Green PhytoFoods Ingredients & Drug Interactions

Theoretically, black psyllium might reduce the effects of carbamazepine and increase the risk for convulsions.
Theoretically, black psyllium might reduce carbamazepine absorption. A preliminary study using blond psyllium reported decreased carbamazepine bioavailability due to binding of the drug to psyllium, as well as reduction of available fluid in the gut for dissolution of the drug. This interaction may also occur with black psyllium.

Theoretically, taking black psyllium at the same time as lithium might reduce lithium absorption.
The fiber in black psyllium might reduce lithium absorption and plasma levels. Some case reports describe a reduction in plasma lithium levels with concomitant administration of blond psyllium. This was reversed when psyllium was stopped. This interaction may also occur with black psyllium.

Theoretically, black psyllium might increase the therapeutic and adverse effects of metformin.
Animal research shows that concurrent consumption of blond psyllium with metformin slows and increases the absorption of metformin. This interaction may also occur with black psyllium. To avoid changes in absorption, take psyllium 30-60 minutes after metformin.

Theoretically, taking black psyllium at the same time as olanzapine might reduce olanzapine absorption.
The fiber in black psyllium might decrease the absorption of olanzapine. A single case report describes a reduction in the effectiveness of olanzapine when it was concomitantly administered with an unspecified type of psyllium 3 grams orally twice daily. This effect was reversed when psyllium was stopped.

Theoretically, taking black psyllium at the same time as digoxin might reduce digoxin absorption and decrease digoxin levels.
Psyllium might bind digoxin in the gut. However, some clinical evidence suggests that psyllium does not impact digoxin absorption.

Theoretically, taking black psyllium at the same time as ethinyl estradiol might alter levels of estradiol.
Concurrent use of blond psyllium with ethinyl estradiol results in a slight increase in the extent of ethinyl estradiol absorption and a slower rate of absorption. This is unlikely to be clinically significant.

Theoretically, psyllium might increase, decrease, or have no effect on the absorption of oral drugs.
Psyllium seems to have variable effects on drug absorption. To avoid changes in absorption, take psyllium 30-60 minutes after oral medications. Animal research shows that blond psyllium delays and increases the absorption of metformin and ethinyl estradiol. Case reports and animal research suggest that blond psyllium might reduce absorption of lithium, digoxin, olanzapine, and carbamazepine. Finally, some pharmacokinetic studies show that psyllium does not affect the absorption of levothyroxine or warfarin. Although many of these studies evaluated blond psyllium, the fiber content in black psyllium may have similar effects.

Green tea extract seems to reduce the levels and clinical effects of atorvastatin.
In healthy humans, taking green tea extract 300 mg or 600 mg along with atorvastatin reduces plasma levels of atorvastatin by approximately 24%. The elimination of atorvastatin is not affected. Atorvastatin is a substrate of organic anion-transporting polypeptides (OATPs). Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs. Some OATPs are expressed in the small intestine and are responsible for the uptake of drugs and other compounds, which may have resulted in reduced plasma levels of atorvastatin. It is not clear if drinking green tea alters the absorption of atorvastatin.

Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Green tea contains caffeine. 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.

Green tea seems to reduce the levels and clinical effects of nadolol.
Preliminary clinical research shows that green tea consumption reduces plasma concentrations of nadolol. Compared to a control group, both peak levels and total drug exposure (AUC) of nadolol were reduced by approximately 85% in subjects who drank green tea daily for two weeks. Drinking green tea with nadolol also significantly reduced nadolol's systolic blood pressure lowering effect. Other clinical research shows that a single dose of green tea can affect plasma nadolol levels for at least one hour. Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is involved in the uptake of nadolol in the intestine The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea.

Theoretically, high doses of green tea might increase the effects and side effects of 5-fluorouracil.
Animal research shows that taking green tea in amounts equivalent to about 6 cups daily in humans for 4 weeks prior to receiving a single injection of 5-fluorouracil increases the maximum plasma levels of 5-fluorouracil by about 2.5-fold and the area under the curve by 425%.

Theoretically, green tea might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Green tea contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine doesn't seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine. It is recommended that methylxanthines and methylxanthine-containing products 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, green tea may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Conflicting reports exist regarding the effect of green tea on bleeding risk when used with anticoagulant or antiplatelet drugs; however, most evidence suggests that drinking green tea in moderate amounts is unlikely to cause a significant interaction. Green tea contains small amounts of vitamin K, approximately 7 mcg per cup. Some case reports have associated the antagonism of warfarin with the vitamin K content of green tea. However, these reports are rare, and very large doses of green tea (about 8-16 cups daily) appear to be needed to cause these effects. Furthermore, the catechins and caffeine in green tea are reported to have antiplatelet activity.

Green tea contains caffeine. Theoretically, concomitant use of large amounts of caffeine might increase cardiac inotropic effects of beta-agonists.

Theoretically, green tea might interfere with the effects of bortezomib.
In vitro research shows that green tea polyphenols, such as epigallocatechin gallate (EGCG), interact with bortezomib and block its proteasome inhibitory action. This prevents the induction of cell death in multiple myeloma or glioblastoma cancer cell lines. Advise patients taking bortezomib, not to take green tea.

Theoretically, green tea might reduce the effects of carbamazepine and increase the risk for convulsions.
Green tea contains caffeine. Animal research suggests that taking 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 2-fold in healthy individuals.

Theoretically, green tea might reduce the levels and clinical effects of celiprolol.
In a small human study, taking green tea daily for 4 days appears to decrease blood and urine levels of celiprolol by at least 98%. This interaction is possibly due to the inhibition of organic anion transporting polypeptide (OATP). Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is found in the intestine The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea.

Theoretically, concomitant use might increase the effects and adverse effects of caffeine in green tea.
Green tea contains caffeine. Cimetidine can reduce caffeine clearance by 31% to 42%.

Theoretically, green tea might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Animal research suggests that, although green tea extract does not affect the elimination of clozapine, it delays the time to reach peak concentration and reduces the peak plasma levels. Also, concomitant administration of green tea and clozapine might theoretically cause acute exacerbation of psychotic symptoms due to the caffeine in green tea. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients be more sensitive to the interaction between clozapine and caffeine.

Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in green tea.
Green tea contains caffeine. Oral contraceptives can decrease caffeine clearance by 40% to 65%.

Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
Green tea contains caffeine. Caffeine is metabolized by cytochrome P450 1A2 (CYP1A2),. Theoretically, drugs that inhibit CYP1A2 may decrease the clearance rate of caffeine from green tea and increase caffeine levels.

Theoretically, green tea might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Green tea contains caffeine. Caffeine might inhibit dipyridamole-induced vasodilation. It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests. Methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing.

Theoretically, disulfiram might increase the risk of adverse effects from caffeine.
In human research, disulfiram decreases the clearance and increases the half-life of caffeine.

Theoretically, using green tea with diuretic drugs might increase the risk of hypokalemia.
Green tea contains caffeine. In excessive amounts, caffeine 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 caffeine.
Green tea contains caffeine. Estrogen inhibits caffeine metabolism.

Theoretically, green tea might reduce the effects of ethosuximide and increase the risk for convulsions.
Green tea contains caffeine. Animal research suggests that caffeine 92.4 mg/kg can decrease the anticonvulsant activity of ethosuximide. However, this effect has not been reported in humans.

Theoretically, green tea might reduce the effects of felbamate and increase the risk for convulsions.
Green tea contains caffeine. Animal research suggests 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.

Green tea can decrease blood levels of fexofenadine.
Clinical research shows that green tea can significantly decrease blood levels and excretion of fexofenadine. Taking green tea extract with a dose of fexofenadine decreased bioavailability of fexofenadine by about 30%. In vitro, green tea inhibits the cellular accumulation of fexofenadine by inhibiting the organic anion transporting polypeptide (OATP) drug transporter. Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs, specifically OATP1A2, OATP1B1, and OATP2B1. In addition, green tea has been shown to reduce the absorption of some drugs that are OATP substrates.

Theoretically, green tea might increase the levels and adverse effects of flutamide.
Green tea contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide. Theoretically, concomitant use of caffeine and flutamide might increase serum concentrations of flutamide and increase the risk adverse effects.

Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
Green tea contains caffeine. Fluvoxamine reduces caffeine metabolism.

Theoretically, concomitant use might have additive adverse hepatotoxic effects.
Green tea extract supplements have been linked to several cases of hepatotoxicity and might have additive hepatotoxic effects with other drugs..

Theoretically, green tea might reduce the levels and clinical effects of imatinib.
In animal research, a single dose of green tea extract reduces the area under the curve (AUC) of imatinib by up to approximately 64% and its main metabolite N-desmethyl imatinib by up to approximately 81%. This interaction has not been shown in humans. The mechanism of action is unclear but may involve multiple pathways.

Theoretically, eleuthero may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal research shows that a constituent of eleuthero, dihydroxybenzoic acid, appears to inhibit platelet aggregation. Concomitant use with anticoagulant or antiplatelet drugs might increase the risk of bleeding. This effect has not been reported in humans.

Theoretically, eleuthero might have additive effects when used with antidiabetes drugs.
Animal research suggests that certain constituents of eleuthero have hypoglycemic activity in both healthy and diabetic animals. A small study in adults with type 2 diabetes also shows that taking eleuthero for 3 months can lower blood glucose levels. However, one very small study in healthy individuals shows that taking powdered eleuthero 3 grams, 40 minutes prior to a 75-gram oral glucose tolerance test, significantly increases postprandial blood glucose levels when compared with placebo. These contradictory findings might be due to patient-specific variability and variability in active ingredient ratios.

Theoretically, eleuthero might increase levels of drugs metabolized by CYP1A2.
In vitro and animal research suggest that standardized extracts of eleuthero inhibit CYP1A2. This effect has not been reported in humans.

Theoretically, eleuthero might increase levels of drugs metabolized by CYP2C9.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2C9. This effect has not been reported in humans.

Eleuthero might increase serum digoxin levels and increase the risk of side effects.
In one case report, a 74-year-old male who was stabilized on digoxin presented with an elevated serum digoxin level after starting an eleuthero supplement, without symptoms of toxicity. After stopping the supplement, serum digoxin levels returned to normal. It is not clear whether this was due to a pharmacokinetic interaction or to interference with the digoxin assay. Although the product was found to be free of digoxin and digitoxin, it was not tested for other contaminants.

Theoretically, eleuthero might interfere with immunosuppressive drugs because of its immunostimulant activity.
Animal and in vitro research shows that eleuthero extracts have immunomodulatory effects, including increasing cellular and humoral activity.

Theoretically, eleuthero might increase levels of P-glycoprotein substrates.
In vitro research suggests that eleuthero can inhibit the multi-drug transporter protein, P-glycoprotein. However, it is too soon to tell if this is clinically important. This interaction has not been reported in humans.

Theoretically, eleuthero might increase levels of drugs metabolized by CYP2D6.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2D6. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP2D6 drug metabolism.

Theoretically, eleuthero might increase levels of drugs metabolized by CYP3A4.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP3A4. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP3A4 drug metabolism.

Theoretically, eleuthero might decrease levels of drugs metabolized by OATP.
In vitro research suggests that eleuthero inhibits OATP2B1, which might reduce the bioavailability of oral drugs that are substrates of OATP2B1. Due to the weak inhibitory effect identified in this study, this interaction is not likely to be clinically significant.

Although Panax ginseng has shown antiplatelet effects in the laboratory, it is unlikely to increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro evidence suggests that ginsenoside constituents in Panax ginseng might decrease platelet aggregation. However, research in humans suggests that ginseng does not affect platelet aggregation. Animal research indicates low oral bioavailability of Rb1 and rapid elimination of Rg1, which might explain the discrepancy between in vitro and human research. Until more is known, use with caution in patients concurrently taking anticoagulant or antiplatelet drugs.

Theoretically, taking Panax ginseng with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical research suggests that Panax ginseng might decrease blood glucose levels. Monitor blood glucose levels closely.

Theoretically, taking Panax ginseng with caffeine might increase the risk of adverse stimulant effects.
Panax ginseng has been shown to have stimulant effects. Theoretically, caffeine might have an additive effect on the stimulant effects of Panax ginseng.

Theoretically, Panax ginseng might increase levels of drugs metabolized by CYP2D6. However, research is conflicting.
There is some evidence that Panax ginseng can inhibit the CYP2D6 enzyme by approximately 6%. In addition, in animal research, Panax ginseng inhibits the metabolism of dextromethorphan, a drug metabolized by CYP2D6, by a small amount. However, contradictory research suggests Panax ginseng might not inhibit CYP2D6. Until more is known, use Panax ginseng cautiously in patients taking drugs metabolized by these enzymes.

Theoretically, Panax ginseng might increase or decrease levels of drugs metabolized by CYP3A4.
Panax ginseng may affect the clearance of drugs metabolized by CYP3A4. One such drug is imatinib. Inhibition of CYP3A4 was believed to be responsible for a case of imatinib-induced hepatotoxicity. In contrast, Panax ginseng has been shown to increase the clearance of midazolam, another drug metabolized by CYP3A4. Clinical research shows that Panax ginseng can reduce midazolam area under the curve by 44%, maximum plasma concentration by 26%, and time to reach maximum plasma concentration by 29%. Midazolam metabolism was also increased in animals given Panax ginseng. Until more is known, use Panax ginseng cautiously in combination with CYP3A4 substrates.

Theoretically, concomitant use of large amounts of Panax ginseng might interfere with hormone replacement therapy.
Laboratory research and some case reports suggest that Panax ginseng can have estrogenic effects due to competition for estrogen receptors. The estrogenic activity is attributed to the ginsenoside constituents of Panax ginseng.

Theoretically, Panax ginseng might reduce the effects of furosemide.
There is some concern that Panax ginseng might contribute to furosemide resistance. There is one case of resistance to furosemide diuresis in a patient taking a germanium-containing ginseng product.

Theoretically, Panax ginseng might increase the effects and adverse effects of imatinib.
A case of imatinib-induced hepatotoxicity has been reported for a 26-year-old male with chronic myelogenous leukemia stabilized on imatinib for 7 years. The patient took imatinib 400 mg along with a Panax ginseng-containing energy drink daily for 3 months. Since imatinib-associated hepatotoxicity typically occurs within 2 years of initiating therapy, it is believed that Panax ginseng affected imatinib toxicity though inhibition of cytochrome P450 3A4. CYP3A4 is the primary enzyme involved in imatinib metabolism.

Theoretically, Panax ginseng use might interfere with immunosuppressive therapy.
Panax ginseng might have immune system stimulating properties.

Theoretically, taking Panax ginseng with insulin might increase the risk of hypoglycemia.
Clinical research suggests that Panax ginseng might decrease blood glucose levels. Insulin dose adjustments might be necessary in patients taking Panax ginseng; use with caution.

Theoretically, Panax ginseng may increase the clearance of midazolam.
Midazolam is metabolized by cytochrome P450 3A4 (CYP3A4). Clinical research suggests that Panax ginseng can reduce midazolam area under the curve by 44%, maximum plasma concentration by 26%, and time to reach maximum plasma concentration by 29%. Midazolam metabolism was also increased in animals given Panax ginseng.

Theoretically, Panax ginseng can interfere with MAOI therapy.
Concomitant use of Panax ginseng with phenelzine (Nardil) is associated with insomnia, headache, tremors, and hypomania.

Theoretically, taking Panax ginseng with nifedipine might increase serum levels of nifedipine and the risk of hypotension.
Preliminary clinical research shows that concomitant use can increase serum levels of nifedipine in healthy volunteers. This might cause the blood pressure lowering effects of nifedipine to be increased when taken concomitantly with Panax ginseng.

Theoretically, Panax ginseng has an additive effect with drugs that prolong the QT interval and potentially increase the risk of ventricular arrhythmias. However, research is conflicting.
Clinical research shows that short-term use of Panax ginseng can increase the QT interval. However, no changes in QT interval have been identified with prolonged use.

Theoretically, taking Panax ginseng with raltegravir might increase the risk of liver toxicity.
A case report suggests that concomitant use of Panax ginseng with raltegravir can increase serum levels of raltegravir, resulting in elevated liver enzymes levels.

Theoretically, Panax ginseng might increase or decrease levels of selegiline, possibly altering the effects and side effects of selegiline.
Animal research shows that taking selegiline with a low dose of Panax ginseng extract (1 gram/kg) reduces selegiline bioavailability, while taking a high dose of Panax ginseng extract (3 grams/kg) increases selegiline bioavailability. More research is needed to confirm these effects.

Theoretically, taking Panax ginseng with stimulant drugs might increase the risk of adverse stimulant effects.
Panax ginseng has been shown to have stimulant effects.

Panax ginseng might affect the clearance of warfarin. However, this interaction appears to be unlikely.
There has been a single case report of decreased effectiveness of warfarin in a patient who also took Panax ginseng. However, it is questionable whether Panax ginseng was the cause of this decrease in warfarin effectiveness. Some research in humans and animals suggests that Panax ginseng does not affect the pharmacokinetics of warfarin. However, other research in humans suggests that Panax ginseng might modestly increase the clearance of the S-warfarin isomer. More evidence is needed to determine whether Panax ginseng causes a significant interaction with warfarin.

Theoretically, Panax ginseng might decrease blood levels of oral or intravenous fexofenadine.
Animal research suggests that taking Panax ginseng in combination with oral or intravenous fexofenadine may reduce the bioavailability of fexofenadine. Some scientists have attributed this effect to the ability of Panax ginseng to increase the expression of P-glycoprotein.

Although Panax ginseng has demonstrated variable effects on cytochrome P450 3A4 (CYP3A4), which metabolizes lopinavir, Panax ginseng is unlikely to alter levels of lopinavir/ritonavir.
Lopinavir is metabolized by CYP3A4 and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Panax ginseng has shown variable effects on CYP3A4 activity in humans. However, taking Panax ginseng (Vitamer Laboratories) 500 mg twice daily for 14 days did not alter the pharmacokinetics of lopinavir/ritonavir in 12 healthy volunteers.

Taking milk thistle with antidiabetes drugs may increase the risk of hypoglycemia.
Clinical research shows that milk thistle extract, alone or along with tree turmeric extract, can lower blood glucose levels and glycated hemoglobin (HbA1c) in patients with type 2 diabetes, including those already taking antidiabetes drugs. Additionally, animal research shows that milk thistle extract increases the metformin maximum plasma concentration and area under the curve and decreases the renal clearance of metformin, due to inhibition of the multi-drug and toxin extrusion protein 1 (MATE1) renal tubular transport protein.

Theoretically, milk thistle might inhibit CYP2B6.
An in vitro study shows that silybin, a constituent of milk thistle, binds to and noncompetitively inhibits CYP2B6. Additionally, silybin might downregulate the expression of CYP2B6 by decreasing mRNA and protein levels.

Theoretically, milk thistle might affect the clearance of drugs that undergo glucuronidation.
Laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation. Theoretically, this could decrease the clearance and increase levels of glucuronidated drugs. Other laboratory research suggests that a milk thistle extract of silymarin might inhibit beta-glucuronidase, although the significance of this effect is unclear.

Theoretically, milk thistle might increase the levels and clinical effects of ledipasvir.
Animal research in rats shows that milk thistle increases the area under the curve (AUC) for ledipasvir and slows its elimination.

Theoretically, concomitant use of milk thistle with morphine might affect serum levels of morphine and either increase or decrease its effects.
Animal research shows that milk thistle reduces serum levels of morphine by up to 66%. In contrast, laboratory research shows that milk thistle constituents inhibit uridine diphosphoglucuronosyl transferase (UGT), the major phase 2 enzyme that is responsible for glucuronidation. Theoretically, this could decrease the clearance and increase morphine levels. The effect of taking milk thistle on morphine metabolism in humans is not known.

Theoretically, milk thistle might decrease the clearance and increase levels of raloxifene.
Laboratory research suggests that the milk thistle constituents silibinin and silymarin inhibit the glucuronidation of raloxifene in the intestines.

Milk thistle might decrease the clearance of sirolimus.
Pharmacokinetic research shows that a milk thistle extract of silymarin decreases the apparent clearance of sirolimus in hepatically impaired renal transplant patients. It is unclear if this interaction occurs in patients without hepatic impairment.

Theoretically, milk thistle might decrease the levels and clinical effects of sofosbuvir.
Animal research in rats shows that milk thistle reduces the metabolism of sofosbuvir, as well as the hepatic uptake of its active metabolite.

Theoretically, the milk thistle constituent silibinin might increase tamoxifen levels and interfere with its conversion to an active metabolite.
Animal research suggests that the milk thistle constituent silibinin might increase plasma levels of tamoxifen and alter its conversion to an active metabolite. The mechanism appears to involve inhibition of pre-systemic metabolism of tamoxifen by cytochrome P450 (CYP) 2C9 and CYP3A4, and inhibition of P-glycoprotein-mediated efflux of tamoxifen into the intestine for excretion. Whether this interaction occurs in humans is not known.

Theoretically, milk thistle might increase the effects of warfarin.
In one case report, a man stabilized on warfarin experienced an increase in INR from 2.64 to 4.12 after taking a combination product containing milk thistle 200 mg daily, as well as dandelion, wild yam, niacinamide, and vitamin B12. Levels returned to normal after stopping the supplement. Although a direct correlation between milk thistle and the change in INR cannot be confirmed, some in vitro research suggests that milk thistle might inhibit cytochrome P450 2C9 (CYP2C9), an enzyme involved in the metabolism of various drugs, including warfarin.

It is unclear if milk thistle inhibits CYP2C9; research is conflicting.
In vitro research suggests that milk thistle might inhibit CYP2C9. Additionally, 3 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are CYP2C9 substrates, including imatinib and capecitabine. However, contradictory clinical research shows that milk thistle extract does not inhibit CYP2C9 or significantly affect levels of the CYP2C9 substrate tolbutamide. Differences in results could be due to differences in dosages or formulations utilized.

It is unclear if milk thistle inhibits CYP3A4; research is conflicting.
While laboratory research shows conflicting results, pharmacokinetic research shows that taking milk thistle extract 420-1350 mg daily does not significantly affect the metabolism of the CYP3A4 substrates irinotecan, midazolam, or indinavir. However, 8 case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are CYP3A4 substrates, including gefitinib, sorafenib, doxorubicin, and vincristine.

Theoretically, milk thistle might interfere with estrogen therapy through competition for estrogen receptors.
Animal research suggests that a milk thistle extract of silymarin binds to estrogen receptor beta.

Theoretically, milk thistle might interfere with statin therapy by decreasing the activity of organic anion transporting polypeptide 1B1 (OATB1B1) and inhibiting breast cancer resistance protein (BCRP).
Preliminary evidence suggests that a milk thistle extract of silymarin can decrease the activity of the OATP1B1, which transports HMG-CoA reductase inhibitors into the liver to their site of action, and animal research shows this increases the maximum plasma concentration of pitavastatin and pravastatin. The silibinin component also inhibits BCRP, which transports statins from the liver into the bile for excretion. However, in a preliminary study in healthy males, silymarin 140 mg three times daily had no effect on the pharmacokinetics of a single 10 mg dose of rosuvastatin.

Theoretically, milk thistle may induce cytochrome P450 3A4 (CYP3A4) enzymes and increase the metabolism of indinavir; however, results are conflicting.
One pharmacokinetic study shows that taking milk thistle (Standardized Milk Thistle, General Nutrition Corp.) 175 mg three times daily in combination with multiple doses of indinavir 800 mg every 8 hours decreases the mean trough levels of indinavir by 25%. However, results from the same pharmacokinetic study show that milk thistle does not affect the overall exposure to indinavir. Furthermore, two other pharmacokinetic studies show that taking specific milk thistle extract (Legalon, Rottapharm Madaus; Thisilyn, Nature's Way) 160-450 mg every 8 hours in combination with multiple doses of indinavir 800 mg every 8 hours does not reduce levels of indinavir.

Milk thistle may inhibit one form of OATP, OATP-B1, which could reduce the bioavailability and clinical effects of OATP-B1 substrates.
In vitro research shows that milk thistle inhibits OATP-B1. Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking milk thistle and cancer medications that are OATP substrates, including sorafenib and methotrexate. OATPs are expressed in the small intestine and liver and are responsible for the uptake of drugs and other compounds into the body. Inhibition of OATP may reduce the bioavailability of oral drugs that are substrates of OATP.

Theoretically, milk thistle might increase the absorption of P-glycoprotein substrates. However, this effect does not seem to be clinically significant.
In vitro research shows that milk thistle can inhibit P-glycoprotein activity and 1 case report from the World Health Organization (WHO) adverse drug reaction database describes increased abdominal pain in a patient taking milk thistle and the cancer medication vincristine, a P-glycoprotein substrate, though this patient was also taking methotrexate. However, a small pharmacokinetic study in healthy volunteers shows that taking milk thistle (Enzymatic Therapy Inc.) 900 mg, standardized to 80% silymarin, in 3 divided doses daily for 14 days does not affect absorption of digoxin, a P-glycoprotein substrate.

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, peppermint oil might increase the levels and adverse effects of cyclosporine.
In animal research, peppermint oil inhibits cyclosporine metabolism and increases cyclosporine levels. Inhibition of cytochrome P450 3A4 (CYP3A4) may be partially responsible for this interaction. An interaction between peppermint oil and cyclosporine has not been reported in humans.

Theoretically, peppermint might increase the levels of CYP2C19 substrates.
In vitro research shows that peppermint oil inhibits CYP2C19. So far, this interaction has not been reported in humans.

Theoretically, peppermint might increase the levels of CYP2C9 substrates.
In vitro research shows that peppermint oil inhibits CYP2C9. So far, this interaction has not been reported in humans.

Theoretically, peppermint might increase the levels of CYP3A4 substrates.
Clinical research in healthy volunteers shows that a single dose of peppermint oil 600 mg inhibits CYP3A4 enzymes and increases the AUC of felodipine, a CYP3A4 substrate. However, in vitro research suggests that peppermint oil only inhibits CYP3A4 at very high concentrations.

Theoretically, peppermint might increase the levels of CYP1A2 substrates.
In vitro and animal research shows that peppermint oil and peppermint leaf inhibit CYP1A2. However, in clinical research, peppermint tea did not significantly affect the metabolism of caffeine, a CYP1A2 substrate. It is possible that the 6-day duration of treatment may have been too short to identify a difference.

Theoretically, cranberry might increase levels and adverse effects of atorvastatin.
In one case report, a patient taking atorvastatin experienced upper back pain, rhabdomyolysis, and abnormal liver function after drinking cranberry juice 16 ounces daily for 2 weeks. Theoretically, this may have been caused by inhibition of cytochrome P450 3A4 (CYP3A4) enzymes by cranberry juice, as atorvastatin is a CYP3A4 substrate. Creatinine kinase and liver enzymes normalized within 2 weeks of stopping cranberry juice. Patients taking atorvastatin should avoid large quantities of cranberry juice.

Theoretically, cranberry might increase the levels and adverse effects of CYP3A4 substrates.
A case of upper back pain, rhabdomyolysis, and abnormal liver function has been reported for a patient taking atorvastatin, a CYP3A4 substrate, in combination with cranberry juice 16 ounces daily for 2 weeks. Creatinine kinase and liver enzymes normalized within 2 weeks of stopping cranberry juice. Also, animal research suggests that cranberry juice, administered intraduodenally 30 minutes prior to nifedipine, a CYP3A4 substrate, inhibits nifedipine metabolism and increases the area under the concentration-time curve by 1.6-fold compared to control.

Theoretically, cranberry might increase the levels and adverse effects of nifedipine.
Animal research suggests that cranberry juice, administered intraduodenally 30 minutes prior to nifedipine treatment, inhibits nifedipine metabolism and increases the area under the concentration-time curve by 1.6-fold compared to control. This interaction has not been reported in humans.

Theoretically, cranberry might increase the levels and adverse effects of warfarin. However, research is conflicting.
There is contradictory evidence about the effect of cranberry juice on warfarin. Case reports have linked cranberry juice consumption to increases in the international normalized ratio (INR) in patients taking warfarin, resulting in severe spontaneous bleeding and excessive postoperative bleeding. Daily consumption of cranberry sauce for one week has also been linked to an increase in INR in one case report. In a small study in healthy young males, taking a high dose of 3 grams of cranberry juice concentrate capsules, equivalent to 57 grams of fruit daily, for 2 weeks produced a 30% increase in the area under the INR-time curve after a single 25-mg dose of warfarin. However, 3 very small clinical studies in patients stabilized on warfarin reported that cranberry juice 250 mL once or twice daily for 7 days (27% cranberry juice or pure cranberry juice) or 240 mL once daily for 14 days does not significantly increase INR or affect plasma warfarin levels. The reasons for these discrepant findings are unclear. It is possible that the form and dose of cranberry may play a role, as cranberry extracts and juices contain different constituents. Additionally, an in vitro study evaluating 5 different cranberry juices found varying effects, with only a cranberry concentrate, and not diluted cranberry juices, inhibiting CYP2C9. However, this concentrate did not inhibit CYP2C9 activity in humans.

Theoretically, cranberry might increase the levels and adverse effects of CYP2C9 substrates. However, research is conflicting.
There is contradictory evidence about the effect of cranberry on CYP2C9 enzymes. In vitro evidence suggests that flavonoids in cranberry inhibit CYP2C9 enzymes. However, clinical research shows that cranberry juice does not significantly affect the levels, metabolism, or elimination of the CYP2C9 substrates flurbiprofen or diclofenac. Also, in patients stabilized on warfarin, drinking cranberry juice 250 mL daily for 7 days does not significantly increase the anticoagulant activity of warfarin, a CYP2C9 substrate. Additional pharmacokinetic research shows that cranberry juice does not increase peak plasma concentrations or area under the concentration-time curve of warfarin.

Theoretically, cranberry might modestly increase the levels and adverse effects of diclofenac.
In vitro evidence suggests that cranberry juice inhibits diclofenac metabolism by human liver microsomes. However, drinking cranberry juice does not seem to affect diclofenac metabolism in humans.

Theoretically, alfalfa might reduce the anticoagulant activity of warfarin.
Alfalfa contains a large amount of vitamin K. This could theoretically interfere with the activity of warfarin.

Theoretically, alfalfa might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Animal research suggests that alfalfa decreases blood sugar in diabetic mice. Also, in one case report, a diabetic patient experienced hypoglycemia after consuming alfalfa extract. Monitor blood glucose levels closely. Dose adjustments might be necessary.

Theoretically, alfalfa might interfere with the activity of contraceptive drugs.
Alfalfa contains coumestrol, a phytoestrogen, and isoflavonoids, which have estrogenic effects.

Theoretically, alfalfa might interfere with hormone therapy.
Alfalfa contains coumestrol, a phytoestrogen, and isoflavonoids, which have estrogenic effects.

Theoretically, alfalfa might decrease the efficacy of immunosuppressive therapy.
In vitro research and human case reports suggest that alfalfa may have immunostimulant effects.

Theoretically, concomitant use of alfalfa with photosensitizing drugs might have additive effects.
Animal research suggests that excessive doses of alfalfa may increase photosensitivity, possibly due to its chlorophyll content. It is unclear if this effect would be clinically relevant in humans.

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.

Theoretically, spirulina blue-green algae might increase the risk of bleeding if used with other anticoagulant or antiplatelet drugs. However, this is unlikely.
Spirulina blue-green algae have shown antiplatelet and anticoagulant effects in vitro. However, one preliminary study in 24 patients receiving spirulina blue-green algae 2.3 grams daily for 2 weeks showed no effect on platelet activation or measures of clotting time.

Theoretically, taking blue-green algae with antidiabetes drugs might increase the risk of hypoglycemia.
Human research shows that spirulina blue-green algae can have hypoglycemic effects in patients with diabetes, at least some of whom were using antidiabetes drugs. However, blue-green algae does not seem to improve glycated hemoglobin (HbA1c) levels in patients with diabetes. A meta-analysis of animal studies also suggests that spirulina blue-green algae have hypoglycemic effects.

Theoretically, concurrent use of blue-green algae might interfere with immunosuppressive therapy.
Blue-green algae have been shown to stimulate the immune system.

In vitro and animal research suggests that strawberry extract can inhibit platelet aggregation due to its phenolic content. Theoretically, strawberry 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.

In vitro research suggests that strawberry extract can inhibit p-glycoprotein efflux. Theoretically, strawberry might inhibit p-glycoprotein mediated drug efflux and potentially increase levels of drugs that are substrates of p-glycoprotein. Until more is known, strawberry should be used cautiously in people taking p-glycoprotein substrates.
Drugs that might be affected include some chemotherapeutic agents (etoposide, paclitaxel, vinblastine, vincristine, vindesine), antifungals (ketoconazole, itraconazole), protease inhibitors (amprenavir, indinavir, nelfinavir, saquinavir), H2 antagonists (cimetidine, ranitidine), some calcium channel blockers (diltiazem, verapamil), corticosteroids, erythromycin, cisapride (Propulsid), fexofenadine (Allegra), cyclosporine, loperamide (Imodium), quinidine, and others.

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.