Table of Contents > Interactions & Depletions > Vitamin D Print

Vitamin D



Interactions

Vitamin D/Drug Interactions:
  • AcitretinAcitretin: In human research, the effects of acitretin were enhanced with the addition of topical calcipotriene, a synthetic derivative of vitamin D used for psoriasis (380).
  • AluminumAluminum: In animal research and clinical review, the calcium transport protein calbindin-D28k, which transports aluminum, was stimulated by vitamin D and may therefore increase aluminum absorption (381; 382; 383).
  • AnalgesicsAnalgesics: In a systematic review, vitamin D resulted in reduced need for analgesics (312).
  • AntacidsAntacids: Hypermagnesemia (high blood magnesium levels) may develop when magnesium-containing antacids are used concurrently with vitamin D, particularly in patients with chronic renal failure.
  • AntiasthmaticsAntiasthmatics: According to a review, vitamin D inhibited the influx of inflammatory cytokines in the lungs and increased the secretion of interleukin-10 by T-regulatory cells and dendritic cells (93). Experts have suggested that vitamin D supplementation in patients with asthma may improve the severity of the disease and improve treatment (384).
  • AnticonvulsantsAnticonvulsants: In human research, certain anticonvulsant agents (e.g., carbamazepine, phenobarbital, and phenytoin) have been shown to decrease levels of vitamin D (385; 386; 387; 388; 389) by inducing hepatic conversion of vitamin D to inactive metabolites. Concurrent use of vitamin D and anticonvulsant agents has also been found to improve bone health vs. anticonvulsants alone (390; 391).
  • Antidiabetic agentsAntidiabetic agents: According to clinical review and human research, vitamin D may lower blood glucose and hemoglobin A1C (38; 276; 392). Theoretically, concurrent use with antidiabetic agents may increase the risk of hypoglycemia. However, results are not consistent (393; 394).
  • AntihypertensivesAntihypertensives: According to secondary sources, vitamin D may lower blood pressure (38). Theoretically, concurrent use with antihypertensive agents may increase the risk of hypotension. However, another study has found no effect (393). In human research, hypertension treated with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker were associated with low 25-hydroxyvitamin D(3) levels (395).
  • Anti-inflammatory agentsAnti-inflammatory agents: Based on mechanism of action, use of vitamin D and calcium together may alter inflammatory response. In human research, vitamin D in combination with nonsteroidal anti-inflammatory drugs (NSAIDs) reduced the risk of colorectal adenoma more strongly than vitamin D alone (124)
  • Antilipemic agents, bile acid sequestrantsAntilipemic agents, bile acid sequestrants: Intestinal absorption of vitamin D may be impaired with the use of bile acid sequestrants (cholestyramine, colestipol) (396; 397; 398; 399).
  • Antilipemic agents, HMG-CoA reductase inhibitorsAntilipemic agents, HMG-CoA reductase inhibitors: In human research, the effects of HMG-CoA reductase inhibitors ("statins") on vitamin D levels were mixed but may improve cholesterol levels (400; 401; 402; 403; 404). In human research, vitamin D supplementation lowered concentrations of atorvastatin and its metabolites, likely due to induction of CYP450 3A4; a synergistic effect on cholesterol lowering was also noted (402). In other human research, atorvastatin increased vitamin D levels and also improved cholesterol levels (403). This increase could explain some of the beneficial effects of atorvastatin at the cardiovascular level that are unrelated to cholesterol levels. In vivo, pretreatment with vitamin D had favorable effects on bone metabolism and formation in patients with heterozygous familial hypercholesterolemia and with pretreatment vitamin D levels >50pg/mL (405). However, other research has found no effect (393).
  • AntineoplasticsAntineoplastics: According to secondary sources, in vitro, vitamin D, specifically calcitriol (1,25-dihydroxyvitamin D(3), the most active form of vitamin D), enhanced cell differentiation, inhibited cell proliferation, stimulated apoptosis, suppressed inflammation, and inhibited tumor angiogenesis, invasion, and metastasis (406; 407; 408).
  • BisphosphonatesBisphosphonates: In human research, concurrent use of vitamin D with bisphosphonates may have added benefit and further increase bone mineral density (BMD) over bisphosphonates alone (409; 410; 411; 412; 40; 413; 414). It may also provide added benefit in cancer treatment, according to human research (415). Clinical trials involving bisphosphonates often include vitamin D and calcium and are compared with vitamin D and calcium alone (416).
  • CalcipotrieneCalcipotriene: Calcipotriene, a vitamin D analog, may be systemically absorbed and cause effects such as hypercalcemia. Theoretically, combined used with vitamin D may increase the risk of adverse effects such as hypercalcemia.
  • Calcium saltsCalcium salts: Vitamin D is essential for the utilization of calcium in the body. It regulates and enhances absorption efficiency of calcium (417; 418; 419; 420). In human research, calcium carbonate plus vitamin D resulted in significantly higher calcium excretion compared with that of milk (418). In elderly patients, however, higher amounts of vitamin D have not been found to normalize calcium malabsorption (421).
  • Cardiac glycosidesCardiac glycosides: According to secondary sources, vitamin D should be used with caution in patients taking digoxin, as high amounts of vitamin D may cause hypercalcemia.
  • CimetidineCimetidine: In human and animal research, cimetidine has been shown to inhibit the action of vitamin D-hydroxylase (a hepatic mixed-function oxidase), the enzyme involved in the conversion of vitamin D to its active form (422; 423; 424). Theoretically, concurrent use may lead to vitamin D depletion.
  • CinacalcetCinacalcet: Cinacalcet (Sensipar®), a calcimimetic agent, may be used in combined with vitamin D for hyperparathyroidism (425; 426; 427; 428). Cinacalcet is metabolized by CYP3A4, CYP2D6, and CYP1A2, and vitamin D is metabolized by multiple cytochrome P450 enzymes. Theoretically, there is a potential for interaction; however, data are lacking.
  • ContraceptivesContraceptives: In human research, progesterone-only contraceptives had no effect on vitamin D levels in breast milk (378).
  • CorticosteroidsCorticosteroids: Use of corticosteroids can cause osteoporosis and calcium depletion with long-term administration. The use of vitamin D has been shown to prevent corticosteroid-induced osteoporosis (429; 42; 430). In animal and laboratory studies, a relationship between vitamin D receptors and the regulation of glucocorticoid signaling was observed; vitamin D3 and glucocorticoids demonstrated a cross-talk in hippocampal models (431). Glucocorticoid use was associated with decreased vitamin D status in human research (48).
  • CyclosporineCyclosporine: In human research, the effects of cyclosporine were enhanced with the addition of topical calcipotriene, a synthetic derivative of vitamin D used for psoriasis (380).
  • Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: Vitamin D is metabolized in the liver, and cytochrome P450 enzymes are responsible for metabolism (38; 349; 344; 432). In particular, in human study, vitamin D supplementation lowered concentrations of atorvastatin and its metabolites, likely due to induction of CYP450 3A4; a synergistic effect on cholesterol lowering was also noted (402). Theoretically, vitamin D may alter the effects and levels of drugs metabolized by cytochrome P450.
  • DiltiazemDiltiazem: According to secondary sources, vitamin D should be used with caution in patients taking non-dihydropyridine calcium channel blockers like diltiazem and verapamil, as high amounts of vitamin D may cause hypercalcemia and increase the risk of atrial fibrillation.
  • DiureticsDiuretics: Concurrent use of thiazide diuretics (which decrease urinary calcium excretion) and vitamin D may decrease vitamin D levels and increase the risk of hypercalcemia (433).
  • Drugs used for osteoporosisDrugs used for osteoporosis: According to human research, concurrent use of vitamin D with drugs used for osteoporosis (e.g., bisphosphonates, selective estrogen receptor modulators (SERMs)) may have added benefit and further increase bone mineral density (BMD) over these agents alone (409; 410; 411; 412; 434; 40; 435).
  • HeparinHeparin: According to human research, heparin may cause bone loss and inhibit the formation of 1,25-dihydroxyvitamin by the kidneys (436).
  • Hormonal agentsHormonal agents: In human research in elderly women, oral administration of hormone replacement therapy (HRT; estrogen and progesterone), calcium, and vitamin D produced a bone-sparing effect that was more beneficial than calcium and vitamin D alone (437).
  • ImmunosuppressantsImmunosuppressants: According to secondary sources, vitamin D may have immunomodulatory effects. Theoretically, vitamin D may interfere with immunosuppressive therapy.
  • KetoconazoleKetoconazole: According to secondary sources and human research, ketoconazole, an inhibitor of CYP450 enzymes, acted as a vitamin D inhibitor (438). In laboratory research, ketoconazole combined with 1,25-dihydroxyvitamin D3 (calcitriol) enhanced the antitumor activities of vitamin D compounds for prostate cancer and alleviated side effects of vitamin D deficiency (439)
  • LaxativesLaxatives: According to secondary sources, stimulant laxatives may reduce dietary vitamin D absorption.
  • Mineral oilMineral oil: According to secondary sources, mineral oil may reduce the absorption of vitamin D.
  • Opiate agonistsOpiate agonists: In human research, vitamin D deficiency has been associated with opioid analgesic use among patients with chronic pain (440).
  • OrlistatOrlistat: According to the manufacturer and human research, orlistat can reduce the absorption of fat-soluble vitamins, particularly vitamin D (441). According to secondary sources, patients should consider taking a multivitamin with fat-soluble vitamins at least two hours before or after orlistat or at bedtime.
  • RifampinRifampin: In human research, rifampin increased vitamin D metabolism and reduced vitamin D blood levels, as rifampin increased hepatic metabolism of 25-hydroxyvitamin D (442; 443; 444).
  • SevelamerSevelamer: According to the manufacturer, sevelamer may reduce the absorption of vitamin D. In human research, researchers found the combination of sevelamer and vitamin D metabolites controlled hyperphosphatemia and hyperparathyroidism trial (445).
  • SunscreensSunscreens: In human research, sunscreens have been shown to interfere with the cutaneous production of vitamin D3 (446).
  • Tar-based shampooTar-based shampoo: The limited benefit of a combination of tar-based shampoo with 50mcg/mL of calcipotriol solution on scalp psoriasis was discussed (447). Further details are lacking at this time.
  • VaccinesVaccines: The Bacille Calmette-Guérin (BCG) vaccine, a live vaccine developed to prevent tuberculosis (TB), has also been shown to influence vitamin D concentrations and enhance the immune response of the vaccine (258; 257; 259). Mycobacterial antigens in the vaccine may increase production of 25-hydroxylase enzymes, resulting in increased production of 25-hydroxyvitamin D (259).
  • Vitamin D receptor agonistsVitamin D receptor agonists: Theoretically, concurrent use of vitamin D receptor (VDR) agonists with vitamin D supplementation may increase the risk of vitamin D toxicity. Curcumin, a ligand of the vitamin D receptor, was found to facilitate chemoprevention by directly binding the nuclear vitamin D receptor (448); however, the effects with vitamin D supplementation are unknown.

Vitamin D/Herb/Supplement Interactions:
  • AluminumAluminum: In animal research and clinical review, the calcium transport protein calbindin-D28k, which transports aluminum, was stimulated by vitamin D and may therefore increase aluminum absorption (381; 382; 383).
  • AnalgesicsAnalgesics: In a systematic review, vitamin D resulted in reduced need for analgesics (312).
  • AntacidsAntacids: Hypermagnesemia (high blood magnesium levels) may develop when magnesium-containing antacids are used concurrently with vitamin D, particularly in patients with chronic renal failure.
  • AntiasthmaticsAntiasthmatics: According to a review, vitamin D inhibited the influx of inflammatory cytokines in the lungs and increased the secretion of interleukin-10 by T-regulatory cells and dendritic cells (93). Experts have suggested that vitamin D supplementation in patients with asthma may improve the severity of the disease and improve treatment (384).
  • Anticonvulsant herbs and supplementsAnticonvulsant herbs and supplements: In human research, certain anticonvulsant agents have been shown to decrease levels of vitamin D (385; 386; 387; 388; 389) by inducing hepatic conversion of vitamin D to inactive metabolites. Concurrent use of vitamin D and anticonvulsant agents has also been found to improve bone health vs. anticonvulsants alone (390; 391).
  • Anti-inflammatory herbs and supplementsAnti-inflammatory herbs and supplements: Based on mechanism of action, use of vitamin D and calcium together may alter inflammatory response. In human research, vitamin D in combination with nonsteroidal anti-inflammatory drugs (NSAIDs) reduced the risk of colorectal adenoma more strongly than vitamin D alone (124)
  • AntilipemicsAntilipemics: Intestinal absorption of vitamin D may be impaired with the use of bile acid sequestrants (cholestyramine, colestipol) (396; 397; 398; 399). In human research, the effects of HMG-CoA reductase inhibitors ("statins") on vitamin D levels were mixed but may improve cholesterol levels (400; 401; 402; 403; 404). In human research, vitamin D supplementation lowered concentrations of atorvastatin and its metabolites, likely due to induction of CYP450 3A4; a synergistic effect on cholesterol lowering was also noted (402). In other human research, atorvastatin increased vitamin D levels and also improved cholesterol levels (403). This increase could explain some of the beneficial effects of atorvastatin at the cardiovascular level that are unrelated to cholesterol levels. However, other research has found no effect (393). In vivo, pretreatment with vitamin D had favorable effects on bone metabolism and formation in patients with heterozygous familial hypercholesterolemia and with pretreatment vitamin D levels >50pg/mL (405).
  • AntineoplasticsAntineoplastics: According to secondary sources, in vitro, vitamin D, specifically calcitriol (1,25-dihydroxyvitamin D(3), the most active form of vitamin D), enhanced cell differentiation, inhibited cell proliferation, stimulated apoptosis, suppressed inflammation, and inhibited tumor angiogenesis, invasion, and metastasis (406; 407; 408).
  • CalciumCalcium: Vitamin D is essential for the utilization of calcium in the body. It regulates and enhances absorption efficiency of calcium (417; 418; 419; 420; 421). In human research, calcium carbonate plus vitamin D resulted in significantly higher calcium excretion compared with that of milk (418). In elderly patients, however, higher amounts of vitamin D have not been found to normalize calcium malabsorption (421). In elderly subjects, vitamin D plus calcium, but not vitamin D alone, might benefit physical performance (449).
  • Cardiac glycosidesCardiac glycosides: According to secondary sources, vitamin D should be used with caution in patients taking digoxin, as high amounts of vitamin D may cause hypercalcemia.
  • ContraceptivesContraceptives: In human research, progesterone-only contraceptives had no effect on vitamin D levels in breast milk (378).
  • Cytochrome P450-metabolized herbs and supplementsCytochrome P450-metabolized herbs and supplements: Vitamin D is metabolized in the liver, and cytochrome P450 enzymes are responsible for metabolism (38; 349; 344; 432). In particular, in human research, vitamin D supplementation lowered concentrations of atorvastatin and its metabolites, likely due to induction of CYP450 3A4; a synergistic effect on cholesterol lowering was also noted (402). Theoretically, vitamin D may alter the effects and levels of drugs metabolized by cytochrome P450.
  • DiureticsDiuretics: Concurrent use of thiazide diuretics (which decrease urinary calcium excretion) and potassium may decrease vitamin D levels and increase the risk of hypercalcemia (433).
  • Herbs/supplements that decrease Herbs/supplements that decrease calcium: Vitamin D is essential for the utilization of calcium in the body. It regulates and enhances absorption efficiency of calcium. Agents that decrease the effects of calcium may interfere with the effects of vitamin D.
  • Hormonal herbs and supplementsHormonal herbs and supplements: In human study of elderly women, oral administration of hormone replacement therapy (HRT; estrogen and progesterone), calcium, and vitamin D produced a bone-sparing effect that was more beneficial than calcium and vitamin D alone (437).
  • Hormone replacement therapy (HRT)Hormone replacement therapy (HRT): In human study of elderly women, oral administration of hormone replacement therapy (HRT; estrogen and progesterone), calcium, and vitamin D produced a bone-sparing effect that was more beneficial than calcium and vitamin D alone (437).
  • HypoglycemicsHypoglycemics: Based on clinical review and human study, vitamin D may lower blood glucose and hemoglobin A1c (38; 276; 392). Theoretically, concurrent use with antidiabetic agents may increase the risk of hypoglycemia. However, results are not consistent (393; 394).
  • HypotensivesHypotensives: Based on secondary sources, vitamin D may lower blood pressure (38). Theoretically, concurrent use with hypotensives may increase the risk of hypotension. However, another study has found no effect (393).
  • ImmunosuppressantsImmunosuppressants: Based on human study, vitamin D may have immunomodulatory effects. Theoretically, vitamin D may interfere with immunosuppressive therapy.
  • LaxativesLaxatives: Based on secondary sources, stimulant laxatives can reduce dietary vitamin D absorption.
  • MagnesiumMagnesium: Based on clinical review and studies in humans and animals, vitamin D increases magnesium absorption and may reduce magnesium retention through increases in urinary magnesium excretion (450). However, the interaction is not well understood (451). Concurrent use of vitamin D and magnesium may also improve immune function (452).
  • MicronutrientsMicronutrients: In human study, calcium/vitamin D in combination with micronutrient supplementation provided an added benefit in reducing the risk of osteomalacia and osteoporosis in premenopausal women with hypovitaminosis D (453).
  • Mineral oilMineral oil: Based on secondary sources, mineral oil may reduce the absorption of vitamin D.
  • Osteoporosis herbs/supplementsOsteoporosis herbs/supplements: Based on human study, concurrent use of vitamin D with drugs used for osteoporosis (e.g., bisphosphonates, selective estrogen receptor modulators (SERMs)) may have added benefit and further increase bone mineral density (BMD) than these agents alone (409; 410; 409; 411; 412; 434; 40; 435).
  • SiliconSilicon: In human research, orthosilicic acid (soluble silica) supplementation in combination with calcium/vitamin D3 was found to have a greater benefit in stimulating markers of bone formation in osteopenic females than calcium/vitamin D3 alone (454).
  • SunscreensSunscreens: In human research, sunscreens have been shown to interfere with the cutaneous production of vitamin D3 (446).
  • Vitamin AVitamin A: In animal research, an antagonistic interaction was noted between vitamin D and vitamin A, as vitamin A may interfere with the absorption and metabolism of vitamin D (455). In laboratory research, vitamin D3 was found to interfere with the uptake and metabolism of retinol by human epidermal keratinocytes (456).
  • Vitamin KVitamin K: In human research, vitamin D supplementation had no effect on undercarboxylated osteocalcin (%ucOC, a marker of vitamin K status) (457).

Vitamin D/Food Interactions:
  • Cod liver oilCod liver oil: In elderly nursing home residents, use of cod liver oil increased serum vitamin D levels (458).
  • Fortified vitamin D foodsFortified vitamin D foods: Various foods may be fortified with vitamin D, including milk (459; 460; 461), bread (462; 463), and orange juice (464; 461); according to human research, this may increase 25(OH)D concentrations (459; 462; 156; 465; 461; 464; 463; 466).

Vitamin D/Lab Interactions:
  • Alkaline phosphatase (ALP)Alkaline phosphatase (ALP): In preterm infants, high doses of vitamin D were associated with increased serum ALP levels (467).
  • Blood glucoseBlood glucose: According to clinical review and human research, vitamin D may lower blood glucose (38; 276).
  • Blood pressureBlood pressure: According to secondary sources, vitamin D may lower blood pressure (38). In human research on white individuals, lower 25(OH)D concentrations were associated with a higher blood pressure; specifically, systolic blood pressure was inversely associated with serum vitamin D concentrations in nonhypertensive white persons (116).
  • Body mass indexBody mass index: In human research, body mass index was inversely correlated with plasma 25-hydroxyvitamin D(3) concentrations (468).
  • Bone mineral density (BMD)Bone mineral density (BMD): In human research, vitamin D supplementation lowered BMD (252).
  • CalciumCalcium: According to human research, vitamin D supplementation may also cause hypercalcemia, particularly at high doses (340; 284). In human research, 8,400 IU of vitamin D3 weekly caused hypercalciuria (284).
  • C-peptideC-peptide: In human research, vitamin D intake was associated with lower C-peptide in men with plasma concentrations of 25(OH)D in the highest quartile compared with those in the lowest quartile; no association was noted in women (469).
  • C-reactive protein concentrationsC-reactive protein concentrations: In human research, C-reactive protein concentrations were inversely correlated with plasma 25-hydroxyvitamin D(3) concentrations (395; 468).
  • CreatinineCreatinine: In human research, 8,400 IU of vitamin D3 weekly caused elevated creatinine (284).
  • Deoxypyridinoline (DPD)Deoxypyridinoline (DPD): In preterm infants, a high dose of vitamin D was associated with increased urinary DPD levels (467).
  • Hemoglobin A1cHemoglobin A1c: In human research, serum 25(OH)D levels were inversely associated with hemoglobin A1c; patients with elevated A1c were found to be deficient in vitamin D (392).
  • Inflammatory markersInflammatory markers: In human research, vitamin D3 improved cytokines' lowering interleukin-10 and tumor necrosis factor-alpha (470). In human research, plasma 25-hydroxyvitamin D was inversely associated with urinary isoprostane concentration, an indicator of oxidative stress, and associations with inflammatory mediators were inconsistent (471).
  • Lipid profileLipid profile: In human research, vitamin D supplementation lowered concentrations of atorvastatin and its metabolites, likely due to induction of CYP450 3A4; a synergistic effect on cholesterol lowering was also noted (402). In other human research, atorvastatin increased vitamin D levels and also improved cholesterol levels (403). This increase could explain some of the beneficial effects of atorvastatin at the cardiovascular level that are unrelated to cholesterol levels.
  • MagnesiumMagnesium: According to clinical review and studies in humans and animals, vitamin D increased magnesium absorption and may reduce magnesium retention through increases in urinary magnesium excretion (450). However, the interaction is not well understood (451).
  • OsteocalcinOsteocalcin: In preterm infants, a high dose of vitamin D was associated with increased serum osteocalcin levels (467).
  • Parathyroid hormone (PTH)Parathyroid hormone (PTH): In human research, vitamin D supplementation lowered circulating PTH (472; 252; 473; 470; 474; 475). In order to reduce serum parathyroid hormone levels in the elderly to levels considered normal in the young, vitamin D intakes much higher than recommended dietary allowance would be required (476).
  • Prostate-specific antigen (PSA)Prostate-specific antigen (PSA): In human research, administration of vitamin D (cholecalciferol) was associated with a decreased rate of PSA elevation (477).
  • Renal function testsRenal function tests: In human research, glomerular filtration rate (GFR) was inversely correlated with plasma 25-hydroxyvitamin D(3) concentrations (468).
  • Vitamin D levelsVitamin D levels: In human research, vitamin D has been found to raise circulating 24(OH)D levels (252; 309; 473; 273; 475; 330; 470; 478). Certain agents, including anticonvulsants, antilipemic agents, corticosteroids, diuretics, laxatives, mineral oil, orlistat, opiate agonists, rifampin and sunscreen, may reduce vitamin D levels (385; 386; 387; 388; 396; 397; 398; 399; 429; 433; 38; 276; 440; 441; 442; 443; 444; 446). Various foods may be fortified with vitamin D, including milk (459; 460; 461), bread (462), and orange juice (464; 461); according to human study, this may increase 25(OH)D concentrations (459; 462; 156; 465; 461).
  • Urine calcium:creatinine ratio (UCa:Cr)Urine calcium:creatinine ratio (UCa:Cr): In infants, vitamin D3 prophylaxis was associated with hypercalciuria, and some infants had low Ca:Cr ratios (376).

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The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.
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