Black tea

Black tea/Drug Interactions:

  • GeneralGeneral: Drug interactions associated with black tea are predominantly theoretical and generally based upon the adverse effect profile of caffeine.
  • AcetaminophenAcetaminophen: Multiple reports suggest that caffeine enhances the analgesic efficacy of acetaminophen (291; 292; 293; 294), although conflicting evidence exists (295).
  • AdenosineAdenosine: Theoretically, caffeine may inhibit the hemodynamic and antiarrhythmic effects of adenosine (12).
  • AlcoholAlcohol: Alcohol consumption may increase plasma caffeine concentrations and the risk of caffeine adverse effects (13).
  • AmphetamineAmphetamine: There is one known case report of ischemic stroke after the nasal ingestion of amphetamine and caffeine (296).
  • AnalgesicsAnalgesics: In animal research, a synergistic effect on antinociception was noted between caffeine and tramadol (297).
  • AntibioticsAntibiotics: According to secondary sources, certain antibiotics may interfere with the breakdown of caffeine. Ciprofloxacin has been suggested to significantly inhibit caffeine elimination (14; 15). Enoxacin (no longer available in the United States) significantly inhibited caffeine elimination (14). Tea with milk inhibited tetracycline absorption, in human research (138). This appears to be due to the calcium in even small amounts of milk and not due to the tea itself.
  • Anticoagulants/antiplateletsAnticoagulants/antiplatelets: According to anecdotal evidence, caffeine may prolong bleeding time. Both catechins and caffeine in black tea have been reported to have antiplatelet activity (16; 17). In human research, black tea resulted in decreased production of leukocyte-platelet aggregates (18). Black tea contains significant amounts of vitamin K, approximately 262mcg of vitamin K per 100g of leaf (19).
  • Antidepressant agents,monoamine oxidase inhibitors (MAOIs)Antidepressant agents,monoamine oxidase inhibitors (MAOIs): In theory, concomitant administration with monoamine oxidase inhibitors (MAOIs) may increase blood pressure.
  • AntidiabeticsAntidiabetics: Caffeine might increase or decrease blood sugar. Theoretically, concomitant use of black tea and diabetes drugs might interfere with blood glucose control (298).
  • AntihypertensivesAntihypertensives: Caffeine may increase systolic and diastolic blood pressure (89; 90; 91; 92; 93; 94; 95; 96; 97). However, there is controversy in this area, and several studies have not shown these effects (218; 219; 220; 221).
  • AntilipemicsAntilipemics: In animal research, black tea lowered serum cholesterol (299). In humans, consumption of black tea may reduce levels of apolipoprotein B and lipoprotein (a) (168). In laboratory research, rosuvastatin combined with caffeine was not found to increase ecto-5'-nucleotidase activity (300). However, the research is not consistent, as the effect of black tea on cholesterol and triglyceride levels was lacking in other human and animal studies (301; 302; 299; 303; 304; 169; 305; 306). In clinical review, meta-analysis and animal research, caffeine was found to increase cholesterol and triglyceride levels (73; 88; 307).
  • Anti-inflammatoriesAnti-inflammatories: In vitro, epigallocatechin-3-gallate (EGCG), a component of black tea, inhibited the expression of matrix metalloproteinase-1 and -13 in human chondrocytes treated with interleukin (IL)-1beta, as well as activation of mitogen-activated protein kinase subgroup c-Jun N-terminal kinase (308; 309). EGCG also reduced the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS), as well as the production of NO and prostaglandin E(2), in human chondrocytes treated with IL-1beta (310; 311). A greater reduction of pain (2.4-2.8 times) occurred when ibuprofen was used in combination with caffeine, in comparison with ibuprofen alone (312). The combination of ibuprofen and caffeine had a greater analgesic effect for tension-type headache (313).
  • AntineoplasticsAntineoplastics: Epidemiological research suggests that, overall, black tea has anticancer effects (33; 34). According to animal research, black tea polyphenols may reduce the expression of glutathione S-transferase P (GST-P) gene expression in azoxymethane-induced colon tumors, which may improve response to chemotherapy (314). In animal and in vitro research, growth of cancer cells was reduced (36; 37; 38; 39; 40; 41; 42; 43). The combination of green tea, the same species as black tea, and doxorubicin induced a 37% reduction in tumor weight and a 2.5-fold increase in doxorubicin's inhibitory effect on tumor growth in Ehrlich ascites carcinoma tumor-bearing mice (315). There was no increase in doxorubicin concentration in normal tissue. The effect of black tea is unknown.
  • AntipsychoticsAntipsychotics: Coffee and tea withdrawal did not increase the bioavailability of chlorpromazine, haloperidol, fluphenazine, and trifluoperazine or affect the individual variation in plasma levels (316). The cataleptic effect of chlorpromazine was significantly reduced by the simultaneous administration of tea when consumed by rats (317). Tannic acid formed complexes with antipsychotics and influenced the pharmacokinetics of fluphenazine (318). Tannins form a strong complex and significant precipitation with several phenothiazines, amitriptyline, haloperidol, imipramine, and loxapine (319). High doses of caffeine (400-1,000mg daily) may inhibit clozapine metabolism (320).
  • AspirinAspirin: Caffeine does not enhance the analgesic effect of aspirin, according to a meta-analysis (321). However, in treatment of menstruation-associated migraine, a combination of acetaminophen, aspirin, and caffeine was found to be highly effective in treating pain and disability (293). Others have reported that the addition of caffeine to aspirin has significant benefits on mood and performance (322). A combination of aspirin, butalbital, caffeine, and codeine has been found superior to acetaminophen plus codeine in relieving oral surgery pain (323).
  • Antiulcer agentsAntiulcer agents: According to secondary sources, some antiulcer drugs may decrease the rate at which the body metabolizes caffeine. Cimetidine may decrease (inhibit) caffeine clearance by 30-50% (20; 21).
  • BenzodiazepinesBenzodiazepines: Caffeine (125-500mg) counteracted both the effect of reducing anxiety and the reduction in mental performance associated with 2.5mg of lorazepam (26). In human research, caffeine has been shown to antagonize the effects of CNS depressants, including but not limited to diazepam, triazolam, and midazolam (22; 23; 24; 25; 26; 27; 28).
  • Beta-agonistsBeta-agonists: According to anecdotal evidence, combination use may increase the positive inotropic effects of beta-agonists on the heart.
  • Beta-blockersBeta-blockers: According to anecdotal evidence, use with caffeine may reduce the effectiveness of beta-blocking agents. Additionally, in dogs, propranolol reduced caffeine-induced hyperglycemia at rest, but not during hind limb contraction (29). Caffeine consumption did not appear to affect timolol treatment of the eyes (30).
  • CaffeineCaffeine: Black tea is a source of caffeine. Thus, there may be additive effects with other products containing caffeine.
  • Calcium saltsCalcium salts: Theoretically, caffeine can increase urinary calcium levels (112). Experts report that tea polyphenols do not interfere with the bioavailability of calcium (276; 111). Additionally, a 1994 NIH advisory panel concluded that the absorption and excretion of calcium are not significantly affected by caffeine consumption (324).
  • CarbamazepineCarbamazepine: The plasma half-life of carbamazepine was increased twofold by concomitant administration of caffeine (44).
  • ClozapineClozapine: High doses of caffeine may inhibit clozapine metabolism (via CYP1A2) to an extent, which may yield clinically significant elevations in clozapine levels for some individuals (320).
  • ContraceptivesContraceptives: Estrogen has been shown to inhibit CYP1A2-mediated caffeine metabolism (78). Estrogen contained in oral contraceptives (OCP) has been shown to lengthen the half-life of caffeine. One study demonstrated an impaired caffeine clearance in healthy female volunteers who used oral contraceptives for greater than three months (7.88 hours), compared to a control group (5.37 hours) (79). In another report, oral contraceptives increased the residence time of caffeine in young women by a factor of two (80; 81).
  • CNS depressantsCNS depressants: Caffeine counteracted both the effect of reducing anxiety and the reduction in mental performance associated with lorazepam (26). In human research, caffeine has been shown to antagonize the effects of CNS depressants, including but not limited to diazepam, triazolam, midazolam, zolpidem, and zopiclone (22; 23; 24; 25; 26; 27; 28). According to clinical review, the additive effects of caffeine on zolpidem sedation were caused by a reduction of reactive oxygen species and increased bioavailability of endogenous melatonin (27). Theoretically, the caffeine in black tea might negate the hypnotic effects of pentobarbital.
  • Cytochrome P450metabolized agentsCytochrome P450-metabolized agents: In animal and laboratory research and clinical review, cytochrome P450 1A2 was involved in the metabolism of caffeine (46; 47; 48; 49; 50; 51; 52; 53; 54; 55; 56; 57; 58; 59; 60; 61; 62; 63; 64; 65; 66; 67). In human research, ticlopidine and diethyldithiocarbamate (DDC) were found to inhibit caffeine metabolism through the CYP1A2 enzyme system (59).
  • Dental and periodontal agentsDental and periodontal agents: In human research, tea-induced stain was reduced by whitening agents (325).
  • Dermatological agentsDermatological agents: In human research, topical application of epigallocatechin gallate (EGCG), a constituent of black tea, before UVB exposure significantly blocked UVB-induced infiltration of leukocytes, produced fewer prostaglandins, reduced myeloperoxidase activity, and decreased UVB-induced erythema compared to control (326).
  • DexamethasoneDexamethasone: Theoretically, caffeine levels may be lowered by taking dexamethasone (Decadron?).
  • DipyridamoleDipyridamole: Caffeine appeared to block the vasodilatory effects and inhibit the hemodynamic response to dipyridamole infusion in a dose-dependent fashion (68; 69; 70). In human research, adverse outcomes were noted in patients undergoing a myocardial perfusion stress test (70).
  • DisulfiramDisulfiram: Disulfiram may inhibit the elimination of caffeine, decreasing the clearance (by 24%) and increasing the half-life (up to 39%) of caffeine (327).
  • DiureticsDiuretics: Theoretically, caffeine may add to the effects of other diuretics.
  • Drugs that may lower seizure thresholdDrugs that may lower seizure threshold: According to a review, methylxanthines like caffeine have been linked to seizures, likely due to adenosine-antagonizing effects (131). In a case series of six depressed patients receiving electroconvulsive therapy (ECT), the effect of caffeine increased the length of the seizure and potentially enhanced the therapeutic effect (246). Also, seizures have been reported from caffeine overdose (232).
  • Drugs used for osteoporosisDrugs used for osteoporosis: Preliminary evidence exists from epidemiological studies for the use of black tea in increasing bone mineral density and preventing osteoporosis in older women (328; 329).
  • EphedrineEphedrine: According to one meta-analysis, the use of ephedra or ephedrine and caffeine was associated with an increased risk of psychiatric, autonomic, or gastrointestinal symptoms, and heart palpitations (77). Caffeine may enhance the thermogenic activity of ephedrine (330; 331; 332). Other adverse effects due to the combination include abnormal heart rhythms, insomnia, anxiety, headache, irritability, poor concentration, blurred vision, and dizziness.
  • Ergot derivativesErgot derivatives: Caffeine may enhance the effectiveness of ergot derivatives, particularly in the treatment of migraine headaches (333).
  • EstrogensEstrogens: Estrogen has been shown to inhibit CYP1A2-mediated caffeine metabolism (78). Estrogen contained in oral contraceptives (OCP) and hormone replacement therapy has been shown to lengthen the half-life of caffeine. One study demonstrated impaired caffeine clearance in healthy female volunteers using oral contraceptives (79).
  • FlubendiamideFlubendiamide: In laboratory research, flubendiamide (an insecticide) marginally reduced the sensitivity of caffeine on lepidopterous ryanodine receptors (334).
  • FluconazoleFluconazole: According to human evidence, fluconazole may inhibit the metabolic elimination of caffeine (82; 83).
  • FluorideFluoride: When used as a mouth rinse, approximately 34% of fluoride found in black tea may bind to soft- and hard-tissue surfaces in the oral cavity (335). However, this binding of fluoride and other constituents from tea to enamel particles may be quite strong, and therefore the fluoride may only be released during demineralization of the enamel (335).
  • FluvoxamineFluvoxamine: Fluvoxamine blocks the liver enzyme responsible for the metabolism of caffeine, thus increasing the blood concentrations of caffeine (84). Fluvoxamine reduced the apparent oral clearance of caffeine and prolonged its elimination half-life (according to secondary sources).
  • FurafyllineFurafylline: According to anecdotal evidence, furafylline may inhibit the metabolism and/or clearance of caffeine.
  • HydrocortisoneHydrocortisone: Caffeine may enhance topically applied hydrocortisone in the treatment of atopic dermatitis (336).
  • ImmunosuppressantsImmunosuppressants: In human research, caffeine ingestion before resistance exercise was found to increase total leukocyte count, neutrophils, and monocytes but not significantly compared to placebo (99). In other human research, caffeine reduced alterations in circulating leukocyte and neutrophil counts after exercise (100).
  • InotropesInotropes: According to anecdotal evidence, combination use may increase positive inotropic effects on the heart.
  • Iron saltsIron salts: According to anecdotal evidence, caffeine may inhibit iron absorption, which can lead to iron deficiency anemia. In thalassemia major and intermedia patients, tea caused inhibition of iron absorption (337). Impaired iron metabolism and microcytic anemia may occur in infants of breastfeeding women consuming caffeine (101). Experts report that tea polyphenols may inhibit iron absorption by binding to iron in the gastrointestinal tract and forming insoluble complexes. This binding appears specific to nonheme forms of iron only, with black tea demonstrating greater inhibition than green tea. Ascorbic acid may overcome this binding. It has been recommended that vegetarians drink tea between meals, as binding by tea could exacerbate the low availability of iron found in plant sources (276). The effect of tea consumption on iron status has been investigated by various authors (338; 339; 340).
  • LithiumLithium: Caffeine withdrawal may produce lithium toxicity in patients maintained at high lithium blood levels. In such patients, abrupt discontinuation of daily caffeine has resulted in a significant increase (24%) in lithium blood levels (105).
  • MethoxsalenMethoxsalen: Methoxsalen may inhibit caffeine clearance and has been shown to increase the mean elimination half-life of caffeine (106).
  • Methylenedioxymethamphetamine (MDMA, "Ecstasy")Methylenedioxymethamphetamine (MDMA, "Ecstasy"): In animal research, caffeine has been shown to exacerbate MDMA-induced hyperthermia, likely due to adenosine receptor antagonism, phosphodiesterase (PDE) inhibition, and promotion of dopamine D(1) over D(2) receptor-related responses (163; 164). In animal research, combined use increased glial activation, leading to harmful consequences (165)
  • MethylphenidateMethylphenidate: In animal research, coadministration of caffeine and methylphenidate resulted in long-term changes in locomotor activity and cross-sensitization through dopamine- and cAMP-regulated phosphoproteins of 32kDa (DARPP-32)-dependent pathways (341).
  • MexiletineMexiletine: Mexiletine has been shown to decrease caffeine elimination (107; 108).
  • NicotineNicotine: In a study to examine the interaction between nicotine and caffeine on thermogenesis, it was shown that in healthy men, caffeine greatly enhanced the thermogenic response observed following ingestion of nicotine gum (342). Additive effects on cardiovascular parameters may occur with nicotine (97). Concomitant consumption of caffeine and cigarettes during pregnancy may place the developing fetus at a higher risk for diminished growth (343). In human research, patients with schizophrenia who smoked had higher serum caffeine levels (130).
  • OpiatesOpiates: Caffeine may bind to opiate receptors (344).
  • OseltamivirOseltamivir: In animal research, caffeine with oseltamivir (Tamiflu?) enhanced the effects on light-dark behavior and open-field behavior, likely due to adenosine antagonism (345).
  • PerazinePerazine: In in vitro research, perazine, a phenothiazine drug, was found to be a potent inhibitor of CYP1A2 (64). It was found to inhibit caffeine 3-N-demethylation and 1-N-demethylation, as well as to moderately reduce the rate of 7-N-demethylation in supersomes CYP1A2 and liver microsomes and attenuate C-8-hydroxylation in liver microsomes.
  • PhenytoinPhenytoin: In human research, phenytoin increased the clearance of caffeine and reduced its half-life from 4.8 to 2.4 hours (116). It also impaired the validity of caffeine liver function tests (116).
  • Potassium dichromatePotassium dichromate: In vitro, damage due to potassium dichromate was reduced significantly when administered with a black tea infusion (346).
  • Proton pump inhibitors (PPIs)Proton pump inhibitors (PPIs): When administered in therapeutically recommended doses, PPIs did not appear to induce CYP1A2 or alter caffeine metabolism (347).
  • QuinolonesQuinolones: Various quinolone antibiotics may inhibit cytochrome P450 1A2 enzyme activity (348; 56). In human and animal research, quinolones, including pipemidic acid (an agent similar to nalidixic acid) and enrofloxacin, increased the elimination half-life of caffeine (348; 56); marbofloxacin decreased the metabolism of caffeine (56); ciprofloxacin slightly increases the t1/2 of caffeine from 5.2 hours to 8.2 hours (349; 15); and ofloxacin and rufloxacin had a lack of an effect on caffeine clearance (14; 350).
  • RiluzoleRiluzole: According to anecdotal evidence, combination use may result in increased concentrations of both caffeine and riluzole.
  • SedativesSedatives: In human research, caffeine has been shown to antagonize the effects of sedatives (22; 23; 24; 25; 26; 27).
  • TerbinafineTerbinafine: Terbinafine decreased intravenous caffeine clearance (137).
  • TetracyclinesTetracyclines: Tea with milk inhibited tetracycline absorption in human research (138). This appears to be due to the calcium in even small amounts of milk and not due to the tea itself.
  • TheophyllineTheophylline: Caffeine may reduce theophylline clearance, increase elimination half-life, and increase serum levels (139).
  • VasodilatorsVasodilators: In human research, both caffeine and theophylline attenuated adenosine-induced vasodilation (12).
  • VerapamilVerapamil: Verapamil increased plasma caffeine concentrations (351).

    • Black Tea/Herb/Supplement Interactions

  • GeneralGeneral: Herb or supplement interactions associated with black tea are predominantly theoretical and generally based upon the adverse effect profile of caffeine.
  • AnalgesicsAnalgesics: In animal research, a synergistic effect was noted between caffeine and analgesics (297; 352).
  • AntibacterialsAntibacterials: According to secondary sources, certain antibacterials may interfere with the breakdown of caffeine.
  • Anticoagulants and antiplateletsAnticoagulants and antiplatelets: According to anecdotal evidence, caffeine may prolong bleeding time. Both catechins and caffeine in black tea have been reported to have antiplatelet activity (16; 17). In human research, black tea resulted in decreased production of leukocyte-platelet aggregates (18). Black tea contains significant amounts of vitamin K, approximately 262mcg of vitamin K per 100g of leaf (19).
  • Antidepressant agents,monoamine oxidase inhibitors (MAOIs)Antidepressant agents,monoamine oxidase inhibitors (MAOIs): In theory, concomitant administration with monoamine oxidase inhibitors (MAOIs) may increase blood pressure.
  • Anti-inflammatoriesAnti-inflammatories: Black tea polyphenols modulated cyclooxygenase, inducible nitric oxide synthase, and glutathione-related gene expression in tumors (314). In vitro, epigallocatechin-3-gallate (EGCG), a component of black tea, inhibited IL-1beta-induced expression of matrix metalloproteinase-1 and -13 in human chondrocytes, as well as activation of mitogen-activated protein kinase subgroup c-Jun N-terminal kinase (308; 309). EGCG also inhibited the IL-1beta-induced activity and expression of cyclooxygenase-2 and nitric oxide synthase-2 in human chondrocytes, as well as the production of nitric oxide (310; 311).
  • AntilipemicsAntilipemics: In animal research, black tea lowered serum cholesterol (299). However, the research is not consistent, as other human and animal research did find any effects on cholesterol and triglyceride levels (301; 302; 299; 168; 303; 304; 169; 305; 306). In clinical review, meta-analysis, and animal research, caffeine increased cholesterol and triglyceride levels (73; 88; 307).
  • AntineoplasticsAntineoplastics: Epidemiological research suggests that, overall, black tea has anticancer effects (33; 34). In animal and in vitro research, growth of cancer cells was reduced (36; 37; 38; 39; 40; 41; 42; 43).
  • Antiobesity agentsAntiobesity agents: According to human research, caffeine either alone or in combination with other agents like ephedra may have weight-reducing effects (100; 353; 354).
  • AntioxidantsAntioxidants: In vitro studies have demonstrated antioxidant activity from polyphenols in black tea (355; 356; 357; 358). According to human and animal research, the consumption of black tea may or may not alter the susceptibility of LDL to oxidation (359; 171; 301; 360; 361; 362; 363). Some (358; 364), but not all (168), human studies suggest that black tea consumption increased plasma antioxidant activity or decreased malondialdehyde levels.
  • AntipsychoticsAntipsychotics: Coffee and tea withdrawal did not increase the bioavailability of chlorpromazine, haloperidol, fluphenazine, and trifluoperazine or affect the individual variation in plasma levels (316). The cataleptic effect of chlorpromazine was significantly reduced by the simultaneous administration of tea when consumed by rats (317). Tannic acid formed complexes with antipsychotics drugs and influenced the pharmacokinetics of fluphenazine (318). Tannins form a strong complex and significant precipitation with several phenothiazines, amitriptyline, haloperidol, imipramine, and loxapine (319). High doses of caffeine may inhibit clozapine metabolism (320).
  • Antiulcer agentsAntiulcer agents: According to secondary sources, some antiulcer drugs may decrease the rate at which the body metabolizes caffeine. Cimetidine may decrease (inhibit) caffeine clearance by 30-50% (20; 21).
  • Bitter orangeBitter orange: Theoretically, bitter orange may add to the possible hypertensive effects of caffeine.
  • Caffeine-containing herbsCaffeine-containing herbs: Black tea is a source of caffeine. Thus, there may be additive effects with other products containing caffeine.
  • CalciumCalcium: Theoretically, caffeine can increase urinary calcium levels (112). Experts report that tea polyphenols do not interfere with the bioavailability of calcium (276; 111). Additionally, a 1994 NIH advisory panel concluded that caffeine has not been found to affect calcium absorption or excretion significantly and that two tablespoons of milk added to one cup of coffee can counteract any of the calcium lost.
  • CapsicumCapsicum: According to anecdotal evidence, red pepper capsaicin may increase caffeine concentrations and thereby increase its effects.
  • Cola nutCola nut: Theoretically, caffeine from black tea may add to the effects of caffeine from cola nut.
  • CordycepsCordyceps: In laboratory research, fermented powder caterpillar fungus (Cordyceps) induced CYP1A2, thereby accelerating the metabolism of caffeine (62).
  • ContraceptivesContraceptives: Estrogen has been shown to inhibit CYP1A2-mediated caffeine metabolism (78). Estrogen contained in oral contraceptives (OCP) has been shown to lengthen the half-life of caffeine. One study demonstrated an impaired caffeine clearance in healthy female volunteers who used oral contraceptives (79). In another report, oral contraceptives increased the residence time of caffeine in young women (80; 81).
  • Cytochrome P450-metabolized herbs and supplementsCytochrome P450-metabolized herbs and supplements: In animal and laboratory research and clinical review, cytochrome P450 1A2 was involved in the metabolism of caffeine (46; 47; 48; 49; 50; 51; 52; 53; 54; 55; 56; 57; 58; 59; 60; 61; 62; 63; 64; 65; 66; 67).
  • DamianaDamiana: A combination of caffeine, yerba mate, and damiana has been reported to cause weight loss, slowing of the gastrointestinal tract, and a feeling of stomach fullness (365).
  • DanshenDanshen: In laboratory research, single and continuous danshen aqueous extract administration reduced the metabolism of caffeine to paraxanthine (54).
  • Dental herbs and supplementsDental herbs and supplements: In human research, tea-induced stains were reduced by whitening agents (325).
  • Dermatological herbs and supplementsDermatological herbs and supplements: In human research, topical application of epigallocatechin gallate (EGCG), a constituent of black tea, before UVB exposure significantly blocked UVB-induced infiltration of leukocytes, produced fewer prostaglandins, reduced myeloperoxidase activity, and decreased UVB-induced erythema compared to control (326).
  • DiureticsDiuretics: Theoretically, caffeine may add to the effects of other diuretics.
  • EchinaceaEchinacea: According to clinical review, echinacea was found to alter the clearance of caffeine via CYP1A2 modulation (66).
  • Ephedra (ma huang)Ephedra (ma huang): According to secondary sources, increased risk of heart attack, stroke, seizures, and death may occur when ephedra and caffeine are taken concurrently. According to one meta-analysis, the concomitant use of ephedra or ephedrine and caffeine may increase symptoms associated with psychiatric, autonomic, or gastrointestinal disorders, as well as heart palpitations (77).
  • Ergogenic herbs and supplementsErgogenic herbs and supplements: According to clinical evidence, caffeine may exert ergogenic effects (366).
  • FluorideFluoride: When used as a mouth rinse, approximately 34% of fluoride found in black tea may bind to soft- and hard-tissue surfaces in the oral cavity (335). However, this binding of fluoride and other constituents from tea to enamel particles may be quite strong, and therefore the fluoride may only be released during demineralization of the enamel (335).
  • FolateFolate: In human research, both green and black teas reduced folate bioavailability (85).
  • GuaranaGuarana: Due to high caffeine concentration in guarana, combination use may result in additive effects (367). A combination supplement containing guarana, yerba mate, and damiana has been reported to cause increased gastric emptying time and increased weight loss over 45 days (365).
  • Herbs and supplements that may lower seizure thresholdHerbs and supplements that may lower seizure threshold: According to a review, methylxanthines like caffeine have been linked to seizures, likely due to adenosine-antagonizing effects (131). In a case series, the effect of caffeine increased the length of the seizure and potentially enhanced the therapeutic effect of electroconvulsive therapy (246). Also, seizures have been reported from caffeine overdose (232).
  • HypoglycemicsHypoglycemics: Caffeine might increase or decrease blood sugar. Theoretically, concomitant use of black tea and diabetes drugs might interfere with blood glucose control (298).
  • HypotensivesHypotensives: Caffeine may increase systolic and diastolic blood pressure (89; 90; 91; 92; 93; 94; 95; 96; 97). However, there is controversy in this area, and several studies have not shown these effects (218; 219; 220; 221).
  • ImmunomodulatorsImmunomodulators: In human research, caffeine ingestion before resistance exercise was found to increase total leukocyte count, neutrophils, and monocytes, but not significantly compared to placebo (99). In other human research, caffeine reduced alterations in circulating leukocyte and neutrophil counts after exercise (100).
  • InotropesInotropes: According to anecdotal evidence, combination use may increase the positive inotropic effects on the heart.
  • IronIron: Caffeine may inhibit iron absorption, which can lead to iron deficiency anemia In thalassemia major and intermedia patients, tea caused inhibition of iron absorption (337). Impaired iron metabolism and microcytic anemia may occur in infants of breastfeeding women consuming caffeine (101). Experts report that tea polyphenols may inhibit iron absorption by binding to iron in the gastrointestinal tract and forming insoluble complexes. This binding appears specific to nonheme forms of iron only, with black tea demonstrating greater inhibition than green tea. Ascorbic acid may overcome this binding. Vegetarians are recommended to drink tea between meals, as binding by tea could exacerbate the low availability of iron found in plant sources (276). The effect of tea consumption on iron status has been investigated by various authors (338; 339; 340).
  • MagnesiumMagnesium: According to secondary sources, at high levels (more than 744mg daily), caffeine may increase magnesium loss in urine.
  • MateMate: Due to the caffeine content of mate, combination use may result in additive effects.
  • Nicotine/tobaccoNicotine/tobacco: In humans, caffeine enhanced the thermogenic response observed following ingestion of nicotine gum (342). Additive effects on cardiovascular parameters may occur with nicotine (97). Concomitant consumption of caffeine and cigarettes during pregnancy may place the developing fetus at higher risk for diminished growth (343). In human research, patients with schizophrenia who smoked had higher serum caffeine levels (130).
  • Osteoporosis herbs and supplementsOsteoporosis herbs and supplements: Preliminary evidence exists from epidemiological studies for the use of black tea in increasing bone mineral density and preventing osteoporosis in older women (328; 329).
  • PhytoestrogensPhytoestrogens: Estrogen has been shown to inhibit CYP1A2-mediated caffeine metabolism (78). Estrogen contained in oral contraceptives (OCP) and hormone replacement therapy has been shown to lengthen the half-life of caffeine. One study has demonstrated an impaired caffeine clearance in healthy female volunteers who used oral contraceptives (79).
  • Rutin-containing herbsRutin-containing herbs: According to secondary sources, black tea is a rich dietary source of rutin.
  • SedativesSedatives: In human research, caffeine was shown to antagonize the effects of sedatives (22; 23; 24; 25; 26; 27).
  • Tannin-containing herbsTannin-containing herbs: There is evidence that tannin of tea is linked to a high rate of esophageal cancer in regions of heavy tea consumption, although other studies suggest a protective effect of green tea in relation to esophageal cancer (187; 186). Caution is advised with concomitant use with other tannin-containing herbs and supplements.
  • ThiamineThiamine: Both urinary and blood serum levels of thiamine were lowered after tea ingestion (368).
  • VasodilatorsVasodilators: In human research, both caffeine and theophylline attenuate adenosine-induced vasodilation (12).
  • VasoconstrictorsVasoconstrictors: In human research, both caffeine and theophylline attenuated adenosine-induced vasodilation (12).
  • Vitamin EVitamin E: Vitamin E was substantially increased with black tea (369).
  • Yerba mateYerba mate: Theoretically, caffeine from black tea may add to the effects of caffeine from yerba mate. A combination supplement containing guarana, yerba mate, and damiana has been reported to cause increased gastric emptying time and increased weight loss over 45 days (365).

    • Black Tea/Food Interactions:

  • GeneralGeneral: Food interactions associated with black tea are predominantly theoretical and based upon the adverse effect profile of caffeine. Experts recommended that vegetarians drink tea between meals, since plants do not provide a high source of iron. The binding of nonheme iron by tea could exacerbate this low availability (276). Theoretically, the bioavailability of catechins, constituents of black tea, may decrease when ingested with food. Consumption of food may alter the acute effects of tea on vascular function and blood pressure.
  • CapsaicinCapsaicin: According to anecdotal evidence, red pepper capsaicin may increase caffeine concentrations and thereby increase its effects.
  • CarbohydrateCarbohydrate: In human research, extract of green, black, and mulberry teas resulted in decreased carbohydrate absorption (370). In human research, co-ingestion of caffeine with a high-carbohydrate meal resulted in reduced insulin sensitivity (76).
  • Catechin-containing foods (onions, apples)Catechin-containing foods (onions, apples): Flavonoids in foods may have additive effects to those in tea (371).
  • Grapefruit juiceGrapefruit juice: Clinical studies have shown that the ingestion of grapefruit juice should not cause any pharmacokinetic or pharmacodynamic interactions when coadministered with caffeine (372; 373; 374).
  • Iron-containing foodsIron-containing foods: Caffeine may inhibit iron absorption, which can lead to iron deficiency anemia. In thalassemia major and intermedia patients, tea caused inhibition of iron absorption (337). Impaired iron metabolism and microcytic anemia may occur in infants of breastfeeding women consuming caffeine (101). Experts report that tea polyphenols may inhibit iron absorption by binding to iron in the gastrointestinal tract and forming insoluble complexes. This binding appears specific to nonheme forms of iron only, with black tea demonstrating greater inhibition than green tea. Ascorbic acid may overcome this binding. Vegetarians are recommended to drink tea between meals, as binding by tea could exacerbate the low availability of iron found in plant sources (276). The effect of tea consumption on iron status has been investigated by various authors (338; 339; 340).
  • MilkMilk: The antimutagenic activity of black tea was reduced in the presence of milk (375). The addition of milk also diminished the antioxidant potential of black tea (376). Milk did not reduce polyphenol bioavailability. Polyphenols have a strong affinity for proline rich proteins (casein, milk, gelatin, saliva). However, the addition of milk to green or black tea did not appear to affect the polyphenol concentration in blood (355; 377; 358; 378). Some studies have found the tannin component to be protein bound by adding milk, thereby preventing its potential detrimental effects (355), although other studies have presented conflicting results (379; 358).
  • Tannin-containing foodsTannin-containing foods: There is evidence that the tannin of tea is linked to a high rate of esophageal cancer in regions of heavy tea consumption, although other studies suggest a protective effect of green tea in relation to esophageal cancer (187; 186). Caution is advised with concomitant use with other tannin-containing herbs and supplements.
  • Vitamin EVitamin E: Vitamin E was substantially increased with black tea (369).

    • Black Tea/Lab Interactions:

  • GeneralGeneral: Lab interactions associated with black tea are predominantly theoretical and based upon the adverse effect profile of caffeine.
  • 5-Hydroxyindoleacetic acid5-Hydroxyindoleacetic acid: Caffeine may increase 5-hydroxyindoleacetic acid concentrations (anecdotally).
  • Adenosine stress testAdenosine stress test: Given caffeine's antagonism at adenosine receptors and the common use of adenosine as an agent in pharmacologic stress tests, patients are instructed to refrain from using caffeine for 12-24 hours before undergoing an adenosine stress test (380; 381). For patients undergoing dipyridamole-induced (201)T1 stress tests, caffeine levels above 2mg/mL may cause false-negative findings in dipyridamole (201)T1 myocardial perfusion imaging (381).
  • Blood pressureBlood pressure: Caffeine may increase systolic and diastolic blood pressure (89; 90; 91; 92; 93; 94; 95; 96; 97).
  • CalciumCalcium: Theoretically, caffeine can increase urinary calcium levels (112). Experts report that tea polyphenols do not interfere with the bioavailability of calcium (276; 111). Additionally, a 1994 NIH advisory panel concluded that caffeine has not been found to affect calcium absorption or excretion significantly and that two tablespoons of milk added to one cup of coffee can counteract any of the calcium lost.
  • CatecholaminesCatecholamines: In human research, caffeine consumption was associated with elevated catecholamines (382; 383; 384; 385).
  • Coagulation panelCoagulation panel: According to anecdotal reports, the caffeine in black tea can prolong bleeding time. Both catechins and caffeine in black tea have been reported to have antiplatelet activity (16; 17). In human research, black tea resulted in decreased production of leukocyte-platelet aggregates (18).
  • Creatine kinaseCreatine kinase: In human research, caffeine ingestion before resistance exercise was found to increase creatine kinase (CK) concentrations (99).
  • CreatinineCreatinine: Caffeine may increase urinary creatinine concentrations (anecdotally). Creatinine in combination with caffeine inhibited net muscle phosphocreatine resynthesis during exercise (386).
  • EicosanoidsEicosanoids: In vitro, theaflavins enhanced the formation of prostaglandin E(2) in tumor microsomes by modulating the interactions between COX-2 and microsomal factors; however, the formation of thromboxane and 12-hydroxyheptadecatrienoic acid, two metabolites formed from prostaglandin E(2), was inhibited by theaflavins (387).
  • ErythropoietinErythropoietin: In preterm infants, caffeine has been found to be equivalent to theophylline in attenuating erythropoietin production (388).
  • EstrogenEstrogen: In epidemiological research, caffeine consumption is associated with the estrogen metabolite 2-hydroxyestrone (2-OHE1) (389).
  • FerritinFerritin: Theoretically, drinking black tea may reduce serum ferritin.
  • FolateFolate: In humans, both green and black teas reduced folate bioavailability (85).
  • GlucoseGlucose: Caffeine consumption has resulted in an increase and decrease in glucose (384). In human research, black tea decreased postprandial plasma glucose (390).
  • Glycosylated hemoglobin (HbA1c)Glycosylated hemoglobin (HbA1c): In human research, tea consumption had no effect on glycosylated hemoglobin levels (391).
  • Heart rateHeart rate: In animals, caffeine consumption resulted in increased heart rate (392)
  • HemoglobinHemoglobin: Theoretically, drinking black tea may reduce hemoglobin levels.
  • Hemostatic factorsHemostatic factors: According to some clinical research, plasma fibrinogen, tissue-type plasminogen activator and plasminogen activator inhibitor-1 may not be affected by tea (393), although plasminogen activator inhibitor activity was shown to be reduced in others (169). P-selectin levels have decreased or demonstrated a lack of change (172; 18). Black tea consumption reduced levels of C-reactive protein in human research (18).
  • HomocysteineHomocysteine: According to clinical review, caffeine may increase blood homocysteine concentrations (307; 394; 395).
  • InsulinInsulin: In human research, black tea increased postprandial plasma insulin (390).
  • LactateLactate: The combination of ephedrine and caffeine may increase blood lactate levels (384).
  • LDL oxidationLDL oxidation: In vitro studies have demonstrated antioxidant activity from polyphenols in black tea (355; 356; 357). In humans and animals, the consumption of black tea altered susceptibility of LDL to oxidation (359; 171; 301; 360; 361; 362; 363). Some (358; 364), but not all (168), human studies have suggested that black tea consumption increased plasma antioxidant activity or decreased malondialdehyde levels.
  • Lipid profileLipid profile: According to clinical review, meta-analysis, and animal research, caffeine may increase cholesterol and triglyceride levels (73; 88; 307; 396). Moderate (224mg) and high (674mg) tea catechins reduced postprandial triglyceride levels in healthy adults (397).
  • Magnetic resonance imaging (MRI)Magnetic resonance imaging (MRI): Use cautiously in individuals undergoing gastrointestinal magnetic resonance imaging (MRI), due to the potential for enhancement of the gastrointestinal tract (102). In human research, a single 200mg dose of caffeine increased the linearity of blood oxygenation level dependent (BOLD) response, as well as the agreement between nonlinear and linear estimates of the hemodynamic response function (103).
  • Plasma reninPlasma renin: In human research, caffeine is a stimulator of plasma renin activity (398).
  • PotassiumPotassium: According to clinical review and human reports, caffeine, particularly in large amounts, may reduce potassium levels (399; 400; 401; 402).
  • ProlactinProlactin: Increasing tea intake induced an increase in serum prolactin concentrations by an average of 0.38mcg/L (p=0.003) (403).
  • QTc intervalQTc interval: A combination of caffeine, green tea extract, Garcinia cambogia extract, and yerba mate extract did not alter the QTc interval in healthy adults (404).
  • Saliva amylaseSaliva amylase: In human research, black tea inhibited amylase and streptococcal amylase in human saliva, as well as the release of maltose at higher levels of inhibition than green teas (405).
  • Theophylline levelsTheophylline levels: Intakes of caffeine may cause increases in serum levels of theophylline (383).
  • Urate (serum; Bittner method)Urate (serum; Bittner method): According to anecdotal evidence, caffeine may cause false-positive tests.
  • Vanillylmandelic acid (VMA)Vanillylmandelic acid (VMA): According to anecdotal evidence, caffeine may cause small increases in VMA concentrations.
  • WeightWeight: In animals, caffeine lowered weight (73).
  • White blood countWhite blood count: In humans, caffeine ingestion before resistance exercise was found to increase total leukocyte count, neutrophils, and monocytes, but not significantly compared to placebo (99). In other human research, caffeine reduced alterations in circulating leukocyte and neutrophil counts after exercise (100).