Vitamin D consists of a group of similar molecules called vitamers, which are involved in calcium homeostasis and in bone metabolism.
The human body makes vitamin D by the effects of ultraviolet light on the skin’s cholecalciferol also known as D3. Plants make a slightly different version of vitamin D called D2; however this form of vitamin D can also be used by humans.
Since vitamin D works on specific target tissues, and does not have to be supplied by the diet, it is by definition a hormone, and not truly a vitamin. Vitamin D hormone usually functions as a steroid.
Vitamin D is best absorbed when ingested with lipids. Vitamin D will be incorporated into micelles and these will be absorbed by the intestine by passive diffusion. In the intestinal cells, chylomicrons will be formed, and these will enter the lymphatic system and enter the plasma. Vitamin D will then be transported to the liver by chylomicron remnants and to specific target with the help of carrier vitamin D binding protein (DBP) or transcalciferin.
D3 will change into its biologically active forms: 25-(OH) D3 and 1, 25-(OH) 2D3 also known as calcitriol. In the liver vitamin D will undergo sequential hydrolxylations which will result in 25-hydroxycholecalciferol. In the kidney, vitamin D will be acted upon by alpha 1 hydroxylase and this will yield 1, 25 dihydroxyvitamin D3 (or calcitriol).
Calcitriol is the predominant form of vitamin D found in the circulation. And the production of calcitriol is regulated by enzymes which lead to a feedback inhibition mechanism. Efficacy of absorption for vitamin D is 50% from the diet.
Vitamin D plays an important role in calcium and phosphorus homeostasis by regulating bone resorption, affecting absorption of calcium in the gut, and by regulating calcium losses in urine.
In the kidney vitamin D works with estrogen to regulate renal tubular reabsorption of calcium and phosphorus.In bones, vitamin D works in conjunction with PTH to regulate the release of calcium and phosphorus from the bones into the bloodstream.
Vitamin D also plays a genetic role by regulating the gene coding for calcium binding protein known as Calbindin.
Vitamin D’s genetic role has been confirmed in over 50 genes extending beyond balancing mineral metabolism. New findings have confirmed direct effects by vitamin D on various nuclear receptors of different cells such as those of the prostate, liver, thyroid, and brain.
Cells of the prostate gland respond to vitamin D levels. These findings have lead to new potential chemotherapeutic treatments targeting specific lesions on cancer cells using doses of 1alpha25 (OH) 2D3.
Another group of cells directly affected by vitamin D levels appear to be the T helper cells of the immune system.
Polymorphisms in vitamin D receptors in brain cells, (due to low levels of vitamin D early in life), also appear to be linked to schizophrenia. This new information has also lead to further research by the scientific community.
In light of the recent findings many experts and professional associations have recommended an increase in the recommended amount of vitamin D intake. Most experts call for an increase in of vitamin D intake to 1000 IU for an adult which is substantially higher than the currently recommended of 200 IU. Increases in both the recommended dose as well as in the upper tolerable intakes are currently under review by the Institute of Medicine and changes in favor of increases are expected by the scientific community. Vitamin D: Dietary Reference Intake 1
mcg/day
IU/d
Tolerable Upper Intake Levels (UL) mcg/day*
Infants* 0 to 6 months 7 to 12 months
5 5
200 200
25 25
Children 1 to 3 years 4 to 8 years
5 5
200 200
50 50
Males/Females 9 to 18 years 19 to 70 years 51 to 70 years > 70 years
5 5 10 15
200 200 400 600
50 50 50 50
Pregnancy <= 18 years 19 to 30 years 31 to 50 years
5 5
200 200
50 50
Lactation <= 18 years 19 to 30 years 31 to 50 years
Vitamins D deficiency is relatively common in the U.S. Studies have demonstrated that nearly 60% of people over 70 years are vitamin D deficient. Furthermore, the average daily intake of vitamin D in the United States is only 30% of the RDA.
Symptoms of vitamin D deficiency include Rickets in children and osteomalacia in adults resulting from poor ossification of bone tissue, resulting in weak bones that bend readily.
Symptoms in adults include painful softening and bending of bones, low serum calcium concentrations and tetany. Less severe vitamin D deficiency can result in hyperparathyroidism and increased bone turnover leading to bone loss and osteoporosis.
A vitamin D deficiency can result from inadequate intake, limited exposure to sunlight, kidney and/or liver dysfunctions which inhibit conversion of vitamin D to its metabolically active forms, or fat-malabsorption syndromes
Symptoms of toxicity include loss of appetite, excessive thirst, nausea, vomiting, irritability, weakness and weight loss, however these are not commonly seen. These symptoms were seen during decades when parents would give their children massive doses of cold liver oil to prevent rickets.
The only frequently consumed dietary source of vitamin D is milk fortified with D2, as well as dried whole milk. Cereals, infant formulas, including soy, are usually also fortified with vitamin D. Cod liver oil and fatty fish oils are also excellent sources of vitamin D.
Dark skinned individuals are at risk. NHANES III reported a high prevalence of vitamin D deficiency among African American women. The results reflected that 41% of African American women between the ages 15-49 were vitamin D deficient.
Due to the skin’s decreased capacity to synthesize vitamin D3 in the elderly, people over age of 70 are at particularly high risk for developing vitamin D deficiency. (The capacity of skin to synthesize vitamin D3 in these later years is approximately half what it is in younger people).
Breastfed infants who ingest only breast milk and no supplements: Human milk contains approximately 25 IU/L or less of vitamin D, which is not enough to meet the infant’s needs. Therefore supplementation of vitamin D is recommended for all breastfed infants within the first 2 months of life. (Conversely, all infant formulas sold in the United States contain at least 400 IU of vitamin D).
Vegetarians are also at risk for vitamin D deficiency
Obese individuals are also at high risk of vitamin D deficiency. Though the skin is able to manufacture vitamin D normally, it is not able to enter into the circulation as well as it does in non-obese persons.
Use of alcohol may alter absorption of vitamin D and may lead to deficiency.
Smoking may increase the rate of bone turnover, therefore increasing the requirement of vitamin D.
Vitamin D supplements are also recommended for individuals shielded from sunlight, those who are homebound, for those who reside in northern latitudes or in areas of high atmospheric pollution. In addition they are also recommended for those individuals who routinely dress in clothing which covers their entire body, for those who work night-shifts, or who tend to spend the majority of their day indoors.
Warfarin [Coumadinâ], an anticoagulant drug, may decrease the absorption of vitamin D.
The chronic use of laxatives that contain mineral oil can reduce the intestinal absorption of many nutrients, including vitamin D. This action may be due to an increase in motility or a direct inhibition of absorption. Excessive use of mineral oil-containing drugs should be limited when taking vitamin D.
Substances that bind bile in the intestine such as bile acid sequestrants (cholestyramine [Questranâ] and colestipol [Colestidâ] also reduce absorption of vitamin D. Patients using these drugs should adhere to timing regimens set by a medical expert in order to maximize efficacy. IM ergocalciferol supplements may be required.
Concurrent administration of thiazide diuretics, used for symptoms of edema and hypertension, and vitamin D analogs in patients with hypoparathyroidism may result in hypercalcemia. Hypercalcemia in these patients results from increased bone resorption.
Anticonvulsant drugs such as Phenobarbital [Luminalâ] and phenytoin [Dilantinâ] may reduce the plasma concentrations of vitamin D by inhibiting enzyme activity in the liver and by preventing the conversion of the vitamin to its active form. Long-term use can lead to vitamin D deficiency and eventually bone loss.
The concentrations of magnesium-containing antacids, such as aluminum/magnesium hydroxide [Maaloxâ] and aluminum/ magnesium hydroxide/simethicone [Mylantaâ], are increased by vitamin D
Vitamin D may cause hypocalcaemia in patients on digitalis [Lanoxinâ], a cardiac drug. This may precipitate cardiac arrhythmias. Taking dietary calcium or supplements may be advisable.
Ketoconazole [Nizoralâ], an antifungal agent, may inhibit vitamin D synthetic and catabolic enzymes. Reductions in serum endogenous vitamin D concentrations have been observed following the administration of 300 to 1200 mg/day ketoconazole for a week to healthy men and calcium and vitamin D supplementation may be necessary in these cases.
Vitamin D may interfere with the effectiveness of verapamil [Isoptinâ], a calcium-channel blocker, which is used to lower high blood pressure. During this therapy, patients should consult their doctors before using vitamin D-containing supplements. Long-term therapy (longer than 2 weeks) with corticosteroids, anti-inflammatory drugs, reduces the body's ability to activate vitamin D, increasing the rate of bone loss.
Orlistat [Xenicalâ], a weight loss agent, may decrease the gastrointestinal absorption of fat-soluble vitamins such as vitamin D. An interval of at least two hours (before or after) between Orlistat and vitamin D analog administration is recommended. However, taking multivitamins including fat-soluble vitamins did not decrease drug concentrations in clinical studies.
Information on the relationship between substances and disease is provided for general information, in order to convey a balanced review of the scientific literature. In many cases the relationship between a substance and a disease is tentative and additional research is needed to confirm such a relationship.
Putting cardiovascular disease and vitamin D insufficiency into perspective
This review article summarizes data supporting the hypothesis that an insufficient vitamin D status may contribute to the worldwide high prevalence of CVD. It examines several potential mechanisms by which vitamin D can have a protective effect, including inhibition of vascular smooth muscle proliferation, suppression of vascular calcification, and the regulation of cytokines affecting inflammation.5
Vitamin D and disease prevention with special reference to cardiovascular disease
This article analyzes the relationship between circulating 25-hydroxyvitamin D [25(OH)D] and the link to cardiovascular disease. Authors find a correlation between vitamin D levels and morbidity and mortality and call for appropriately increased recommendations for this nutrient.6
Vitamin D supplementation improves cytokine profiles in patients with congestive heart failure: a double-blind, randomized, placebo-controlled trial
One hundred twenty-three patients randomly received either 50 mug vitamin D(3)/d plus 500 mg Ca/d [D(+) group] or placebo plus 500 mg Ca/d [D(-) group] for 9 mo. End results suggest Vitamin D(3) reduces the inflammatory milieu in CHF patients and might serve as a new anti-inflammatory agent for the future treatment of the disease.7
Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women's Health Study
A prospective cohort study of 29,368 women of ages 55-69 years without a history of RA at study baseline. Through the 11 year follow up there were 152 confirmed cases of RA. Results showed that greater intake (highest versus lowest tertile) of vitamin D was inversely associated with risk of RA (RR 0.67, 95% CI 0.44-1.00, P for trend = 0.05) 8
Vitamin D and its role in immunology: Multiple sclerosis, and inflammatory bowel disease.
An analysis done on identical twins observes the relationship between genetics, environmental factors, and autoimmune disease on identical twins. Findings suggest a regulatory effect by vitamin D on T cells. 9
Vitamin D supplement in early childhood and risk for Type I (insulin-dependent) diabetes mellitus. The EURODIAB Substudy 2 Study Group.
A case-control study focusing on early exposures and risk of Type I diabetes. Altogether data from 820 patients and 2335 control subjects were analyzed. The findings indicate that activated vitamin D might contribute to immune modulation and thereby protect or arrest an ongoing immune process initiated in susceptible people by early environmental exposures.10
Mounting evidence for vitamin D as an environmental factor affecting autoimmune disease prevalence
Excellent review of the relationship between vitamin D status and it’s etiology in a variety of autoimmune disorders such as rheumatoid arthritis, multiple sclerosis, diabetes type 1, and inflammatory bowel disease. 11
Cytokine profile in patients with multiple sclerosis following vitamin D supplementation.
A randomized double-blind study was conducted on multiple sclerosis (MS) patients who either received 800 mg of supplemental calcium plus placebo (control), or 800 mg supplemental calcium plus 1000 IU vitamin D (treatment). After 6 months of vitamin D supplementation, serum vitamin D concentrations increased significantly from baseline in MS patients. Overall results suggest that vitamin D supplementation may be helpful to patients with multiple sclerosis. 12
Concentrations of Serum Vitamin D and the Metabolic Syndrome Among U.S. Adults
Cross sectional analysis including 8421 men and non-pregnant women. The mean concentration of 25(OH)D was 67.1 nmol/l (median 64.1 [range 12.5–192.2]) among those with the metabolic syndrome and 75.9 nmol/l (73.1 [8.7–227.9]) among those without the metabolic syndrome (P < 0.001). End results present significant inverse associations for quintiles of concentration of 25(OH)D and abdominal adiposity, hypertriglyceridemia, and hyperglycemia. 13
A study of 19 healthy whites of normal body weight [body mass index (BMI; in kg/m2) 25] and 19 healthy, obese subjects (skin types II and III; BMI > 30). Both groups received UV irradiation as well as the same dose of vitamin D (5000 IU). End results showed increase in blood vitamin D3 concentrations was 57% less in the obese than in the non-obese subjects 24 h after the exposure. 14
Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis
Clinical Nutrition SPECIAL ARTICLE Vitamin D: importance in the prevention of cancers, type 1 diabetes, heart disease, and chronic diseases. This publication reviews various dose recommendations for vitamin D and concludes that a healthy dose is one which results in a 78-100 nmol/L concentration of 25(OH)D. The conclusion is that an adequate dose of vitamin D is alternatively, one multivitamin containing 400 IU vitamin D and a vitamin D supplement containing either 400 or 1000 IU vitamin D is appropriate. 15
A study of 19 healthy whites of normal body weight [body mass index (BMI; in kg/m2) 25] and 19 healthy, obese subjects (skin types II and III; BMI > 30). Both groups received UV irradiation as well as the same dose of vitamin D (5000 IU). End results showed increase in blood vitamin D3 concentrations was 57% less in the obese than in the non-obese subjects 24 h after the exposure. 14
Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third National Health and Nutrition Examination Survey, 1988–1994.
Involved 1546 African American women and 1426 white women aged 15–49 y who participated in the third National Health and Nutrition Examination Survey. Results showed that among African Americans, hypovitaminosis D was independently associated with consumption of milk or breakfast cereal, no use of vitamin D supplements, season, urban residence, low body mass index, and no use of oral contraceptives. 17
Vitamin D, Calcium Supplementation, and Colorectal Adenomas: Results of a Randomized Trial
Involved 803 subjects in a multi-center, placebo-controlled randomized clinical trial which also measured levels of Serum levels of 25-hydroxy [25-(OH)] vitamin D and 1,25-dihydroxy [1,25-(OH)2] vitamin D levels were determined. Calcium supplementation and vitamin D status appear to act largely together, not separately, to reduce the risk of colorectal adenoma recurrence. 18
Circulating Vitamin D Metabolites, Polymorphism in Vitamin D Receptor, and Colorectal Adenoma Risk
Cases with advanced adenoma of the distal large bowel and gender- and ethnicity-matched controls with a negative sigmoidoscopy were randomly selected from participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. End results suggest that higher serum 25(OH)D levels were associated with decreased adenoma risk, and serum 1,25(OH)2D and VDR Taq (vitamin D receptor) genotype were not associated with adenoma risk. 19
Analysis of 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. Overall evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects. 20
Dose-response gradients from observational studies of Vitamin D intake and serum 25-hydroxyvitamin D were analyzed by plotting them as trend lines. Results suggest that intake of 1000IU/day of Vitamin D, half the safe upper intake established by the National Academy of Sciences, was associated with 50% lower risk. Serum 25-hydroxyvitamin D of 33ng/ml, which is known to be safe, also was associated with 50% lower risk. 21
Based on 5 randomized controlled trials involving 1237 participants, vitamin D reduced the corrected odds ratio (OR) of falling by 22% (corrected OR, 0.78; 95% confidence interval [CI], 0.64-0.92) compared with patients receiving calcium or placebo. From the pooled risk difference, the number needed to treat (NNT) was 15 (95% CI, 8-53), or equivalently 15 patients would need to be treated with vitamin D to prevent 1 person from falling.22
The dietary supplement information contained on this site has been compiled from published sources thought to be reliable, but it cannot be guaranteed. Efforts have been made to assure this information is accurate and current. However, some of this information may be purported or outdated due to ongoing research or discoveries. The authors, editors and publishers cannot accept responsibility for errors or omissions or for any consequences from applications of the information in this site and make no warranty, expressed or implied, with respect to the contents herein.
Print this page
Contact an Expert
Herbs
