Super Flora Ingredients & Drug Interactions

Theoretically, the caffeine in yerba mate might increase the risk for stimulant adverse effects when used concomitantly with ephedrine.
Use of ephedrine with caffeine can increase the risk of stimulatory adverse effects. There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death.

Theoretically, the caffeine in yerba mate might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Yerba mate contains caffeine. Some evidence shows that caffeine is a competitive inhibitor of adenosine and can reduce the vasodilatory effects of adenosine in humans. However, other research shows that caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine. Still, some researchers recommend that methylxanthines, such as caffeine, as well as methylxanthine-containing products, should be stopped 24 hours prior to pharmacological stress tests. However, methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing.

Theoretically, the caffeine in yerba mate may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Yerba mate contains caffeine. Caffeine is reported to have antiplatelet activity. Theoretically, it might increase the risk of bleeding when used concomitantly with these agents; however, this interaction has not been reported in humans.

Theoretically, the caffeine in yerba mate might reduce the efficacy of benzodiazepines.
Yerba mate contains caffeine. Caffeine can antagonize the anxiolytic effects of benzodiazepines.

Theoretically, the caffeine in yerba mate might increase the cardiac inotropic effects of beta-agonists, especially if taken in large amounts.
Yerba mate contains caffeine. Caffeine can increase cardiac inotropic effects of beta-agonists.

Theoretically, the caffeine in yerba mate might reduce the effects of carbamazepine and increase the risk for convulsions.
Yerba mate contains caffeine. Animal research suggests that caffeine can lower the anticonvulsant effects of carbamazepine and can induce seizures when taken in doses above 400 mg/kg. Human research has shown that taking caffeine 300 mg in three divided doses along with carbamazepine 200 mg reduces the bioavailability of carbamazepine by 32% and prolongs the plasma half-life of carbamazepine two-fold in healthy individuals.

Theoretically, cimetidine might increase the levels and adverse effects of the caffeine contained in yerba mate.
Yerba mate contains caffeine. Cimetidine decreases caffeine clearance by 31% to 42%.

Theoretically, the caffeine in yerba mate might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Yerba mate contains caffeine. Caffeine might increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg per day inhibit clozapine metabolism. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Although researchers speculate that caffeine might inhibit CYP1A2, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients more sensitive to an interaction between clozapine and caffeine.

Theoretically, the caffeine in yerba mate might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Yerba mate contains caffeine. Caffeine inhibits dipyridamole-induced vasodilation. Still, some researchers recommend that methylxanthines, such as caffeine, as well as methylxanthine-containing products, should be stopped 24 hours prior to pharmacological stress. Methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing.

Theoretically, disulfiram might increase the levels and adverse effects of the caffeine in yerba mate.
Yerba mate contains caffeine. Disulfiram decreases the rate of caffeine clearance.

Theoretically, the caffeine in yerba mate might increase the risk of hypokalemia when used concomitantly with other diuretics.
Yerba mate contains caffeine. Caffeine, especially in excessive amounts, can reduce potassium levels due to stimulation of the sodium-potassium pump. Diuretics can also cause lower potassium levels.

Theoretically, estrogens might increase the levels and adverse effects of the caffeine in yerba mate.
Yerba mate contains caffeine. Estrogen inhibits caffeine metabolism.

Theoretically, the caffeine in yerba mate might reduce the effects of ethosuximide and increase the risk for convulsion.
Yerba mate contains caffeine. Animal research shows that caffeine 92.4 mg/kg can decrease the anticonvulsant activity of ethosuximide. However, this effect has not been reported in humans.

Theoretically, the caffeine in yerba mate might reduce the effects of felbamate and increase the risk for convulsion.
Yerba mate contains caffeine. Animal research shows that a high dose of caffeine 161.7 mg/kg can decreases the anticonvulsant activity of felbamate. However, this effect has not been reported in humans.

Theoretically, the caffeine in yerba mate might increase the levels and adverse effects of flutamide.
Yerba mate contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide. However, this effect has not been reported in humans.

Theoretically, fluvoxamine might increase the levels and adverse effects of the caffeine in yerba mate.
Yerba mate contains caffeine. Fluvoxamine reduces caffeine metabolism.

Theoretically, abrupt withdrawal of the caffeine in yerba mate might increase serum lithium levels.
Yerba mate contains caffeine, which has diuretic activity. When abruptly discontinued, it might alter the clearance of lithium. There are two case reports of lithium tremor that worsened upon abrupt coffee withdrawal.

Theoretically, use of yerba mate with midazolam might increase midazolam metabolite levels and adverse effects.
In vitro research shows that yerba mate extract containing 6.75% chlorogenic acid significantly inhibits the metabolism of midazolam via inhibition of cytochrome P450 3A4 (CYP3A4).

Theoretically, the caffeine in yerba mate might increase risk of a hypertensive crisis when used concomitantly with MAOIs.
Yerba mate contains caffeine. Caffeine has been shown to inhibit monoamine oxidase (MAO) A and B in laboratory studies. Concomitant intake of large amounts of caffeine with MAOIs might precipitate a hypertensive crisis. In a case report, a patient that consumed 10-12 cups of caffeinated coffee and took the MAOI tranylcypromine presented with severe hypertension. Hypertension was resolved after the patient switched to drinking decaffeinated coffee.

Theoretically, the caffeine in yerba mate might increase risk of hypertension when used concomitantly with nicotine.
Yerba mate contains caffeine. Concomitant use of caffeine and nicotine has been shown to have additive cardiovascular effects, including increased heart rate and blood pressure. Blood pressure was increased by 10.8/12.4 mmHg when the agents were used concomitantly.

Theoretically, the caffeine in yerba mate might decrease the effects of pentobarbital.
The caffeine in yerba mate might negate the hypnotic effects of pentobarbital.

Theoretically, the caffeine in yerba mate might reduce the effects of phenobarbital and increase the risk for convulsions.
Yerba mate contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of phenobarbital. However, the exact mechanism of this interaction is unclear.

Theoretically, phenylpropanolamine might increase the risk of hypertension as well as the levels and adverse effects of the caffeine in yerba mate.
Yerba mate contains caffeine. Concomitant use of phenylpropanolamine and caffeine might cause an additive increase in blood pressure. Phenylpropanolamine also seems to increase caffeine serum levels.

Theoretically, the caffeine in yerba mate might reduce the effects of phenytoin and increase the risk for convulsions.
Yerba mate contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of phenytoin. The effect does not seem to be related to the seizure threshold-lowering effects of caffeine. However, the exact mechanism of this interaction is unclear.

Theoretically, the caffeine in yerba mate might increase the levels and clinical effects of pioglitazone.
Yerba mate contains caffeine. Animal research suggests that caffeine can modestly increase the maximum concentration, area under the curve, and half-life of pioglitazone, and also reduce its clearance. This increased the antidiabetic effects of pioglitazone. However, the exact mechanism of this interaction is unclear.

Ginger may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.
Laboratory research suggests that ginger inhibits thromboxane synthetase and decreases platelet aggregation. However, this has not been demonstrated unequivocally in humans, with mixed results from clinical trials. Theoretically, excessive amounts of ginger might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.

Theoretically, taking ginger with antidiabetes drugs might increase the risk of hypoglycemia.
Animal and human research suggests that ginger might increase insulin levels and/or decrease blood glucose levels.

Ginger might increase or decrease the levels of CYP3A4 substrates.
In vitro research and some case reports suggest that ginger inhibits CYP3A4 activity. Three case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are CYP3A4 substrates (imatinib, dabrafenib, and crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration.
Conversely, other in vitro research suggests that ginger induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates. However, this interaction has not been reported in humans.

Theoretically, ginger might increase levels of losartan and the risk of hypotension.
In animal research, ginger increased the levels and hypotensive effects of a single dose of losartan. It is not clear if ginger alters the concentration or effects of losartan when taken continuously. Additionally, this interaction has not been shown in humans.

Ginger may have antiplatelet effects and increase the risk of bleeding if used with nifedipine.
Clinical research shows that combined treatment with ginger 1 gram plus nifedipine 10 mg significantly inhibits platelet aggregation when compared to nifedipine or ginger alone.

Ginger might increase the absorption and blood levels of P-glycoprotein (P-gp) substrates.
In vitro research and case reports suggest that ginger inhibits drug efflux by P-gp, potentially increasing absorption and serum levels of P-gp substrates. Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are P-gp substrates (trametinib, crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration.

Ginger might increase the risk of bleeding with phenprocoumon.
Phenprocoumon, a warfarin-related anticoagulant, might increase the international normalized ratio (INR) when taken with ginger. There is one case report of a 76-year-old woman with a stable INR on phenprocoumon that increased to greater than 10 when she began consuming dried ginger and ginger tea.

Ginger might increase the risk of bleeding with warfarin.
Laboratory research suggests that ginger might inhibit thromboxane synthetase and decrease platelet aggregation. In one case report, ginger increased the INR when taken with phenprocoumon, which has similar pharmacological effects as warfarin. In another case report, ginger increased the INR when taken with a combination of warfarin, hydrochlorothiazide, and acetaminophen. A longitudinal analysis suggests that taking ginger increases the risk of bleeding in patients taking warfarin for at least 4 months. However, research in healthy people suggests that ginger has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin. Until more is known, monitor INRs closely in patients taking large amounts of ginger.

Theoretically, taking ginger with calcium channel blockers might increase the risk of hypotension.
Some animal and in vitro research suggests that ginger has hypotensive and calcium channel-blocking effects. Another animal study shows that concomitant administration of ginger and the calcium channel blocker amlodipine leads to greater reductions in blood pressure when compared with amlodipine alone.

Theoretically, when taken prior to cyclosporine, ginger might decrease cyclosporine levels.
In an animal model, ginger juice taken 2 hours prior to cyclosporine administration reduced the maximum concentration and area under the curve of cyclosporine by 51% and 40%, respectively. This effect was not observed when ginger juice and cyclosporine were administered at the same time.

Theoretically, ginger might increase the levels of CYP1A2 substrates.
In vitro research shows that ginger inhibits CYP1A2 activity. However, this interaction has not been reported in humans.

Theoretically, ginger might increase the levels of CYP2B6 substrates.
In vitro research shows that ginger inhibits CYP2B6 activity. However, this interaction has not been reported in humans.

Theoretically, ginger might increase the levels of CYP2C9 substrates.
In vitro research shows that ginger inhibits CYP2C9 activity. However, this interaction has not been reported in humans.

Theoretically, ginger might increase levels of metronidazole.
In an animal model, ginger increased the absorption and plasma half-life of metronidazole. In addition, the elimination rate and clearance of metronidazole was significantly reduced.

Theoretically, concomitant use of clove extracts with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical and laboratory research suggest that polyphenol extracts from clove flower buds might lower blood glucose levels. Dosing adjustments for insulin or oral hypoglycemic agents may be necessary when taken with clove. Monitor blood glucose levels closely.

Theoretically, concomitant use of clove may increase levels of drugs metabolized by CYP1A2.
In vitro research shows that eugenol, the principal constituent of clove, can inhibit CYP1A2 in a dose-dependent manner,. This effect has not been reported in humans.

Theoretically, concomitant use of clove may increase levels of drugs metabolized by CYP2C9.
In vitro research shows that eugenol, the principal constituent of clove, inhibits CYP2C9 in a dose-dependent manner. This effect has not been reported in humans.

Theoretically, concomitant use of clove may increase levels of drugs metabolized by CYP2D6.
In vitro research shows that eugenol, the principal constituent of clove, can inhibit CYP2D6 in a dose-dependent manner. This effect has not been reported in humans.

Theoretically, concomitant use of clove may increase levels of drugs metabolized by CYP3A4.
In vitro research shows that eugenol, the principal constituent of clove, can inhibit CYP3A4 in a dose-dependent manner. This effect has not been reported in humans.

Theoretically, clove oil may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Laboratory research suggests that eugenol, a constituent of clove, has antiplatelet activity. This interaction has not been reported in humans.

Theoretically, topical application of clove oil with ibuprofen might increase the absorption and side effects of topical ibuprofen.
Laboratory research shows that topical application of clove oil increases the absorption of topical ibuprofen. This interaction has not been reported in humans.

Theoretically, grape extracts may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro evidence suggests that grape extracts might decrease platelet aggregation.

Ingesting grape juice with cyclosporine can reduce cyclosporine absorption.
A small pharmacokinetic study in healthy young adults shows that intake of purple grape juice 200 mL along with cyclosporine can decrease the absorption of cyclosporine by up to 30% when compared with water. Separate doses of grape juice and cyclosporine by at least 2 hours to avoid this interaction.

Theoretically, grape juice might reduce the levels of CYP1A2 substrates.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of CYP1A2.

Theoretically, grape seed extract may increase the levels of CYP2D6 substrates.
In vitro evidence suggests that grape seed extract might inhibit CYP2D6 enzymes. However, this interaction has not been reported in humans.

Theoretically, grape seed extract might increase the levels of CYP2E1 substrates.
In vitro and animal research suggests that grape seed proanthocyanidin extract inhibits CYP2E1 enzymes. However, this interaction has not been reported in humans.

It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
In vitro evidence suggests that grape seed extract might inhibit CYP3A4 enzymes. However, evidence from animal research shows that grape seed extract may induce CYP3A4 in the liver. So far, these interactions have not been reported in humans.

Theoretically, long-term intake of grape seed extract might decrease the effects of midazolam.
Animal research shows that subchronic ingestions of grape seed extract can increase the elimination of intravenous midazolam by increasing hepatic CYP3A4 activity. Single doses of grape seed extract do not appear to affect midazolam elimination.

Grape juice might decrease phenacetin absorption.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of cytochrome P450 1A2 (CYP1A2).

It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.
In vitro evidence shows that grape seed extract or grape juice might inhibit CYP2C9 enzymes. However, a small pharmacokinetic study in healthy adults shows that drinking 8 ounces of grape juice once does not affect the clearance of flurbiprofen, a probe-drug for CYP2C9 metabolism. The effects of continued grape juice consumption are unclear.

Theoretically, beet might increase the levels of CYP3A4 substrates.
In vitro research suggests that betanin, the major pigment in beet, competitively inhibits CYP3A4 in a dose-dependent manner similarly to strong CYP3A4 inhibitor ketoconazole.

Beet and beetroot contain nitrates, which can cause vasodilation, potentially leading to lower blood pressure. However, a study published in the European Journal of Clinical Nutrition using concentrated beetroot juice found no significant impact on blood pressure or heart rate in different age groups. Other small clinical studies suggest that while beet consumption might transiently lower blood pressure due to vessel dilation, there's no consistent evidence of a lasting effect. Overall, the theoretical risk of reduced blood pressure due to beet's nitrate content exists, but studies generally indicate a low and temporary impact rather than a sustained decrease.

Theoretically, beet might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research suggests that beet induces CYP1A2 enzymes.

Theoretically, lemongrass might decrease the metabolism of CYP3A4 substrates.
Animal research shows that lemongrass and its constituent citral inhibit CYP3A4.

Theoretically, lemongrass might increase the clearance and decrease the levels of glucuronidated drugs.
Animal research shows that lemongrass and its constituent citral induce uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation.

Theoretically, lemongrass might increase the effects and adverse effects of pentobarbital.
Animal research shows that high doses of lemongrass essential oil increases sleep time and decreases time to fall asleep in animals administered pentobarbital.

Theoretically, zedoary might increase levels of drugs metabolized by CYP3A4.
In-vitro research shows that a methanol extract of zedoary strongly inhibits the CYP3A4 metabolism of the tyrosine kinase inhibitors lapatinib and sorafenib, and to a lesser extent, gefitinib.

Taking soy products containing high amounts of tyramine along with MAOIs can increase the risk of hypertensive crisis.
Fermented soy products such as tofu and soy sauce contain tyramine, a naturally occurring chemical that affects blood pressure regulation. The metabolism of tyramine is decreased by MAOIs. Consuming more than 6 mg of tyramine while taking an MAOI can increase the risk of hypertensive crisis. The amount of tyramine in fermented soy products is usually less than 0.6 mg per serving; however, there can be significant variation depending on the specific product used, storage conditions, and length of storage. Storing one brand of tofu for a week can increase tyramine content from 0.23 mg to 4.8 mg per serving. Advise patients taking MAOIs to avoid fermented soy products that contain high amounts of tyramine.

Soy can lower blood glucose and have additive effects with antidiabetes drugs.
Clinical research shows that whole soy diets and soy-based meals reduce fasting glucose levels in diabetic and non-diabetic individuals. Also, individuals following a soy-based meal replacement plan seem to require lower doses of sulfonylureas and metformin to manage blood glucose levels when compared with individuals following a diet plan recommended by the American Diabetes Association.

Theoretically soy protein may have additive effects with antihypertensive drugs and increase the risk of hypotension.
Although some contradictory research exists, most clinical evidence suggests that consuming soy protein modestly reduces systolic and diastolic blood pressure in individuals with prehypertension or hypertension.

Theoretically, soy might reduce the clearance of caffeine.
Soy contains genistein. Taking genistein 1 gram daily for 14 days seems to inhibit caffeine clearance and metabolism in healthy females. This effect has been attributed to inhibition of the cytochrome P450 1A2 (CYP1A2) enzyme, which is involved in caffeine metabolism. It is unclear if this effect occurs with the lower amounts of genistein found in soy.

Theoretically, soy might have additive effects when used with diuretic drugs.
Animal research suggests that genistein, a soy isoflavone, increases diuresis within 6 hours of subcutaneous administration in rats. The effects seem to be similar to those of furosemide. This effect has not been reported in humans.

Theoretically, soy might competitively inhibit the effects of estrogen replacement therapy.
Soy contains phytoestrogens and has been shown to have estrogenic activity in some patients. Although this has not been demonstrated in humans, theoretically, concomitant use of soy with estrogen replacement therapy might reduce the effects of the estrogen replacement therapy.

Soy products might reduce the absorption of levothyroxine in some patients.
Preliminary clinical research and a case report suggest that soy-based formulas inhibit the absorption of levothyroxine in infants with congenital hypothyroidism. A levothyroxine dosage increase may be needed for infants with congenital hypothyroidism while using soy-based formulas, and the dose may need to be reduced when soy-based formulas are no longer administered. However, in postmenopausal adults, clinical research shows that taking a single dose of soy extract containing isoflavones 60 mg along with levothyroxine does not affect the oral bioavailability of levothyroxine.

Theoretically, combining soy isoflavones with transdermal progesterone may worsen bone density.
Clinical research suggests that significant bone loss may occur in females with osteoporosis who receive a combination of transdermal progesterone with soy milk containing isoflavones when compared with placebo, soy milk alone, or progesterone alone.

Theoretically, estrogenic soy isoflavones might alter the effects of tamoxifen.
Laboratory research suggests that genistein and daidzen, isoflavones from soy, can antagonize the antitumor effects of tamoxifen under some circumstances; however, soy isoflavones might have different effects when used at different doses. A relatively low in vitro concentration of soy isoflavones such as 1 microM/L seems to interfere with tamoxifen, whereas high in vitro concentrations such as those >10 microM/L might actually enhance tamoxifen effects. People on a high-soy diet have soy isoflavones levels ranging from 0.1-6 microM/L. Until more is known, advise patients taking tamoxifen to avoid therapeutic use of soy products.

Theoretically, soy might interfere with the effects of warfarin.
Soy milk has been reported to decrease the international normalized ratio (INR) in a patient taking warfarin. The mechanism of this interaction is not known. However, animal and in vitro research suggests that soy may also inhibit platelet aggregation. Dosing adjustments for warfarin may be necessary.

Theoretically, antibiotics may decrease the activity of soy isoflavones.
Intestinal bacteria are responsible in part for converting soy isoflavones into their active forms. Antibiotics may decrease the amount of intestinal bacteria and decrease its ability to convert isoflavones.

Soy might modestly induce CYP2C9 enzymes. However, this effect does not seem to be clinically significant.
In vitro research suggests that an unhydrolyzed soy extract might induce CYP2C9. However, the significance of this interaction is likely minimal. In healthy females taking a specific extract of soy (Genistein Soy Complex, Source Naturals), blood levels of losartan, a CYP2C9 substrate, were not significantly affected.

Taking sesame oil with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical studies show that sesame oil can decrease plasma glucose and glycated hemoglobin (HbA1c) levels. Some clinical research in patients taking glibenclamide shows that using sesame oil or a blend of sesame oil and rice bran oil in place of other oil for cooking reduces plasma glucose more than glibenclamide alone. Monitor blood glucose levels closely. Dose adjustments might be necessary.

Taking sesame oil with antihypertensive drugs might increase the risk of hypotension.
Clinical research shows that replacing other cooking oil with sesame oil can lower systolic blood pressure (SBP) and diastolic blood pressure (DBP) in patients with or without hypertension. There is also some evidence that sesame oil has additive effects in patients also taking atenolol, nifedipine, and/or hydrochlorothiazide. In patients using nifedipine, using a blend of sesame oil and rice bran oil for cooking reduces both SBP and DBP more than nifedipine alone.

Theoretically, sesame might increase the levels and clinical effects of CYP2C9 substrates.
In vitro, sesame inhibits CYP2C9. However, this interaction has not been reported in humans.

Theoretically, sesame might interfere with tamoxifen.
In animal research, sesame seed reduces the tumor-inhibitory effect of tamoxifen by reducing apoptosis and increasing proliferation. This interaction has not been reported in humans.

Theoretically, sesame might alter the transport of P-glycoprotein substrates.
In vitro research suggests that sesamin, a constituent of sesame, can inhibit the multi-drug transporter protein, P-glycoprotein. However, this interaction has not been reported in humans.

Theoretically, cassia cinnamon may have additive effects with antidiabetes drugs.
Cassia cinnamon may lower blood glucose levels, and have additive effects in patients treated with antidiabetic agents. Dose adjustments to diabetes medications might be necessary.

Theoretically, large doses of cassia cinnamon might cause additive effects when used with hepatotoxic drugs.
There is some concern that ingesting large amounts of cassia cinnamon for an extended duration might cause hepatotoxicity in some people. Cassia cinnamon contains coumarin, which can cause hepatotoxicity in animal models. In humans, very high doses of coumarin from 50-7000 mg/day can result in hepatotoxicity that resolves when coumarin use is discontinued. Lower amounts might also cause liver problems in sensitive people, such as those with liver disease or those taking potentially hepatotoxic agents.

Theoretically, chlorella might have additive effects with photosensitizing drugs.
Chlorella has been reported to cause photosensitization. In five case reports, patients who had ingested chlorella exhibited swelling followed by erythematopurpuric lesions on sun-exposed areas of the body. Theoretically, concomitant use with photosensitizing drugs may exacerbate effects.

Theoretically, chlorella might reduce the clinical effects of warfarin.
Chlorella contains significant amounts of vitamin K. There is at least one case report of warfarin therapy becoming sub-therapeutic after initiation of chlorella supplements.

Cabbage might increase clearance and reduce the effects of acetaminophen.
A small clinical study shows that daily consumption of cabbage and Brussels sprout decreases acetaminophen levels by as much as 16%, with some evidence suggesting that this effect is due to increased elimination through glucuronide conjugation.

Theoretically, cabbage might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Animal and in vivo research suggests that cabbage might have hypoglycemic effects.

Theoretically, cabbage might decrease levels of drugs metabolized by CYP1A2.
Some animal research suggests that cabbage or its constituent indole-3-carbinol might increase drug metabolism and elimination by stimulating CYP1A2 activity.

Theoretically, cabbage might increase clearance and decrease the effects of drugs metabolized through glucuronide conjugation.
A small clinical study shows that daily consumption of cabbage and Brussels sprout decreases levels of some drugs metabolized through glucuronide conjugation.

Cabbage might increase clearance and reduce the effects of oxazepam.
A small clinical study shows that daily consumption of cabbage and brussels sprout decreases oxazepam levels by as much as 17%, with some evidence suggesting that this effect is due to increased elimination through glucuronide conjugation.

Theoretically, cabbage might decrease the anticoagulant effects of warfarin.
Cabbage contains vitamin K. If consumed in large quantities, cabbage might decrease the anticoagulant effects of warfarin.

Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of OATP substrates.
Research shows that consuming apple juice inhibits OATP, which reduces bioavailability of oral drugs that are substrates of OATP. Fexofenadine, atenolol, and aliskiren are substrates of OATP. Clinical research shows that coadministration of apple juice decreases bioavailability of fexofenadine by up to 78%, aliskiren by 63%, and atenolol by up to 82%. These effects appear to increase with larger quantities of apple juice. It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction.

Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of aliskiren.
Pharmacokinetic research shows that coadministration of apple juice 200 mL along with aliskiren 150 mg decreases the bioavailability of aliskiren by 63%. Apple juice seems to inhibit organic anion transporting polypeptide (OATP), which is involved in drug uptake in the gut, liver, and kidney. It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction.

Theoretically, consuming apple juice with antidiabetes drugs might interfere with blood glucose control.
Clinical research suggests that consuming apples or drinking apple juice can raise blood glucose levels, with the effects of drinking apple juice being more significant than consuming apples.

Consuming apple juice with antihypertensive drugs might interfere with blood pressure control.
Some clinical evidence suggests that consuming apple and cherry juice can increase blood pressure in elderly patients.

Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of atenolol.
Pharmacokinetic research shows that coadministration of apple juice 600-1200 mL decreases levels of atenolol by 58% to 82% in a dose-dependent manner. Apple juice seems to inhibit organic anion transporting polypeptide (OATP), which is involved in drug uptake in the gut, liver, and kidney. It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction.

Concomitant consumption of apple juice can significantly decrease oral absorption and blood levels of fexofenadine.
Pharmacokinetic research shows that coadministration of apple juice 400-1200 mL along with fexofenadine 60-120 mg decreases bioavailability of fexofenadine by up to 78%. Coadministration with smaller quantities of apple juice (150 mL or less) does not appear to affect the bioavailability of fexofenadine. Apple juice seems to inhibit organic anion transporting polypeptide (OATP), which is involved in drug uptake in the gut, liver, and kidney. It is thought that apple juice might affect OATP for only a short time. Therefore, separating drug administration and consumption of apple juice by at least 4 hours might avoid this interaction.

There is some concern that concomitant consumption of apple juice might decrease oral absorption and blood levels of lithium.
In one case report, a patient had an undetectable serum lithium level when lithium citrate was administered with apple juice. When lithium was administered with an alternative beverage, the lithium level became detectable and the patient demonstrated clinical improvement.

Clinical research suggests that kiwi inhibits platelet aggregation. Theoretically, kiwi might increase the risk of bleeding when used with antiplatelet or anticoagulant drugs. Some anticoagulant or antiplatelet drugs include aspirin, clopidogrel (Plavix), dalteparin (Fragmin), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), warfarin (Coumadin), and others.

Clinical research suggests that consuming kiwi reduces systolic and diastolic blood pressure in hypertensive individuals. Theoretically, concomitant use of kiwi and antihypertensive drugs may increase the risk of hypotension when used in combination with drugs that lower blood pressure. These include captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), amlodipine (Norvasc), hydrochlorothiazide (HydroDiuril), furosemide (Lasix), and many others.

Consuming sweet orange with celiprolol can decrease oral absorption of celiprolol.
A pharmacokinetic study in healthy volunteers shows that celiprolol levels, after a single dose of 100 mg, are decreased by up to 90% in people who drink sweet orange juice 200 mL three times daily. It's not known if lower consumption of sweet orange juice will have the same effect. Theoretically, this occurs due to short-term inhibition of organic anion transporting polypeptide (OATP). Recommend separating drug administration and consumption of sweet orange by at least 4 hours.

Consuming sweet orange juice with ivermectin can decrease the oral absorption of ivermectin.
A pharmacokinetic study in healthy volunteers shows that taking ivermectin orally with sweet orange juice 750 mL over 4 hours reduces the bioavailability of ivermectin. This effect does not seem to be related to effects on P-glycoprotein. The effect on ivermectin is more pronounced in males compared to females.

Consuming sweet orange juice can decrease oral absorption of OATP substrates. Separate administration by at least 4 hours.
Clinical research shows that consuming sweet orange juice inhibits OATP, which reduces bioavailability of oral drugs that are substrates of OATP. For example, sweet orange juice decreases bioavailability of fexofenadine, a substrate of OATP, by about 72% and of celiprolol, another OATP substrate, by up to 90%. Since sweet orange juice seems to affect OATP for a short time, recommend separating drug administration and consumption of sweet orange juice by at least 4 hours.

Consuming sweet orange juice with pravastatin can increase the absorption of pravastatin.
A small pharmacokinetic study in healthy volunteers shows that consuming sweet orange juice 800 mL over 3 hours, including before, during, and after taking pravastatin 10 mg, increases pravastatin levels by about 149%, without affecting pravastatin elimination. Theoretically this effect might be due to modulation of organic anion transporting polypeptides (OATPs) by sweet orange juice. Sweet orange juice does not seem to affect simvastatin levels, but it is not known if sweet orange affects any of the other statins.

Consuming sweet orange juice with fexofenadine can decrease oral absorption of fexofenadine.
Clinical research shows that coadministration of sweet orange juice 1200 mL decreases bioavailability of fexofenadine by about 72%. In an animal model, sweet orange juice decreased bioavailability of fexofenadine by 31%. Fexofenadine manufacturer data indicates that concomitant administration of sweet orange juice and fexofenadine results in larger wheal and flare sizes in research models. This suggests that sweet orange reduces the clinical response to fexofenadine. Theoretically, this occurs due to short-term inhibition of organic anion transporting polypeptide (OATP). Recommend separating drug administration and consumption of sweet orange by at least 4 hours.

Sweet orange juice seems to modulate P-glycoprotein (P-gp), which might affect the blood levels of P-gp substrates.
Animal and in vitro research suggest that orange juice extract inhibits drug efflux by P-gp, increasing absorption and levels of P-gp substrates. In contrast, pharmacokinetic research in humans shows that drinking large amounts of sweet orange juice decreases absorption and levels of the P-gp substrate celiprolol. This suggests that orange juice actually induces drug efflux by P-gp or affects drug levels by another mechanism such as inhibiting the gut drug transporter called organic anion transporting polypeptide (OATP). Until more is known, sweet orange juice should be used cautiously in people taking P-gp substrates.

Calcium-fortified sweet orange juice might reduce quinolone absorption.
Calcium binds to quinolones in the gut. Theoretically, the calcium in certain fortified orange juices can also bind to quinolone antibiotics and reduce their absorption and levels.

Theoretically, anise seed might increase the risk of hypoglycemia when taken with antidiabetes drugs.
A small clinical study shows that anise seed powder decreases fasting blood glucose levels by 36% when compared to baseline.

Theoretically, anise oil might decrease the efficacy of caffeine.
Animal research shows that taking anise oil with caffeine decreases the bioavailability of caffeine. Whether this interaction will occur in humans is unclear.

Theoretically, anise oil might increase the effects and adverse effects of codeine.
Animal research shows that anise oil increases the analgesic effects of codeine, possibly by inducing its phase I metabolism and increasing conversion to morphine. Whether this interaction occurs in humans is unclear.

Theoretically, anise might interfere with contraceptive drug therapy.
Some in vitro research suggests that anise has estrogenic effects, while other in vitro research suggests that anise has antiestrogenic effects.

Theoretically, anise oil might increase the effects and adverse effects of diazepam.
Animal research shows that taking anise oil with diazepam increases the motor impairment associated with diazepam, possibly by inhibiting its breakdown by cytochrome P450 3A4. Whether this interaction occurs in humans is unclear.

Theoretically, anise might interfere with estrogen-based hormone replacement therapy.
Some in vitro research suggests that anise has estrogenic effects, while other in vitro research suggests that anise has antiestrogenic effects.

Theoretically, anise oil might decrease the efficacy of fluoxetine.
Animal research shows that taking anise oil with fluoxetine reduces the antidepressant effects of fluoxetine, possibly by promoting its breakdown by cytochrome P450 2D6. Whether this interaction occurs in humans is unclear.

Theoretically, anise oil might decrease the efficacy of imipramine.
Animal research shows that taking anise oil with imipramine reduces the antidepressant effects of imipramine, possibly by promoting its breakdown by cytochrome P450 2D6. Whether this interaction occurs in humans is unclear.

Theoretically, anise oil might increase the effects and adverse effects of midazolam.
Animal research shows that taking anise oil with midazolam increases the motor impairment associated with midazolam, possibly by inhibiting its breakdown by cytochrome P450 3A4. Whether this interaction occurs in humans is unclear.

Theoretically, anise might interfere with tamoxifen therapy.
Some in vitro research suggests that anise has estrogenic effects, while other in vitro research suggests that anise has antiestrogenic effects.

Theoretically, anise oil might decrease the levels and clinical effects of acetaminophen.
Animal research shows that taking anise oil with acetaminophen decreases peak plasma levels of acetaminophen but does not reduce overall bioavailability. Whether this interaction will occur in humans is unclear.

Theoretically, capsicum may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro research shows that capsicum might increase the effects of antiplatelet drugs. Also, population research shows that capsicum is associated with an increased risk of self-reported bleeding in patients taking warfarin. However, clinical research shows that taking a single dose of capsaicin (Asian Herbex Ltd.), the active ingredient in capsicum, 400-800 mcg orally in combination with aspirin 500 mg does not decrease platelet aggregation when compared with taking aspirin 500 mg alone. Also, there was no notable effect on measures of platelet aggregation with capsaicin. It is unclear whether capsaicin must be used in more than a single dose to affect platelet aggregation.

Theoretically, taking capsicum with antidiabetes drugs might increase the risk of hypoglycemia.
Preliminary clinical research shows that consuming capsicum 5 grams along with a glucose drink attenuates the rise in plasma glucose after 30 minutes by 21%, decreases the 2-hour postprandial area under the curve of plasma glucose by 11%, and increases the 2-hour postprandial area under the curve of plasma insulin by 58% in healthy individuals when compared with placebo. Other clinical research shows that taking capsicum 5 mg daily for 28 days significantly reduces postprandial blood glucose and insulin levels, but not fasting blood glucose and insulin levels, in patients with gestational diabetes.

Theoretically, taking capsicum with aspirin might reduce the bioavailability of aspirin.
Animal research shows that acute or chronic intake of capsicum pepper reduces oral aspirin bioavailability. This has not been shown in humans.

Theoretically, taking capsicum with theophylline might increase the levels and adverse effects of theophylline.
In animal research, oral administration of capsicum reduced excretion of theophylline. However, capsicum does not seem to affect the pharmacokinetics of theophylline when administered intravenously.

Theoretically, using topical capsaicin may increase the risk of ACE inhibitor-induced cough.
There is one case report of a topically applied capsaicin cream contributing to the cough reflex in a patient using an ACEI. However, it is unclear if this interaction is clinically significant.

Theoretically, taking capsicum with ciprofloxacin might increase levels and adverse effects of ciprofloxacin.
Animal research shows that concomitant use of capsaicin, the active constituent of capsicum, and ciprofloxacin increases the bioavailability of ciprofloxacin by up to 70%.

Theoretically, concurrent use of lotus with other antiplatelet drugs might reduce platelet aggregation and increase the risk of bleeding.
Neferine and isoliensinine, constituents of lotus, have been shown to inhibit platelet aggregation, in vitro. These constituents can inhibit the production of pro-aggregating factors like prostaglandins.

Theoretically, lotus might have additive effects with antidiabetes drugs and increase the risk of hypoglycemia.
Animal research shows that the ethanolic extract of lotus reduces blood glucose levels and potentiates the effects of injected insulin. Monitor blood glucose levels closely. Dose adjustments might be necessary.

Theoretically, taking lotus concomitantly with pentobarbital might increase sedation.
Animal research shows that lotus extract increases pentobarbitone-induced sleeping time. It is not known if this occurs in humans or if this effect occurs with other barbiturates or sedatives.

Theoretically, taking antibiotics with Bacillus coagulans might decrease the effectiveness of B. coagulans.
B. coagulans preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms. Tell patients to separate administration of antibiotics and B. coagulans preparations by at least two hours.

Theoretically, taking Bacillus subtilis with antibiotic drugs might decrease the effectiveness of B. subtilis.
Since B. subtilis preparations usually contain live and active organisms, simultaneously taking antibiotics might kill a significant number of the organisms. Tell patients to separate administration of antibiotics and B. subtilis preparations by at least 2 hours.

Theoretically, the antioxidant effects of acerola might reduce the effectiveness of alkylating agents.
Acerola contains vitamin C, an antioxidant. There is concern that antioxidants might reduce the activity of chemotherapy drugs that generate free radicals, such as alkylating agents. In contrast, other researchers theorize that antioxidants might make alkylating chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin C have on chemotherapy.

Theoretically, the antioxidant effects of acerola might reduce the effectiveness of antitumor antibiotics.
Acerola contains vitamin C, an antioxidant. There is concern that antioxidants might reduce the activity of chemotherapy drugs that generate free radicals, such as antitumor antibiotics. In contrast, other researchers theorize that antioxidants might make antitumor antibiotic chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effects, if any, antioxidants such as vitamin C have on antitumor antibiotic chemotherapy.

Theoretically, concomitant use of acerola with aluminum salts might increase the amount of aluminum absorbed.
Acerola contains vitamin C. It is thought that vitamin C chelates aluminum, keeping it in solution and available for absorption. In people with normal renal function, urinary excretion of aluminum likely increases, making aluminum retention and toxicity unlikely. However, patients with renal failure who take aluminum-containing compounds, such as phosphate binders, should avoid acerola in doses that provide more vitamin C than the recommended dietary allowances.

Theoretically, acerola might reduce the clearance of aspirin; however, its vitamin C content is likely too low to produce clinically significant effects.
Acerola contains vitamin C. It has been suggested that acidification of the urine by vitamin C can decrease the urinary excretion of salicylates, increasing plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion. The vitamin C content of acerola is typically about 2000 mg per 100 grams. Thus, a clinically significant interaction between acerola and aspirin is unlikely.

Theoretically, concomitant use of acerola with estrogens might increase estrogenic effects.
Acerola contains vitamin C. Increases in plasma estrogen levels of up to 55% have occurred under some circumstances when vitamin C is taken concurrently with oral contraceptives or hormone replacement therapy, including topical products. It is suggested that vitamin C prevents oxidation of estrogen in the tissues, regenerates oxidized estrogen, and reduces sulfate conjugation of estrogen in the gut wall. When tissue levels of vitamin C are high, these processes are already maximized and supplemental vitamin C does not have any effect on estrogen levels. However, increases in plasma estrogen levels may occur when women who are deficient in vitamin C take supplements.

Theoretically, acerola might reduce the effectiveness of warfarin; however, its vitamin C content is likely too low to produce clinically significant effects.
Acerola contains vitamin C. High doses of vitamin C may reduce the response to warfarin, possibly by causing diarrhea and reducing warfarin absorption. This occurred in two people who took up to 16 grams daily of vitamin C, and resulted in decreased prothrombin time. Lower doses of 5-10 grams daily of vitamin C can also reduce warfarin absorption, but this does not seem to be clinically significant. The vitamin C content of acerola is typically about 2000 mg per 100 grams. Thus, a clinically significant interaction between acerola and warfarin is unlikely.

Theoretically, plum juice might have antiplatelet effects.
Consuming plum juice while taking anticoagulant or antiplatelet drugs might increase the risk of bruising and bleeding. In healthy volunteers, drinking plum juice 200 mL daily for 28 days prolonged clotting time and inhibited platelet aggregation.

Theoretically, papaya extract may increase the levels and clinical effects of amiodarone.
Animal research in rats shows that a single oral dose of papaya extract, as well as multiple doses of papaya extract daily over 14 days, prior to a single dose of amiodarone delays the time to maximum amiodarone concentration. However, only the 14-day papaya extract regimen increases systemic amiodarone exposure by 60% to 70%. This interaction has not been reported in humans.

Concomitant use of antidiabetic drugs with fermented papaya can produce additive effects. It is unclear if other forms of papaya have the same effect.
A small low-quality clinical study in patients with type 2 diabetes who are taking glibenclamide shows that taking a fermented papaya preparation 3 grams daily for 2 months decreases fasting and postprandial blood glucose levels when compared to baseline. Additionally, of the 25 patients in the study, 9 required a reduction in glibenclamide dose.

Theoretically, consuming large quantities of papaya fruit can reduce the clinical effects of levothyroxine.
In one case-report, a 37-year-old male with a history of thyroidectomy who was stabilized on levothyroxine for 5 years presented with hypothyroidism after consuming 5-6 papaya fruits daily for 14 days during vacation. In a controlled re-challenge test involving 5-6 papayas daily, the patient remained euthyroid for 7 days, but developed mild hypothyroidism after 14 days. Both times, thyroid levels normalized 40-45 days after discontinuing papaya.

Theoretically, concomitant use of warfarin with papain-containing papaya extract might increase the effects and side effects of warfarin.
In one case report, a patient previously stable on warfarin was found to have an international normalization ratio (INR) of 7.4, which was attributed to ingestion of a supplement containing papain from papaya extract.

Theoretically, chicory might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Animal and in vitro research shows that chicory extracts have antidiabetic effects.

Theoretically, concomitant use with antidiabetes drugs might have additive effects and increase the risk of hypoglycemia. Animal research shows that guava leaf extract or guava fruit can have hypoglycemic effects. Monitor blood glucose levels closely. Medication dose adjustments may be necessary. Some antidiabetes drugs include glimepiride (Amaryl), glyburide (Diabeta, Glynase PresTab, Micronase), insulin, metformin, pioglitazone (Actos), rosiglitazone (Avandia), and others.

Theoretically, oats may have additive effects with antidiabetic agents and might increase the risk of hypoglycemia.
Consuming oats can decrease blood glucose in patients with diabetes. In those who require insulin, taking oats 100 grams daily for 2 days reduces the insulin dose required to achieve metabolic control.

Concomitant use of oats and insulin might increase the risk of hypoglycemia.
In patients with insulin-dependent type 2 diabetes, taking oats 100 grams daily for 2 days reduces the insulin dose required to achieve metabolic control.

Eating a diet that consists of high amounts of cashew might increase fasting blood glucose levels. However, other evidence shows that eating 30 grams of cashew daily does not significantly affect glycemic measures. Until more is known, use with caution in combination with antidiabetes drugs. Theoretically, concomitant use might reduce the effects of antidiabetes drugs. Dosing adjustments for insulin or oral hypoglycemic agents may be necessary.
Oral hypoglycemic drugs include glimepiride (Amaryl), glipizide (Glucotrol), glyburide (Diabeta, Micronase), tolazamide (Tolinase), tolbutamide (Orinase), and others.

In an animal study, an aqueous extract of collard leaves and stems has been shown to reduce glucose levels. Collard extract 60 mg/kg lowers blood glucose levels in a rat model of diabetes after both single- and multi-dose oral administration similarly to glibenclamide 5 mg/kg. Theoretically, collard extract might have additive effects when used concomitantly with antidiabetes drugs and may increase the risk of hypoglycemia. Monitor blood glucose levels closely. Dose adjustments may be necessary. Some antidiabetes drugs include glimepiride (Amaryl), glyburide (DiaBeta, Glynase PresTab, Micronase), insulin, pioglitazone (Actos), rosiglitazone (Avandia), chlorpropamide (Diabinese), glipizide (Glucotrol), and tolbutamide (Orinase).

Evidence from human and animal research suggests that cassava root has marked antithyroid effects, particularly if poorly processed or if consumed as part of a protein-deficient diet. Also, clinical research shows that consuming boiled cassava leaves 200 grams twice daily for 9 days significantly reduces levels of the thyroid hormones triiodothyronine and thyroxine. Theoretically, cassava may alter thyroid function, reduce thyroid hormone levels, and interfere with thyroid hormone-replacement therapy.

Taking banana may reduce the effectiveness of levodopa.
A case report describes apparent wearing off in a patient with Parkinson disease after eating a banana every day. The wearing off subsided after removing dietary bananas.

Avocado may antagonize the anticoagulant effects of warfarin.
Avocado may antagonize the anticoagulant effects of warfarin; however, there has been only one case report of this interaction.

Theoretically, taking itraconazole capsules or tablets with a beverage containing lemon might increase the levels and clinical effects of itraconazole.
In one case report, dissolving itraconazole tablets in a small amount of specific beverages containing lemon prior to administration increased the level of itraconazole in a lung transplant patient. In this case, the increased bioavailability was desirable and was likely due to improved tablet dissolution in the acidic beverage.