Retinol
Vitamin A/Drug Interactions:
AlcoholAlcohol: According to in vitro and animal research, concurrent use of alcohol and vitamin A may increase the risk of adverse effects, as alcohol induces cytochrome P450 2E1 metabolism of vitamin A (69; 71). According to human reports, chronic alcohol consumption may cause vitamin A deficiency (262; 71). Additionally, the combination of beta-carotene and ethanol resulted in hepatotoxicity (71). Smokers consuming alcohol and beta-carotene are at an increased risk for pulmonary cancer and possibly cardiovascular complications (71). AntibioticsAntibiotics: According to human reports, concurrent use with tetracycline antibiotics may cause benign intracranial hypertension and pseudotumor cerebri (96; 97; 98). In human research, neomycin reduced the absorption of vitamin A (66). In human research, vitamin A treatment was associated with reduced risk of antibiotic failure in children with nonmeasles pneumonia (226). Clindamycin phosphate (1.2%) combined with partially solubilized and crystalline tretinoin (0.025%) suspended in an aqueous-based, alcohol-free gel, improved overall appearance to a greater extent than either ingredient alone in patients with acne (263). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Vitamin A supplements in high doses may interfere with vitamin K absorption (99) and theoretically increase the risk of bleeding. AntidepressantsAntidepressants: Anecdotal reports and clinical reports of isotretinoin use and associated depression and suicidal ideation exist (93; 94; 95). In a subgroup of vulnerable individuals, an association between depression and suicide with isotretinoin administration exists (225). AntidiarrhealsAntidiarrheals: In a systematic review, vitamin A supplementation and all-trans retinoic acid (ATRA) resulted in reports of diarrhea (84). AntifungalsAntifungals: According to secondary sources, vitamin A may interact with antifungal agents.AntihelminthicsAntihelminthics: According to secondary sources, vitamin A may interact with antihelminthic agents.AntihypertensivesAntihypertensives: In clinical research, vitamin A and all-trans retinoic acid (ATRA) supplementation, alone or in combination with chemotherapy, resulted in reports of hypotension (84; 85). AntilipemicsAntilipemics: According to secondary sources, the use of bile acid sequestrants may reduce the absorption of fat-soluble vitamins like vitamin A. In clinical research, vitamin A and all-trans retinoic acid (ATRA) supplementation, alone or in combination with chemotherapy, resulted in reports of hypertriglyceridemia and hyperlipidemia (84; 85). AntimalarialsAntimalarials: Research suggests that vitamin A may reduce fever, morbidity, and parasite blood levels in patients with malaria (Plasmodium falciparum infection) (185), and, according to secondary sources, vitamin A may interact with antimalarial agents. AntineoplasticsAntineoplastics: The use of antioxidants like vitamin A with chemotherapy is controversial; some studies suggest that antioxidants may lessen the toxic effects of chemotherapy, while others suggest that antioxidants may interfere with chemotherapeutic efficacy (70). Significantly increased toxicity has been observed in individuals who received vitamin A plus busulfan compared to those given busulfan alone (232). In human research, vitamin A increased the response to chemotherapy more than twofold (38% vs. 15%, p<0.02). In chronic myelogenous leukemia (CML) patients, those given oral vitamin A in addition to oral pulse busulfan had somewhat longer progression-free survival times than those given busulfan alone; however, the differences were not statistically significant (p=0.11 for clinical progression-free survival, p=0.081 for survival) (232). In a pilot phase II study, 13-cis-retinoic acid (13-cis-RA) in combination with gemcitabine was well tolerated, but there was no improvement in response to gemcitabine in pancreatic cancer (264). In systematic reviews and meta-analyses, treatment with all-trans retinoic acid with chemotherapy increased the rate of complete remission and event-free survival in individuals with acute promyelocytic leukemia (84; 111). Antiobesity agentsAntiobesity agents: According to secondary sources, vitamin A may interact with antiobesity agents.Antithyroid agentsAntithyroid agents: In a systematic review, reversible hypothyroidism was reported (85). AntiviralsAntivirals: According to secondary sources, vitamin A may interact with antiviral agents.ContraceptivesContraceptives: In human research, oral contraceptives increased vitamin A levels (59; 60; 61; 62; 63; 64). Vitamin A in human breast milk was shown to have a statistically significant positive association with oral contraceptive use (261). However, use of progestogen-only oral contraceptives have been shown to have little or insignificant effect on vitamin A levels in the plasma (65; 60) or breast milk (65) of lactating women. Cytochrome P450 substratesCytochrome P450 substrates: According to in vitro research and secondary sources, cytochrome P450 enzymes participate in the metabolism of vitamin A (71). Dermatologic agentsDermatologic agents: In clinical research, vitamin A reduced lesions, inflammation, and symptoms in individuals with acne and psoriasis (158; 95; 82; 149; 83). According to human research and secondary sources, topical tretinoin, all-trans retinoic acid (ATRA), and prescription vitamin A therapy (such as Retin-A?, Renova?, and isotretinoin) may cause skin irritation, redness, rash, dryness, peeling, grade I-II mucocutaneous symptoms, stinging, itching, and pain (76; 77; 78; 79; 80; 81; 82; 83; 84; 85). Folate analogsFolate analogs: In pregnant women, supplementation with iron and folic acid had no overall effect on serum retinol (265). Gastrointestinal agentsGastrointestinal agents: In systematic reviews and meta-analyses, vitamin A supplementation and all-trans retinoic acid (ATRA) resulted in reports of diarrhea, nausea, vomiting, abdominal pain, and other mild gastrointestinal symptoms (86; 87; 88; 85; 89; 90; 91; 84; 92). HepatotoxinsHepatotoxins: According to secondary sources, concurrent use of vitamin A and hepatotoxic agents may increase the risk of liver damage. In clinical trials, elevated liver enzymes were reported with vitamin A supplementation (85). Iron saltsIron salts: Vitamin A supplementation improved hematological parameters and enhanced the efficacy of iron supplementation in patients with vitamin A deficiency and iron deficiency anemia (266). However, in pregnant women, supplementation with iron (or iron plus folic acid) had no overall effect on serum retinol (265). Mineral oilMineral oil: Mineral oil reduced absorption of all fat-soluble vitamins, according to secondary sources. With occasional use, the effect on vitamin A levels does not appear to be significant.Neurologic agentsNeurologic agents: In human research, clinical reports include headache, irritability, seizure, and fatigue (85; 90; 84; 92). NicotineNicotine: Smokers consuming alcohol and beta-carotene are at an increased risk for pulmonary cancer and possibly cardiovascular complications (71; 72). OrlistatOrlistat: According to human research, orlistat may decrease the absorption of fat-soluble vitamins like vitamin A (67; 68). The manufacturer of orlistat recommends that all patients take a multivitamin supplement containing all the fat-soluble vitamins (including vitamins A, D, E, and K unless otherwise contraindicated), separating the dosing time by at least two hours from orlistat. Osteoporosis drugsOsteoporosis drugs: In human research, an increased fracture risk has been reported in individuals with high serum retinol levels, as well as in individuals supplemented with vitamin A daily at 25,000 IU and higher for several months or more (73; 74; 75). PhytonadionePhytonadione: Vitamin A supplements in high doses may interfere with vitamin K absorption (99). Retinoid-containing agentsRetinoid-containing agents: Theoretically, concurrent use of retinoids with vitamin A may increase the risk of toxicity. According to secondary sources, vitamin A supplements should not be taken simultaneously with retinoids, such as acitretin (Soriatane?), anticoagulants such as warfarin (Coumadin?), bexarotene (Targretin?), all-trans retinoic acid or tretinoin (ATRA, Vesanoid?, Vesabiod?, Avita?, Renova?, Retin-A?, Retin-A? Micro, Altinac?), etretinate (Tegison?), or isotretinoin (Accutane?, Amnesteem?).VaccinesVaccines: Vitamin A may reduce seroconversion rates to the measles virus and vaccine, rendering the vaccine less effective, according to secondary sources. Other vaccines may be enhanced by vitamin A, including the Haemophilus influenzae type b vaccine and the diphtheria vaccine. Other vaccines have been demonstrated to be unaffected by vitamin A supplementation. These include the oral polio vaccine (OPV), tetanus toxoid, pertussis, and hepatitis B vaccines. Vitamin A may also alter the immune response to the Bacille Calmette-Gu?rin (BCG) vaccine, but this interaction is unclear.Valproic acidValproic acid: All-trans retinoic acid (ATRA) enhanced the effects of valproic acid, a histone deacetylase inhibitor used to treat hematological malignancies such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) (267). Vitamin A/Herb/Supplement Interactions:
AntibacterialsAntibacterials: According to human reports, concurrent use with tetracycline antibiotics may cause benign intracranial hypertension and pseudotumor cerebri (96; 97; 98). In human research, neomycin reduced the absorption of vitamin A (66). In human research, vitamin A treatment was associated with reduced risk of antibiotic failure in children with nonmeasles pneumonia (226). Clindamycin phosphate (1.2%) combined with partially solubilized and crystalline tretinoin (0.025%) suspended in an aqueous-based, alcohol-free gel, improved overall appearance to a greater extent than either ingredient alone in patients with acne (263). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Vitamin A supplements in high doses may interfere with vitamin K absorption (99) and theoretically increase the risk of bleeding. AntidepressantsAntidepressants: Anecdotal reports and clinical reports of isotretinoin use and associated depression and suicidal ideation exist (93; 94; 95). In a subgroup of vulnerable individuals, an association between depression and suicide with isotretinoin administration exists (225). AntidiarrhealsAntidiarrheals: In a systematic review, vitamin A supplementation and all-trans retinoic acid (ATRA) resulted in reports of diarrhea (84). AntifungalsAntifungals: According to secondary sources, vitamin A may interact with antifungals.AntihelminthicsAntihelminthics: According to secondary sources, vitamin A may interact with antihelminthics.AntihypertensivesAntihypertensives: In clinical research, vitamin A and all-trans retinoic acid (ATRA) supplementation, alone or in combination with chemotherapy, resulted in reports of hypotension (84; 85). AntilipemicsAntilipemics: According to secondary sources, the use of bile acid sequestrants may reduce the absorption of fat-soluble vitamins like vitamin A. In clinical research, vitamin A and all-trans retinoic acid (ATRA) supplementation, alone or in combination with chemotherapy, resulted in reports of hypertriglyceridemia and hyperlipidemia (84; 85). AntimalarialsAntimalarials: Research suggests that vitamin A may reduce fever, morbidity, and parasite blood levels in patients with malaria (Plasmodium falciparum infection) (185), and, according to secondary sources, vitamin A may interact with antimalarial agents. AntineoplasticsAntineoplastics: The use of antioxidants like vitamin A with chemotherapy is controversial; some studies suggest that antioxidants may lessen the toxic effects of chemotherapy, while others suggest that antioxidants may interfere with chemotherapeutic efficacy (70). Significantly increased toxicity has been observed in individuals who received vitamin A plus busulfan compared to those given busulfan alone (232). Israel et al. showed that in human study, vitamin A increased the response to chemotherapy more than twofold (38% vs. 15%, p<0.02). In chronic myelogenous leukemia (CML) patients, those given oral vitamin A in addition to oral pulse busulfan had somewhat longer progression-free survival times than those given busulfan alone; however, the differences were not statistically significant (p=0.11 for clinical progression-free survival, p=0.081 for survival) (232). In a pilot phase II study, 13-cis-retinoic acid (13-cis-RA) in combination with gemcitabine was well tolerated, but there was no improvement in response to gemcitabine in pancreatic cancer (264). In systematic reviews and meta-analyses, all-trans retinoic acid with chemotherapy increased the rate of complete remission and event-free survival in individuals with acute promyelocytic leukemia (84; 111). Antiobesity agentsAntiobesity agents: According to secondary sources, vitamin A may interact with antiobesity agents.AntioxidantsAntioxidants: According to secondary sources, vitamin A may interact with antioxidant herbs and supplements.AntiviralsAntivirals: According to secondary sources, vitamin A may interact with antivirals.ApplepectinApplepectin: In healthy female subjects, postprandial serum vitamin A concentrations were significantly higher when vitamin A palmitate (300,000 IU) was given with a test diet containing 15g of apple pectin compared to a control diet (268). CarobCarob: In normal female subjects, postprandial serum vitamin A concentrations were significantly higher when vitamin A palmitate (300,000 IU) was given with a test diet containing 15g of carob bean flour compared to a control diet (268). CarrageenanCarrageenan: In normal female subjects, postprandial serum vitamin A concentrations were significantly higher when vitamin A palmitate (300,000 IU) was given with a test diet containing 20g of carrageenan compared to a control diet (268). ContraceptivesContraceptives: In human research, oral contraceptives increased vitamin A levels (59; 60; 61; 62; 63; 64). Vitamin A in human breast milk was shown to have a statistically significant positive association with oral contraceptive use (261). However, use of progestogen-only oral contraceptives have been shown to have little or insignificant effect on vitamin A levels in the plasma (65; 60) or breast milk (65) of lactating women. Cytochrome P450 substratesCytochrome P450 substrates: According to in vitro research and secondary sources, cytochrome P450 enzymes participate in the metabolism of vitamin A (71). Fat-soluble vitaminsFat-soluble vitamins: According to secondary sources, vitamin A may interact with fat-soluble vitamins.FiberFiber: In normal female subjects, postprandial serum vitamin A concentrations were significantly higher when vitamin A palmitate (300,000 IU) was given with a test diet containing 15-40g of dietary fiber (40g of wheat bran, 40g of microcrystalline cellulose, 15g of apple pectin, 15g of guar flour, 15g of carob bean flour, or 20g of carrageenan) compared to a control diet (268). Folic acidFolic acid: In pregnant women, supplementation with iron and folic acid had a lack of an overall effect on serum retinol (265). Gastrointestinal agentsGastrointestinal agents: In systematic reviews and meta-analyses, vitamin A supplementation and all-trans retinoic acid resulted in reports of diarrhea, nausea, vomiting, abdominal pain, and other mild gastrointestinal symptoms (86; 87; 88; 85; 89; 90; 91; 84; 92). GuarGuar: In normal female subjects, postprandial serum vitamin A concentrations were significantly higher when vitamin A palmitate (300,000 IU) was given with a test diet containing 15g of guar flour compared to a control diet (268). Hepatotoxic agentsHepatotoxic agents: According to secondary sources, concurrent use of vitamin A and hepatotoxic agents may increase the risk of liver damage. In clinical trials, elevated liver enzymes were reported with vitamin A supplementation (85). IronIron: Vitamin A supplementation improved hematological parameters and enhanced the efficacy of iron supplementation in patients with vitamin A deficiency and iron deficiency anemia (266). However, in pregnant women, supplementation with iron (or iron plus folic acid) had no overall effect on serum retinol (265). Microcrystalline celluloseMicrocrystalline cellulose: In normal female subjects, postprandial serum vitamin A concentrations were significantly higher when vitamin A palmitate (300,000 IU) was given with a test diet containing 40g of microcrystalline cellulose compared to a control diet (268). Multiple micronutrient supplementsMultiple micronutrient supplements: In children, multiple micronutrient supplementation had small but statistically significant increases in serum retinol (269). However, in pregnant women, supplementation with multiple micronutrients, iron, or iron plus folic acid had no overall effect on serum retinol (265). Neurologic agentsNeurologic agents: In human research, clinical reports include headache, irritability, seizure, and fatigue (85; 90; 84; 92). Osteoporosis agentsOsteoporosis agents: In human research, increased fracture risk has been reported in individuals with high serum retinol levels, as well as in individuals supplemented with vitamin A daily at 25,000 IU and higher for several months or more (73; 74; 75). Plant stanols, sterolsPlant stanols, sterols: A meta-analysis of 14 trials, vitamin A (as assessed by plasma retinol levels) was not affected by stanols or sterols (270). Thyroid herbs and supplementsThyroid herbs and supplements: In a systematic review, reversible hypothyroidism was reported (85). TobaccoTobacco: Smokers consuming alcohol and beta-carotene are at increased risk for pulmonary cancer and possibly cardiovascular complications (71; 72). Wheat branWheat bran: In normal female subjects, postprandial serum vitamin A concentrations were significantly higher when vitamin A palmitate (300,000 IU) was given with a test diet containing 40g of wheat bran compared to a control diet (268). Vitamin EVitamin E: In human study, alpha-tocopherol enhanced the absorption of vitamin A (271). Vitamin KVitamin K: Vitamin A supplements in high doses may interfere with vitamin K absorption (99). ZincZinc: In children with vitamin A deficiency, combined zinc and vitamin A supplementation improved vitamin A status (272). Vitamin A/Food Interactions:
AppleApple: In normal female subjects, postprandial serum vitamin A concentrations were significantly higher when vitamin A palmitate (300,000 IU) was given with a test diet containing 15g of apple pectin compared to a control diet (268). CarobCarob: In normal female subjects, postprandial serum vitamin A concentrations were significantly higher when vitamin A palmitate (300,000 IU) was given with a test diet containing 15g of carob bean flour compared to a control diet (268). CarrageenanCarrageenan: In normal female subjects, postprandial serum vitamin A concentrations were significantly higher when vitamin A palmitate (300,000 IU) was given with a test diet containing 20g of carrageenan compared to a control diet (268). FiberFiber: In normal female subjects, postprandial serum vitamin A concentrations were significantly higher when vitamin A palmitate (300,000 IU) was given with a test diet containing 15-40g of dietary fiber (40g of wheat bran, 40g of microcrystalline cellulose, 15g of apple pectin, 15g of guar flour, 15g of carob bean flour, or 20g of carrageenan) compared to a control diet (268). Fruits and vegetablesFruits and vegetables: In a review, the authors found diets rich in fruits and vegetables, and fruit and vegetable supplements increased serum concentrations of antioxidants from plants, including beta-carotene (273). GuarGuar: In normal female subjects, postprandial serum vitamin A concentrations were significantly higher when vitamin A palmitate (300,000 IU) was given with a test diet containing 15g of guar flour compared to a control diet (268). IronIron: Vitamin A supplementation improved hematological parameters and enhanced the efficacy of iron supplementation in patients with vitamin A deficiency and iron deficiency anemia (266). However, in pregnant women, supplementation with iron (or iron plus folic acid) had no overall effect on serum retinol (265). Plant stanols, sterolsPlant stanols, sterols: A meta-analysis of 14 trials, vitamin A (as assessed by plasma retinol levels) was not affected by stanols or sterols (270). WheatWheat: In normal female subjects, postprandial serum vitamin A concentrations were significantly higher when vitamin A palmitate (300,000 IU) was given with a test diet containing 40g of wheat bran compared to a control diet (268). Vitamin K-containing foodsVitamin K-containing foods: Vitamin A supplements in high doses may interfere with vitamin K absorption (99). Vitamin A/Lab Interactions:
Beta-caroteneBeta-carotene: In a review, the authors found diets rich in fruits and vegetables, and fruit and vegetable supplements increased serum concentrations of antioxidants from plants, including beta-carotene (273). Iron levelsIron levels: Vitamin A supplementation improved hematological parameters and enhance the efficacy of iron supplementation in patients with vitamin A deficiency and iron deficiency anemia (266). Liver enzymesLiver enzymes: In clinical trials, elevated liver enzymes were reported with vitamin A supplementation (85). Vitamin KVitamin K: Vitamin A supplements in high doses may interfere with vitamin K absorption (99).