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Vitamin C (ascorbic acid)



Interactions

Vitamin C/Drug Interactions:
  • AcetaminophenAcetaminophen: In humans, high doses of oral vitamin C (3g) competitively inhibited sulfate conjugation of acetaminophen (56). However, there was also an increase in the elimination of acetaminophen glucuronide and unconjugated acetaminophen.
  • Acidifying agentsAcidifying agents: In humans, vitamin C supplementation (400-500mg daily) reduced serum uric acid levels (57; 58).
  • AntacidsAntacids: In humans, vitamin C (in the form of orange juice) enhanced aluminum absorption following the administration of the antacid preparation Aludrox® (59).
  • AntibioticsAntibiotics: In a systematic review, the effects of vitamin C were decreased by tetracycline antibiotics such as doxycycline (Vibramycin®), minocycline (Minocin®), or tetracycline (Sumycin®) (21).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In case reports from the 1970s, high doses of vitamin C (i.e., >2,000mg) interfered with the anticoagulation effects of warfarin by lowering prothrombin time (PT) (22; 23; 24; 25).
  • Antidiabetic agentsAntidiabetic agents: Vitamin C may affect glycogenolysis and increase blood sugar, according to secondary sources. In postmenopausal women with diabetes, supplemental vitamin C in doses greater than 300mg daily has been associated with an increased risk of cardiovascular mortality (14).
  • AntihypertensivesAntihypertensives: In patients with hypertension, concurrent administration of 500mg of vitamin C daily and 1000mg of grape seed polyphenols daily significantly increased systolic and diastolic blood pressure (60).
  • Antilipemic agentsAntilipemic agents: In humans with coronary artery disease, a combination of simvastatin and niacin increased low HDL cholesterol levels; however, the addition of antioxidant vitamins attenuated this increase in HDL (61).
  • Antineoplastic agentsAntineoplastic agents: Vitamin C has been hypothesized to antagonize the effects of reactive oxygen species-generating antineoplastic drugs, due to its antioxidant properties. In vitro, pretreatment with vitamin C caused a dose-dependent attenuation of cytotoxicity, as measured by trypan blue exclusion and colony formation after treatment with all antineoplastic agents tested (doxorubicin, cisplatin, vincristine, methotrexate, and imatinib) (62). In an animal lymphoma model, vitamin C pretreatment reduced the efficacy of doxorubicin (62).
  • Antiretroviral agentsAntiretroviral agents: According to a systematic review, a potential interaction may exist between vitamin C and HIV medications (26). Additional details are currently lacking.
  • AspirinAspirin: In humans on a low-ascorbic acid-intake diet, administration of acetylsalicylic acid increased urinary ascorbic acid, but at high ascorbic acid intake, acetylsalicylic acid decreased urinary ascorbic acid (63). Vitamin C may increase blood levels and adverse effects of aspirin, whereas aspirin may decrease blood levels of vitamin C, according to secondary sources. In humans, the addition of vitamin C to buffered aspirin results in less gastric irritation (64). In humans, treatment with vitamin C-releasing aspirin (ASA-VitC) induced significantly less gastric mucosal lesions than plain aspirin and also resulted in a stronger inhibition of cNOS and increase in iNOS expression in the gastric mucosa (65).
  • BarbituratesBarbiturates: In mice, pharmacological doses of ascorbic acid prolonged the effects of pentobarbital anesthesia (28).
  • Cigarette smokeCigarette smoke: In children and adolescents exposed to environmental tobacco smoke, serum ascorbic acid levels were linearly related to serum cotinine levels (r=0.19), and after controlling for confounders, environmental tobacco exposure remained significantly associated with lower levels of serum ascorbic acid in children who were exposed to both high and low levels of ETS (66; 67). The relationship of plasma and dietary vitamins C and E and tobacco use in adults has also been examined (68). Additional details are pending.
  • DiureticsDiuretics: In individuals with chronic renal failure, a 20mg intravenous dose of furosemide (Lasix) increased urinary losses of vitamin C (69).
  • EstrogensEstrogens: In monkeys, administration of combined-type (i.e., estrogen and progesterone) oral contraceptives and 100mg of ascorbic acid significantly decreased ascorbic acid excretion, and intravenous administration of radiolabeled ascorbic acid following three months of contraceptives indicated a faster ascorbic acid turnover rate (70). Oral estrogens may decrease the effects of vitamin C in the body (29). In human research, when taken together with ethinyl estradiol, vitamin C increased blood levels of ethinyl estradiol (71; 72).
  • FluphenazineFluphenazine: Vitamin C supplementation may decrease levels of the drug fluphenazine in the body (30).
  • IndinavirIndinavir: In humans, concomitant administration of high doses of vitamin C and indinavir may reduce steady-state indinavir plasma concentrations (27).
  • LevodopaLevodopa: In vitro, ascorbic acid prevented levodopa toxicity in cultured human neuroblastoma cells (73). There is limited case report evidence that high-dose vitamin C reduces the side effects of levodopa therapy such as nausea or malcoordination, according to secondary sources.
  • Nephrotoxic agentsNephrotoxic agents: High doses of vitamin C are not recommended in patients with kidney failure. Caution is advised when taking vitamin C and drugs that may damage the kidneys, due to an increased risk of kidney failure.
  • NicardipineNicardipine: In vitro, dihydropyridine calcium channel blockers inhibited ascorbic acid accumulation in human intestinal Caco-2 cells (74).
  • NicotineNicotine: In mice, ascorbic acid administration reduced the acquisition and expression of nicotine-induced place conditioning and the acquisition of nicotine sensitization (but not the expression) (75). Nicotine products, such as cigarettes, cigars, chewing tobacco, and nicotine patches, may decrease the effects of vitamin C (76).
  • ProgesteronesProgesterones: In monkeys, administration of combined-type (i.e., estrogen and progesterone) oral contraceptives and 100mg of ascorbic acid significantly decreased ascorbic acid excretion, and intravenous administration of radiolabeled ascorbic acid following three months of contraceptives indicated a faster ascorbic acid turnover rate (70).
  • Proton pump inhibitors (PPIs)Proton pump inhibitors (PPIs): In healthy volunteers, omeprazole 40mg daily for four weeks reduced plasma vitamin C levels (77).
  • SalicylatesSalicylates: In humans, vitamin C administration was not associated with a significant change in serum salicylate (78).

Vitamin C/Herb/Supplement Interactions:
  • AcerolaAcerola: Acerola contains high concentrations of vitamin C (79).
  • AntacidsAntacids: In humans, vitamin C (in the form of orange juice) enhanced aluminum absorption following administration of the antacid preparation Aludrox® (59).
  • AntibacterialsAntibacterials: In a review, the effects of vitamin C were decreased by tetracycline antibiotics such as doxycycline (Vibramycin®), minocycline (Minocin®), or tetracycline (Sumycin®) (21).
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: In case reports from the 1970s, high doses of vitamin C (i.e., >2,000mg) interfered with the anticoagulation effects of warfarin by lowering prothrombin time (PT) (22; 23; 24; 25).
  • AntilipemicsAntilipemics: In humans with coronary artery disease, a combination of simvastatin and niacin increased low HDL cholesterol levels; however, the addition of antioxidant vitamins attenuated this increase in HDL (61).
  • AntineoplasticsAntineoplastics: Vitamin C has been hypothesized to antagonize the effects of reactive oxygen species-generating antineoplastic drugs, due to its antioxidant properties. In vitro, pretreatment with vitamin C caused a dose-dependent attenuation of cytotoxicity, as measured by trypan blue exclusion and colony formation after treatment with all antineoplastic agents tested (doxorubicin, cisplatin, vincristine, methotrexate, and imatinib) (62). In animal lymphoma model, vitamin C pretreatment reduced the efficacy of doxorubicin (62).
  • AntioxidantsAntioxidants: According to secondary sources, vitamin C readily undergoes reversible oxidation and reduction in the body. Vitamin C decreases oxidants in gastric juice, lipid peroxidation, and oxidative DNA and protein damage (80).
  • AntiviralsAntivirals: According to a systematic review, a potential interaction may exist between vitamin C and HIV medications (26). Additional details are currently lacking.
  • Cherokee rosehipCherokee rosehip: Cherokee rosehip contains high concentrations of vitamin C, according to secondary sources.
  • ChromiumChromium: Vitamin C may increase chromium absorption, according to secondary sources.
  • CopperCopper: In adult men, moderate supplemental intakes of ascorbic acid reduced ceruloplasmin oxidase activity but did not depress intestinal copper absorption or overall body copper status (81). Copper decreased ascorbic acid stability in total parenteral nutrition solutions (82).
  • DiureticsDiuretics: In individuals with chronic renal failure, a 20mg intravenous dose of furosemide (Lasix) increased urinary losses of vitamin C (69).
  • Grape seed extractGrape seed extract: In patients with hypertension, concurrent administration of 500mg of vitamin C daily and 1,000mg of grape seed polyphenols daily significantly increased systolic and diastolic blood pressure (60).
  • HypoglycemicsHypoglycemics: Vitamin C may affect glycogenolysis and increase blood sugar, according to secondary sources. In postmenopausal women with diabetes, supplemental vitamin C in doses greater than 300mg daily has been associated with an increased risk of cardiovascular mortality (14).
  • HypotensivesHypotensives: In patients with hypertension, concurrent administration of 500mg of vitamin C daily and 1,000mg of grape seed polyphenols daily significantly increased systolic and diastolic blood pressure (60).
  • IronIron: Administration of ascorbic acid (molar ratio of 0.6:1 or 25mg) has been shown to increase iron absorption (17; 18; 19), although this effect appears to be variable and may not be clinically significant. In women, iron absorption from ferrous fumarate was increased following administration of ascorbic acid (83). Ascorbic acid has also been shown to increase iron absorption more in subjects with iron deficiency anemia when compared to normal controls; iron absorption was measured using radiolabeled (57)Fe and (58)Fe 14 days later (84). However, in women with low iron stores, supplementation with ascorbic acid did not affect most biochemical indices of iron status or the absorption of iron; slight increases in serum ferritin were observed (85). In healthy men, administration of ferric sodium citrate and vitamin C (under resting conditions) increased serum iron concentrations; during exercise, increases in serum iron concentrations were also observed. However, vitamin C did not further increase these levels (86). Based on a cohort study, increased intakes of vitamin C and iron may increase the risk of lung cancer (37). Possible interactions between iron and vitamin C have been systematically reviewed (87). However, additional details are currently lacking.
  • LuteinLutein: In humans, vitamin C may increase absorption of lutein vitamin supplements (88).
  • Nephrotoxic agentsNephrotoxic agents: High doses of vitamin C are not recommended in patients with kidney failure. Caution is advised when taking vitamin C and drugs that may damage the kidneys, due to an increased risk of kidney failure.
  • NiacinNiacin: In humans, a combination of simvastatin and niacin increased low HDL cholesterol levels in patients with coronary artery disease; however, the addition of antioxidant vitamins attenuated this increase in HDL (61).
  • PhytoestrogensPhytoestrogens: In monkeys, administration of combined-type oral contraceptives and 100mg of ascorbic acid significantly decreased ascorbic acid excretion, and intravenous administration of radiolabeled ascorbic acid following three months of contraceptives indicated a faster ascorbic acid turnover rate (70). Oral estrogens may decrease the effects of vitamin C in the body (29). In human research, when taken together with ethinyl estradiol, vitamin C increased blood levels of ethinyl estradiol (71; 72).
  • TobaccoTobacco: In children and adolescents exposed to environmental tobacco smoke, serum ascorbic acid levels were linearly related to serum cotinine levels (r=0.19) and, after controlling for confounders, environmental tobacco exposure remained significantly associated with lower levels of serum ascorbic acid in children who were exposed to both high and low levels of ETS (66; 67). The relationship of plasma and dietary vitamins C and E and tobacco use in adults has also been examined (68). Additional details are pending.
  • Urine-acidifying herbs and supplementsUrine-acidifying herbs and supplements: In humans, vitamin C supplementation (400-500mg daily) reduced serum uric acid levels (57; 58).
  • Vitamin B12Vitamin B12: Large doses of vitamin C may interfere with the absorption and metabolism of vitamin B12, according to secondary sources.
  • Vitamin EVitamin E: In male smokers who had high dietary intakes of vitamin C, vitamin E supplementation was linked to an increased risk of tuberculosis (40). In a randomized controlled trial, no beneficial effects for several cardiovascular risk factors were observed with vitamins C and E (89).

Vitamin C/Food Interactions:
  • Orange juiceOrange juice: During refrigeration, ascorbic acid in orange juice is oxidized (90).
  • GrapefruitGrapefruit: When taken together with vitamin C, grapefruit may increase vitamin C levels, according to secondary sources.

Vitamin C/Lab Interactions:
  • BilirubinBilirubin: Based on secondary sources, large amounts of vitamin C may cause a false increase in serum bilirubin test results.
  • Blood pressureBlood pressure: In patients with hypertension, concurrent administration of 500mg of vitamin C daily and 1,000mg of grape seed polyphenols daily significantly increased systolic and diastolic blood pressure (60).
  • Carbamazepine levelsCarbamazepine levels: Vitamin C supplements may cause false increases in blood carbamazepine levels, according to secondary sources.
  • CholesterolCholesterol: In humans with coronary artery disease, a combination of simvastatin and niacin increased low HDL cholesterol levels; however, the addition of antioxidant vitamins attenuated this increase in HDL (61).
  • Colorectal cancer screeningColorectal cancer screening: Based on expert opinion, the only dietary restrictions that patients should adhere to prior to undergoing a fecal occult blood test (FOBT) is to eliminate vitamin C supplements and citrus fruits and juices for three days prior to and during stool collection (91).
  • CortisolCortisol: Administration of ascorbic acid resulted in a significant alteration in serum cortisol levels 24 hours postexercise (92).
  • CreatineCreatine: Vitamin C supplements may cause false increases in blood creatinine levels, according to secondary sources.
  • GlucoseGlucose: Vitamin C supplements may interfere with the accuracy of blood glucose tests, according to secondary sources.
  • HbA1cHbA1c: In a population-based study, mean plasma vitamin C levels were higher in individuals with HbA1c levels <7% than in those with self-reported diabetes (93).
  • InsulinInsulin: Administration of vitamin C and zinc decreased fasting plasma insulin in postmenopausal women with type 2 diabetes (94).
  • IronIron: Administration of ascorbic acid (molar ratio of 0.6:1 or 25mg) has been shown to increase iron absorption (17; 18; 19), although this effect appears to be variable and may not be clinically significant. In women, iron absorption from ferrous fumarate was increased following administration of ascorbic acid (83). Ascorbic acid has also been shown to increase iron absorption more in subjects with iron deficiency anemia when compared to normal controls; iron absorption was measured using radiolabeled (57)Fe and (58)Fe 14 days later (84). However, in women with low iron stores, supplementation with ascorbic acid did not affect most biochemical indices of iron status or the absorption of iron; slight increases in serum ferritin were observed (85). In healthy men, administration of ferric sodium citrate and vitamin C (under resting conditions) increased serum iron concentrations; during exercise, increases in serum iron concentrations were also observed. However, vitamin C did not further increase these levels (86). Based on a cohort study, increased intakes of vitamin C and iron may increase the risk of lung cancer (37). Possible interactions between iron and vitamin C have been systematically reviewed (87). However, additional details are currently lacking.
  • LeadLead: Based on a cross-sectional analysis of a probability sample of children in the United States, children in the highest serum ascorbic acid tertile had a significantly decreased prevalence of elevated blood lead levels compared with those in the lowest serum ascorbic acid (95).
  • Liver enzymesLiver enzymes: Although specific information for vitamin C is currently unknown, antioxidant supplements may increase liver enzymes, based on a systematic review (96). Vitamin C may cause a false decrease in blood lactose dehydrogenase (LDH) levels, according to secondary sources. Vitamin C supplements may cause false increases in blood glutamic oxaloacetic transaminase (SGOT) levels, according to secondary sources.
  • Prothrombin time (PT)Prothrombin time (PT): In case reports from the 1970s, high doses of vitamin C (i.e., >2,000mg) interfered with the anticoagulation effects of warfarin by lowering prothrombin time (PT) (22; 23; 24; 25). Complications have not been reported (such as increased blood clots).
  • Stool occult blood (guaiac)Stool occult blood (guaiac): Vitamin C supplements may cause false-negative stool occult blood tests within 48-72 hours after vitamin C ingestion, according to secondary sources.
  • Theophylline levelsTheophylline levels: Vitamin C supplements may cause false decreases in blood theophylline levels, according to secondary sources.
  • Uric acidUric acid: In humans, vitamin C supplementation (400-500mg daily) reduced serum uric acid levels (57; 58).
  • Urinary acetaminophen (Tylenol)Urinary acetaminophen (Tylenol): Vitamin C supplements may cause false-negative urine acetaminophen tests, according to secondary sources.
  • Urinary glucoseUrinary glucose: Vitamin C supplements may cause false-positive urinary glucose results with the cupric sulfate reagent test, and false-negative urinary glucose results with the glucose oxidase test, within 48-72 hours after vitamin C ingestion, according to secondary sources.

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