.

[Source 59 ]

Am I getting enough vitamin D?

Because you get vitamin D from food, sunshine, and dietary supplements, one way to know if you’re getting enough is a blood test that measures the amount of vitamin D in your blood. In the blood, a form of vitamin D known as 25-hydroxyvitamin D is measured in either nanomoles per liter (nmol/L) or nanograms per milliliter (ng/mL). One nmol/L is the same as 0.4 ng/mL.

  • Levels of 50 nmol/L (20 ng/mL) or above are adequate for most people for bone and overall health.
  • Levels below 30 nmol/L (12 ng/mL) are too low and might weaken your bones and affect your health.
  • Levels above 125 nmol/L (50 ng/mL) are too high and might cause health problems.

In the United States, most people have adequate blood levels of vitamin D. However, almost one out of four people have vitamin D blood levels that are too low or inadequate for bone and overall health.

Some people are more likely than others to have trouble getting enough vitamin D:

  • Breastfed infants. Breast milk alone does not provide infants with an adequate amount of vitamin D. Breastfed infants should be given a supplement of 10 mcg (400 IU) of vitamin D each day.
  • Older adults. As you age, your skin’s ability to make vitamin D when exposed to sunlight declines.
  • People who seldom expose their skin to sunshine because they do not go outside or because they keep their body and head covered. Sunscreen also limits the amount of vitamin D your skin produces.
  • People with dark skin. The darker your skin, the less vitamin D you make from sunlight exposure.
  • People with conditions that limit fat absorption, such as Crohn’s disease, celiac disease, or ulcerative colitis. This is because the vitamin D you consume is absorbed in the gut along with fat, so if your body has trouble absorbing fat, it will also have trouble absorbing vitamin D.
  • People who are obese or have undergone gastric bypass surgery. They may need more vitamin D than other people.

Can you get vitamin D from the sun?

Most people meet at least some of their vitamin D needs through exposure to sunlight 10, 4. Ultraviolet (UV) B radiation with a wavelength of 290–320 nanometers penetrates uncovered skin and converts cutaneous 7-dehydrocholesterol to previtamin D3, which in turn becomes vitamin D3 10. 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 10. Perhaps surprisingly, geographic latitude does not consistently predict average serum 25(OH)D levels in a population. Ample opportunities exist to form vitamin D (and store it in the liver and fat) from exposure to sunlight during the spring, summer, and fall months even in the far north latitudes 10. Older people and people with dark skin are less able to produce vitamin D from sunlight 10.

Complete cloud cover reduces UV energy by 50%; shade (including that produced by severe pollution) reduces it by 60% 26. UVB radiation does not penetrate glass, so exposure to sunshine indoors through a window does not produce vitamin D 60.  Sunscreens with a sun protection factor (SPF) of 8 or more appear to block vitamin D-producing UV rays, although in practice people generally do not apply sufficient amounts, cover all sun-exposed skin, or reapply sunscreen regularly 10, 61. Therefore, skin likely synthesizes some vitamin D even when it is protected by sunscreen as typically applied.

The factors that affect UV radiation exposure and research to date on the amount of sun exposure needed to maintain adequate vitamin D levels make it difficult to provide general guidelines. It has been suggested by some vitamin D researchers, for example, that approximately 5–30 minutes of sun exposure between 10 AM and 3 PM at least twice a week to the face, arms, legs, or back without sunscreen usually lead to sufficient vitamin D synthesis and that the moderate use of commercial tanning beds that emit 2%–6% UVB radiation is also effective 1, 62. Individuals with limited sun exposure need to include good sources of vitamin D in their diet or take a supplement to achieve recommended levels of intake.

Despite the importance of the sun for vitamin D synthesis, it is prudent to limit exposure of skin to sunlight 61 and UV radiation from tanning beds 63. UV radiation is a carcinogen responsible for most of the estimated 1.5 million skin cancers and the 8,000 deaths due to metastatic melanoma that occur annually in the United States 61. Lifetime cumulative UV damage to skin is also largely responsible for some age-associated dryness and other cosmetic changes. The American Academy of Dermatology advises that photoprotective measures be taken, including the use of sunscreen, whenever one is exposed to the sun 29. Assessment of vitamin D requirements cannot address the level of sun exposure because of these public health concerns about skin cancer, and there are no studies to determine whether UVB-induced synthesis of vitamin D can occur without increased risk of skin cancer 10.

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

How long should you spend in the sun?

Most people can make enough vitamin D from being out in the sun daily for short periods with their forearms, hands or lower legs uncovered and without sunscreen from late March or early April to the end of September, especially from 11am to 3pm.

It’s not known exactly how much time is needed in the sun to make enough vitamin D to meet your body’s requirements. This is because there are a number of factors that can affect how vitamin D is made, such as your skin color or how much skin you have exposed. But you should be careful not to burn in the sun, so take care to cover up, or protect your skin with sunscreen, before your skin starts to turn red or burn.

Your risk of sunburn depends on 2 things. How sun-sensitive your skin is, and how strong the UV rays are you’re exposed to. Different people will have a different risk of sunburn on the same day, so it’s a good idea to know when your risk is high, so you can protect your skin.

In general people who have one or more of the following are at more risk:

  • skin that burns easily
  • light or fair colored skin, hair, or eyes
  • lots of moles or freckles
  • a history of sunburn
  • a personal or family history of skin cancer

People with dark skin, such as those of African, African-Caribbean or south Asian origin, will need to spend longer in the sun to produce the same amount of vitamin D as someone with lighter skin.

  • Children aged under six months should be kept out of direct strong sunlight. To ensure they get enough vitamin D, babies and children aged under five years should be given vitamin D supplements even if they do get out in the sun.

How long it takes for your skin to go red or burn varies from person to person. You’re the best person to know how your skin reacts in the sun. The more easily you get sunburnt, the more careful you need to be. Remember, you don’t need to peel – if your skin’s gone red or pink in the sun, that’s sunburn, and it’s dangerous. For people with darker skin it may feel irritated, tender or itchy. The longer you stay in the sun, especially for prolonged periods without sun protection, the greater your risk of skin cancer. Using sunbeds is not a recommended way of making vitamin D.

Other things that affect the strength of UV rays are the:

  • Time of year – the highest risk months in the US are April to September. Near the equator, there are strong UV rays all year round.
  • Altitude – UV rays are stronger the higher you go. So skiers and mountaineers can easily get caught out.
  • Cloud cover – over 90% of UV can pass through light cloud.
  • Reflection – up to 80% of UV rays are reflected back from snow, 15% from sand, 10% from concrete and up to 30% from water (depending on how choppy it is).

What kinds of vitamin D dietary supplements are available?

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

In supplements and fortified foods, vitamin D is available in two forms, D2 (ergocalciferol) and D3 (cholecalciferol) that differ chemically only in their side-chain structure. Vitamin D2 is manufactured by the UV irradiation of ergosterol in yeast, and vitamin D3 is manufactured by the irradiation of 7-dehydrocholesterol from lanolin and the chemical conversion of cholesterol 1. The two forms of vitamin D (vitamins D2 or vitamin D3) have traditionally been regarded as equivalent based on their ability to cure rickets 2. In addition, most steps in the metabolism and actions of vitamins D2 and D3 are identical 2. Both forms (as well as vitamin D in foods and from cutaneous synthesis) effectively raise serum Calcidiol [25-hydroxyvitamin D or 25(OH)D] levels 64. However, most evidence indicates that vitamin D3 (cholecalciferol) increases serum hydroxyvitamin D or 25(OH)D] levels to a greater extent and maintains these higher levels longer than vitamin D2 (ergocalciferol), even though both forms are well absorbed in the gut 3.

Some studies have used dietary supplements containing the 25-hydroxyvitamin D3 [25(OH)D3 or 25-hydroxycholecalciferol] form of vitamin D. Per equivalent microgram dose, 25-hydroxyvitamin D3 [25(OH)D3 or 25-hydroxycholecalciferol] is three to five times as potent as vitamin D3 65. However, no 25-hydroxyvitamin D3 [25(OH)D3 or 25-hydroxycholecalciferol] dietary supplements appear to be available to consumers on the U.S. market at this time 48.

  • Vitamin D3 (cholecalciferol) is available in 400, 800, 1000, 2000, 5000, 10,000, and 60,000 IU capsules. It is available in some countries as an intramuscular injection (Arachital 600,000 IU, which maintains vitamin D levels for 1 year). However, it can be extremely painful 19.
  • Vitamin D2 (ergocalciferol) is available for oral use in 400 and 50,000 unit capsules or in a liquid form (8000 IU/mL) 19.

The American Academy of Pediatrics (AAP) recommends that exclusively and partially breastfed infants receive supplements of 400 IU/day of vitamin D shortly after birth and continue to receive these supplements until they are weaned and consume ≥1,000 mL/day of vitamin D-fortified formula or whole milk 66. Similarly, all non-breastfed infants ingesting <1,000 mL/day of vitamin D-fortified formula or milk should receive a vitamin D supplement of 400 IU/day 66. The American Academy of Pediatrics also recommends that older children and adolescents who do not obtain 400 IU/day through vitamin D-fortified milk and foods should take a 400 IU vitamin D supplement daily. However, this latter recommendation (issued November 2008) needs to be reevaluated in light of the Food and Nutrition Board’s vitamin D RDA of 600 IU/day for children and adolescents (issued November 2010 and which previously was an AI of 200 IU/day).

Vitamin D supplement interactions with medications

Vitamin D supplements may interact with several types of medications. A few examples are provided below. Individuals taking these and other medications on a regular basis should discuss their vitamin D intakes and status with their healthcare providers.

Orlistat

The weight-loss drug orlistat (Xenical® and alli®), together with a reduced-fat diet, can reduce the absorption of vitamin D from food and supplements, leading to lower 25(OH)D levels 67.

Statins

Statin medications reduce cholesterol synthesis. Because endogenous vitamin D is derived from cholesterol, statins may also reduce vitamin D synthesis 67. 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 67.

Steroids

Corticosteroid medications, such as prednisone (Deltasone®, Rayos®, and Sterapred®), are often prescribed to reduce inflammation. These medications can reduce calcium absorption and impair vitamin D metabolism 68. 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%) 69.

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 70.

Vitamin D2 versus Vitamin D3

Vitamins D2 (ergocalciferol) and D3 (cholecalciferol), as described previously, differ only in their side chain structure.

  • Vitamin D2 or ergocalciferol, is found naturally in mushrooms that have been exposed to the sun. Mushrooms contain a yeast compound called ergosterol, which is converted to ergocalciferol on exposure to UV light. Maitake mushrooms are one of the best sources of vitamin D2 at 786 IU per cup, followed closely by portobello mushrooms (634 IU/cup). Chanterelle mushrooms contain a lot less D2 (114 IU/cup). Vitamin D2 derived from mushrooms is vegetarian/vegan-friendly. Vitamin D2 supplements can also be made synthetically by irradiating fungus and plant matter that naturally contain ergosterol. Drisdol is another name for supplemental vitamin D2. Supplemental D2 is cheaper to produce than supplemental D3; however, it is not as effective at raising levels of vitamin D in the blood nor as stable as synthetic vitamin D3. Vitamin D2 still requires conversion in the body to become vitamin D3 active.
  • Vitamin D3 or cholecalciferol, is made when cholesterol in your skin is exposed to sunlight and it is also contained in small amounts in some animal-sourced foods. Your skin stores a specific type of cholesterol, called 7-dehydrocholesterol, which is converted to previtamin D3 on exposure to UVB (wavelengths of 290 to 315 nanometers). Another process changes this into cholecalciferol before it undergoes activation in the liver and kidneys to become active vitamin D. Active vitamin D is called 1,25 dihydroxyvitamin D3 (1,25(OH)D) or calcitriol. The process of converting 7-dehydrocholesterol into active vitamin D3, although complex, is reasonably efficient and it has been estimated that only 10 minutes of summer sun on your hands and face is required to generate our daily requirement of 10 micrograms of vitamin D3. Foods that naturally contain vitamin D3 include beef liver, cheese, cod liver oil, egg yolks, and fatty fish (such as mackerel, tuna, and salmon). Supplements of vitamin D3 can be made by extracting cholesterol from lanolin derived from sheep wool, then subjecting it to a series of chemical reactions to yield 7-dehydrocholesterol. This is then irradiated to produce D3 (cholecalciferol). Supplements obtained from lanolin are not vegan-friendly; however, a D3 supplement extracted from lichen is vegan and vegetarian-friendly.

Physiological responses to both forms of the vitamin include regulation of calcium and phosphate homeostasis and regulation of cell proliferation and cell differentiation of specific cell types, as described above. Qualitatively, vitamins D2 and D3 exhibit virtually identical biological responses throughout the body (i.e., through gene expression) that are mediated by the vitamin D receptor 71.

Regarding the potency of the two forms of vitamin D, there are reports that certain animals, such as avian species and New World monkeys 72, discriminate against vitamin D2. However, it has been assumed for several decades that the two forms are essentially equipotent in humans 73. Recent reports involving human dietary studies have argued for 74 or against 75 a metabolic discrimination against vitamin D2, compared with vitamin D3. Part of the apparent conflict between these different studies 75 is almost certainly due to differences in size and frequency of dose (which have ranged from 1,000 IU daily doses to 50,000 IU in a single dose); the differences reported suggest a difference in pharmacokinetic parameters between vitamin D2 and vitamin D3.

This debate runs parallel to the suggestion that vitamin D2 is less toxic than its vitamin D3 counterpart. Experimental animal data from a number of mammalian species ranging from rodents to primates 76, support the concept that the D2 form is less toxic than D3, but there is no evidence available in humans. Nonetheless, the implication of these diverse studies in several mammalian species is that vitamin D2 compounds may show differences in pharmacokinetics that manifest as lower toxicity from high doses.

There is considerable evidence that most of the steps involved in the metabolism and actions of vitamin D2 and vitamin D3 are identical 77. The identification of the series of vitamin D3 metabolites in the late 1960s and early 1970s was followed by the identification of their vitamin D2 counterparts: 25OHD2, 1α,25(OH)2D2, and 24,25(OH)2D2 78. Noteworthy here is the fact that the structural features unique to the vitamin D2 side chain did not preclude either the 25- or 1α-hydroxylation steps in activation of the molecule or the first step of inactivation, namely 24-hydroxylation. Studies have also shown that the steps in the specific vitamin D signal transduction cascade do not appear to discriminate discernibly between the two vitamin D homologues at the molecular level (e.g., binding to the transport protein, vitamin D binding protein 78 or binding to the receptor, vitamin D receptor 79. Overall, it can be concluded that specific signal transduction systems designed to respond to vitamin D3 respond to physiological doses of vitamin D2 equally well.

At this time, firm conclusions about different effects of the two forms of vitamin D cannot be drawn; however, most evidence indicates that vitamin D3 (cholecalciferol) increases serum hydroxyvitamin D or 25(OH)D] levels to a greater extent and maintains these higher levels longer than vitamin D2 (ergocalciferol), even though both forms are well absorbed in the gut 3.

Some studies have used dietary supplements containing the 25-hydroxyvitamin D3 [25(OH)D3 or 25-hydroxycholecalciferol] form of vitamin D. Per equivalent microgram dose, 25-hydroxyvitamin D3 [25(OH)D3 or 25-hydroxycholecalciferol] is three to five times as potent as vitamin D3 65. However, no 25-hydroxyvitamin D3 [25(OH)D3 or 25-hydroxycholecalciferol] dietary supplements appear to be available to consumers on the U.S. market at this time 48.

Are you getting enough vitamin D?

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

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

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

Certain other groups may not get enough vitamin D:

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

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

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

A lack of vitamin D has been associated with:

  • An impairment in memory and thinking skills in older adults
  • Bone, back, or muscle pain
  • Cancer (particularly colon cancer)
  • Cardiovascular disease, and an increased risk of dying from a stroke or a heart attack
  • Constant fatigue and tiredness
  • Frequent infections (such as colds and flu)
  • Hair loss
  • Kidney disease
  • Low mood or depression
  • Osteomalacia
  • Osteoporosis
  • Poor dental health
  • Rickets
  • Severe asthma in children
  • Skin wounds that take a long time to heal.

Research also suggests low vitamin D may be a factor in several other conditions such as type 2 diabetes, high blood pressure, and multiple sclerosis.

Multiple sclerosis

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 80. Some people with multiple sclerosis eventually lose the ability to write, speak, or walk.

The geographical distribution of multiple sclerosis 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 80.

Many epidemiological and genetic studies have shown an association between multiple sclerosis and low 25-hydroxyvitamin D [25(OH)D or calcidiol] levels before and after the disease begins 80. Observational studies suggest that adequate vitamin D levels might reduce the risk of contracting multiple sclerosis and, once multiple sclerosis is present, decrease the risk of relapse and slow the disease’s progression 81. One study, for example, tested 25(OH)D levels in 1,092 women in Finland an average of 9 years before their multiple sclerosis diagnosis and compared their outcomes with those of 2,123 similar women who did not develop multiple sclerosis 82. More than half the women who developed multiple sclerosis 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 multiple sclerosis 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 multiple sclerosis, and 25(OH)D levels less than 30 nmol/L were associated with an multiple sclerosis 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 83 and the other with 576 individuals in northern Sweden 84—found that levels of 25-hydroxyvitamin D [25(OH)D or calcidiol] 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 multiple sclerosis.

No clinical trials have examined whether vitamin D supplementation can prevent the onset of multiple sclerosis, 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 multiple sclerosis; the reviewers judged all of these trials to be of low quality 80. 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 multiple sclerosis given the lack of clinical trial evidence 85. In addition, studies have not consistently shown that vitamin D supplementation tempers the signs and symptoms of active multiple sclerosis 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 86. 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 87.

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 obese and were therefore more predisposed to developing diabetes and having lower 25(OH)D levels 10. 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 88.

In contrast to observational studies, clinical trials provide little support for the benefits of vitamin D supplementation for glucose homeostasis. One trial included 65 overweight or obese adult men and women (mean age 32 years) who were otherwise healthy, did not have diabetes, and had low serum vitamin D levels (at or below 50 nmol/L [20 ng/mL]) 89. The investigators randomly assigned participants to receive either a bolus oral dose of 2,500 mcg (100,000 IU) vitamin D3 followed by 100 mcg (4,000 IU)/day or a placebo for 16 weeks. In the 54 participants who completed the study, vitamin D supplementation did not improve insulin sensitivity or insulin secretion in comparison with placebo.

One systematic review and meta-analysis evaluated 35 clinical trials that included 43,407 adults with normal glucose tolerance, prediabetes, or type 2 diabetes who received a median of 83 mcg (3,332 IU)/day vitamin D supplements or placebo for a median of 16 weeks 90. Vitamin D had no significant effects on glucose homeostasis, insulin secretion or resistance, or hemoglobin A1c levels (HbA1c, 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 aged 25–80 years (mean age 62 years) with prediabetes received 500 mcg (20,000 IU) vitamin D3 or a placebo each week for 5 years 91. 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 aged 25 years and older (mean age 60 years) with prediabetes who were overweight or obese (mean BMI of 32.1) to 100 mcg (4,000 IU)/day vitamin D3 or placebo for a median of 2.5 years 87. 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 92.

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 86. 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, were not obese, and were of Middle Eastern ethnicity. However, the supplementation had no significant effects on fasting blood glucose, hemoglobin A1c (HbA1c) 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.

Vitamin D Deficiency

Nutrient deficiencies are usually the result of dietary inadequacy, impaired absorption and use, increased requirement, or increased excretion. A vitamin D deficiency can occur when usual intake is lower than recommended levels over time, exposure to sunlight is limited, the kidneys cannot convert calcidiol (25-hydroxyvitamin D3 or 25(OH)D) to its active form, or absorption of vitamin D from the digestive tract is inadequate. Vitamin D-deficient diets are associated with milk allergy, lactose intolerance, ovo-vegetarianism, and veganism 10.

Rickets and osteomalacia are the classical vitamin D deficiency diseases. In children, vitamin D deficiency causes rickets, a disease characterized by a failure of bone tissue to properly mineralize, resulting in soft bones and skeletal deformities 93. In the late 19th and early 20th centuries, German physicians noted that consuming 1–3 teaspoons/day of cod liver oil could reverse rickets 94. The fortification of milk and other staples, such as breakfast cereals and margarine, with vitamin D beginning in the 1930s has made rickets a rare disease in the United States, although it is still reported periodically, particularly among African American infants and children, immigrants from African, Middle-Eastern, and Asian countries 27, 93, 29. Possible explanations for this increase include genetic differences in vitamin D metabolism, dietary preferences, and behaviors that lead to less sun exposure 30.

Prolonged exclusive breastfeeding without the American Academy of Pediatrics-recommended vitamin D supplementation is a significant cause of rickets, particularly in dark-skinned infants breastfed by mothers who are not vitamin D replete 31. Additional causes of rickets include extensive use of sunscreens and placement of children in daycare programs, where they often have less outdoor activity and sun exposure 93, 94. Rickets is also more prevalent among immigrants from Asia, Africa, and the Middle East, possibly because of genetic differences in vitamin D metabolism and behavioral differences that lead to less sun exposure.

In adults 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 33. Signs and symptoms of osteomalacia are similar to those of rickets and include bone deformities and pain, hypocalcemic seizures, tetanic spasms, and dental abnormalities 34.

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 16. No studies have examined whether such screening for vitamin D deficiency results in improved health outcomes 17. 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 18. 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) 95. The vitamin D content of human milk is related to the mother’s vitamin D status; studies suggest that the breastmilk of mothers who take daily supplements containing at least 50 mcg (2,000 IU) vitamin D3 have higher levels of the nutrient 96.

Although UVB exposure can produce vitamin D in infants, the American Academy of Pediatrics 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 97. The American Academy of Pediatrics 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 95. The American Academy of Pediatrics 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 98.

Older adults

Older adults are at increased risk of developing vitamin D insufficiency in part because, as they age, skin cannot synthesize vitamin D as efficiently 99, they are likely to spend more time indoors, and they may have inadequate intakes of the vitamin 10. As many as half of older adults in the United States with hip fractures could have serum 25(OH)D levels <30 nmol/L (<12 ng/mL) 64.

Vitamin D deficiency is common among elderly patients in temperate countries, especially in early spring due to reduced cutaneous synthesis during the winter months 100 and in housebound individuals 101 and medical inpatients 102. The prevalence of vitamin D deficiency is even higher in elderly patients with fragility fractures, ranging from 55%–91.6% 103. A recent study in Singapore showed a vitamin D deficiency prevalence of 57.5% and vitamin D insufficiency of 34.5% in elderly patients admitted to hospital with hip fractures 104.

People with limited sun exposure

Homebound individuals, women who wear long robes and head coverings for religious reasons, and people with occupations that limit sun exposure are unlikely to obtain adequate vitamin D from sunlight 105. 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 10. Ingesting RDA levels of vitamin D from foods and/or supplements will provide these individuals with adequate amounts of this nutrient.

People with dark skin

Greater amounts of the pigment melanin in the epidermal layer result in darker skin and reduce the skin’s ability to produce vitamin D from sunlight 10. Various reports consistently show lower serum 25(OH)D levels in persons identified as black compared with those identified as white. However, it is not clear that lower levels of 25(OH)D for persons with dark skin have significant health consequences. Those of African American ancestry, for example, have reduced rates of fracture and osteoporosis compared with Caucasians 40. Ingesting RDA levels of vitamin D from foods and/or supplements will provide these individuals with adequate amounts of this nutrient.

People with inflammatory bowel disease and other conditions causing fat malabsorption

Because vitamin D is a fat-soluble vitamin, its absorption depends on the gut’s ability to absorb dietary fat 2. Individuals who have a reduced ability to absorb dietary fat might require vitamin D supplementation 106. Fat malabsorption is associated with a variety of medical conditions, including some forms of liver disease, cystic fibrosis, celiac disease, and Crohn’s disease, as well as ulcerative colitis when the terminal ileum is inflamed 10, 27, 106. In addition, people with some of these conditions might have lower intakes of 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 106.

People who are obese 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 nonobese individuals. Obesity does not affect the skin’s capacity to synthesize vitamin D. However, greater amounts of subcutaneous fat sequester more of the vitamin 10. Obese people might need greater intakes of vitamin D to achieve 25(OH)D levels similar to those of people with normal weight 107.

Obese individuals 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 108. 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 109.

What are some effects of vitamin D on health?

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

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 110. 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 111. About 2.3 million osteoporotic fractures occurred in the United States in 2015 112. 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 10. All adults should consume recommended amounts of vitamin D and calcium from foods and supplements if needed. Older women and men should consult their healthcare providers about their needs for both nutrients as part of an overall plan to maintain bone health and to prevent or treat osteoporosis.

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) 10.

Bone mineral density, bone mass, and fracture risk are correlated with serum 25-hydroxyvitamin D [25(OH)D or calcidiol] levels in White Americans and Mexican Americans, but not in Black Americans 113. Factors such as adiposity, skin pigmentation, vitamin D binding protein polymorphisms, and genetics contribute to differences in 25-hydroxyvitamin D [25(OH)D or calcidiol] levels between Black and White Americans 113.

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.

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 114. 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 United States Preventive Services Task Force evaluated 11 randomized clinical trials of vitamin D and/or calcium supplementation in a total of 51,419 healthy, community-dwelling adults aged 50 years and older who did not have osteoporosis, vitamin D deficiency, or prior fractures 115. It concluded that the current evidence was insufficient to evaluate the benefits and harms of vitamin D and/or calcium supplementation to prevent fractures. In addition, the United States Preventive Services Task Force 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 United States Preventive Services Task Force 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 aged 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 116. Another recent systematic review also found that vitamin D and calcium supplements had no beneficial effects on fractures, falls, or bone mineral density 117. In contrast, a meta-analysis of 6 trials in 49,282 older adults found that daily vitamin D (10 or 20 mcg [400 IU or 800 IU]/day) and calcium (800 or 1,200 mg/day) supplementation for a mean of 5.9 years reduced the risk of any fracture by 6% and of hip fracture by 16% 118.

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 118.

One clinical trial randomized 260 Black women aged 60 years and older (mean age 68.2 years) to receive 60 to 120 mcg (2,400 to 4,800 IU) per day vitamin D3 supplementation to maintain serum 25-hydroxyvitamin D [25(OH)D or calcidiol] levels above 75 nmol/L (30 ng/mL) for 3 years 119. The results showed no association between 25-hydroxyvitamin D [25(OH)D or calcidiol] 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 113. Furthermore, the bone health of older Black American women does not appear to benefit from raising serum 25-hydroxyvitamin D [25(OH)D or calcidiol] levels beyond 50 nmol/L (20 ng/mL) 119.

Studies examining the effects of supplemental vitamin D on muscle strength and on rate of decline in muscle function have had inconsistent results 17. One recent clinical trial, for example, randomized 78 frail and near-frail adults aged 65 years and older to receive 20 mcg (800 IU) vitamin D3, 10 mcg 25-hydroxyvitamin D [25(OH)D or calcidiol], or placebo daily for 6 months. The groups showed no significant differences in measures of muscle strength or performance 120. Another study randomized 100 community-dwelling men and women aged 60 years and older (most were White) with serum 25-hydroxyvitamin D [25(OH)D or calcidiol] levels of 50 nmol/L (20 ng/ml) or less to 800 IU vitamin D3 or placebo for 1 year 121. Participants in the treatment group whose serum 25-hydroxyvitamin D [25(OH)D or calcidiol] level was less than 70 nmol/L (28 ng/ml) after 4 months received an additional 800 IU/day vitamin D3. Despite increasing serum 25-hydroxyvitamin D [25(OH)D or calcidiol] 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.

Cancer

Early epidemiologic research showed that incidence and death rates for certain cancers were lower among individuals living in southern latitudes, where levels of sunlight exposure are relatively high, than among those living at northern latitudes. Because exposure to ultraviolet light from sunlight leads to the production of vitamin D, researchers hypothesized that variation in vitamin D levels might account for this association. However, additional research based on stronger study designs is required to determine whether higher vitamin D levels are related to lower cancer incidence or death rates. Experimental evidence has also suggested a possible association between vitamin D and cancer risk. In studies of cancer cells and of tumors in mice, vitamin D has been found to have several activities that might slow or prevent the development of cancer, including promoting cellular differentiation, decreasing cancer cell growth, stimulating cell death (apoptosis), and reducing tumor blood vessel formation (angiogenesis) 122.

A number of epidemiologic studies have investigated whether people with higher vitamin D intakes or higher blood levels of vitamin D have lower risks of specific cancers. The results of these studies have been inconsistent, possibly because of the challenges in carrying out such studies. For example, dietary studies do not account for vitamin D made in the skin from sunlight exposure, and the level of vitamin D measured in the blood at a single point in time (as in most studies) may not reflect a person’s true vitamin D status. Also, it is possible that people with higher vitamin D intakes or blood levels are more likely to have other healthy behaviors. It may be one of these other behaviors, rather than vitamin D intake, that influences cancer risk.

Several randomized trials of vitamin D intake have been carried out, but these were designed to assess bone health or other non-cancer outcomes. Although some of these trials have yielded information on cancer incidence and mortality, the results need to be confirmed by additional research because the trials were not designed to study cancer specifically.

The cancers for which the most human data are available are colorectal, breast, prostate, and pancreatic cancer. 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 123. A 50 nmol/L (20 ng/mL) increase in 25-hydroxyvitamin D [25(OH)D or calcidiol] 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-hydroxyvitamin D [25(OH)D or calcidiol] 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-hydroxyvitamin D [25(OH)D or calcidiol] levels 124. 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% 125. In the most recent meta-analysis, 10 randomized clinical trials (including the Vitamin D and Omega-3 Trial [VITAL] trial described below) that included 6,537 cancer cases provided 10 to 50 mcg (400 to 2,000 IU) vitamin D3 daily (six trials) or 500 mcg (20,000 IU)/week to 12,500 mcg (500,000 IU)/year boluses of vitamin D3 (four trials) 125. The study reports included 3–10 years of followup 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, Vitamin D and Omega-3 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 D3 supplements with or without 1,000 mg/day marine omega-3 fatty acids or a placebo for a median of 5.3 years 126. The study included 25,871 men aged 50 years and older and women aged 55 years and older who had no history of cancer, and most had adequate serum 25(OH)D levels at baseline. Rates of 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 who were overweight or obese.

Numerous epidemiologic studies have shown that higher intake or blood levels of vitamin D are associated with a reduced risk of colorectal cancer 127, 128. In contrast, the Women’s Health Initiative randomized trial found that healthy women who took vitamin D and calcium supplements for an average of 7 years did not have a reduced incidence of colorectal cancer 129. Some scientists have pointed out that the relatively low level of vitamin D supplementation (10 mcg or 400 IU, once a day), the ability of participants to take additional vitamin D on their own, and the short duration of participant follow-up in this trial might explain why no reduction in colorectal cancer risk was found. Evidence on the association between vitamin D and the risks of all other malignancies studied is inconclusive.

Taken together, the available data are not comprehensive enough to establish whether taking vitamin D can prevent cancer 130. To fully understand the effects of vitamin D on cancer and other health outcomes, new randomized trials need to be conducted 131. However, the appropriate dose of vitamin D to use in such trials is still not clear 132. Other remaining questions include when to start taking vitamin D, and for how long, to potentially see a benefit.

The United States Preventive Services Task Force stated that, due to insufficient evidence, it was unable to assess the balance of benefits and harms of supplemental vitamin D to prevent cancer 133. 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-hydroxyvitamin D [25(OH)D or calcidiol] 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.

Breast cancer

Some observational studies support an inverse association between 25-hydroxyvitamin D [25(OH)D or calcidiol] levels and breast cancer risk and mortality, but others do not 134. The Women’s Health Initiative clinical trial randomized 36,282 postmenopausal women to receive 400 IU vitamin D3 plus 1,000 mg calcium daily or a placebo for a mean of 7 years 129. The vitamin D3 and calcium supplements did not reduce breast cancer incidence, and 25-hydroxyvitamin D [25(OH)D or calcidiol] levels at the start of the study were not associated with breast cancer risk 135.

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 136. 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-hydroxyvitamin D [25(OH)D or calcidiol] levels were assessed a median of 5.5 years from blood draw to cancer diagnosis and 7,105 matched controls 137. The results showed an association between 25-hydroxyvitamin D [25(OH)D or calcidiol] 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, vitamin D3 and calcium supplements had no effect on rates of colorectal cancer. In a subsequent investigation for 4.9 years after the study’s end, women who had taken the vitamin D and calcium supplements (many of whom continued to take them) still had the same colorectal cancer risk as those who received placebo 135.

Another study included 2,259 healthy individuals aged 45 to 75 years who had had one or more serrated polyps (precursor lesions to colorectal cancer) that had been removed 138. These participants were randomized to take 25 mcg (1,000 IU) vitamin D3, 1,200 mg calcium, both supplements, or a placebo daily for 3–5 years, followed by an additional 3–5 years of observation after participants stopped the treatment. Vitamin D alone did not significantly affect the development of new serrated polyps, but the combination of vitamin D with calcium increased the risk almost fourfold. The Vitamin D and Omega-3 Trial (VITAL) trial found no association between vitamin D supplementation and the risk of colorectal adenomas or serrated polyps 138.

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-hydroxyvitamin D [25(OH)D or calcidiol] levels and risk of subsequent lung cancer, even when the investigators analyzed the data by sex, age, race and ethnicity, and smoking status 139.

Pancreatic cancer

One study comparing 738 men who developed pancreatic cancer to 738 matched controls found no relationship between serum 25-hydroxyvitamin D [25(OH)D or calcidiol] levels and risk of pancreatic cancer 140. 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-hydroxyvitamin D [25(OH)D or calcidiol] 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]) 141. An investigation that pooled data from 10 studies of cancer in 12,205 men and women found that concentrations of 25-hydroxyvitamin D [25(OH)D or calcidiol] 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-hydroxyvitamin D [25(OH)D or calcidiol] levels of 100 nmol/L (40 ng/mL) or above 142.

Prostate cancer

Research to date provides mixed evidence on whether levels of 25-hydroxyvitamin D [25(OH)D or calcidiol] are associated with the development of prostate cancer. Several studies published in 2014 suggested that high levels of 25-hydroxyvitamin D [25(OH)D or calcidiol] 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-hydroxyvitamin D [25(OH)D or calcidiol] 143. 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-hydroxyvitamin D [25(OH)D or calcidiol] 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 144. 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-hydroxyvitamin D [25(OH)D or calcidiol] levels and prostate cancer risk 145. However, higher serum 25-hydroxyvitamin D [25(OH)D or calcidiol] 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-hydroxyvitamin D [25(OH)D or calcidiol] levels and prostate cancer risk 146, 147. For example, an analysis was conducted of 19 prospective studies that provided data on prediagnostic levels of 25-hydroxyvitamin D [25(OH)D or calcidiol] for 13,462 men who developed prostate cancer and 20,261 control participants 148. Vitamin D deficiency or insufficiency did not increase the risk of prostate cancer, and higher 25-hydroxyvitamin D [25(OH)D or calcidiol] concentrations were not associated with a lower risk.

Several studies have examined whether levels of 25-hydroxyvitamin D [25(OH)D or calcidiol] 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-hydroxyvitamin D [25(OH)D or calcidiol] 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-hydroxyvitamin D [25(OH)D or calcidiol] levels were not associated with risk of death from prostate cancer or any cause 149. However, a meta-analysis of 7 cohort studies that included 7,808 men with prostate cancer found higher 25-hydroxyvitamin D [25(OH)D or calcidiol] levels to be significantly associated with lower mortality rates from prostate cancer or any other cause 150. A dose-response analysis found that each 20 nmol/L [8 ng/mL] increase in 25-hydroxyvitamin D [25(OH)D or calcidiol] 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 3 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 151.

Weight loss

Observational studies indicate that greater body weights are associated with lower vitamin D status, and obese individuals frequently have marginal or deficient circulating 25-hydroxyvitamin D [25(OH)D or calcidiol] levels 152. 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-hydroxyvitamin D [25(OH)D or calcidiol] levels than those who maintained their weight 153. 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 154. 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 155.

Overall, the available research suggests that consuming higher amounts of vitamin D or taking vitamin D supplements does not promote weight loss.

Other conditions

A growing body of research suggests that vitamin D might play some role in the prevention and treatment of type 1 156 and type 2 diabetes 157, hypertension 158, glucose intolerance 159, multiple sclerosis 160, and other medical conditions 161, 162. However, most evidence for these roles comes from in vitro, animal, and epidemiological studies, not the randomized clinical trials considered to be more definitive 10. Until such trials are conducted, the implications of the available evidence for public health and patient care will be debated. One meta-analysis found use of vitamin D supplements to be associated with a statistically significant reduction in overall mortality from any cause 163, 164, but a reanalysis of the data found no association 165. A systematic review of these and other health outcomes related to vitamin D and calcium intakes, both alone and in combination, was published in August 2009 165.

Vitamin D and Cardiovascular Disease

Observational studies support an association between higher serum 25-hydroxyvitamin D [25(OH)D or calcidiol] levels and a lower risk of cardiovascular disease 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-hydroxyvitamin D [25(OH)D or calcidiol] levels were inversely associated with total number of cardiovascular disease events (including myocardial infarction, ischemic heart disease, heart failure, and stroke) and mortality risk 166. Overall, the risk of cardiovascular disease events was 10% lower for each 25 nmol/L (10 ng/mL) increase in serum 25-hydroxyvitamin D [25(OH)D or calcidiol].

Another large observational study that followed 247,574 adults from Denmark for 0–7 years found that levels of 25-hydroxyvitamin D [25(OH)D or calcidiol] 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 cardiovascular disease, stroke, and acute myocardial infarction 167. Other meta-analyses of prospective studies have found associations between lower vitamin D status measured by serum 25-hydroxyvitamin D [25(OH)D or calcidiol] levels or vitamin D intakes and an increased risk of ischemic stroke, ischemic heart disease, myocardial infarction, and early death 168, 169.

In contrast to the observational studies, clinical trials have provided little support for the hypothesis that supplemental vitamin D reduces the risk of cardiovascular disease or cardiovascular disease mortality. For example, a 3-year trial in New Zealand randomized 5,110 adults (mean age 65.9 years) to a single dose of 5,000 mcg (200,000 IU) vitamin D3 followed by 2,500 mcg (100,000 IU) each month or a placebo for a median of 3.3 years 170. Vitamin D supplementation had no effect on the incidence rate of myocardial infarction, angina, heart failure, arrhythmia, arteriosclerosis, stroke, venous thrombosis, or death from cardiovascular disease. Similarly, the VITamin D and Omega-3 TriaL (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 126. Moreover, the effects did not vary by baseline serum 25-hydroxyvitamin D [25(OH)D or calcidiol] 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 D3 (with or without calcium) or a placebo in 5,292 adults aged 70 years and older for a median of 6.2 years offered protection from cardiac failure, but not myocardial infarction or stroke 171.

High serum cholesterol levels and hypertension are two of the main risk factors for cardiovascular disease. 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 172.

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 173. In contrast, another meta-analysis of 30 clinical trials in 4,744 participants (mean age 54.5 years) that administered 5 mcg (200 IU) to 300 mcg (12,000 IU)/day vitamin D3 for a mean of 5.6 months showed that more than 20 mcg (800 IU)/day significantly reduced systolic and diastolic blood pressure in normal-weight participants who had hypertension 174. However, more than 20 mcg (800 IU)/day vitamin D3, when taken with calcium supplements, significantly increased blood pressure in overweight and obese participants. 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-hydroxyvitamin D [25(OH)D or calcidiol] 175.

Overall, clinical trials show that vitamin D supplementation does not reduce cardiovascular disease risk, even for people with low 25-hydroxyvitamin D [25(OH)D or calcidiol] status (below 20 nmol/L [12 ng/mL]) at baseline 126, 170.

Vitamin D and Multiple Sclerosis

Many epidemiological and genetic studies have shown an association between multiple sclerosis (MS) and low 25(OH)D levels before and after the disease begins 176. Vitamin D appears to have no effect on recurrence of multiple sclerosis (MS) relapse, worsening of disability measured by the Expanded Disability Status Scale (EDSS), and MRI lesions 176. Effects on health‐related quality of life and fatigue are unclear. Vitamin D₃ at the doses and treatment durations used in the included trials appears to be safe, although available data are limited. Observational studies suggest that adequate vitamin D levels might reduce the risk of contracting multiple sclerosis (MS) and, once MS is present, decrease the risk of relapse and slow the disease’s progression 81. 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 82. 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 83 and the other with 576 individuals in northern Sweden 84 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 176. 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 85. In addition, studies have not consistently shown that vitamin D supplementation tempers the signs and symptoms of active MS or reduces rates of relapse.

A study conducted by researchers at the University of Oxford and another conducted at the New Jersey Medical School have suggested that maintaining adequate levels of vitamin D may have a protective effect and lower the risk of developing multiple sclerosis (MS) 177.

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

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

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

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

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

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

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

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

Vitamin D and Depression

Vitamin D is involved in various brain processes, and vitamin D receptors are present on neurons and glia in areas of the brain thought to be involved in the pathophysiology of depression 178. 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-hydroxyvitamin D [25(OH)D or calcidiol] and depression 178. Clinical trials, however, do not support these findings. For example, a meta-analysis of 9 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 179. 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-hydroxyvitamin D [25(OH)D or calcidiol] 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 180, 181, 182. One trial included 206 adults (mean age 52 years) who were randomized to take a bolus dose of 2,500 mcg (100,000 IU) vitamin D3 followed by 500 mcg (20,000 IU)/week or a placebo for 4 months 180. 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 aged 60–80 years who had clinically relevant depressive symptoms, no major depressive disorder, and serum 25-hydroxyvitamin D [25(OH)D or calcidiol] levels less than 50 to 70 nmol/L (20 to 28 ng/mL) depending on the season; in addition, they were not taking antidepressants 181. Participants were randomized to take either 30 mcg (1,200 IU)/day vitamin D3 or a placebo for 1 year. In the VITAL trial described above, 16,657 men and women 50 years of age and older with no history of depression and 1,696 with an increased risk of recurrent depression (that had not been medically treated for the past 2 years) were randomized to take 50 mcg (2,000 IU)/day vitamin D3 (with or without fish oil) or a placebo for a median of 5.3 years 183. 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-aged 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-hydroxyvitamin D [25(OH)D or calcidiol] levels and are taking antidepressant medication.

Can Vitamin D prevent Alzheimer’s disease & Dementia?

Maybe. But it’s too soon to say for certain. New research suggests people with very low levels of vitamin D in their blood, known as vitamin D deficiency, are more likely to develop Alzheimer’s disease and other forms of dementia 184. Multiple meta-analyses and systematic reviews of observational research have examined the relationship between vitamin D levels and cognitive function. A few studies have tested the effects of vitamin D treatment on cognition, but randomized controlled trials on dementia risk or cognitive decline are lacking.

For example, a large 2014 study published in Neurology 185 showed people with extremely low blood levels of vitamin D were more than twice as likely to develop Alzheimer’s disease or other types of dementia than those with normal vitamin D levels. Other studies 186, 187, 188 also showed people with low levels or low dietary intake of vitamin D appear to be more likely to develop mild cognitive impairment (MCI) or dementia, but no clinical research has yet tested whether treatment with vitamin D can protect from this risk. It’s important to point out that the association between vitamin D deficiency and dementia risk is only observational at this point. More research is needed to show cause and effect. In a small non-randomized clinical trial, elderly people receiving vitamin D3 supplements had better cognitive function compared to untreated people, with particular improvement in executive function 189, but the study was not controlled or designed to look at the risk of cognitive decline.

Research on the benefits of vitamin D for dementia patients is very limited and has produced mixed results. In a small, six-month pilot study, Alzheimer’s patients who were treated with memantine plus vitamin D improved their cognitive scores, whereas those taking memantine alone or vitamin D alone remained the same 190. A larger trial testing the effects of vitamin D in combination with memantine was scheduled to be completed in 2013 191, but the results have not been published. A small randomized trial of Parkinson’s disease patients suggested that vitamin D supplementation stabilized the disease, possibly by improving strength and balance 192.

Clinical trials are underway to examine the effects of vitamin D on cognitive function in older adults who have low vitamin D levels 193, memory complaints 194, mild cognitive impairment 195, and type 2 diabetes 196, as well as those in good health 197. Another trial is testing whether vitamin D can reduce the risk of cancer, heart disease, and stroke in 20,000 men and women 198, with a subgroup undergoing testing for cognitive decline and dementia 190.

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

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

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

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

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

Vitamins D and type 2 diabetes

Vitamin D plays a role in glucose metabolism. Vitamin D 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 86. 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 87.

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 obese and were therefore more predisposed to developing diabetes and having lower 25(OH)D levels 10. 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 88.

In contrast to observational studies, clinical trials provide little support for the benefits of vitamin D supplementation for glucose homeostasis. One trial included 65 overweight or obese adult men and women (mean age 32 years) who were otherwise healthy, did not have diabetes, and had low serum vitamin D levels (at or below 50 nmol/L [20 ng/mL]) 89. The investigators randomly assigned participants to receive either a bolus oral dose of 2,500 mcg (100,000 IU) vitamin D3 followed by 100 mcg (4,000 IU)/day or a placebo for 16 weeks. In the 54 participants who completed the study, vitamin D supplementation did not improve insulin sensitivity or insulin secretion in comparison with placebo.

One systematic review and meta-analysis evaluated 35 clinical trials that included 43,407 adults with normal glucose tolerance, prediabetes, or type 2 diabetes who received a median of 83 mcg (3,332 IU)/day vitamin D supplements or placebo for a median of 16 weeks 199. 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 aged 25–80 years (mean age 62 years) with prediabetes received 500 mcg (20,000 IU) vitamin D3 or a placebo each week for 5 years 91. 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 aged 25 years and older (mean age 60 years) with prediabetes who were overweight or obese (mean BMI of 32.1) to 100 mcg (4,000 IU)/day vitamin D3 or placebo for a median of 2.5 years 87. 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 92.

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 86. 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, were not obese, 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.

Can Excessive Vitamin D be harmful?

Yes, 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]) 200. Hypercalcemia (high blood calcium), in turn, can lead to nausea, poor appetite, vomiting, constipation, muscle weakness, weight loss, neuropsychiatric disturbances, pain, loss of appetite, dehydration, polyuria, excessive thirst, and kidney stones. And by raising blood levels of calcium, too much vitamin D can cause confusion, disorientation, and problems with heart rhythm. Excess vitamin D can also damage the kidneys.

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 201.

Vitamin D toxicity can cause non-specific symptoms such as anorexia, weight loss, polyuria, and heart arrhythmias. More seriously, it can also raise blood levels of calcium which leads to vascular and tissue calcification, with subsequent damage to the heart, blood vessels, and kidneys 10. The use of supplements of both calcium (1,000 mg/day) and vitamin D (10 mcg (400 IU)/day vitamin D) by postmenopausal women was associated with a 17% increase in the risk of kidney stones over 7 years in the Women’s Health Initiative 202. A serum 25(OH)D concentration consistently >500 nmol/L (>200 ng/mL) is considered to be potentially toxic 203. 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 204.

Experts do not believe that excessive sun exposure does not result in vitamin D toxicity because the sustained heat on the skin is thought to photodegrade previtamin D3 and vitamin D3 as it is formed 38. In addition, thermal activation of previtamin D3 in the skin gives rise to various non-vitamin D forms that limit formation of vitamin D3 itself. Some vitamin D3 is also converted to nonactive forms 10. Intakes of vitamin D from food that are high enough to cause toxicity are very unlikely. Toxicity is much more likely to occur from high intakes of dietary supplements containing vitamin D. 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) 205.

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

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

Table 5: Tolerable Upper Intake Levels (ULs) for Vitamin D

AgeMaleFemalePregnancyLactation
0–6 months1,000 IU
(25 mcg)
1,000 IU
(25 mcg)
7–12 months1,500 IU
(38 mcg)
1,500 IU
(38 mcg)
1–3 years2,500 IU
(63 mcg)
2,500 IU
(63 mcg)
4–8 years3,000 IU
(75 mcg)
3,000 IU
(75 mcg)
9–18 years4,000 IU
(100 mcg)
4,000 IU
(100 mcg)
4,000 IU
(100 mcg)
4,000 IU
(100 mcg)
19+ years4,000 IU
(100 mcg)
4,000 IU
(100 mcg)
4,000 IU
(100 mcg)
4,000 IU
(100 mcg)
[Source 10 ]

Vitamin D Side Effects and Warnings

Vitamin D is a fat-soluble vitamin, hence, toxicity is possible, although rarely noted. Hypervitaminosis D results from excess oral intake and not due to excessive sunlight exposure. Toxicity has been reported at a serum 25-hydroxyvitamin D level of more than 88 ng/mL. Acute intoxication can lead to acute hypercalcemia that can cause confusion, anorexia, vomiting, polyuria, polydipsia, and muscle weakness. Chronic intoxication can lead to nephrocalcinosis and bone pain.

Vitamin D is likely safe when taken by mouth in doses of 100 micrograms of vitamin D3 daily (4,000 IU) and when applied to the skin alone or in combination with corticosteroids for up to three months 206.

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

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

Children age 9 years and older, adults, and pregnant and breastfeeding women who take more than 4,000 IU a day of vitamin D might experience:

  • Nausea and vomiting
  • Poor appetite and weight loss
  • Constipation
  • Weakness
  • Confusion and disorientation
  • Heart rhythm problems
  • Kidney stones and kidney damage

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

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

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

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

Use cautiously in breastfeeding women.

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

Avoid in people with abnormal calcium excretion or levels.

Pregnancy and Breastfeeding

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

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

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