Shengmai
Ginseng/Drug Interactions:
GeneralGeneral: Potential interactions with ginseng have been reviewed (408). Additional details are lacking. ACE inhibitorsACE inhibitors: In laboratory research, extracts of Panax ginseng (G115?) inhibited angiotensin-converting enzyme (ACE) activity (409). AlcoholAlcohol: In humans, Panax ginseng reduced blood concentration of alcohol (ethanol) and enhanced blood alcohol clearance (32; 33; 34; 225; 226). Alzheimer's agentsAlzheimer's agents: In human research, ginseng constituents or supplements containing ginseng have been shown to improve symptoms of dementia (294; 410; 295; 411; 38; 290; 412). AnalgesicsAnalgesics: Panax ginseng potentiated the antinociceptive effects of pentazocine and aspirin (413) and appears to have independent effects, based on pharmacological research (353). AnestheticsAnesthetics: Of surveyed presurgical patients, 9% were taking an herbal remedy, including ginseng, known to have an effect on the perioperative period (245). It is important for anesthetists to be aware of its use. Antianxiety agentsAntianxiety agents: In mice using the elevated plus-maze model, ginsenosides Rg3 and Rh2 from red ginseng significantly increased the time spent on the open arms and the number of open-arm entries; these effects were antagonized by flumazenil but not by WAY-100635 (414). AntiarrhythmicsAntiarrhythmics: Shenmai injection had antiarrhythmic action (415). AntiasthmaticsAntiasthmatics: In vitro, ginsenoside induced relaxation of human bronchial smooth muscle (17). In mice, ginsan, a polysaccharide derived from Panax ginseng, reduced airway hyperresponsiveness, remodeling, and eosinophilia, and decreased IL-5 levels in the supernatant of cultured splenocytes, with a lack of an effect on IFN-gamma and serum IgE (416). AntibioticsAntibiotics: In animal and human research, ginseng has displayed antibacterial effects against bacteria including, but not limited to, Staphylococcus aureus, Helicobacter pylori, and Pseudomonas aeruginosa (417; 418; 58; 229). In individuals with chronic bronchitis, treatment with ginseng was asssociated with significantly improved bacterial clearance (38). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Panax ginseng inhibited the aggregation of platelets (191; 259), reduced platelet adhesiveness (260), reduced or increased the international normalized ratio (INR) (261; 37; 226), and reduced warfarin concentrations or effects and increased clearance (32; 33; 34; 35; 36; 37; 38). However, other research has found a lack of changes in warfarin pharmacokinetics (419; 420; 421). In a case report, shengmai-yin, a source of ginseng, was determined to be responsible for the development of an intracerebral hematoma in a man stable on warfarin (422). Whether American ginseng interferes with other anticoagulant drugs (such as heparin) or with antiplatelet drugs (clopidogrel, Ticlid?) is unclear. According to a review, American ginseng interfered with metabolism of antiplatelet or anticoagulant agents (423). Additional details are lacking. In another review, it was advised that ginseng not be combined with anticoagulants (424). Antidepressants: MAOIsAntidepressants: MAOIs: Panax ginseng may induce mania in depressed patients who take MAOI antidepressants, such as phenelzine (221; 222). Panax ginseng or Panax quinquefolius affected MAOI inhibitors (36). Panax ginseng induced mania when used concomitantly with phenelzine (32; 33; 19; 34; 36). Ginseng has also demonstrated antidepressive effects in mice (425; 426). The potential interactions of herbal medicines with antipsychotics, antidepressants, and hypnotics have been discussed (further details are lacking) (427). AntidiabeticsAntidiabetics: In clinical trials, ginseng reduced blood glucose levels (39; 19; 40; 41; 42; 43; 38; 44). However, this is an area of controversy, because different species of ginseng may exhibit different effects (45; 46); hyperglycemia has also been reported (38), and the experimental data are inconsistent in this area (25; 47; 42; 38; 48). AntiemeticsAntiemetics: In vitro, ginseng saponins, especially the panaxatriol saponin fraction, had substantial inhibitory effects on the recombinant serotonin type 3A receptor, suggesting that some specific ginsenosides might have an antagonistic action against serotonin type 3A receptor related to nausea and vomiting (16). These antiemetic results are supported by an animal study using Korean red ginseng total extract (27). AntifungalsAntifungals: Juzen-taiho-to, a Japanese traditional medicine containing Ginseng radix, enhanced the anti-Candida activity of macrophages in Candida albicans-infected mice (428). AntihistaminesAntihistamines: In rats, 14 days of ginseng decreased the bioavailability of a single dose of fexofenadine, likely due to p-glycoprotein modulation (429). In laboratory research, ginsenosides have displayed antiallergenic properties (430; 8). AntihypertensivesAntihypertensives: Both hypertension and hypotension, as well as general increases and decreases in blood pressure, have been reported in ginseng users and may be dependent on the dose used (181; 182; 183; 184; 185; 186; 187; 188; 189; 190; 191; 38; 48; 192). A lack of changes in blood pressure has also been reported in patients taking ginseng (193; 194; 25). Animal research has suggested that ginsenosides may have biphasic actions on blood pressure, with initial decreases in blood pressure followed by increases (431; 354). Anti-inflammatoriesAnti-inflammatories: Panax ginseng reduced muscle inflammation following exercise in animals (432). In a clinical trial, Salvia miltiorrhiza and shengmai inhibited inflammatory mediators (149). AntilipemicsAntilipemics: In animals and humans, red ginseng powder reduced plasma total cholesterol, triglycerides, and nonesterified fatty acids, while elevating plasma high-density lipoprotein (HDL) cholesterol (260). Hepatic cholesterol and triglyceride contents were decreased and phospholipids were increased following ginseng administration in rats fed a high-cholesterol diet, corresponding to improvement of the fatty liver. AntineoplasticsAntineoplastics: In laboratory research and animals, ginseng preparations acted synergistically with cytotoxic drugs, chemotherapy, and radiation (433; 434; 435; 30). In theory, their effectiveness may be increased when multiple agents are used in optimal combinations. Antineoplastic effects of ginseng and ginsenosides have been found in vitro and in vivo (436; 437; 438; 439; 29; 440; 441; 442; 443; 444; 445; 446; 447; 448; 449). In animals, Korean red ginseng may interact synergistically with paclitaxel and attenuate cisplatin-induced nausea and vomiting (435; 27). In vitro, a combination of American ginseng berry extract (AGBE) or Asian ginseng and 5-fluorouracil (5-FU) decreased cell growth in human colorectal cancer cell lines more than when either was used alone (450; 451). Similar effects were observed for ginseng neutral polysaccharides and 5-FU in sarcoma-180 (S180) tumor-bearing mice (452). In vitro, ginseng and doxorubicin treatment of a doxorubicin-resistant human breast cancer cell line downregulated the multidrug resistance1 (MDR1) protein (453). In vitro, panaxytriol from Panax ginseng acted synergistically with mitomycin C (454). In vitro, KG-135, a quality-controlled standardized ginsenoside formulation, potentiated etoposide-induced apoptosis in HeLa cells (455). In animals, Korean red ginseng total extract significantly attenuated cisplatin-induced nausea and vomiting when administered 1-2 hours before cisplatin (27). Korean red ginseng also inhibited cisplatin-induced oxidation and apoptosis in vitro in an auditory cell line (456). In a case study, coadministration of imatinib and a ginseng energy drink resulted in right upper-quadrant pain and increased liver enzyme levels (356). The patient's only lifestyle change was daily ingestion of Panax ginseng via energy drinks for the previous three months. Both imatinib and ginseng were discontinued, and the patient was treated with a short course of corticosteroids. Imatinib was later restarted at the same dose, with no recurrent elevations in his liver enzyme levels. The potential for interactions with anticancer agents of herbal products, including ginseng, has been reviewed (457). Antiobesity agentsAntiobesity agents: Protopanaxadiol from American ginseng prevented obesity in mice fed a high-fat diet (458). AntiparasiticsAntiparasitics: In mice, aluminum hydroxide, with ginseng extract as an adjuvant for an inactivated whole vaccine against Neospora caninum infection, reduced the number of parasites circulating in the blood during the acute phase of infection but failed to limit the establishment of chronic infection (459). AntipsychoticsAntipsychotics: Anecdotal reports have noted a possible interaction between ginseng and antipsychotics. Combined use may cause additive effects or increased risk of adverse effects, although scientific data are lacking. The potential interactions of herbal medicines with antipsychotics, antidepressants, and hypnotics have been discussed. Further details are lacking (427).Antiretrovirals, protease inhibitorsAntiretrovirals, protease inhibitors: In vitro, kaempferol from ginseng interacted with HIV protease inhibitors by inhibiting the efflux and CYP3A4-mediated metabolism of xenobiotics (460). Another study showed that ginseng did not alter the in vivo pharmacokinetics of indinavir in HIV-positive patients (461). Potential interactions of ginseng and highly active antiretroviral treatment (HAART) have been reviewed (462). In a case report, elevated liver enzymes were indicated as resulting from an interaction between raltegravir and Panax ginseng; the authors suggested that an increase in plasma raltegravir played a role (463). Antiulcer agentsAntiulcer agents: A polysaccharide fraction of the leaves of Panax ginseng prevented gastric ulcer formation in rats after administration of necrotizing agents (HCl-ethanol, ethanol), and after pylorus ligation (464). This effect was observed not only after oral administration, but also after systemic administration, suggesting a possible nonlocal effect. Rats administered tissue-cultured and cultivated ginseng had reduced gastric secretion and acid output (465). AntiviralsAntivirals: Theoretically, Cold-fX?, and other ginseng preparations may have additive effects when taken concomitantly with other antivirals, such as rimantadine, amantadine, zanamivir, and oseltamivir (Tamiflu?). Cytochrome P450 enzymes may be involved in some interactions (460). American ginseng induced phase II and antioxidant enzymes in vitro and might increase the clearance of zidovudine or enhance antioxidant activity (466). CaffeineCaffeine: Controversy exists about whether caffeine and other stimulants are safe to take with ginseng. Some secondary sources indicate that, when taken in the suggested dosages, Asian ginseng is considered safe, while others disagree. However, in rare cases, ginseng may cause insomnia and headaches, and enhance the effects of caffeine.Calcium-channel blockersCalcium-channel blockers: In case reports, ginseng altered the effects of blood pressure or heart medications, including calcium channel blockers such as nifedipine (Procardia?). Ginseng increased serum levels of nifedipine in healthy volunteers (467).Cardiac glycosidesCardiac glycosides: In humans, ginseng enhanced the effects of digoxin (Lanoxin?) in patients with congestive heart failure (177), and according to a systematic review of human research, in patients with mitral valve disease, treatment with P. ginseng saponins had a protective effect against ischemia reperfusion injury; in individuals with coronary heart disease, treatment with P. ginseng reduced symptoms of angina pectoris (38). According to a pharmacokinetic study in patients with congestive heart failure taking digoxin, shengmai injection may significantly lower serum digoxin levels (468). Immunoassays have indicated that ginseng may interfere with digoxin measurement (469). CNS depressantsCNS depressants: In humans and animals, insomnia was a common side effect of ginseng use (207; 302; 223; 470; 157; 471). CNS stimulantsCNS stimulants: Based on animal research, there is a theoretical interaction between ginseng and stimulants (470; 157; 471), although scientific data are lacking. Because it is a nonspecific CNS stimulant, Panax ginseng may increase the effects and side effects of prescription drugs that also stimulate the CNS, such as amphetamine salts (Adderall?), dextroamphetamine (Dexedrine?), methylphenidate (Concerta?, Methlyn?, Ritalin?), and phentermine (Adipex-P?, Ionamin?). CorticosteroidsCorticosteroids: Panax ginseng extract may have glucocorticoid-like activities in homeostasis and regulation of immunity (472). Ginseng affects the thymus gland and theoretically may interact with steroid or hormone drugs, based on anecdotal evidence. Cytochrome P450-modifying agentsCytochrome P450-modifying agents: Based on laboratory research, Panax ginseng may inhibit CYP2D6 (230). In vitro, eight ginsenosides and aglycones potently induced CYP1A1 expression; deglycosylated ginsenosides were more potent inducers of CYP1A1, CYP1A2, and CYP3A4 than the glycosylated ginsenosides in HepG2 cells (231). Although Panax ginseng has been shown to activate CYP3A4 in vitro, there is a lack of an in vivo correlation with the in vitro effects (232; 233; 234; 235; 236). In vitro, Panax notoginseng saponins had a lack of an effect on testosterone metabolism in a test of CYP3A4 metabolism (237). In rats, Panax notoginseng induced CYP3A1 mRNA and CYP1A1, but a lack of an effect was seen on CYP1B1 mRNA expression in lung tissue (238) or on the expression of CYP2B1 and CYP4A1 genes in liver tissues of rats (239). Laboratory studies demonstrated a lack of an effect of ginseng preparations or Cold-fX? on CYP450 activity (240; 241). In vitro, nine ginseng products studied had little to no effect on the activity of CYP3A4 (242). In rats, shenmai injection (SMI), a mixture of radix ginseng and radix Ophiopogonis, caused a rise in AUC for midazolam (CYP450 3A1/2) and an increase in AUC for diclofenac (CYP4502C6) (243). The pharmacokinetics of chlorzoxazone (CYP4502E1) and theophylline (CYP4501A2) in rats was not altered markedly. In rat liver microsomes, linear mixed-type inhibition by SMI of the enzyme activities of CYP3A1/2, CYP2C6, and CYP1A2 was shown with IC50 values of 3.3%, 2.0%, and 3.1%, respectively, and Ki values of 3.8%, 1.5%, and 1.9%, respectively. However, the effects of ginseng alone are unclear. However, according to a systematic review of herbal drugs and pharmacokinetic drug interactions, of 66 studies identified, clinical evidence for ginseng was considered "limited" (a lack of potent or moderate inhibitory effect on cytochrome P450 or p-glycoprotein) (244). DisulfiramDisulfiram: Many ginseng tinctures contain high levels of alcohol and may theoretically cause nausea or vomiting when taken with disulfiram (Antabuse?) (theoretical).DiureticsDiuretics: One case report linked ginseng to furosemide (Lasix?) diuresis resistance (473). EstrogensEstrogens: There is limited laboratory evidence that ginseng may contain estrogen-like chemicals and may affect medications with estrogen-like or estrogen-blocking properties (195; 196; 198; 13). This has not been well demonstrated in humans (474). However, one study found a lack of estrogenic activity evident in the sample of Panax ginseng extract tested or in a sample of the combination product ArginMax? (197). HepatotoxinsHepatotoxins: Ginseng is typically considered a hepatoprotective agent (357; 358; 359; 360), but there is also evidence of hepatotoxic effects (36). In a case report, a 65 year-old man with nocturia developed jaundice and severe pruritus after two weeks of taking a multi-ingredient product, Prostata?, containing Panax ginseng (396). HypnoticsHypnotics: The potential interactions of herbal medicines with antipsychotics, antidepressants, and hypnotics have been discussed (further details are lacking) (427).ImmunosuppressantsImmunosuppressants: In clinical trials and laboratory research, Cold-fX? and ginseng in general have been shown to enhance the immune system or reduce the occurrence or symptoms associated with colds (25; 105; 24; 26; 38; 226; 227; 207; 228; 229). Impotence agentsImpotence agents: Theoretically, Panax ginseng may have additive effects when taken concomitantly with agents used for impotence (141). MetronidazoleMetronidazole: Many ginseng tinctures contain high levels of alcohol and may cause nausea or vomiting when taken with metronidazole (Flagyl?) (theoretically).OpiatesOpiates: In animals, ginseng inhibited tolerance formation to opioids (223; 470; 157) and inhibited cocaine-induced hyperactivity (471). Morphine-induced analgesia was antagonized by ginseng total saponins, which also inhibited the development of analgesic tolerance to, and physical dependence on, morphine in guinea pigs (223). PhenelzinePhenelzine: According to a systematic review and case reports, ginseng has been associated with the induction of mania from depression when used with phenelzine (226). PhenytoinPhenytoin: In laboratory research, Panax ginseng affected phenytoin via human liver cytochrome P450 enzyme interaction (36; 475). PhotosensitizersPhotosensitizers: In laboratory research, Panax ginseng acted as a photoprotector at low concentrations and as a photosensitizer at high concentrations (210). QT-prolonging drugsQT-prolonging drugs: There is preliminary evidence that ginseng increased the QTc interval (thus increasing the risk of abnormal heart rhythms) (209). Therefore, caution is advised with other medications that may alter QTc. Radioprotective drugsRadioprotective drugs: Panax ginseng offered radioprotective effects in humans (329; 344).SteroidsSteroids: In vitro, Panax ginseng extract had glucocorticoid-like activities in homeostasis and regulation of immunity (472). Ginseng affects the thymus gland and theoretically may interact with steroid or hormonal drugs (anecdotal). SympathomimeticsSympathomimetics: Use with sympathomimetics may lead to additive effects, based on anecdotal evidence.VaccinesVaccines: In laboratory research, ginsenoside Re, isolated from the root of Panax ginseng, enhanced the immune response to influenza vaccine (H3N2) (33). VasodilatorsVasodilators: In healthy men, P. ginseng or red ginseng was associated with enhanced cerebrovascular reactivity and cerebral blood flow (38; 476). In vitro, ginsenosides Rb1 and Rg1 appeared to have vasodilatory effects (477). Ginseng/Herb/Supplement Interactions:
AcupunctureAcupuncture: In rats, acupuncture combined with American ginseng lowered heart rate, systolic blood pressure, diastolic blood pressure, and cardiac output compared with normal controls, but differences were lacking when compared to rats that received ginseng alone (478). AlcoholAlcohol: In humans, Panax ginseng reduced blood concentration of alcohol (ethanol) and enhanced blood alcohol clearance (32; 33; 34; 225; 226). Alzheimer's agentsAlzheimer's agents: In human research, ginseng constituents or supplements containing ginseng have been shown to improve symptoms of dementia (294; 410; 295; 411; 38; 290; 412). AnalgesicsAnalgesics: Panax ginseng potentiated the antinociceptive effects of analgesics (413) and appeared to have independent effects, in pharmacological research (353). AnestheticsAnesthetics: Of presurgical patients surveyed, 9% were taking an herbal remedy, including ginseng, known to interact with the perioperative period (245). It is important for anesthetists to be aware of ginseng use. Antiallergy agentsAntiallergy agents: In laboratory studies, ginsenoside Rh2 exhibited antiallergic activity originating from cell membrane-stabilizing activity and anti-inflammatory activity, as shown by the inhibition of nitric oxide (NO) and prostaglandin (PGE) 2 production (430). In laboratory research, ginsenosides isolated from the root of Panax ginseng and their metabolites had antiallergenic properties (8). AntiarrhythmicsAntiarrhythmics: Shenmai injection may have antiarrhythmic action (415). AntiasthmaticsAntiasthmatics: In vitro, ginsenoside induced relaxation of human bronchial smooth muscle (17). In mice, ginsan, a polysaccharide derived from Panax ginseng, reduced airway hyperresponsiveness, remodeling, and eosinophilia, and decreased IL-5 levels in the supernatant of cultured splenocytes, with a lack of an effect on IFN-gamma and serum IgE (416). AntibacterialsAntibacterials: In animal and human research, ginseng has displayed antibacterial effects against bacteria including, but not limited to, Staphylococcus aureus, Helicobacter pylori, and Pseudomonas aeruginosa (417; 418; 58; 229). In individuals with chronic bronchitis, treatment with ginseng was asssociated with significantly improved bacterial clearance (38). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: Panax ginseng inhibited the aggregation of platelets (191; 259), reduced platelet adhesiveness (260), reduced or increased the international normalized ratio (INR) (261; 37; 226), and reduced anticoagulant concentrations or effects and increased clearance (32; 33; 34; 35; 36; 37; 38). However, other research has found a lack of changes in warfarin pharmacokinetics (419; 420; 421). In a case report, shengmai-yin, a source of ginseng, was determined to be responsible for the development if a intracerebral hematoma in a man stable on warfarin (422). Whether American ginseng interferes with other anticoagulant drugs (such as heparin) or with antiplatelet drugs (clopidogrel, Ticlid?) is unclear. According to a review, American ginseng interfered with metabolism of antiplatelet or anticoagulant agents (423). Additional details are lacking. According to another review, it is advised that ginseng not be combined with anticoagulants (424). Antidepressants: MAOIsAntidepressants: MAOIs: Panax ginseng may induce mania in depressed patients who take MAOI antidepressants, such as phenelzine (221; 222). Panax ginseng or Panax quinquefolius affected MAOI inhibitors (36). Panax ginseng induced mania when used concomitantly with phenelzine (32; 33; 19; 34; 36). Ginseng has also demonstrated antidepressive effects in mice (425; 426). The potential interactions of herbal medicines with antipsychotics, antidepressants, and hypnotics have been discussed (further details are lacking) (427). AntiemeticsAntiemetics: In vitro, ginseng saponins, especially the panaxatriol saponin fraction, had substantial inhibitory effects on the recombinant serotonin type 3A receptor, suggesting that some specific ginsenosides might have an antagonistic action against serotonin type 3A receptor related to nausea and vomiting (16). These antiemetic results are supported by an animal research using Korean red ginseng total extract (27). AntihistaminesAntihistamines: In rats, 14 days of ginseng decreased the bioavailability of a single dose of antihistamines, likely due to p-glycoprotein modulation (429). In laboratory research, ginsenosides have displayed antiallergenic properties (430; 8). Anti-inflammatoriesAnti-inflammatories: Panax ginseng reduced muscle inflammation following exercise in animals (432). In a clinical trial, Salvia miltiorrhiza and shengmai inhibited inflammatory mediators (149). AntilipemicsAntilipemics: In animals and humans, red ginseng powder reduced plasma total cholesterol, triglycerides, and nonesterified fatty acids, while elevating plasma high-density lipoprotein (HDL) cholesterol (260). Hepatic cholesterol and triglyceride contents were decreased and phospholipids were increased following ginseng administration in rats fed a high-cholesterol diet, corresponding to improvement of the fatty liver. AntineoplasticsAntineoplastics: Based on laboratory research and animals, ginseng preparations may act synergistically with antineoplastics and radiation (433; 434; 435; 30). In theory, their effectiveness may be increased when multiple agents are used in optimal combinations. Antineoplastic effects of ginseng and ginsenosides have been found in vitro and in vivo (436; 437; 438; 439; 29; 440; 441; 442; 443; 444; 445; 446; 447; 448; 449). Antiobesity herbs and supplementsAntiobesity herbs and supplements: Protopanaxadiol from American ginseng prevented obesity in mice fed a high-fat diet (458). AntioxidantsAntioxidants: Panax ginseng and Panax quinquefolius had antioxidant activity (479; 93). This is thought to have been due to ginsenoside content (480) and saponins, which decreased oxidation of low-density lipoprotein in vitro (481; 482). In addition, Panax ginseng extracts had antioxidant activity in vitro in brain tissue (483), and its properties may be enhanced by heat-treated ginseng (62). Benzoic acid derivatives, salicylic acid, and vanillic acid also showed antioxidant activity in assays (484). Shenmai (Panax ginseng, Schizandra fruit, Ophiopogon) has also shown antioxidant activity in vitro, in rats, and in heart attack patients (160; 485). Lee et al. found a reduction of oxidative deoxyribonucleic acid (DNA) damage and protein oxidation in smokers who were supplemented with ginseng (486); the compounds that mediate such effects remain unclear. In vitro, American ginseng in combination with antioxidants or a specific inhibitor of the NF-kappaB pathway induced apoptosis in colorectal cancer cells (487). In animal research, trilinolein, isolated from Panax pseudoginseng, had antioxidant effects (488). AntiparasiticsAntiparasitics: In mice, aluminum hydroxide, with ginseng extract as an adjuvant for an inactivated whole vaccine against Neospora caninum infection, reduced the number of parasites circulating in the blood during the acute phase of infection but failed to limit the establishment of chronic infection (459). AntipsychoticsAntipsychotics: Anecdotal reports have noted a possible interaction between ginseng and antipsychotics. Combined use may cause additive effects or increased risk of adverse effects, although scientific data are lacking. The potential interactions of herbal medicines with antipsychotics, antidepressants, and hypnotics have been discussed (further details are lacking) (427).Antiulcer agentsAntiulcer agents: A polysaccharide fraction of the leaves of Panax ginseng prevented gastric ulcer formation in rats after administration of necrotizing agents (HCl-ethanol, ethanol), and after pylorus ligation (464). This effect was observed not only after oral administration, but also after systemic administration, suggesting a possible nonlocal effect. Rats administered tissue-cultured and cultivated ginseng had reduced gastric secretion and acid output (465). AntiviralsAntivirals: Theoretically, Cold-fX? and other ginseng preparations may have additive effects when taken concomitantly with other antivirals. Cytochrome P450 enzymes may be involved in some interactions (460). American ginseng induced phase II and antioxidant enzymes in vitro and might increase the clearance of antivirals or enhance antioxidant activity (466). AnxiolyticsAnxiolytics: In mice using the elevated plus-maze model, ginsenosides Rg3 and Rh2 from red ginseng significantly increased the time spent on the open arms and the number of open-arm entries; these effects were antagonized by flumazenil but not by WAY-100635 (414). AphrodisiacsAphrodisiacs: Traditionally, ginseng has been used as an aphrodisiac. It is thought that Panax ginseng enhances NO synthesis in corpora cavernosa endothelium and ginsenosides enhance acetylcholine-induced and transmural nerve stimulation-activated relaxation associated with increased tissue cGMP (141). Ashwagandha (Withania somnifera)Ashwagandha (Withania somnifera): The combination of Panax ginseng and ashwagandha was studied in rats for 90 days, and toxicity was not observed (489). CaffeineCaffeine: Controversy exists about whether caffeine and other stimulants are safe to take with ginseng. Some secondary sources indicate that, when taken in the suggested dosages, Asian ginseng is considered safe, while others disagree. However, in rare cases, ginseng may cause insomnia and headaches, and enhance the effects of caffeine.Calcium channel blockersCalcium channel blockers: Based on case reports, ginseng may alter the effects of blood pressure or heart medications, including calcium channel blockers such as nifedipine (Procardia?). Ginseng increased serum levels of nifedipine in healthy volunteers (467).Cardiac glycosidesCardiac glycosides: In humans, ginseng enhanced the effects of digoxin (Lanoxin?) in patients with congestive heart failure (177), and according to a systematic review of human research, in patients with mitral valve disease, treatment with P. ginseng saponins had a protective effect against ischemia reperfusion injury; in individuals with coronary heart disease, treatment with P. ginseng reduced symptoms of angina pectoris (38). According to a pharmacokinetic study in patients with congestive heart failure taking digoxin, shengmai injection may significantly lower serum digoxin levels (468). Immunoassays have indicated that ginseng may interfere with digoxin measurement (469). Cardiovascular agentsCardiovascular agents: Based on case reports, ginseng may alter the effects of blood pressure or heart medications, including calcium channel blockers. Ginseng increased serum levels of a calcium channel blocker in healthy volunteers (467).Carthamus tinctoriusCarthamus tinctorius: In vitro, a combination of Panax notoginseng and Carthamus tinctorius was more effective in scavenging hydroxyl radicals than either agent alone (490). Cytochrome P450-modifying agents Cytochrome P450-modifying agents : Based on laboratory research, Panax ginseng may inhibit CYP2D6 (230). In vitro, eight ginsenosides and aglycones potently induced CYP1A1 expression; deglycosylated ginsenosides were more potent inducers of CYP1A1, CYP1A2, and CYP3A4 than the glycosylated ginsenosides in HepG2 cells (231). Although Panax ginseng has been shown to activate CYP3A4 in vitro, there is a lack of an in vivo correlation with the in vitro effects (232; 233; 234; 235; 236). In vitro, Panax notoginseng saponins had a lack of an effect on testosterone metabolism in a test of CYP3A4 metabolism (237). In rats, Panax notoginseng induced CYP3A1 mRNA and CYP1A1, but a lack of an effect was seen on CYP1B1 mRNA expression in lung tissue (238) or on the expression of CYP2B1 and CYP4A1 genes in liver tissues of rats (239). Laboratory studies demonstrated a lack of an effect of ginseng preparations or Cold-fX? on CYP450 activity (240; 241). In vitro, nine ginseng products studied had little to no effect on the activity of CYP3A4 (242). In rats, shenmai injection (SMI), a mixture of radix ginseng and radix Ophiopogonis, caused a rise in AUC (243). In rat liver microsomes, linear mixed-type inhibition by SMI of the enzyme activities of CYP3A1/2, CYP2C6, and CYP1A2 was shown. However, the effects of ginseng alone are unclear. However, according to a systematic review of herbal drugs and pharmacokinetic drug interactions, of 66 studies identified, clinical evidence for ginseng was considered "limited" (a lack of potent or moderate inhibitory effect on cytochrome P450 or p-glycoprotein) (244). Dehydroepiandrosterone (DHEA)Dehydroepiandrosterone (DHEA): In humans, ginseng enhanced the effectiveness of DHEA (491). DiureticsDiuretics: One case report linked ginseng to diuresis resistance (473). EpicatechinEpicatechin: In a letter to the editor, it was described that in vitro, panaxadiol, an active compound in steamed ginseng, was enhanced by epicatechin in human HCT-116 colorectal cancer cells (492). Ginkgo bilobaGinkgo biloba: According to a systematic review, interactions between ginkgo and ginseng may exist (493). Ginseng is often combined with Ginkgo biloba in formula. When used in combination, it has caused decreases in systolic blood pressure at low or high doses, and decreases in diastolic blood pressure at high doses (191). In epidemiological research, long-term use of ginseng and Ginkgo biloba was not associated with improved memory performance (494). GlycyrrhizaGlycyrrhiza: There has been at least one case report of ginseng's use with licorice in the treatment of postpartum hypopituitarism, although the adverse effects are not well known (407). In vitro, a combination of Panax quinquefolius and licorice (Glycyrrhiza uralensis) root extracts had an antagonistic effect on cell viability and increased cultured Hep-G2 survival (495). GuaranaGuarana: Although ginseng demonstrated positive outcomes on the Cognitive Drug Research assessment battery when given alone, these effects were lacking in combination with guarana (326). HepatotoxinsHepatotoxins: Ginseng is typically considered a hepatoprotective agent (357; 358; 359; 360), but there is also evidence of hepatotoxic effects (36). In a case report, a 65 year-old man with nocturia developed jaundice and severe pruritus after two weeks of taking a multi-ingredient product, Prostata?, containing Panax ginseng (396). HypnoticsHypnotics: The potential interactions of herbal medicines with antipsychotics, antidepressants, and hypnotics have been discussed (further details are lacking) (427).HypoglycemicsHypoglycemics: In clinical trials, ginseng reduced blood glucose levels (39; 19; 40; 41; 42; 43; 38; 44). However, this is an area of controversy, because different species of ginseng may exhibit different effects (45; 46), hyperglycemia has also been reported (38), and the experimental data are inconsistent in this area (25; 47; 42; 38; 48). HypotensivesHypotensives: Both hypertension and hypotension, as well as general increases and decreases in blood pressure, have been reported in ginseng users and may be dependent on the dose used (181; 182; 183; 184; 185; 186; 187; 188; 189; 190; 191; 38; 48; 192). A lack of changes in blood pressure has also been reported in patients taking ginseng (193; 194; 25). Animal research has suggested that ginsenosides may have biphasic actions on blood pressure, with initial decreases in blood pressure followed by increases (431; 354). ImmunosuppressantsImmunosuppressants: In clinical trials and laboratory research, Cold-fX? and ginseng in general have been shown to enhance the immune system or reduce the occurrence or symptoms associated with colds (25; 105; 24; 26; 38; 226; 227; 207; 228; 229). Impotence agentsImpotence agents: Theoretically, Panax ginseng may have additive effects when taken concomitantly with agents used for impotence (141). MateMate: Theoretically, ginseng may potentiate the stimulant effects of mate.OpioidsOpioids: In animals, ginseng may inhibit tolerance to opioids (223; 470; 157) and inhibit cocaine-induced hyperactivity (471). Opiate-induced analgesia has been shown to be antagonized by ginseng total saponins, which also inhibit the development of analgesic tolerance to, and physical dependence on, the opiate in guinea pigs (223). PhotosensitizersPhotosensitizers: In laboratory research, Panax ginseng acted as a photoprotector at low concentrations and as a photosensitizer at high concentrations (210). Radioprotective agentsRadioprotective agents: Panax ginseng offered radioprotective effects in humans (329; 344).Radix AstragaliRadix Astragali: Radix ginseng combined with radix Astragali showed better antioxidant activity when compared to radix ginseng alone (496). Red cloverRed clover: In postmenopausal women, a combination of American ginseng, black cohosh, dong quai, milk thistle, red clover, and chaste tree berry decreased menopausal symptoms (497). SedativesSedatives: In humans and animals, insomnia was a common side effect of ginseng use (207; 302; 223; 470; 157; 471). Theoretically, ginseng may interfere with the effects of CNS depressants. SteroidsSteroids: In vitro, Panax ginseng extract had glucocorticoid-like activities in homeostasis and regulation of immunity (472). Ginseng affects the thymus gland and theoretically may interact with steroid or hormone drugs (anecdotal). StimulantsStimulants: In animals, a theoretical interaction between ginseng and stimulants was noted (470; 157; 471), although scientific data are lacking. Because it is a nonspecific CNS stimulant, Panax ginseng may increase the effects and the side effects of prescription drugs that also stimulate the CNS. SympathomimeticsSympathomimetics: Use with sympathomimetics may lead to additive effects (anecdotal).VasodilatorsVasodilators: In healthy men, P. ginseng or red ginseng was associated with enhanced cerebrovascular reactivity and cerebral blood flow (38; 476). In vitro, ginsenosides Rb1 and Rg1 appeared to have vasodilatory effects (477). Vitamin CVitamin C: In a laboratory research using human plasma, the presence of vitamin C (1-10mcM) significantly enhanced the protective effects of Panax quinquefolius saponins (481). Ginseng/Food Interactions:
Caffeine-containing productsCaffeine-containing products: There is controversy over whether caffeine and other stimulants, such as coffee, tea, or soda, are safe to take with ginseng. Some secondary sources indicate that when taken at the suggested dosages, Asian ginseng is considered safe, while others disagree. However, in rare cases, it may cause insomnia and headaches and enhance the effects of caffeine.Ginseng/Lab Interactions:
Adrenocorticotropic hormone (ACTH) testAdrenocorticotropic hormone (ACTH) test: In animal research, ginseng was found to stimulate adrenocorticotropic hormone (ACTH) (498). AlcoholAlcohol: In humans, Panax ginseng reduced blood concentration of alcohol (ethanol) and enhanced blood alcohol clearance (32; 33; 34; 225; 226). Blood glucoseBlood glucose: In clinical trials, ginseng reduced blood glucose levels (39; 19; 40; 41; 42; 43; 38; 44). However, this is an area of controversy, because different species of ginseng may exhibit different effects (45; 46), hyperglycemia has also been reported (38), and the experimental data are inconsistent in this area (25; 47; 42; 38; 48). Blood pressureBlood pressure: Both hypertension and hypotension, as well as general increases and decreases in blood pressure, have been reported in ginseng users and may be dependent on the dose used (181; 182; 183; 184; 183; 185; 186; 187; 188; 185; 189; 190; 191; 38; 48; 192). A lack of changes in blood pressure has also been reported in patients taking ginseng (193; 194; 25). Animal research has suggested that ginsenosides may have biphasic actions on blood pressure, with initial decreases in blood pressure followed by increases (431; 354). CD4 countCD4 count: In human laboratory assays, Cold-fX? significantly increased helper T (CD4+) counts (25). Coagulation panelCoagulation panel: Panax ginseng inhibited the aggregation of platelets (191; 259), reduced platelet adhesiveness (260), reduced or increased the international normalized ratio (INR) (261; 37; 226), and reduced anticoagulant concentrations or effects and increased clearance (32; 33; 34; 35; 36; 37; 38). However, other research has found a lack of changes in warfarin pharmacokinetics (419; 420; 419; 421). In a case report, shengmai-yin, a source of ginseng, was determined to be responsible for the development if a intracerebral hematoma in a man stable on warfarin (422). Whether American ginseng interferes with other anticoagulant drugs (such as heparin) or with antiplatelet drugs (clopidogrel, Ticlid?) is unclear. According to a review, American ginseng interfered with metabolism of antiplatelet or anticoagulant agents (423). Additional details are lacking. According to another review, it is advised that ginseng not be combined with anticoagulants (424). CortisolCortisol: In animals, ginseng stimulated ACTH and thereby increased plasma cortisol levels (498). It has been suggested anecdotally that ginseng lowers cortisol levels in diabetics while increasing cortisol levels in nondiabetics. Creatine kinaseCreatine kinase: In human research, ginseng decreased creatine kinase levels (38). Digoxin levelsDigoxin levels: According to a pharmacokinetic study in patients with congestive heart failure taking digoxin, shengmai injection may significantly lower serum digoxin levels (468). EstrogensEstrogens: There is limited laboratory evidence that ginseng may contain estrogen-like chemicals and may affect medications with estrogen-like or estrogen-blocking properties (195; 196; 198; 13). In a clinical trial in postmenopausal women investigating an herbal mixture, including ginseng, there was a lack of an effect on estradiol (497). The traditional Japanese herbal medicine unkei-to, which contains Panax ginseng and other herbs, stimulated the secretions of 17beta-estradiol from highly luteinized granulosa cells obtained from in vitro fertilization patients; the stimulated effect on estradiol secretion occurred with 0.3mcg/mL (110). Follicle-stimulating hormone (FSH)Follicle-stimulating hormone (FSH): Men treated with ginseng experienced an increase in follicle-stimulating hormone (FSH) concentrations (508). In a clinical trial in postmenopausal women investigating an herbal mixture, including ginseng, there was a lack of an effect on FSH (497). Heart rateHeart rate: In human research, ginseng and combination ginseng products have been found to alter heart rate (389; 191; 391). In human research, heart rate decreased with a 200mg ginseng-ginkgo combination product but not with the 100mg product (191). A clinical trial in healthy humans showed that a combination of ginseng, oriental bezoar, and glycyrrhiza decreased heart rate (391). In human research, ginseng lacked an effect on heart rate recovery (38). Hemoglobin A1cHemoglobin A1c: Ginseng decreased HbA1c in both diabetics and nondiabetics (41). Lipid profileLipid profile: In animals and hyperlipidemic humans, oral administration of ginseng reduced plasma total cholesterol, triglycerides, LDL cholesterol, and nonessential fatty acids, while increasing levels of HDL cholesterol (260; 509). Liver function tests (LFTs)Liver function tests (LFTs): Ginseng is typically considered a hepatoprotective agent (357; 358; 359; 360), but there is also evidence of hepatotoxic effects (36). In a case report, a 65 year-old man with nocturia developed jaundice and severe pruritus after two weeks of taking a multi-ingredient product, Prostata?, containing Panax ginseng (396). The metabolite of oral ginsenosides, 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol, protected mouse liver cells from cytotoxicity induced by tert-butyl hydroperoxide and significantly inhibited the increment of alanine amino transferase (ALT) and aspartate transaminase (AST) induced by tert-butyl hydroperoxide in mice (510). Prostata? is a combination product of zinc picolinate, pyridoxine, L-alanine, glutamic acid, Apis mellifica pollen, silica, hydrangea extract, Panax ginseng, Serenoa serrulata, and Pygeum africanum. Conversely, in a clinical trial in postmenopausal women investigating an herbal mixture, including ginseng, there was a lack of an effect on liver enzymes (497). Luteinizing hormone (LH)Luteinizing hormone (LH): Men treated with ginseng experienced an increase in luteinizing hormone (LH) concentrations (508). Posterior pituitary hormonesPosterior pituitary hormones: Intravenous administration of Panax ginseng in rats showed that the physiological effect of ginseng was not affected by translation, conversion rate, or the chemical structure of hormones from the posterior pituitary (511). ProgesteroneProgesterone: The traditional Japanese herbal medicine unkei-to, which contains Panax ginseng and other herbs, stimulated the secretion of progesterone from highly luteinized granulosa cells obtained from in vitro fertilization patients; the stimulated effect on progesterone secretion was obtained at 10mcg/mL (110). ProlactinProlactin: Men treated with ginseng have experienced a decrease in or a lack of an effect on prolactin concentrations (508; 332). Sperm countSperm count: Men treated with ginseng have experienced an increase in spermatozoon number and improvement of motility (508). In human research, ginseng lacked an effect on body temperature (38; 512). TestosteroneTestosterone: Men treated with ginseng experienced an increase in testosterone and dihydrotestosterone concentrations (508). In rats fed with ginseng, a significant increase of blood testosterone levels was found, combined with a significantly reduced prostate weight (513). A lack of changes has been observed in other clinical trials (332). Thyroid-stimulating hormoneThyroid-stimulating hormone: In a clinical trial in postmenopausal women investigating an herbal mixture, including ginseng, there was a lack of an effect on thyroid-stimulating hormone (497). WarfarinWarfarin: In humans and animals, Panax ginseng reduced the blood concentrations of warfarin and increased clearance (37; 38; 32; 33; 34; 35; 36).