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Natural Medicine Journal

March 22, 2014

The Latest Research on Vitamin D

Bottom Line Monograph

Natural Standard

Vitamin D is one of the most publicized nutrients today. This monograph assesses the recent research, outlines the most and least promising uses for the vitamin, and explains interactions and contraindications.

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Related Terms

1,25-DHCC, 1,25-dihydroxy-22-ovavitamin D(3), 1,25-dihydroxycholecalciferol, 1,25-dihydroxy-vitamin-D (1,25(OH)(2)D), 1,25-dihydroxyvitamin D3, 1,25-diOHC, 1,25(OH) 2D3, 1-alpha (OH) D3, 19-nor-1, 1-alpha-hydroxycholecalciferol, 1-alpha-hydroxyvitamin D2, 1-hydroxyvitamin D, 22-oxacalcitriol (OCT), 24,25(OH)(2)vitamin D(3), 25 hydroxyvitamin D (25(OH)D), 25-dihydroxyvitamin D2, 25-dihydroxyvitamin D2, 19-nor-1, 25-HCC, 25-hydroxycholecalciferol, 25-hydroxyvitamin D, 25-hydroxyvitamin D3, 25-OHCC, 25-OHD3, activated 7-dehydrocholesterol, activated ergosterol, alfacalcidol, calcifediol, calcipotriene, calcipotriol, calcitriol, cholecalciferol, colecalciferol, dichysterol, dihydrotachysterol, dihydrotachysterol 2, doxercalciferol, ecocalcidiol, ED-21 (vitamin D analog), ED-71 (vitamin D analog), ergocalciferol, ergocalciferolum, falecalcitrol, hexafluoro-1,25dihydroxyvitamin D3, irradiated ergosterol, maxacalcitol, MC903, paracalcin, paricalcitol, tacalcitol, viosterol, vitamin D2, vitamin D3.

Background

  • Vitamin D is found in many dietary sources, such as fish, eggs, fortified milk, and cod liver oil. The sun also contributes significantly to the daily production of vitamin D, and as little as 10 minutes of exposure is thought to be enough to prevent deficiencies. The term "vitamin D" refers to several different forms of this vitamin. Two forms are important in humans: ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3). Vitamin D2 is synthesized by plants. Vitamin D3 is synthesized by humans in the skin when it is exposed to ultraviolet B (UVB) rays from sunlight. Foods may be fortified with vitamin D2 or D3.
  • The major biologic function of vitamin D is to maintain normal blood levels of calcium and phosphorus. Vitamin D aids in the absorption of calcium, helping to form and maintain strong bones. It is used, alone or in combination with calcium, to increase bone mineral density and decrease fractures. Recently, research also suggests that vitamin D may provide protection from osteoporosis, hypertension (high blood pressure), cancer, and several autoimmune diseases.
  • Rickets and osteomalacia are classic vitamin D deficiency diseases. In children, vitamin D deficiency causes rickets, which results in skeletal deformities. In adults, vitamin D deficiency can lead to osteomalacia, which results in muscular weakness in addition to weak bones. Populations who may be at a high risk for vitamin D deficiencies include the elderly, obese individuals, exclusively breastfed infants, and those who have limited sun exposure. Also, individuals who have fat malabsorption syndromes (e.g., cystic fibrosis) or inflammatory bowel disease (e.g., Crohn's disease) are at risk.

Scientific Evidence


Uses
These uses have been tested in humans or animals. Safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider.		Grade*
Familial hypophosphatemia
Familial hypophosphatemia (low blood levels of phosphate in the blood) is a rare inherited disorder that consists of impaired phosphate transport in the blood and diminished vitamin D metabolism in the kidneys. Familial hypophosphatemia is a form of rickets. Taking calcitriol or dihydrotachysterol by mouth along with phosphate supplements is effective for treating bone disorders in people with familial hypophosphatemia. Its management should be under medical supervision.		A
Fanconi syndrome-related hypophosphatemia
Fanconi syndrome is a defect of the proximal tubules of the kidney and is associated with renal tubular acidosis. Taking ergocalciferol orally is effective for treating hypophosphatemia associated with Fanconi syndrome.		A
Hyperparathyroidism due to low vitamin D levels
Some patients may develop secondary hyperparathyroidism (overactive parathyroid) due to low levels of vitamin D. The initial treatment for this type of hyperparathyroidism is vitamin D. For patients with primary or refractory hyperparathyroidism, surgical removal of the parathyroid glands is commonly recommended. Studies also suggest that vitamin D supplementation may reduce the incidence of hypoparathyroidism following surgery for primary hyperparathyroidism (partial or total removal of the parathyroid glands).		A
Hypocalcemia due to hypoparathyroidism
Hypoparathyroidism (low blood levels of parathyroid hormone) is rare and often due to surgical removal of the parathyroid glands. High oral doses of the vitamin D analogs dihydrotachysterol (DHT), calcitriol, or ergocalciferol can assist in increasing serum calcium concentrations in people with hypoparathyroidism or pseudohypoparathyroidism.		A
Osteomalacia (adult rickets)
Adults with severe vitamin D deficiency lose bone mineral content (this is called "hypomineralization") and experience bone pain, muscle weakness, and osteomalacia (soft bones). Osteomalacia may be found among elderly patients with vitamin D-deficient diets, individuals with decreased absorption of vitamin D, individuals with inadequate sun exposure (such as those living in latitudes with seasonal lack of sunlight), patients with gastric or intestinal surgery, patients with aluminum-induced bone disease, patients with chronic liver disease, or patients with kidney disease with renal osteodystrophy. Treatment for osteomalacia depends on the underlying cause of the disease and often includes pain control and orthopedic surgical intervention, as well as vitamin D and phosphate-binding agents.		A
Psoriasis (vitamin D analogs)
A number of different approaches are used in the treatment of psoriasis skin plaques. Mild approaches include light therapy, stress reduction, moisturizers, or salicylic acid to remove scaly skin areas. For more severe cases, treatments may include UVA light, psoralen plus UVA light (PUVA), retinoids such as isotretinoin (Accutane), corticosteroids, or cyclosporine (Neoral®, Sandimmune®). The synthetic vitamin D3 analog calcipotriene (Dovonex®) appears to control skin cell growth and is used for moderately severe skin plaques, particularly for skin lesions resistant to other therapies or those located on the face. Vitamin D3 (tacalcitol) ointment has been reported as being safe and well tolerated. High doses of becocalcidiol (a vitamin D analog) used on the skin may be beneficial in the treatment of psoriasis.		A
Rickets
Rickets (weak bones) develop in children with vitamin D deficiency due to a vitamin D-deficient diet, a lack of sunlight, or both. Infants fed only breast milk (without supplemental vitamin D) may also develop rickets. Although now rare, partially due to the availability of vitamin D-fortified milk, there has been a recent increase in rickets among children in latitudes with periodic, seasonal lack of sunlight. Ergocalciferol or cholecalciferol is effective for treating vitamin D deficiency rickets. Calcitriol should be used in patients with renal (kidney) failure. Treatment should be under medical supervision.		A
Vitamin D deficiency
Vitamin D deficiency is associated with various diseases, such as bone loss, osteoarthritis, cognitive issues, kidney disease, respiratory concerns, diabetes, gastrointestinal issues, cardiovascular disease, etc. Vitamin D supplementation can help prevent or treat vitamin D deficiency.		A
Fall prevention
Multiple trials have found positive results for the effects of vitamin D in the prevention of falls, especially in the elderly. More studies are needed to confirm these results and determine populations of interest.		B
Muscle weakness/pain
Vitamin D deficiency has been associated with muscle weakness and pain in both adults and children. Limited research has reported vitamin D deficiency in patients with low-back pain, and supplementation may reduce pain in many patients.		B
Osteoporosis (general)
Without sufficient vitamin D, inadequate calcium is absorbed, and this may weaken bones and increase the risk of fracture. Vitamin D supplementation has been shown to slow bone loss and reduce fracture, particularly when taken with calcium.		B
Renal osteodystrophy
Renal osteodystrophy is a term that refers to all of the bone problems that occur in patients with chronic kidney failure. Oral calcifediol or ergocalciferol may help manage hypocalcemia and prevent renal osteodystrophy in people with chronic renal failure undergoing dialysis.		B
Anticonvulsant-induced osteomalacia
Supplementation with vitamin D2 has been reported to reduce seizure frequency in initial research. Further research is needed to confirm these results.		C
Asthma
There is a high prevalence of vitamin D deficiency in individuals with asthma. Experts suggest that vitamin D supplementation in patients with asthma may improve the severity of the disease and improve treatment. However, rigorous studies are needed before a conclusion can be made.		C
Autoimmune diseases
Vitamin D has been found to have anti-inflammatory and immunomodulating effects, and it may play a role in preventing autoimmune disorders. Further research is needed to confirm these results.		C
Bone density (pediatric)
Vitamin D improves bone density in children who are vitamin D deficient. However, the data are not clear for healthy children. Further research in healthy children is required.		C
Bone diseases (kidney disease or kidney transplant)
Vitamin D is of interest for patients with chronic kidney disease. Use of vitamin D analogs has been found to increase bone density in patients with kidney disease. The effect of vitamin D itself is not clear. Vitamin D increases vitamin D status and decreases PTH levels but clinical study is lacking. Further research is required before conclusions can be drawn.		C
Cancer prevention (breast, colorectal, prostate, other)
Use of vitamin D supplements, alone or in combination with calcium, has been associated with a decreased risk of certain types of cancers. Studies have suggested an inverse association between vitamin D intake (with or without calcium) and colorectal, cervical, breast, and prostate cancers. Overall, there is a lack of consistent evidence to support claims that vitamin D reduces the risk of ovarian or pancreatic cancer occurrence. Also, some research has shown that elevated vitamin D levels or intakes may increase the risk of certain cancers (prostate, breast, pancreatic, and esophageal). Continued evaluation is needed before a clear conclusion can be made.		C
Cardiovascular disease
Vitamin D is recognized as being important for cardiovascular health, and deficiency of vitamin D is a potential risk factor for several cardiovascular disease processes. Overall, research is not consistent, and further research is required.		C
Cognition
In older patients, intake of vitamin D is associated with better cognitive test performance. Further research is needed.		C
Corticosteroid-induced osteoporosis
Some evidence implies that steroids may impair vitamin D metabolism, further contributing to the loss of bone and development of osteoporosis associated with steroid medications. There is limited evidence that vitamin D may be beneficial to bone strength in patients taking long-term steroids.		C
Fractures (prevention)
Conflicting results have been observed in studies of fracture prevention with vitamin D, with or without calcium.		C
Fractures (treatment)
Studies have suggested that vitamin D status can decrease following hip fracture. However, there is a lack of evidence in support of vitamin D following fractures. Further research is needed.		C
Hepatic osteodystrophy (bone disease in patients with liver disease)
Metabolic bone disease is common among patients with chronic liver disease, and osteoporosis accounts for the majority of cases. Varying degrees of calcium malabsorption may occur in patients with chronic liver disease due to malnutrition and vitamin D deficiency. Oral or injected vitamin D may play a role in the management of this condition.		C
HIV
Although there is a high prevalence of vitamin D deficiency in HIV-positive men, there is lack of strong evidence to support the use of supplementation in this population. Additional research is warranted before a conclusion can be made.		C
Hyperlipidemia (high levels of fatty acid compounds or cholesterol in the blood)
The effects of vitamin D, alone or in combination with other agents, on lipid parameters have been inconsistent. Further research is needed to evaluate the effects of vitamin D alone or in combination with calcium on lipids before a conclusion can be made.		C
Hypertension
Low levels of vitamin D may play a role in the development of high blood pressure. It has been noted that blood pressure is often elevated under the following conditions: during the winter season, at a further distance from the equator, and in individuals with dark skin pigmentation (all of which are associated with lower production of vitamin D via sunlight). However, the evidence is not clear, and a comparison with more proven methods to reduce blood pressure has not been conducted. Patients with elevated blood pressure should be managed by a licensed healthcare professional.		C
Immunomodulation
Preliminary human evidence suggests that vitamin D and its analogs, such as alfacalcidol, may act as immunomodulatory agents (agents that affect the immune system). More studies are needed to confirm these results.		C
Kidney disease (chronic)
Use of vitamin D analogs has been found to increase bone density in patients with kidney disease. The effect of vitamin D itself is not clear, and vitamin D intake may be associated with increased mortality in hemodialysis patients. Further research is required before conclusions can be drawn.		C
Mood disorders
Some studies suggest an association between low vitamin D levels in the blood and various mood disorders, including depression, seasonal affective disorder (SAD), and premenstrual syndrome. Also vitamin D supplementation may improve symptoms of depression associated with seasonal affective disorder. Additional research is needed before a conclusion can be made.		C
Mortality reduction
Intake of vitamin D may be associated with a reduction in total mortality. Additional evidence is needed to confirm this association.		C
Multiple sclerosis (MS)
Scientists have detected MS rates to be lower in areas with greater sunlight and higher consumption of vitamin D rich fish. Preliminary research suggests that long-term vitamin D supplementation decreases the risk of MS. However, additional research is necessary before a firm conclusion can be reached.		C
Muscle strength
Evidence is mixed with respect to the effect of vitamin D on strength in the elderly. Further research is required in order to confirm these results.		C
Myelodysplastic syndrome
Although vitamin D is commonly used by patients with myelodysplastic syndrome, there is insufficient evidence in this area.		C
Osteogenesis imperfecta (OI)
OI is a genetic disease that consists of unusually fragile bones that break easily, often under loads that normal bones bear daily, due to a malfunction in the body's production of collagen. Proper calcium and vitamin D intake is essential to maintaining strong bones.		C
Osteoporosis (cystic fibrosis patients)
Osteoporosis is common in patients with cystic fibrosis (due to fat malabsorption, which leads to a deficiency of fat-soluble vitamins such as vitamin D). Oral calcitriol administration appears to increase the absorption of calcium and decrease parathyroid concentrations.		C
Proximal myopathy
There is insufficient evidence in this area, and further research is needed.		C
Rickets (hypophosphatemic vitamin D-resistant)
There are insufficient data to support a role for vitamin D in this condition.		C
Seasonal affective disorder (SAD)
SAD is a form of depression that occurs during the winter months, possibly due to reduced exposure to sunlight. In one study, vitamin D was found to be better than light therapy in the treatment of SAD. Further studies are necessary to confirm these findings.		C
Senile warts
In early research, senile warts have been treated with topical vitamin D3.		C
Sexual dysfunction
The evidence in support of vitamin D supplementation for sexual dysfunction is mixed. Additional research is needed before a conclusion can be made.		C
Skin conditions
Calcipotriol (Dovonex®) is a synthetic vitamin D3 analog with a high affinity for the vitamin D receptor for the active form of 1,24-hydroxyvitamin D3. It is widely used for the treatment of plaque psoriasis. Calcipotriol may also be effective for skin conditions other than psoriasis.		C
Skin pigmentation disorders (pigmented lesions)
Application of vitamin D3 ointment on the skin, in combination with intense pulsed-radio frequency, may be beneficial in the treatment of pigmented lesions associated with neurofibromatosis 1 (NF1).		C
Tooth retention
Oral bone and tooth loss are correlated with bone loss at nonoral sites. Research suggests that intake levels of calcium and vitamin D aimed at preventing osteoporosis may have a beneficial effect on tooth retention.		C
Type 1 diabetes
It has been reported that infants given calcitriol during the first year of life are less likely to develop type 1 diabetes than infants fed lesser amounts of vitamin D. Other related studies have suggested using cod liver oil as a source of vitamin D to reduce the incidence of type 1 diabetes. There is currently insufficient evidence to form a clear conclusion in this area.		C
Type 2 diabetes
In recent studies, adults given vitamin D supplementation were shown to improve insulin sensitivity. Further research is needed to confirm these results.		C
Vitamin D deficiency (infants and nursing mothers)
High-quality clinical trial evidence suggests that high doses of supplemental vitamin D provided to breastfeeding mothers may improve the vitamin D status of both mother and child. More research is needed to confirm these findings.		C
Vitiligo (analogs)
The effectiveness of vitamin D analogs for vitiligo is controversial, and data are limited. Additional research is needed before a conclusion can be made.		C
Weight gain (postmenopausal)
Vitamin D supplementation (in combination with calcium) may have an effect on postmenopausal weight gain. Evidence suggests that this may be particularly true in women consuming inadequate calcium, and this warrants further research.		C

*Click here for more information on the Natural Standard grading system.

Tradition/Theory

The below uses are based on tradition, scientific theories, or limited research. They often have not been thoroughly tested in humans, and safety and effectiveness have not always been proven. Some of these conditions are potentially serious, and should be evaluated by a qualified healthcare provider. There may be other proposed uses that are not listed below.

  • Actinic keratosis, ankylosing spondylitis, atopic dermatitis, autism, autoimmune diseases (otosclerosis), bone loss (drug-induced), chemotherapy side effects (aromatase inhibitor-induced bone loss), dementia, ear infections, exercise performance, Graves' disease, hyperparathyroidism in renal dialysis, hypocalcemic tetany, inflammatory bowel disease, kidney transplant-related bone loss, knee osteoarthritis, learning disabilities, metabolic disorders (metabolic syndrome), metabolic syndrome (coronary heart disease), muscle atrophy, nervous system disorders (hemichorea), osteitis fibrosa in dialysis, pain, pre-eclampsia, psoriasis (native vitamin D), respiratory tract infections, rheumatoid arthritis, sarcoidosis, schizophrenia, scleroderma, spinal cord injury, stroke, systemic lupus erythematosus, systemic sclerosis, vaginal disorders (atrophy).

Dosing

The below doses are based on scientific research, publications, traditional use, or expert opinion. Many herbs and supplements have not been thoroughly tested, and safety and effectiveness may not be proven. Brands may be made differently, with variable ingredients, even within the same brand. The below doses may not apply to all products. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy.

Adults (18 years and older)

  • Vitamin D is included in most multivitamins, usually in strengths from 50 IU to 1,000 IU (international units), as softgels, capsules, tablets, and liquids. Since 2000, discrepancies have arisen regarding the benefits of vitamin D and how much is sufficient. The Institute of Medicine (IOM) has reviewed and updated the Dietary Reference Intakes (DRIs). The IOM found that there is strong evidence to support the use of vitamin D with calcium for bone health but that it was lacking for other health conditions. The new recommended daily allowance (RDA), as set in 2010, is based on age, as follows: for those 1-70 years of age, 600 IU daily; for those 71 years and older, 800 IU daily; and for pregnant and lactating women, 600 IU daily. Safety research supports an upper limit of a dose of vitamin D to be more than or equal to 250mcg daily (10,000 IU of vitamin D3).
  • Not all doses have been found to be effective for conditions that have been studied.
  • For deficiency, at least 1,000 IU (25 micrograms) of vitamin D has been taken by mouth daily (or 8,400 IU of vitamin D3 weekly). Other doses that have been studied include 50,000 IU daily for six weeks, 300,000 IU of oral vitamin D3 three times a year, 800 IU daily in combination with calcium, 400 IU daily, and 300,000 IU every three months. 300,000 IU of vitamin D has been used intramuscularly as bolus dose of vitamin D2 or D3, three times per year, and 600,000 IU (15 milligrams) of vitamin D has been used as single injections.
  • For anticonvulsant-induced osteomalacia, 2,000 IU of vitamin D2 has been taken by mouth daily plus 390 milligrams of calcium lactate daily for three months.
  • For cancer prevention, individuals taking 1,000 IU of oral vitamin D daily had a lower incidence of colon cancer.
  • For cardiovascular disease, 1,000 IU of vitamin D has been taken by mouth daily. Other doses that have been taken include approximately 528 IU of vitamin D2 or D3 daily.
  • For cognition, 528 IU of vitamin D2 or D3 has been taken by mouth daily.
  • For diabetes (type 2), 400-5714 IU of vitamin D has been taken by mouth daily (with or without calcium) for two months to seven years.
  • For fall prevention, more than 200-1,200 IU of vitamin D has been taken by mouth daily.
  • For fracture prevention, 400-1,100 IU of vitamin D has been taken by mouth daily, 100,000 IU of vitamin D2 has been taken by mouth every four months for 36 months, or 10 micrograms of vitamin D3 has been taken by mouth daily for 24 months. For fracture prevention, 300,000 IU of vitamin D2 every 12 months has been used intramuscularly for 36 months.
  • For hypertension (high blood pressure), 400-8,571 IU of vitamin D has been taken by mouth daily (with or without calcium) for various durations.
  • For hypocalcemia, 0.25 micrograms of calcitriol has been taken by mouth daily, and dosing may be increased by 0.25 micrograms daily at 4-8-week intervals.
  • For hypoparathyroidism, dihydrotachysterol has been taken by mouth at an initial dose of 750 micrograms (0.75 milligrams) to 2.5 milligrams daily for several days. A maintenance dose of 0.2-1 milligram has been taken by mouth daily. Ergocalciferol has been taken by mouth at a dose of 50,000-200,000 IU daily along with four grams of calcium lactate, six times daily.
  • For immunomodulation, the following doses have been taken by mouth: 40 IU of vitamin D3 daily for 20 years to 100,000 IU of vitamin D3 bimonthly for 12 months, or 10,000 IU daily.
  • For mood disorders, 400-800 IU daily or 100,000 IU weekly has been taken by mouth for up to one month to improve symptoms of depression associated with seasonal affective disorder. In obese patients, 20,000-40,000 IU of vitamin D has been taken by mouth per week for one year.
  • For multiple sclerosis, 10,000 IU has been taken by mouth daily for 12 weeks. Other doses of vitamin D taken by mouth include 5,000 IU daily (in the form of cod liver oil), progressive weekly increases of vitamin D3 (700 micrograms per week, escalating to 7,000 micrograms per week) plus 1,200 milligrams of calcium.
  • For muscle weakness or pain, 100,000 IU of calciferol has been taken by mouth daily for 12 months in patients with rheumatoid arthritis.
  • For osteoporosis, up to 5,714 IU of vitamin D3 or 10,000 IU of vitamin D2 has been taken by mouth daily, or up to 200,000 IU every two months for six months or up to 100,000 IU weekly has been used.
  • For parasitic infections, 40 IU of vitamin D has been taken by mouth daily for five days.
  • For physical performance in elderly subjects, 400 IU of vitamin D plus 800 milligrams of calcium has been taken by mouth daily. In older adults, 8,400 IU of vitamin D3 has been taken by mouth weekly for 16 weeks.
  • For psoriasis, the vitamin D analog calcipotriene has been used topically twice daily.
  • For respiratory infections, 2,000 IU per kilogram of body weight has been taken by mouth daily for three days.
  • For rheumatoid arthritis, 50,000 IU of vitamin D has been taken by mouth weekly for 12 weeks.
  • For senile warts, vitamin D analogs have been applied topically in ointments for up to 12 months.
  • For tuberculosis, a single dose of 10,000 IU of vitamin D2 has been taken by mouth.
  • For viral infections, 800 IU of vitamin D has been taken by mouth daily for two years, followed by 2,000 IU of vitamin D daily for 12 months.
  • For vitiligo, calcipotriol ointment has been used topically twice daily.

Children (under 18 years old)

  • Since 2000, discrepancies have arisen regarding the benefits of vitamin D and how much to take. The Institute of Medicine (IOM) has reviewed and updated the Dietary Reference Intakes (DRIs). In 2008, the American Academy of Pediatrics (AAP) increased its recommended daily intake of vitamin D in infants, children, and adolescents to 400 IU. Exclusively breastfed infants who do not consume less than 1L of vitamin D-fortified milk daily will likely need supplementation to reach 400 IU of vitamin D daily. Although the AAP advises against keeping children in direct sunlight exposure, this may increase the risk of vitamin D deficiency. However, the IOM found that there is strong evidence to support the use of vitamin D with calcium for bone health but that it was lacking for other health conditions. The new recommended daily allowance (RDA), as set in 2010, is based on age, as follows: for those 1-70 years of age, 600 IU daily; for infants aged 0-12 months, the upper level intake is 1,000 IU daily. Other research confirms these recommendations.
  • Not all doses have been found effective for conditions that have been studied.
  • Rickets may be treated gradually over several months or in a single day's dose. Based on one clinical trial, a single dose of 600,000 IU of oral vitamin D3 was comparable to a dose of 20,000 IU of oral vitamin D3 daily for 30 days. Gradual dosing may be 125-250 micrograms (5,000-10,000 IU) taken daily for 2-3 months, until recovery is well established and the alkaline phosphatase blood concentration is close to normal limits. Single-day dosing may be 15,000 micrograms (600,000 IU) of vitamin D, taken by mouth divided into 4-6 doses. Intramuscular injection is also an alternative for single-day dosing. For resistant rickets, some authors suggest a higher dose of 12,000 to 500,000 IU daily.
  • For anticonvulsant-induced osteomalacia, 2,000 IU of vitamin D2 has been taken by mouth daily plus 500 milligrams of calcium for three months.
  • For deficiency, 2.5 milligrams of vitamin D has been taken by mouth every three months as prophylaxis during infancy.
  • For tuberculosis (TB), 1,000 IU of vitamin D has been taken by mouth in combination with standard TB therapy.
  • For type 1 diabetes, 2,000 IU of vitamin D taken by mouth daily for a year was associated with a reduced risk of type 1 diabetes.
  • For viral infection, 60,000 IU has been taken by mouth weekly for six weeks.

Safety

The U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy. Consult a healthcare provider immediately if you experience side effects.

Allergies

  • Avoid with known allergy/hypersensitivity to vitamin D, any of its analogs and derivatives, or any component of the formulation.

Side Effects and Warnings

  • Vitamin D is generally well tolerated in recommended "adequate intake (AI)" doses.
  • The Institute of Medicine (IOM) released a report on November 30, 2010, recommending vitamin D upper intake levels (UL) of 3,000 IU for those less than nine years old and 4,000 IU for those over nine years old. According to the Institute of Medicine, recommended upper intake levels (ULs) of vitamin D are 1,000 IU for ages 0-6 months, 1,500 IU for ages 7-12 months, 2,500 IU for ages 1-3 years, 3,000 IU for ages 4-8 years, and 4,000 IU for those over age nine. A clinical review has suggested the use of 250mcg (10,000 IU) of vitamin D3 daily as the UL, based on the lack of observed toxicity in adult trials.
  • Excess vitamin D intake may increase the risk of falls or fractures. Other potential adverse effects include increased risk of urinary tract infections, decreased appetite, weight loss, an elevated international normalized ratio, hypercalcemia (increased calcium in the blood), hypercalciuria (increased calcium in the urine), hypervitaminosis D (high blood levels of vitamin D), elevated creatinine levels, gastrointestinal complaints, and increased cancer risk.
  • Vitamin D toxicity can result from regular excess intake of this vitamin and may lead to hypercalcemia, hypercalciuria, and excess bone loss. Individuals at particular risk include those with hyperparathyroidism (overactive parathyroids), kidney disease, sarcoidosis, tuberculosis, or histoplasmosis (examples of immune disorders). Chronic hypercalcemia may lead to serious or even life-threatening complications and should be managed by a physician. Early symptoms of hypercalcemia may include nausea, vomiting, and anorexia (appetite or weight loss), followed by polyuria (excess urination), polydipsia (excess thirst), weakness, fatigue, somnolence, headache, dry mouth, a metallic taste, vertigo (dizziness), tinnitus (ear ringing), and ataxia (unsteadiness). Kidney function may become impaired, and metastatic calcifications (calcium deposition in organs throughout the body) may occur, particularly affecting the kidneys. Treatment involves stopping the intake of vitamin D or calcium and lowering the calcium levels under strict medical supervision, with frequent monitoring of calcium levels. Acidification of urine and corticosteroids may be necessary. To return vitamin D levels to normal, the supplement is discontinued.
  • One study found a greater likelihood of daytime sleepiness for patients given vitamin D analogs. Other adverse effects associated with topical vitamin D analogs include coronary and vascular calcification. Topical vitamin D analogs may be associated with contact dermatitis and skin irritation.
  • Vitamin D may lower blood sugar levels. Caution is advised in patients with diabetes or hypoglycemia and in those taking drugs, herbs, or supplements that affect blood sugar. Blood glucose levels may need to be monitored by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
  • Vitamin D may cause low blood pressure. Caution is advised in patients taking herbs or supplements that lower blood pressure.
  • Use cautiously in patients with liver disease, as vitamin D is metabolized in the liver.
  • Use cautiously in patients with hyperparathyroidism, as vitamin D may increase calcium levels.
  • Use cautiously in patients with kidney disease, as vitamin D may increase calcium levels and increase the risk of arteriosclerosis.
  • Use cautiously in patients with granulomatous disorders (a type of immune disorder), which are associated with calcium metabolism disorder. Theoretically, concurrent use of high amounts of vitamin D in these patients may increase the risk of hypercalcemia (increased calcium in the blood) and kidney stones.
  • Use cautiously in mothers who are receiving vitamin D supplements and are breastfeeding, as there may be an increased risk of urinary tract infection, particularly in the first three months.
  • Avoid in individuals with known allergy to vitamin D or with vitamin D hypersensitivity syndromes.
  • Avoid in patients with hypercalcemia (high blood calcium levels), due to the potential for increased blood calcium levels.

Pregnancy and Breastfeeding

  • Many pregnant women around the world have been found to be vitamin D deficient. The recommended adequate intake for pregnant women is the same as for nonpregnant adults. Most prenatal vitamins provide 400 IU daily of vitamin D as cholecalciferol. Some authors have suggested that requirements during pregnancy may be greater than these amounts, particularly in sun-deprived individuals, although this has not been clearly established. Risk factors for developing vitamin D deficiency during pregnancy include darker pigmentation, sunscreen use, clothing, latitude, seasons, obesity, race, ethnicity, and low intake of fortified vitamin D milk intake. Due to risks of vitamin D toxicity, any consideration of higher daily doses of vitamin D should be discussed with a physician. Vitamin D deficiency may increase complications in the mother and infant.
  • In mothers who are receiving vitamin D supplements and are breastfeeding, there may be an increased risk of urinary tract infection, particularly in the first three months.
  • Vitamin D is typically low in maternal milk, and to prevent deficiency and rickets in exclusively breastfed infants, supplementation may be necessary, starting within the first two months of life. Many lactating women have been found to be vitamin D deficient.

Interactions

Most herbs and supplements have not been thoroughly tested for interactions with other herbs, supplements, drugs, or foods. The interactions listed below are based on reports in scientific publications, laboratory experiments, or traditional use. You should always read product labels. If you have a medical condition, or are taking other drugs, herbs, or supplements, you should speak with a qualified healthcare provider before starting a new therapy.

Interactions with Drugs

  • Hypermagnesemia (high blood magnesium levels) may develop when magnesium-containing antacids are used concurrently with vitamin D, particularly in patients with chronic renal failure.
  • Decreased vitamin D effects may occur with the use of certain antiseizure drugs, as they may induce liver enzymes and accelerate the conversion of vitamin D to inactive metabolites.
  • Based on mechanism of action, use of vitamin D and calcium together may alter inflammatory response. Vitamin D may increase calcium absorption.
  • Patients taking antilipemic agents (such as cholestyramine or colestipol) or mineral oil should be advised to allow as much time as possible between the ingestion of these drugs and vitamin D. Intestinal absorption of vitamin D may be impaired with the use of these agents.
  • Use of corticosteroids can cause osteoporosis and calcium depletion with long-term administration. This calcium depletion creates a greater need for both supplemental calcium and vitamin D (which is necessary for calcium absorption).
  • Vitamin D should be used with caution in patients taking digoxin, because hypercalcemia (which may result with excess vitamin D use) may precipitate abnormal heart rhythms.
  • Orlistat (an obesity drug) can reduce vitamin D levels. Patients should consider taking a multivitamin with fat-soluble vitamins at least two hours before or after orlistat or at bedtime.
  • Rifampin increases vitamin D metabolism and reduces vitamin D blood levels. The need for vitamin D supplementation with rifampin has not been thoroughly studied, although additional supplementation may be necessary.
  • Stimulant laxatives can reduce dietary vitamin D absorption. Stimulant laxatives should be limited to short-term use if possible.
  • Concurrent administration of thiazide diuretics and vitamin D to hypoparathyroid patients may cause hypercalcemia, which may be transient or may require discontinuation of vitamin D. Examples of thiazide diuretics include chlorothiazide (Diuril®), chlorthalidone (Hygroton®, Thalitone®), hydrochlorothiazide (HCTZ®, Esidrix®, HydroDIURIL®, Ortec®, Microzide®), indapamide (Lozol®), and metolazone (Zaroxolyn®).
  • Vitamin D may lower blood sugar levels. Caution is advised when using medications that may also lower blood sugar. Patients taking insulin or drugs for diabetes by mouth should be monitored closely by a qualified healthcare professional, including a pharmacist. Medication adjustments may be necessary.
  • Vitamin D may interfere with the way the body processes certain drugs using the liver's cytochrome P450 enzyme system. As a result, the levels of these drugs may be increased or decreased in the blood, altering effects or causing potentially serious adverse reactions. Patients using any medications should check the package insert and speak with a qualified healthcare professional, including a pharmacist, about possible interactions.
  • Vitamin D may cause low blood pressure. Caution is advised in patients taking drugs that lower blood pressure.
  • Various agents may be enhanced when used with vitamin D or vitamin D analogs. These include acitretin, bisphosphonates, and other drugs used for osteoporosis, cyclosporine, hormonal agents, and vitamin D analogs (including calcipotriene).
  • Use of vitamin D may reduce the need for analgesics (pain-reducing agents).
  • Use of vitamin D may increase aluminum absorption.
  • Vitamin D levels may be reduced following use of various agents, including cimetidine, heparin, opiates, sevelamer, and sunscreens.
  • Vitamin D may also interact with antiasthmatics, anticancer agents, anti-inflammatory agents, calcium channel blockers (e.g., diltiazem), calcium salts, cardiac glycosides, cinacalcet, contraceptives, immune suppressants, ketoconazole, tar-based shampoos, vaccines, or vitamin D receptor agonists.

Interactions with Herbs and Dietary Supplements

  • Based on mechanism of action, the use of vitamin D and calcium together may alter inflammatory response.
  • Vitamin D is necessary for calcium absorption. Vitamin D is often included in calcium supplement products.
  • Vitamin D should be used with caution in patients taking cardiac glycoside herbs with similar effects on the heart as digoxin, because hypercalcemia (which may result with excess vitamin D use) may cause abnormal heart rhythms.
  • Vitamin D increases magnesium absorption.
  • Vitamin A may interfere with the absorption of vitamin D.
  • Vitamin D may lower blood sugar levels. Caution is advised when using herbs or supplements that may also lower blood sugar. Blood glucose levels may require monitoring, and doses may need adjustment.
  • Vitamin D may interfere with the way the body processes certain herbs or supplements using the liver's cytochrome P450 enzyme system. As a result, the levels of other herbs or supplements may become too high or too low in the blood. It may also alter the effects that other herbs or supplements possibly have on the cytochrome P450 system.
  • Vitamin D may cause low blood pressure. Caution is advised in patients taking herbs and supplements that lower blood pressure.
  • Use of vitamin D may reduce the need for analgesics (pain-reducing agents).
  • Use of vitamin D may increase aluminum absorption.
  • Vitamin D may also interact with antacids, antiasthmatics, anticancer agents, anticonvulsants, anti-inflammatory agents, antilipemics (blood cholesterol-reducing agents), cod liver oil, diuretics, fortified vitamin D foods, herbs and supplements that decrease calcium, herbs and supplements with contraceptive properties, hormonal herbs and supplements, immune suppressant herbs and supplements, laxatives, micronutrients, mineral oil, osteoporosis herbs and supplements, silicon, sunscreens, and vitamin K.

Categorized Under

Natural Standard

This information is based on a systematic review of scientific literature edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).
 
Natural Standard Bottom Line Monograph, Copyright © 2013 (www.naturalstandard.com). Commercial distribution prohibited. This monograph is intended for informational purposes only, and should not be interpreted as specific medical advice. You should consult with a qualified healthcare provider before making decisions about therapies and/or health conditions.
 
While some complementary and alternative techniques have been studied scientifically, high-quality data regarding safety, effectiveness, and mechanism of action are limited or controversial for most therapies. Whenever possible, it is recommended that practitioners be licensed by a recognized professional organization that adheres to clearly published standards. In addition, before starting a new technique or engaging a practitioner, it is recommended that patients speak with their primary healthcare provider(s). Potential benefits, risks (including financial costs), and alternatives should be carefully considered. The below monograph is designed to provide historical background and an overview of clinically-oriented research, and neither advocates for or against the use of a particular therapy.

References

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

1. Autier P, Gandini S. Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med. 2007;167(16):1730-1737.

2. Cameron ID, Murray GR, Gillespie LD, et al. Interventions for preventing falls in older people in nursing care facilities and hospitals. Cochrane Database Syst Rev. 2010;(1):CD005465.

3. Goldstein MR. Myopathy, statins, and vitamin D deficiency. Am J Cardiol. 2007;100(8):1328. Comment on: Am J Cardiol. 2007;99(8):1171-1176.

4. Gorham ED, Garland CF, Garland FC, et al. Optimal vitamin D status for colorectal cancer prevention: a quantitative meta analysis. Am J Prev Med. 2007;32(3):210-216.

5. Helfrich YR, Kang S, Hamilton TA, et al. Topical becocalcidiol for the treatment of psoriasis vulgaris: a randomized, placebo-controlled, double-blind, multicentre study. Br J Dermatol. 2007;157(2):369-374.

6. Izaks GJ. Fracture prevention with vitamin D supplementation: considering the inconsistent results. BMC Musculoskelet Disord. 2007;8:26.

7. Kriegel MA, Manson JE, Costenbader KH. Does vitamin d affect risk of developing autoimmune disease?: a systematic review. Semin Arthritis Rheum. 2011;40(6):512-531.e8.

8. Lyons RA, Johansen A, Brophy S, et al. Preventing fractures among older people living in institutional care: a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation. Osteoporos Int. 2007;18(6):811-818.

9. Pittas AG, Lau J, Hu FB, et al. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007;92(6):2017-2029.

10. Robien K, Cutler GJ, Lazovich D. Vitamin D intake and breast cancer risk in postmenopausal women: the Iowa Women's Health Study. Cancer Causes Control. 2007;18(7):775-782.

11. Sanabria A, Dominguez LC, Vega V, et al. Routine postoperative administration of vitamin D and calcium after total thyroidectomy: a meta-analysis. Int J Surg. 2011;9(1):46-51.

12. Straube S, Derry S, Moore RA, et al. Vitamin D for the treatment of chronic painful conditions in adults. Cochrane Database Syst Rev. 2010;(1):CD007771.

13. Tau C, Ciriani V, Scaiola E, et al. Twice single doses of 100,000 IU of vitamin D in winter is adequate and safe for prevention of vitamin D deficiency in healthy children from Ushuaia, Tierra Del Fuego, Argentina. J Steroid Biochem Mol Biol. 2007;103(3-5):651-654.

14. Wagner CL, Greer FR. Section on Breastfeeding and Committee on Nutrition. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. 2008;122(5):1142-1152.

15. Winzenberg T, Powell S, Shaw KA, Jones G. Effects of vitamin D supplementation on bone density in healthy children: systematic review and meta-analysis. BMJ. 2011;342:c7254.

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