Ergocalciferol
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 (549). 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 (550; 551; 552). AnalgesicsAnalgesics: In a systematic review, vitamin D resulted in reduced need for analgesics (451). AntacidsAntacids: According to secondary sources, hypermagnesemia (high blood magnesium levels) may develop when magnesium-containing antacids are used concurrently with vitamin D, particularly in patients with chronic renal failure.AntiandrogensAntiandrogens: According to systematic reviews, nutrition, including vitamin D and calcium supplementation, is needed to maintain bone health in men on androgen deprivation therapy (ADT) for prostate cancer (463; 553); biochemical, but not clinical, changes occurred in further research (462). 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 (95). Experts have suggested that vitamin D supplementation in patients with asthma may improve the severity of the disease and improve treatment (554). Acording to a review, mechanisms of action of vitamin D in asthma may include the promotion of immune response in the lung, decreasing inflammation, reducing cell cycling and hyperplasia, and promotion of the effects of exogenous steroids (555). AntibioticsAntibiotics: In a systematic review, there was some short-term evidence of benefit on positive sputum smears from patients with tuberculosis (388). AnticonvulsantsAnticonvulsants: In human research, certain anticonvulsant agents (e.g., carbamazepine, phenobarbital, and phenytoin) decreased levels of vitamin D (556; 557; 558; 559; 560) by inducing hepatic conversion of vitamin D to inactive metabolites. Concurrent use of vitamin D and anticonvulsant agents improved bone health vs. anticonvulsants alone (561; 562). Antidiabetic agentsAntidiabetic agents: According to a clinical review and human research, effects of vitamin D on glucose and insulin metabolism were mixed, with studies showing reduced effects or no effects (368; 369; 370; 37; 371; 372; 373; 374), and in a single study included in one of the reviews, healthy men had significantly increased insulin and C-peptide concentrations (369). In another cohort study, even though diabetes risk decreased with increasing vitamin D supplementation, there was a lack of significant effect of dietary vitamin D on the risk of diabetes (369). In human research, vitamin D reduced fasting glucose levels and insulin resistance in patients with abnormal, but not normal, fasting glucose; effects on HbA1c were lacking (375). AntihypertensivesAntihypertensives: According to a systematic review and secondary sources, vitamin D supplementation reduced blood pressure in most studies; however, increases were noted in a single study (369; 37; 381), and there was a lack of effect in separate studies (370; 373; 381). In human research, hypertension treated with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker were associated with low 25-hydroxyvitamin D(3) levels (563). 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 (140) Antilipemic agentsAntilipemic agents: In human research, vitamin D lacked an effect on total cholesterol or triglycerides; however, LDL cholesterol levels increased overall and HDL cholesterol levels decreased in studies lasting longer than one year (363). In a systematic review, effects of native vitamin D on cholesterol were lacking, although three of nine of the included studies reported a decrease in triglyceride levels and one of nine reported a reduction in LDL cholesterol (414). In patients with end-stage renal disease, calcitriol reduced triglyceride levels. AntineoplasticsAntineoplastics: An inverse association between vitamin D intake (with or without calcium) and serum levels of vitamin D has also been noted for colorectal, cervical, breast, and prostate cancers (154; 151; 152; 99; 140; 141; 64; 142; 143; 144; 145; 146; 147; 156; 564; 565; 566; 567; 568; 569; 570), with dietary intakes of 1,000-2,000 IU considered most likely to be of benefit (571). However, some research has shown that elevated 25(OH)D levels or intakes may increase the risk of certain cancers (prostate, breast, pancreatic, and esophageal) (510) or have no effect (various) (572; 145; 573; 574), and supplementation with vitamin D reduced the incidence of cancer in some studies, but not all (147; 379). 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 (575; 576; 577). Antiretroviral agentsAntiretroviral agents: According to a review, vitamin D deficiency is common in HIV patients, and 25-hydroxyvitamin D levels are reduced in patients using antiretrovirals (578). Bile acid sequestrantsBile acid sequestrants: In human research, vitamin D lacked an effect on total cholesterol or triglycerides; however, LDL cholesterol levels increased overall and HDL cholesterol levels decreased in studies lasting longer than one year (363). In a systematic review, effects of native vitamin D on cholesterol were lacking, although three of nine of the included studies reported a decrease in triglyceride levels and one of nine reported a reduction in LDL cholesterol (414). In patients with end-stage renal disease, calcitriol reduced triglyceride levels. Intestinal absorption of vitamin D may be impaired with the use of bile acid sequestrants (cholestyramine, colestipol) (579; 580; 581; 582). BisphosphonatesBisphosphonates: In human research, concurrent use of vitamin D with bisphosphonates had added benefit and further increased bone mineral density (BMD) over bisphosphonates alone (583; 584; 585; 586; 587; 588; 589; 590; 591). It also provided added benefit in cancer treatment, according to human research (592). Clinical trials involving bisphosphonates often include vitamin D and calcium and are compared with vitamin D and calcium alone (593; 594). CalcipotrieneCalcipotriene: According to secondary sources, 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 (595; 596; 597; 598). In human research, calcium carbonate plus vitamin D resulted in significantly higher calcium excretion compared with that of milk (596). In elderly patients, however, higher amounts of vitamin D have not been found to normalize calcium malabsorption (599). In human research, vitamin D supplementation caused hypercalcemia and hypercalciuria, particularly at high doses (392; 393; 394; 395; 396; 397; 398; 379; 399; 388; 367; 400; 401; 380; 386). Authors of a clinical trial suggested that as calcium absorption is increased with increasing blood vitamin D levels, calcium doses may need adjusting downward as blood levels increase in patients with vitamin D deficiency (479). 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. According to a systematic review, the combination of calcium and vitamin D increases the risk of cardiovascular disease over vitamin D alone (414). Cardiovascular agentsCardiovascular agents: In human research, treatment with vitamin D analogs was related to coronary and vascular calcification (359; 360; 361), and a combination of calcium and vitamin D significantly increased the risk of myocardial infarction and stroke in a meta-analysis (362). CimetidineCimetidine: In human and animal research, cimetidine inhibited the action of vitamin D-hydroxylase (a hepatic mixed-function oxidase), the enzyme involved in the conversion of vitamin D to its active form (600; 601; 602). CinacalcetCinacalcet: Cinacalcet (Sensipar?), a calcimimetic agent, may be used in combination with vitamin D for hyperparathyroidism (603; 604; 605; 606). Cinacalcet is metabolized by CYP3A4, CYP2D6, and CYP1A2, and vitamin D is metabolized by multiple cytochrome P450 enzymes. ContraceptivesContraceptives: In human research, progesterone-only contraceptives lacked an effect on vitamin D levels in breast milk (547).CorticosteroidsCorticosteroids: Use of corticosteroids may cause osteoporosis and calcium depletion with long-term administration. The use of vitamin D has been shown to prevent corticosteroid-induced osteoporosis (607; 608; 609). 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 (610). Glucocorticoid use was associated with decreased vitamin D status in human research (116). In systematic reviews, authors concluded that a combination of vitamin D with analogs may be more effective than the vitamin D analogs alone, although vitamin D analogs are also effective (367; 611; 481; 505). Serum vitamin D levels were reduced in users of glucocorticosteroids vs. healthy controls; differences vs. disease controls were lacking (612), and corticosteroid side effects may decrease when used in combination with vitamin D analogs (505). 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 (549). Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: Vitamin D is metabolized in the liver, and cytochrome P450 enzymes are responsible for metabolism (37; 508; 360; 613). 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 (614). Dental agentsDental agents: In human research, there is evidence of benefit of vitamin D from various sources on prevention of dental caries (416). Dermatologic agentsDermatologic agents: In human research, the most common adverse effects associated with vitamin D analogs used for psoriasis was contact dermatitis (364) and skin irritation (365). Rash and skin atrophy have also been reported in human research (366; 367). 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 (615). 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)) has added benefit and further increases bone mineral density (BMD) over these agents alone (583; 584; 585; 586; 616; 587; 617; 590; 591). ExemestaneExemestane: Despite use of calcium and vitamin D, bone density worsened in healthy postmenopausal women being treated with exemestane for breast cancer prevention (618). Fat-soluble agentsFat-soluble agents: According to secondary sources, vitamin D may interact with fat-soluble agents.Fertility agentsFertility agents: In some women, calcium plus vitamin D resulted in menstrual cycle normalization and an increase in dominant ovarian follicles (426). In men, elocalcitol reduced interleukin (IL)-8 levels in semen, which was related to improved semen quality (426). Gastrointestinal agentsGastrointestinal agents: According to secondary sources and case reporting, high amounts of vitamin D may cause gastrointestinal complaints (376), and constipation and gastric symptoms such as diarrhea, abdominal cramps, vomiting, and upset stomach have been reported in clinical research (377; 378; 379; 366; 380). HeparinsHeparins: According to human research, heparin may cause bone loss and inhibit the formation of 1,25-dihydroxyvitamin by the kidneys (619). HMG-CoA reductase inhibitorsHMG-CoA reductase inhibitors: In human research, vitamin D lacked an effect on total cholesterol or triglycerides; however, LDL cholesterol levels increased overall and HDL cholesterol levels decreased in studies lasting longer than one year (363). In a systematic review, effects of native vitamin D on cholesterol were lacking, although three of nine of the included studies reported a decrease in triglyceride levels and one of nine reported a reduction in LDL cholesterol (414). In patients with end-stage renal disease, calcitriol reduced triglyceride levels. In human research, the effects of HMG-CoA reductase inhibitors ("statins") on vitamin D levels were mixed but improved cholesterol levels (620; 621; 614; 622; 623; 624). 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 (614). In other human research, atorvastatin increased vitamin D levels and also improved cholesterol levels (622). According to secondary sources, this increase could explain some of the beneficial effects of atorvastatin at the cardiovascular level that are unrelated to cholesterol levels. 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 (625). ImmunosuppressantsImmunosuppressants: According to secondary sources, vitamin D may have immunomodulatory effects.InsulinInsulin: In human research, vitamin D prevented the insulin-induced decrease in fasting C-peptide (408). Also, vitamin D plus insulin increased the number of patients with maintained or increased fasting C-peptide levels vs. insulin alone, and islet B-cell function was better preserved. InterferonbetaInterferon-beta: In human research, interferon-beta increased the synthesis of 25-hydroxyvitamin D during sun exposure (626). KetoconazoleKetoconazole: According to secondary sources and human research, ketoconazole, an inhibitor of CYP450 enzymes, acted as a vitamin D inhibitor (627). 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 (628) 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.Neurologic agentsNeurologic agents: According to secondary sources, vitamin D may interact with neurologic agents. Headaches have been reported in human research (366). OpioidsOpioids: In human research, vitamin D deficiency has been associated with opioid analgesic use among patients with chronic pain (629).OrlistatOrlistat: According to the manufacturer and human research, orlistat can reduce the absorption of fat-soluble vitamins, particularly vitamin D (630). 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. Respiratory agentsRespiratory agents: According to results of a meta-analysis, use of vitamin D prevents respiratory tract infections; however, effects were significant only in children (470). Other randomized controlled trials have been conducted in children (showing efficacy) (488; 489) and adults (showing a lack of efficacy) (471; 473), with similar conclusions. However, in adults with frequent respiratory tract infections, vitamin D supplementation reduced the disease burden (472). In children diagnosed with pneumonia, vitamin D reduced the risk of a repeat episode but lacked an effect on the time to recovery from the first episode (490). RifampinRifampin: In human research, rifampin increased vitamin D metabolism and reduced vitamin D blood levels, as rifampin increased hepatic metabolism of 25-hydroxyvitamin D (631; 632; 633). 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 (634). SunscreensSunscreens: In human research, sunscreens interfered with the cutaneous production of vitamin D3 (635). However, according to a review, insufficient use is unlikely to inhibit vitamin D sysnthesis (636). 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 (further details lacking) (637). Thyroid hormone antagonistsThyroid hormone antagonists: According to secondary sources, vitamin D may interact with thyroid agents.VaccinesVaccines: The Bacille Calmette-Gu?rin (BCG) vaccine, a live vaccine developed to prevent tuberculosis (TB), influenced vitamin D concentrations and enhanced the immune response of the vaccine (284; 283; 285). Mycobacterial antigens in the vaccine may increase production of 25-hydroxylase enzymes, resulting in increased production of 25-hydroxyvitamin D (285). Vitamin D receptor agonistsVitamin D receptor agonists: According to secondary sources, 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 (638). In human research, vitamin D reduced the need for VDR agonist therapy (399). 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 (550; 551; 552). AnalgesicsAnalgesics: In a systematic review, vitamin D resulted in reduced need for analgesics (451). AntacidsAntacids: According to secondary sources, hypermagnesemia (high blood magnesium levels) may develop when magnesium-containing antacids are used concurrently with vitamin D, particularly in patients with chronic renal failure.AntiandrogenicsAntiandrogenics: According to systematic reviews, nutrition, including vitamin D and calcium supplementation, is needed to maintain bone health in men on androgen deprivation therapy (ADT) for prostate cancer (463; 553); biochemical, but not clinical, changes occurred in further research (462). 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 (95). Experts have suggested that vitamin D supplementation in patients with asthma may improve the severity of the disease and improve treatment (554). According to a review, the mechanisms of action of vitamin D in asthma may include the promotion of immune response in the lung, decreasing inflammation, reducing cell cycling and hyperplasia, and promotion of the effects of exogenous steroids (555). AntibacterialsAntibacterials: In a systematic review, there was some short-term evidence of benefit on positive sputum smears from patients with tuberculosis (388). AnticonvulsantsAnticonvulsants: In human research, certain anticonvulsant agents (e.g., carbamazepine, phenobarbital, and phenytoin) decreased levels of vitamin D (556; 557; 558; 559; 560) by inducing hepatic conversion of vitamin D to inactive metabolites. Concurrent use of vitamin D and anticonvulsant agents improved bone health vs. anticonvulsants alone (561; 562). 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 (140) AntilipemicsAntilipemics: In human research, vitamin D lacked an effect on total cholesterol or triglycerides; however, LDL cholesterol levels increased overall and HDL cholesterol levels decreased in studies lasting longer than one year (363). In a systematic review, effects of native vitamin D on cholesterol were lacking, although three of nine of the included studies reported a decrease in triglyceride levels and one of nine reported a reduction in LDL cholesterol (414). In patients with end-stage renal disease, calcitriol reduced triglyceride levels. In human research, the effects of HMG-CoA reductase inhibitors ("statins") on vitamin D levels were mixed but improved cholesterol levels (620; 621; 614; 622; 623; 624). 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 (614). According to secondary sources, 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 (639). However, other research has found a lack of effect (373). AntineoplasticsAntineoplastics: An inverse association between vitamin D intake (with or without calcium) and serum levels of vitamin D have also been noted for colorectal, cervical, breast, and prostate cancers (154; 151; 152; 99; 140; 141; 64; 142; 143; 144; 145; 146; 147; 156; 564; 565; 566; 567; 568; 569; 570), with dietary intakes of 1,000-2,000 IU considered most likely to be of benefit (571). However, some research has shown that elevated 25(OH)D levels or intakes may increase the risk of certain cancers (prostate, breast, pancreatic, and esophageal) (510) or have no effect (various) (572; 145; 573; 574), and supplementation with vitamin D reduced the incidence of cancer in some studies, but not all (147; 379). 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 (575; 576; 577). Athletic performance enhancersAthletic performance enhancers: According to secondary sources, vitamin D may interact with athletic performance enhancers.CalciumCalcium: Vitamin D is essential for the utilization of calcium in the body. It regulates and enhances absorption efficiency of calcium (595; 596; 597; 598). In human research, calcium carbonate plus vitamin D resulted in significantly higher calcium excretion compared with that of milk (596). In elderly patients, however, higher amounts of vitamin D have not been found to normalize calcium malabsorption (599). In human research, vitamin D supplementation caused hypercalcemia and hypercalciuria, particularly at high doses (392; 393; 394; 395; 396; 397; 398; 379; 399; 388; 367; 400; 401; 380; 386). Authors of a clinical trial suggested that as calcium absorption is increased with increasing blood vitamin D levels, calcium doses may need adjusting downward as blood levels increase in patients with vitamin D deficiency (479). According to a systematic review, the combination of calcium and vitamin D increases the risk of cardiovascular disease over vitamin D alone (414). 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.Cardiovascular agentsCardiovascular agents: In human research, treatment with vitamin D analogs was related to coronary and vascular calcification (359; 360; 361), and a combination of calcium and vitamin D significantly increased the risk of myocardial infarction and stroke in a meta-analysis (362). ContraceptivesContraceptives: In human research, progesterone-only contraceptives lacked an effect on vitamin D levels in breast milk (547).Cytochrome P450-metabolized agentsCytochrome P450-metabolized agents: Vitamin D is metabolized in the liver, and cytochrome P450 enzymes are responsible for metabolism (37; 508; 360; 613). 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 (614). Dental agentsDental agents: In human research, there is evidence of benefit of vitamin D from various sources on prevention of dental caries (416). 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 (615). Fat-soluble vitaminsFat-soluble vitamins: According to secondary sources, vitamin D may interact with fat-soluble herbs and supplements.Fertility agentsFertility agents: In some women, calcium plus vitamin D resulted in menstrual cycle normalization and an increase in dominant ovarian follicles (426). In men, elocalcitol reduced interleukin (IL)-8 levels in semen, which was related to improved semen quality (426). Gastrointestinal agentsGastrointestinal agents: According to secondary sources and case reporting, high amounts of vitamin D may cause gastrointestinal complaints (376), and constipation and gastric symptoms such as diarrhea, abdominal cramps, vomiting, and upset stomach have been reported in clinical research (377; 378; 379; 366; 380). Herbs/supplements that decrease calciumHerbs/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 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 (625). Hormone replacement therapy (HRT)Hormone replacement therapy (HRT): 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 (625). HypoglycemicsHypoglycemics: According to a clinical review and human research, effects of vitamin D on glucose and insulin metabolism were mixed, with studies showing reduced effects or no effects (368; 369; 370; 37; 371; 372; 373; 374), and in a single study included in one of the reviews, healthy men had significantly increased insulin and C-peptide concentrations (369). In another cohort study, even though diabetes risk decreased with increasing vitamin D supplementation, there was a lack of significant effect of dietary vitamin D on the risk of diabetes (369). In human research, vitamin D reduced fasting glucose levels and insulin resistance in patients with abnormal, but not normal, fasting glucose; effects on HbA1c were lacking (375). HypotensivesHypotensives: According to a systematic review and secondary sources, vitamin D supplementation resulted in a reduction in blood pressure in most studies; however, increases were noted in a single study (369; 37; 381), and there was a lack of effect in separate studies (370; 373; 381). In human research, hypertension treated with angiotensin-converting enzyme inhibitor/angiotensin receptor blockers were associated with low 25-hydroxyvitamin D(3) levels (563). ImmunosuppressantsImmunosuppressants: According to secondary sources, vitamin D may have immunomodulatory effects.LaxativesLaxatives: According to secondary sources, stimulant laxatives may 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 (640). However, the interaction is not well understood (641). Concurrent use of vitamin D and magnesium may also improve immune function (642). MicronutrientsMicronutrients: In human research, 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 (643). Mineral oilMineral oil: According to secondary sources, mineral oil may reduce the absorption of vitamin D.Neurologic agentsNeurologic agents: According to secondary sources, vitamin D may interact with neurologic agents. Headaches have been reported in human research (366). Osteoporosis herbs/supplementsOsteoporosis herbs/supplements: According to human research, concurrent use of vitamin D with drugs used for osteoporosis (e.g., bisphosphonates, selective estrogen receptor modulators (SERMs)) has added benefit and further increases bone mineral density (BMD) over these agents alone (583; 584; 585; 586; 616; 587; 617; 590; 591). Respiratory agentsRespiratory agents: According to results of a meta-analysis, use of vitamin D prevents respiratory tract infections; however, effects were significant only in children (470). Other randomized controlled trials have been conducted in children (showing efficacy) (488; 489) and adults (showing a lack of efficacy) (471; 473), with similar conclusions. However, in adults with frequent respiratory tract infections, vitamin D supplementation reduced the disease burden (472). In children diagnosed with pneumonia, vitamin D reduced the risk of a repeat episode but lacked an effect on the time to recovery from the first episode (490). 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 (644). SunscreensSunscreens: In human research, sunscreens interfered with the cutaneous production of vitamin D3 (635). However, according to a review, insufficient use is unlikely to inhibit vitamin D sysnthesis (636). 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 (645). In laboratory research, vitamin D3 was found to interfere with the uptake and metabolism of retinol by human epidermal keratinocytes (646). Vitamin KVitamin K: In human research, vitamin D supplementation lacked an effect on undercarboxylated osteocalcin (%ucOC, a marker of vitamin K status) (647). Vitamin D/Food Interactions:
Cod liver oilCod liver oil: In elderly nursing home residents, use of cod liver oil increased serum vitamin D levels (648). According to a review, cod liver oil, with its vitamin A and omega-3 fatty acids, is a preferable source of vitamin D over vitamin D monotherapy supplements (649). Energy restricted dietEnergy restricted diet: In human research, calcium plus vitamin D, in addition to an energy-restricted diet, decreased fat loss, but not body weight, vs. the energy-restricted diet alone (650). In fasting postmenopausal women, vitamin D resulted in a decline in parathyroid hormone vs. placebo (651). Fortified vitamin D foodsFortified vitamin D foods: Various foods may be fortified with vitamin D, including milk (652; 653; 654), bread (655; 656), and orange juice (657; 654); according to human research, this may increase 25(OH)D concentrations (652; 655; 174; 658; 654; 657; 656; 659). Low cholesterol dietLow cholesterol diet: According to a review, a low-cholesterol diet may result in a decreased intake of fat soluble vitamins such as vitamin D (660). 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 (661). Blood glucoseBlood glucose: According to a clinical review and human research, effects of vitamin D on glucose and insulin metabolism were mixed, with studies showing reduced effects or no effects (368; 369; 370; 37; 371; 372; 373; 374), and in a single study included in one of the reviews, healthy men had significantly increased insulin and C-peptide concentrations (369). In another cohort study, even though diabetes risk decreased with increasing vitamin D supplementation, there was a lack of significant effect of dietary vitamin D on the risk of diabetes (369). In human research, vitamin D reduced fasting glucose levels and insulin resistance in patients with abnormal, but not normal, fasting glucose; effects on HbA1c were lacking (375). Blood pressureBlood pressure: According to a systematic review and secondary sources, vitamin D supplementation resulted in a reduction in blood pressure in most studies; however, increases were noted in a single study (369; 37; 381), and there was a lack of effect in separate studies (370; 373; 381). 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 (124). Body mass indexBody mass index: In human research, body mass index was inversely correlated with plasma 25-hydroxyvitamin D(3) concentrations (662).Bone turnover markersBone turnover markers: In human research, supplementation with calcium and vitamin D increased N-telopeptide, C-telopeptide, bone-specific alkaline phosphatase, and N-terminal propeptide (462). Bone mineral density (BMD)Bone mineral density (BMD): In human research, vitamin D supplementation lowered BMD (274). 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 (663). In human research in healthy men, vitamin D increased C-peptide concentrations (369). C-reactive protein concentrationsC-reactive protein concentrations: In human research, C-reactive protein concentrations were inversely correlated with plasma 25-hydroxyvitamin D(3) concentrations (563; 662). CreatinineCreatinine: In human research, 8,400 IU of vitamin D3 weekly caused elevated creatinine (393). Deoxypyridinoline (DPD)Deoxypyridinoline (DPD): In preterm infants, a high dose of vitamin D increased urinary DPD levels (661). 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 (372). Inflammatory markersInflammatory markers: In human research, vitamin D3 improved cytokines' lowering interleukin-10 and tumor necrosis factor-alpha (664). 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 (665). Lipid profileLipid profile: In human research, vitamin D lacked an effect on total cholesterol or triglycerides; however, LDL cholesterol levels increased overall and HDL cholesterol levels decreased in studies lasting longer than one year (363). In a systematic review, effects of native vitamin D on cholesterol were lacking, although three of nine of the included studies reported a decrease in triglyceride levels and one of nine reported a reduction in LDL cholesterol (414). In patients with end-stage renal disease, calcitriol reduced triglyceride levels. MagnesiumMagnesium: According to a clinical review and studies in humans and animals, vitamin D increased magnesium absorption and may reduce magnesium retention through increases in urinary magnesium excretion (640). However, the interaction is not well understood (641). OsteocalcinOsteocalcin: In preterm infants, a high dose of vitamin D was associated with increased serum osteocalcin levels (661). Parathyroid hormone (PTH)Parathyroid hormone (PTH): In human research, vitamin D supplementation lowered circulating PTH (666; 274; 667; 664; 668; 669; 651; 401; 495). In human research, the vitamin D analog paricalcitol resulted in a reduction in PTH (366). 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 (670). 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 (671). ProteinProtein: In human research, the vitamin D analog paricalcitol resulted in a reduction in proteinuria (366). Renal function testsRenal function tests: In human research, glomerular filtration rate (GFR) was inversely correlated with plasma 25-hydroxyvitamin D(3) concentrations (662).Vitamin D levelsVitamin D levels: In human research, vitamin D has been found to raise circulating 24(OH)D levels (274; 446; 667; 356; 669; 494; 664; 672; 294; 673; 674; 206; 675; 676; 253; 471; 370; 473; 479; 495; 401; 468; 469; 677; 396; 678; 466; 497; 399). Certain agents, including anticonvulsants, antilipemic agents, corticosteroids, diuretics, laxatives, mineral oil, orlistat, opiate agonists, rifampin and sunscreen, may reduce vitamin D levels (556; 557; 558; 559; 579; 580; 581; 582; 607; 615; 37; 371; 629; 630; 631; 632; 633; 635). Various foods may be fortified with vitamin D, including milk (652; 653; 654), bread (655), and orange juice (657; 654); according to human study, this may increase 25(OH)D concentrations (652; 655; 174; 658; 654). 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 (545).