Mantis Cradle Teapills by Plum Flower

There is insufficient reliable information available about the effectiveness of calamus.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atopic dermatitis (eczema). Although there is interest in using oral dong quai for atopic dermatitis, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Chronic kidney disease (CKD). There is limited evidence on the use of dong quai in patients with CKD. Details: A large propensity score-matched observational study over 15 years in Taiwanese adults with CKD suggests that taking dong quai is associated with a 5.1% risk of end-stage renal disease (ESRD) and 38% risk of overall mortality when compared with 7% and 56%, respectively, in controls. Higher cumulative doses (i.e., 15 grams or more) and longer duration of exposure (i.e., > 60 days) are also associated with fewer ESRD events (112362). However, the interpretation of these findings is limited by the lack of exact dosage information and retrospective study design.
• Coronary heart disease (CHD). Intravenous dong quai has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with CHD shows that injecting 20 mL of an intravenous solution containing dong quai, ginseng, and astragalus (Yi-qi Huo-xue Injection) daily for 2 weeks reduces the frequency and severity of angina episodes when compared with placebo. It also seems to increase exercise tolerance and improve left ventricular function when compared with placebo (33046). It is unclear if these benefits are due to dong quai, other ingredients, or the combination.
• Dysmenorrhea. Although there is interest in using oral dong quai for dysmenorrhea, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Hypertension. Although there is interest in using oral dong quai for hypertension, there is insufficient reliable information about the clinical effects of dong quai for this purpose.
• Idiopathic interstitial pneumonia. Oral dong quai has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 17 studies conducted in China in patients with idiopathic interstitial pneumonia concludes that adding traditional Chinese medicine combinations containing dong quai root and astragalus root to treatment with conventional medicines improves pulmonary function index, six-minute walking distance, and the Borg scale of perceived exertion when compared with conventional treatment alone (103618). The included studies are of low quality, include a range of treatment durations from 1-12 months, and vary in the conventional medicines and Chinese herb combinations used. The doses of dong quai used were not stated.
• Infertility. Although there is interest in using oral dong quai for infertility, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Iron deficiency anemia. Although there is interest in using oral dong quai for iron deficiency anemia, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Menopausal symptoms. There is inconsistent and contradictory evidence about the effect of dong quai on menopausal symptoms. Benefits have only been seen when it is used in combination with other ingredients; its effect when used alone is unclear. Details: Some clinical research shows that taking dong quai, 1.5 grams three times daily for 24 weeks, does not affect menopausal symptoms (738). Other clinical research shows that dong quai improves menopausal symptoms when used in combination with other constituents. In one clinical trial, taking five chewable tablets of a specific combination of dong quai and chamomile (Climex) daily for 12 weeks reduced the frequency and severity of hot flushes when compared with placebo (48445). In another trial, taking a combination providing dong quai 75 mg, along with American ginseng, black cohosh, milk thistle, red clover, and vitex agnus-castus (Phyto-Female Complex) twice daily for 3 months reduces menopausal symptoms, including the number and intensity of hot flushes, the number of night sweats, and sleep quality (19552). Taking another combination product containing dong quai, burdock root, licorice root, motherwort, and Mexican wild yam root, 500 mg three times daily for 3 months, also reduces menopausal symptoms when compared with placebo (48522). It is unclear if the beneficial effects in these studies were due to dong quai, other ingredients, or a combination of ingredients.
• Migraine headache. Oral dong quai has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with menstrual migraine shows that taking a combination of soy isoflavones 60 mg, dong quai 100 mg, and black cohosh 50 mg daily for 24 weeks reduces the frequency of attacks when compared with placebo (35797). It is unclear if this effect is due to dong quai, other ingredients, or the combination.
• Osteoporosis. Although there is interest in using oral dong quai for osteoporosis, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Peptic ulcers. Although there is interest in using oral dong quai for peptic ulcers, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Premature ejaculation. Topical dong quai has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In one preliminary clinical trial in patients with premature ejaculation, a multi-ingredient cream preparation (SS Cream) containing dong quai, Panax ginseng root, Cistanches deserticola, Zanthoxyl species, Torlidis seed, clove flower, Asiasari root, cinnamon bark, and toad venom was applied to the glans penis 1 hour prior to intercourse and washed off immediately before intercourse. Patients using the cream had significantly improved ejaculatory latency when compared with placebo cream (2537). It is unclear if this effect is due to dong quai, other ingredients, or the combination.
• Premenstrual syndrome (PMS). Although there is interest in using oral dong quai for PMS, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Psoriasis. Although there is interest in using oral dong quai for psoriasis, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Pulmonary hypertension. Preliminary clinical research shows that intravenous dong quai may be effective in patients with pulmonary hypertension. Details: Some preliminary clinical research in patients with chronic obstructive pulmonary disease (COPD) and pulmonary hypertension shows that intravenous administration of 250 mL of a solution containing dong quai 25%, once daily for 5-10 days, reduces pulmonary arterial pressure and pulmonary vascular resistance when compared to baseline (48438,48442,48443). The validity of these findings is limited by the lack of comparator groups.
• Rheumatoid arthritis (RA). Although there is interest in using oral dong quai for RA, there is insufficient reliable information about the clinical effects of dong quai for this condition.
• Stroke. Preliminary evidence does not support the use of intravenous dong quai for acute ischemic stroke. Details: Preliminary clinical research in patients with acute ischemic stroke shows that administering 200 mL of a solution containing dong quai 25% intravenously daily for 20 days does not improve neurological symptoms when compared with dextran-40 (48483). More evidence is needed to rate dong quai for these uses.

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POSSIBLY EFFECTIVE

• Cognitive function. In middle-aged individuals, but not young adults, oral Panax ginseng seems to improve abstract thinking, attention, arithmetic skills, and reaction time. Any benefit to memory seems to be dependent on the inclusion of ginkgo. Details: Some clinical evidence shows that taking Panax ginseng orally can improve abstract thinking, attention, mental arithmetic skills, and reaction times in healthy, middle-aged people; however, Panax ginseng does not seem to improve these outcomes in young adults (2064,23596,23599,23608,23609,54374). While Panax ginseng alone does not seem to improve memory (2064), there is some evidence that a combination of Panax ginseng (G115) and ginkgo leaf (GK501) extract 80-320 mg daily for 12 weeks can improve memory in otherwise healthy people or people with neurasthenia 38-66 years of age (8591,9759,87984,88046). In clinical trials, various doses have been used. These include a specific Panax ginseng extract (G115, Pharmaton SA, Lugano) 200-400 mg once daily or in two divided doses for up to 12 weeks, or 200-960 mg administered as a single dose (8591,23596,23599,23608,23609,54374,88046). Another extract (Gerimax Ginseng Extract; Dansk Droge A/S Ishoj) 400 mg daily for 8 weeks has also been used (2064).
• Erectile dysfunction (ED). Oral Panax ginseng seems to improve sexual function in people with ED. Details: Taking Panax ginseng orally for 8 weeks seems to improve sexual function in adults with ED (8813,23637,23638,89747). Doses used in clinical research have included extract from the juice and pulp of 4 year-old Panax ginseng berry 700 mg twice daily (89747), tissue-cultured mountain ginseng extract 1000 mg twice daily (23638), and Korean red ginseng, a type of Panax ginseng, 2700 mg daily in three divided doses (8813).
• Influenza. Oral Panax ginseng seems to modestly reduce the risk of developing influenza. However, it might not reduce the severity or duration of symptoms. Details: Some preliminary clinical research shows that taking a specific Panax ginseng extract (G115) 200 mg daily, beginning 4 weeks prior to influenza vaccination and continuing for 8 weeks thereafter, can decrease the relative risk of getting the flu or common cold by 65% when compared with placebo (589). Also, clinical research in healthy adults shows that taking Panax ginseng extract 1 gram three times daily for 12 weeks reduces the relative risk of developing an acute influenza infection by 45% when compared with placebo. However, taking Panax ginseng does not seem to affect symptom duration or severity (89746).
• Multiple sclerosis-related fatigue. Oral Panax ginseng seems to reduce fatigue and improve quality of life in patients with multiple sclerosis. Details: Clinical research shows that taking Panax ginseng 250 mg twice daily for 3 months improves symptoms of fatigue and quality of life when compared with placebo in female patients with relapsing-remitting multiple sclerosis (RRMS). Females taking Panax ginseng experienced a 75% reduction in fatigue, compared with no change in the placebo group; quality of life was increased by 19.9 points in the Panax ginseng group, compared with only 4.2 in the placebo group (89745).
• Sexual arousal. Oral Panax ginseng, alone or in combination with other ingredients, seems to improve sexual arousal in postmenopausal adults or females with sexual dysfunction. Details: Taking Korean red ginseng, a specific form of Panax ginseng, 3 grams daily for 8 weeks seems to improve sexual arousal and satisfaction when compared with placebo in postmenopausal adults (23630). Also, other preliminary clinical research shows that taking a specific combination product (ArginMax for Women, Daily Wellness Company) containing ginkgo leaf extract, Panax ginseng root extract, damiana leaf extract, L-arginine, multivitamins, and minerals for 4 weeks can improve sexual satisfaction when compared with placebo in females who are self-reported to have sexual dysfunction (23635,46933). It is unclear if this effect is due to Panax ginseng, other ingredients, or the combination.

POSSIBLY INEFFECTIVE

• Athletic performance. Most research shows that oral Panax ginseng does not improve athletic performance. Details: Taking Panax ginseng 0.4 to 3 grams daily orally for up to 8 weeks, or as a single dose 200 mg one hour prior to exercise, does not improve aerobic exercise (1427,4230,4231,23646,23647,89737). Higher doses of Panax ginseng also do not seem to improve athletic performance. A small study in young athletes shows that taking Panax ginseng 100 mg/kg (about 5-7 grams, standardized to 10% ginsenosides) daily in three divided doses for 8 days does not improve squat exercise performance, although it might modestly improve perceived exertion, when compared with placebo (103045).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Aging. Although there has been interest in using oral Panax ginseng for aging, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Attention deficit-hyperactivity disorder (ADHD). Oral Panax ginseng has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small low-quality study in children with ADHD aged 6-12 years shows that taking Panax ginseng extract 3 mg with omega-3 fatty acids 500 mg daily for 12 weeks improves overall symptoms, reduces errors of commission, and improves reaction time when compared with baseline (103049). The validity of this study was limited by the lack of a comparator group. Also, it is unclear if these changes are due to Panax ginseng, omega-3 fatty acids, or the combination.
• Age-related cognitive decline. It is unclear if oral Panax ginseng is beneficial in age-related cognitive decline. Details: Clinical research in patients over 50 years of age with memory impairments shows that taking standardized ginseng extract (G115) in combination with vitamins, minerals, and dimethylaminoethanol bitartrate may improve memory when compared to baseline (23600). The validity of this finding is limited by the lack of a comparator group. Also, it is unclear if these changes are due to Panax ginseng, other ingredients, or the combination.
• Allergic rhinitis (hay fever). It is unclear if oral Panax ginseng is beneficial in allergic rhinitis. Details: A small clinical study in adults with allergic rhinitis shows that taking Panax ginseng (Korean Ginseng Corporation) 3 mg/kg daily for 4 weeks improves rhinorrhea, nasal itch, and eye itch when compared with baseline (103047). The validity of this study is limited because it did not report statistical comparisons between the treatment and control groups.
• Alzheimer disease. Some preliminary clinical studies suggest that oral Panax ginseng might improve cognitive performance in patients with this condition. Details: Clinical research shows that taking Panax ginseng root 4.5 to 9 grams daily for 12 weeks can improve cognitive performance in patients with Alzheimer disease when compared with control (23611,23612). The validity of this finding is limited by the lack of patient and caregiver blinding.
• Androgenic alopecia. Topical Panax ginseng has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with androgenic alopecia shows that applying 1 mL of a topical combination product (Hirsuit hair tonic, Dermcor Pharmaceutical) containing Panax ginseng extract, biochanin A (from red clover), acetyl tetrapeptide-3, Salvia officinalis oil, and other ingredients, twice daily for 24 weeks, is similarly effective to minoxidil 3% solution for increasing hair count and mass (105672). It is unclear if the benefit is due to Panax ginseng, other ingredients, or the combination.
• Anxiety. Although there has been interest in using oral Panax ginseng for anxiety, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Aplastic anemia. Although there has been interest in using oral Panax ginseng for aplastic anemia, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Asthma. Although there has been interest in using oral Panax ginseng for asthma, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Breast cancer. It is unclear if oral Panax ginseng is beneficial in breast cancer. Details: Population research in China has found that breast cancer patients who regularly take any form of ginseng, including either Panax ginseng or American ginseng, have higher quality of life scores and a lower risk of overall mortality, breast cancer-related mortality, and breast cancer recurrence when compared with patients who do not take ginseng (14466). However, ginseng users were also significantly more likely to have been treated with tamoxifen.
• Bronchitis. It is unclear if oral Panax ginseng is beneficial in bronchitis. Details: One small clinical study shows that taking a specific Panax ginseng extract (G115) 100 mg twice daily for 9 days might be beneficial when used adjunctively for treating acute exacerbations of chronic bronchitis. Panax ginseng, combined with antibiotic therapy, might reduce bronchial bacterial counts more than antibiotic therapy alone (8814).
• Cancer. It is unclear if oral Panax ginseng is beneficial in preventing cancer. However, it might increase quality of life in some cancer patients. Details: Observational research has found that taking ginseng orally might decrease the incidence of cancer, specifically breast, stomach, lung, liver, ovarian, and skin cancer (2063,3122). But evidence from large-scale clinical research shows that taking Panax ginseng 1 gram once weekly for 3 years does not reduce the risk of cancer development (23622). However, some clinical research suggests that Panax ginseng may slow cancer progression or improve quality of life in patients already diagnosed with cancer. One clinical study shows that taking sun ginseng, a form of Panax ginseng that has been heat treated, 3000 mg daily orally for 12 weeks can improve quality of life for cancer patients (23643). Evidence from a case series suggests that giving Panax ginseng (also called Cultivated Wild Ginseng Pharmacopuncture) 20 mL daily by intravenous infusion for up to 13 cycles lasting 2-4 weeks each may attenuate the progression of advanced non-small cell lung cancer in some patients (23619,23620).
• Cancer-related fatigue. It is unclear if oral Panax ginseng is beneficial in cancer-related fatigue. Details: Preliminary clinical research shows that taking Panax ginseng 400 mg twice daily for 4 weeks reduces fatigue in 63% of adults with cancer-related fatigue when compared to baseline. Panax ginseng also reduces pain and improves appetite and overall quality of life when compared to baseline. The lack of a control group limits the validity of these findings (96217). Another clinical study in patients with colorectal cancer receiving the mFOLFOX-6 chemotherapy regimen shows that taking Panax ginseng 2000 mg daily for 16 weeks improves fatigue as measured on the brief fatigue inventory (BFI) when compared with placebo. However, when evaluated on the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scale, no benefit was seen (103048).
• Chronic fatigue syndrome (CFS). It is unclear if oral Panax ginseng is beneficial in patients with severe CFS. Details: A nonblinded, observational study in patients with severe CFS, most of whom also have fibromyalgia, shows that taking Panax ginseng daily for one month improves patient reports of energy, overall wellbeing, mental clarity, sleep, pain, and stamina when compared with baseline. Patients took Panax ginseng either as capsules (Terry Naturally HRG80 Red Ginseng Energy capsules; EuroPharma, Inc) 200-400 mg daily or chewable tablets (Terry Naturally HRG80 Red Ginseng Energy chewable tablets; EuroPharma, Inc) 100-200 mg daily. There were no dose- or formulation-dependent differences between groups (107746). The validity of these findings is limited by the lack of randomization and placebo-control; additionally, the majority (89%) of patients included in this study were female.
• Cognitive impairment. Oral Panax ginseng has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in elderly patients with mild cognitive impairment shows that taking a specific combination product (Memo, Pharco Pharmaceuticals), which contains natural lyophilized royal jelly 750 mg, standardized ginkgo leaf extract 120 mg, and standardized Panax ginseng root extract 150 mg, orally for 4 weeks improves memory when compared with placebo (89712). It is unclear if this benefit is due to Panax ginseng, other ingredients, or the combination.
• Common cold. It is unclear if oral Panax ginseng is beneficial in preventing the common cold. Details: Preliminary clinical research shows that taking a specific Panax ginseng extract (G115) 200 mg daily orally beginning 4 weeks prior to influenza vaccination and continuing for 8 weeks thereafter can decrease the relative risk of getting the flu or common cold by 65% when compared with placebo (589).
• Congestive heart failure (CHF). It is unclear if oral Panax ginseng is beneficial in CHF. Details: A small clinical study in adults with CHF shows that Panax ginseng 2 grams daily, with or without digoxin 0.25 mg once daily for 15 days, seems to improve heart function according to New York Heart Association (NYHA) classification when compared to baseline. Ginseng might also improve hemodynamics and may work synergistically with digoxin (4243). The validity of these findings is limited by the lack of a comparator group.
• Chronic obstructive pulmonary disease (COPD). Oral Panax ginseng has primarily been evaluated in combination with other ingredients for improving symptoms of COPD; its effect when used alone is unclear. Taking Panax ginseng doesn't seem to prevent exacerbations. Details: A meta-analysis of clinical trials in patients with stable COPD shows that taking Panax ginseng, usually in combination with other ingredients as part of TCM formulations, significantly improves pulmonary function tests and quality of life when compared with placebo after 3-6 months of treatment. These formulations improve COPD symptoms by approximately 53% when compared with placebo. However, they only modestly improve forced expiratory volume in one second (FEV1) (17736). In contrast, Panax ginseng might not reduce the risk of COPD exacerbations. A clinical study in patients with moderate to very severe COPD shows that taking Panax ginseng 200 mg does not reduce the rate of acute COPD exacerbations over 12 months (103044).
• Depression. It is unclear if Panax ginseng is beneficial in depression. Details: In adults with treatment-resistant major depressive disorder, a small clinical study shows that taking Panax ginseng 2 grams daily in addition to current antidepressant medications for 6 weeks produces remission in 39% of patients and decreases scores on the Montgomery-Asberg Depression Rating Scale by a mean of 44% when compared with baseline (104954). The reliability of these findings is limited by the lack of a control group, randomization, blinding, and an intention-to-treat analysis, as well as a high drop-out rate.
• Diabetes. Research on the use of oral Panax ginseng for improving glycemic control in patients with diabetes is inconclusive and conflicting. Details: A meta-analysis of 6 small clinical trials in patients with type 2 diabetes using Panax ginseng for 4-24 weeks and 3 small trials using American or unidentified ginseng for 4-8 weeks, shows that taking these ingredients modestly reduces fasting blood glucose, but does not affect glycated hemoglobin or insulin levels, when compared with control (105689). This analysis is limited by publication bias, as well as the heterogeneity and imprecision of the included trials. Individual small studies have shown modest glycemic benefit with fermented Panax ginseng 2.7 grams daily for 4 weeks or non-fermented Panax ginseng 6 grams daily for 8-12 weeks (23627,89740), and no benefit with Korean red ginseng extract 3-8 grams daily for 4 weeks (17734). It is unclear if the effects of Panax ginseng may be dose- or product-dependent. Panax ginseng has also shown some glycemic benefit when used in combination with other ingredients. Panax ginseng extract 750 mg (standardized to 30% ginsenosides) has been used in combination with American ginseng extract 1500 mg (standardized to 10% ginsenosides), viscous fiber 10 grams, and ground white chia seeds 60 grams daily for 24 weeks (105673). It is unclear if this benefit is due to Panax ginseng, other ingredients, or the combination.
• Diabetic neuropathy. It is unclear if oral Panax ginseng is beneficial in diabetic neuropathy. Details: A small clinical study in patients with diabetic neuropathy shows that taking Panax ginseng extract powder 1 gram daily for 24 weeks seems to improve sensory perception of electric currents, a marker for severity of diabetic neuropathy, when compared with baseline (103051). The validity of this study was limited by the lack of statistical comparison between treatment and placebo groups.
• Exercise-induced muscle damage. Although there has been interest in using oral Panax ginseng for exercise-induced muscle damage, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Fatigue. Most clinical research shows that oral Panax ginseng can reduce fatigue in adults with idiopathic chronic fatigue. However, not all research agrees. Details: Some clinical research in patients with idiopathic chronic fatigue or self-reported fatigue shows that taking Panax ginseng improves self-reported fatigue when compared with baseline or placebo (89743,23623,106665). A small clinical study in patients with idiopathic chronic fatigue shows that taking an ethanolic extract of Panax ginseng 1 gram twice daily for 4 weeks reduces self-reported fatigue by 66% and mental fatigue by 50% when compared with placebo (89743). Another clinical study in adults with chronic fatigue also shows that taking a specific combination product containing Panax ginseng (G115) 80 mg, vitamins, and minerals daily for 7 weeks alleviates fatigue symptoms in 20% more patients when compared with placebo (23623). However, not all research has been positive. A small clinical study in middle-aged patients with idiopathic chronic fatigue shows that taking Panax ginseng, steamed and aged for six years, 3 grams daily for 6 weeks is no different than placebo for reducing fatigue (103052). Notably, this clinical trial had a robust placebo effect.
• Fibromyalgia. It is unclear if oral Panax ginseng is beneficial for fibromyalgia. Details: Clinical research shows that taking Panax ginseng root extract 100 mg daily orally for 12 weeks does not improve pain, fatigue, sleep quality, anxiety, tender point count, or quality of life when compared with placebo in patients with fibromyalgia (89744). A nonblinded, observational study in patients with fibromyalgia, most of whom also have severe chronic fatigue syndrome (CFS), shows that taking Panax ginseng daily for one month improves patient reports of energy, overall wellbeing, mental clarity, sleep, pain, and stamina when compared with baseline. Patients took Panax ginseng, either as a capsule (Terry Naturally HRG80 Red Ginseng Energy capsules; EuroPharma, Inc) 200-400 mg daily, or chewable tablet (Terry Naturally HRG80 Red Ginseng Energy chewable tablets; EuroPharma, Inc) 100-200 mg daily. There were no dose- or formulation-dependent differences between groups (107746). The validity of these findings is limited by the lack of randomization and placebo-control; additionally, the majority (89%) of patients included in this study were female.
• Gallbladder disease. It is unclear if oral Panax ginseng is beneficial for gallbladder disease. Details: Clinical research shows that taking Panax ginseng 7.5 grams as an adjuvant to the bile acids chenodeoxycholic acid (CDCA) 500 mg daily plus ursodeoxycholic acid (UDCA) 500 mg daily, divided into three doses daily for 24 weeks, does not decrease the total volume of gallstones or increase gallstone dissolution when compared to use of bile acids alone (89748).
• Gastritis. Although there has been interest in using oral Panax ginseng for gastritis, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Glaucoma. It is unclear if oral Panax ginseng is beneficial for glaucoma. Details: A clinical crossover study in patients with glaucoma shows that taking oral Panax ginseng 1 gram three times daily for 4 weeks improves dry eye severity, daytime visual function, and eye pain when compared with placebo. In a sub-group of patients with early or moderate glaucoma, nighttime visual function was also improved (107744). The validity of this study is limited due to short duration of treatment.
• Halitosis. It is unclear if oral Panax ginseng is beneficial for halitosis. Details: Preliminary clinical research shows that taking Korean red ginseng, a type of Panax ginseng, 2.7 grams daily for 10 weeks helps reduce bad breath when compared with baseline, particularly in patients with bad breath caused by Helicobacter pylori (H. pylori) infection (23624). The validity of this finding is limited by the lack of a comparator group.
• Hangover. It is unclear if oral Panax ginseng is beneficial for hangover. Details: One small clinical study shows that drinking 100 mL of a drink containing Panax ginseng extract 0.321 mg/mL within 5 minutes of drinking 100 mL blended Scotch whiskey with 40% alcohol and eating a piece of cheese may reduce hangover symptoms by approximately 66% when compared with placebo in healthy males. Levels of alcohol in the blood also appear to be reduced (89742).
• Hearing loss. It is unclear if oral Panax ginseng is beneficial for hearing loss. Details: Preliminary clinical research in male textile workers exposed to continuous noise shows that taking Korean red ginseng, a type of Panax ginseng, 200 mg daily for 14 days reduces temporary hearing loss caused by noises at frequencies of 4, 6, or 16 kHz when compared with control. However, Panax ginseng may be slightly less effective than N-acetyl cysteine at preventing temporary hearing loss caused by noise at 4 kHz frequency (89739).
• HIV/AIDS. It is unclear if oral Panax ginseng is beneficial for this condition. Details: Preliminary clinical research in adults with HIV shows that taking Korean red ginseng, a particular form of Panax ginseng, along with highly active antiretroviral therapy (HAART) modestly increases CD4 count, but does not affect viral load, when compared with HAART alone (23625).
• Hypertension. It is unclear if oral Panax ginseng is beneficial for hypertension. Details: Various forms of Panax ginseng have been evaluated in patients with mild to severe hypertension. Some preliminary clinical research in patients with essential hypertension shows that taking Panax ginseng 4.5 grams daily in three divided doses, alone or with a beta-blocker or calcium channel blocker for 8 weeks, moderately decreases 24-hour systolic blood pressure (23632). However, in patients with prehypertension or mild hypertension, taking protopanaxatriol-enriched Panax ginseng (Ginseol K-g1) 100 mg or 300 mg daily for 8 weeks does not reduce seated systolic or diastolic blood pressure when compared with placebo (89741). Some research has also evaluated Panax ginseng in combination with American ginseng. A clinical study in patients with hypertension shows that taking Panax Ginseng and American ginseng 2.25 grams enriched to contain 30% total ginsenosides daily for 12 weeks reduces central systolic blood pressure by about 5 mmHg, but does not impact diastolic blood pressure, when compared with placebo (103046). It is unclear if these effects are due to Panax ginseng, American ginseng, or the combination. Some research has also evaluated Panax ginseng in combination with American ginseng. A clinical study in patients with hypertension (systolic blood pressure 140-160 mmHg or treated) and type 2 diabetes shows that taking Panax ginseng 0.75 grams and American ginseng 1.5 grams, enriched to contain 30% total ginsenosides, daily for 12 weeks reduces central systolic blood pressure by about 5 mmHg and 24-hour systolic blood pressure by about 4 mmHg, but does not impact diastolic blood pressure, when compared with a control of wheat-bran (103046,107745). Patients receiving this combination also have greater reductions in daytime systolic blood pressure, glycated hemoglobin, total cholesterol levels, and triglyceride levels when compared with control (107745). It is unclear if these effects are due to Panax ginseng, American ginseng, or the combination; additionally, it is unclear if enrichment with ginsenosides alters clinical effects.
• Impaired glucose tolerance (prediabetes). It is unclear if oral Panax ginseng is beneficial for impaired glucose tolerance. Details: In overweight adults with prediabetes, a small clinical study shows that taking hydrolyzed Panax ginseng extract, 320 mg three times daily before meals for 6 months, does not improve fasting blood glucose levels. However, compliance in this study was only 49% (104953). Panax ginseng has also been studied in combination with other ingredients. One clinical study shows that taking a combination of Korean red ginseng, a type of Panax ginseng, and cheonggukjang, a type of fermented soybean paste, 20 grams daily for 8 weeks can decrease fasting blood glucose levels by 17% in patients with prediabetes (23640). Also, taking fermented Panax ginseng 2.7 grams daily for 4 weeks reduces 2-hour postprandial glucose by about 17% and increases 2-hour postprandial insulin levels by about 44% when compared to baseline; when compared with placebo, these changes are significant (89740). It is unclear if these effects are due to Panax ginseng, other ingredients, or the combinations.
• Inflammatory bowel disease (IBD). Although there has been interest in using oral Panax ginseng for Crohn disease and ulcerative colitis, there is insufficient reliable information about the clinical effects of Panax ginseng for these conditions.
• Insomnia. Although there has been interest in using oral Panax ginseng for insomnia, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Liver disease. Although there has been interest in using oral Panax ginseng for liver diseases, there is insufficient reliable information about the clinical effects of Panax ginseng for these conditions.
• Male infertility. It is unclear if oral Panax ginseng is beneficial for male infertility. Details: Chronic prostatitis due to Chlamydia trachomatis infection is associated with reduced male fertility due to decreased sperm concentration and motility. Preliminary clinical research in adults with this condition shows that taking 25 mL of a specific product containing L-arginine 1660 mg, L-carnitine 150 mg, acetyl-L-carnitine 50 mg, and Panax ginseng 200 mg (Fertimev) along with prulifloxacin 600 mg daily for 6 months improves sperm concentration and sperm motility when compared to treatment with prulifloxacin alone (59006). It is unclear if this effect is due to Panax ginseng, other ingredients, or the combination.
• Menopausal symptoms. Research on oral Panax ginseng for menopausal symptoms has yielded conflicting results. Details: One clinical study in postmenopausal adults shows that taking Panax ginseng extract (G115) 200 mg daily orally for 16 weeks does not improve psychological well-being or reduce vasomotor symptoms such as hot flashes when compared with placebo (10981). However, several smaller clinical studies in postmenopausal adults demonstrate beneficial effects with higher doses of Panax ginseng. One study shows that taking Panax ginseng 1 gram (containing 30 mg ginsenosides) three times daily for 12 weeks reduces hot flashes and other symptoms, as measured by the Kupperman index and the Menopause Rating Scale (MRS), when compared with placebo (89749). Another study shows that taking an extract of Korean red ginseng, a specific form of Panax ginseng, 500 mg 4 times daily for 8 weeks improves fatigue severity scores by 21%, compared with 3% in those receiving placebo (106666). In premenopausal adults with menopausal symptoms following surgery for gynecologic cancer, taking Panax ginseng 1 gram three times daily for 12 weeks reduces the total symptom score on the MRS when compared with baseline. However, there was also a robust response in the placebo group, with no significant difference in symptom reduction between groups (104596). Panax ginseng has also been evaluated for improving genitourinary syndrome and cognition after menopause. A small clinical trial in postmenopausal adults with genitourinary syndrome shows that taking a specific Panax ginseng supplement (Ruginseng, Ghaem Daru Pharmaceutical) 500 mg twice daily for 4 weeks does not affect vaginal maturation index or pH, but seems to improve patient-rated symptoms such as vaginal itching and burning, when compared with a lactose placebo (105670). This study was funded by the supplement manufacturer. In another clinical study, taking a specific combination product (Gincosan) containing Panax ginseng 200 mg and ginkgo 120 mg daily for 6-12 weeks does not improve cognition, memory, mood, anxiety, or sleep when compared with placebo (87767).
• Metabolic syndrome. It is unclear if oral Panax ginseng is beneficial for metabolic syndrome. Details: A small clinical study in adults with metabolic syndrome shows that taking Korean red ginseng, a specific form of Panax ginseng, 6 grams daily for 8 weeks modestly reduces systolic blood pressure from baseline, but not when compared with placebo. Additionally, Panax ginseng has no effect on anthropometric measurements, biochemical markers, or other vital signs when compared with placebo (106667).
• Nausea and vomiting. Although there has been interest in using oral Panax ginseng for nausea and vomiting, there is insufficient reliable information about the clinical effects of Panax ginseng for these conditions.
• Neuropathic pain. Although there has been interest in using oral Panax ginseng for neuropathic pain, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral Panax ginseng is beneficial for NAFLD. Details: A small clinical study in adults with NAFLD shows that taking Panax ginseng 2 grams (containing ginsenosides 4.5 mg/gram) daily for 30 days modestly reduces fatigue and plasma levels of alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) when compared with placebo. All patients were also given milk thistle dried extract 450 mg (Legalon, Bukwang Pharmaceutical) daily and asked to exercise daily for at least 30 minutes (105671).
• Osteoarthritis. It is unclear if oral Panax ginseng is beneficial for osteoarthritis of the hand. Details: A small clinical study in postmenopausal adults with degenerative osteoarthritis of the hand shows that taking oral Korean red ginseng, a type of Panax ginseng, 1 gram three times daily for 12 weeks improves pain scores at rest, during daily activity, and at work or sport, and also improves disabilities of the arm, shoulder, and hand (DASH) score when compared with placebo (107747). The validity of this trial is limited due to the lack of objective outcome measures.
• Premature ejaculation. Oral Panax ginseng has primarily been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Applying a multi-ingredient cream preparation containing Panax ginseng, angelica root, Cistanches deserticola, Zanthoxyl species, torlidis seed, clove flower, asiasari root, cinnamon bark, and toad venom (SS Cream) to the glans penis one hour prior to intercourse and washing off immediately before intercourse seems to improve ejaculatory latency in adults with premature ejaculation when compared with placebo (2537). It is unclear if this effect is due to Panax ginseng, other ingredients, or the combination.
• Quality of life. It is unclear if oral Panax ginseng is beneficial for quality of life. Details: While some research suggests that Panax ginseng might improve self-rated quality of life (6254,23644), other studies show no benefit (8601,10314). In studies showing benefit for quality of life, doses have included one capsule daily of a specific Panax ginseng extract (Pharmaton Capsules, Pharmaton Natural Health Products) for 12 weeks (6254) and Panax ginseng extract (G115) 40 mg twice daily for 12 weeks (23644).
• Rheumatoid arthritis (RA). Although there has been interest in using oral Panax ginseng for RA, there is insufficient reliable information about the clinical effects of Panax ginseng for this condition.
• Stress. It is unclear if oral Panax ginseng is beneficial for stress. Details: A small clinical study in healthy patients with occupational stress shows that taking a specific Panax ginseng root preparation (HRG80) high in ginsenosides daily for 14 days modestly reduces perceived stress and improves attention and memory when compared with placebo. However, taking a standard Panax ginseng preparation with a lower quantity of ginsenosides was no better than placebo (103050).
• Wrinkled skin. It is unclear if oral Panax ginseng is beneficial for wrinkled skin. Details: Preliminary clinical research shows that taking 3 grams of a combination of Korean red ginseng root with Torilus fructus and Corni fructus daily for 24 weeks may reduce wrinkles when compared with placebo. However, it does not seem to affect skin elasticity, moisture, thickness, or color (23645). It is unclear if this benefit is due to Panax ginseng, other ingredients, or the combination. More evidence is needed to rate Panax ginseng for these uses.

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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cancer. Although there is interest in using oral poria mushroom for cancer, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Chronic fatigue syndrome (CFS). Although there is interest in using oral poria mushroom for CFS, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Chronic kidney disease (CKD). Although there is interest in using oral poria mushroom for CKD, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Coronavirus disease 2019 (COVID-19). Although there has been interest in using oral poria mushroom for COVID-19, there is insufficient reliable information about the clinical effects of poria mushroom for this purpose.
• Dementia. Although there is interest in using oral poria mushroom for dementia, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Diabetes. Oral poria mushroom has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of generally small clinical trials in patients with type 2 diabetes shows that taking Chinese herbal medicine combinations containing poria mushroom for 2-24 weeks along with hypoglycemic medications modestly reduces fasting blood glucose and glycated hemoglobin levels when compared with control groups taking hypoglycemic agents only. There were also modest improvements in levels of triglycerides and low-density lipoprotein (LDL) cholesterol and in insulin sensitivity (111920). Given the large number of other ingredients in the available formulations, it is unclear if any beneficial effects are related to poria mushroom, other ingredients in the formulation, or their combination.
• Diarrhea. Although there is interest in using oral poria mushroom for diarrhea, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Endometriosis. Although there is interest in using oral poria mushroom for endometriosis, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Influenza. Oral poria mushroom has only been evaluated for influenza vaccine enhancement in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in healthy adults shows that taking a product containing poria mushroom extract, rosemary extract, and aloe gel powder twice daily for 28 days prior to and following an influenza vaccination does not affect upper respiratory tract illness symptoms, severity, duration, or medication-related use when compared with taking placebo (111921). It is unclear if this study was large enough to detect differences between groups. Also, the effect of poria mushroom itself on influenza vaccine enhancement is unclear.
• Tinnitus. Although there is interest in using oral poria mushroom for tinnitus, there is insufficient reliable information about the clinical effects of poria mushroom for this condition.
• Urinary tract infections (UTIs). Although there is interest in using oral poria mushroom for UTIs, there is insufficient reliable information about the clinical effects of poria mushroom for this use. More evidence is needed to rate poria mushroom for these uses.

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LIKELY UNSAFE ...when used orally. The FDA prohibits calamus use in food products due to evidence of carcinogenic effects in animals receiving high doses of a calamus strain high in beta-asarone (93978,94727,94728). However, the beta-asarone content can vary widely among species from 0% to 96% (6); some products may be safer than others. There is insufficient reliable information available about the safety of calamus when used topically.

PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally; avoid using (4,500).

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POSSIBLY SAFE ...when used orally and appropriately. Dong quai has been used with apparent safety in a dose of 4.5 grams daily for 24 weeks, or in combination with other ingredients in doses of up to 150 mg daily for up to 6 months (19552,35797). ...when used intravenously as a 25% solution, in a dose of 200-250 mL daily for up to 20 days (48438,48442,48443,48483).

POSSIBLY UNSAFE ...when used orally in large amounts, long-term. Theoretically, long-term use of large amounts of dong quai could be harmful. Dong quai contains several constituents such as bergapten, safrole, and isosafrole that are considered carcinogenic (7162). There is insufficient reliable information available about the safety of dong quai when used topically.

PREGNANCY: POSSIBLY UNSAFE
when used orally. Dong quai has uterine stimulant and relaxant effects (8142); theoretically, it could adversely affect pregnancy. Observational research has found that intake of An-Tai-Yin, an herbal combination product containing dong quai and parsley, during the first trimester is associated with an increased risk of congenital malformations of the musculoskeletal system, connective tissue, and eyes (15129).

LACTATION:
Insufficient reliable information available; avoid use.

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LIKELY SAFE ...when used orally and appropriately, short-term. Panax ginseng seems to be safe when used for up to 6 months (8813,8814,17736,89741,89743,89745,89746,89747,89748,103044,103477).

POSSIBLY UNSAFE ...when used orally, long-term. There is some concern about the long-term safety due to potential hormone-like effects, which might cause adverse effects with prolonged use (12537). Tell patients to limit continuous use to less than 6 months. There is insufficient reliable information available about the safety of Panax ginseng when used topically.

CHILDREN: LIKELY UNSAFE
when used orally in infants. Use of Panax ginseng in newborns is associated with intoxication that can lead to death (12). There is limited reliable information available about use in older children (24109,103049); avoid using.

PREGNANCY: POSSIBLY UNSAFE
when used orally. Ginsenoside Rb1, an active constituent of Panax ginseng, has teratogenic effects in animal models (10447,24106,24107); avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

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There is insufficient reliable information available about the safety of poria mushroom.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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ANTICHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D In vitro evidence suggests that calamus can inhibit acetylcholinesterase (AChE) (38418). Theoretically, concurrent use of anticholinergic drugs and calamus might decrease the effectiveness of the anticholinergic drug.  Details Some anticholinergic drugs include atropine, benztropine (Cogentin), biperiden (Akineton), procyclidine (Kemadrin), and trihexyphenidyl (Artane).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Animal research suggests that calamus can decrease the rate and strength of the heartbeat, which might lower blood pressure (38444). Theoretically, combining calamus with other antihypertensive medications might increase the risk of hypotension; use with caution.  Details Some antihypertensive drugs include captopril (Capoten), enalapril (Vasotec), losartan (Cozaar), valsartan (Diovan), diltiazem (Cardizem), Amlodipine (Norvasc), hydrochlorothiazide (HydroDiuril), furosemide (Lasix), and many others.

CHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D In vitro evidence suggests that calamus can inhibit acetylcholinesterase (AChE) (38418). Theoretically, concurrent use of calamus with other cholinergic drugs might have additive effects and increase the risk of cholinergic side effects.  Details Cholinergic drugs include bethanechol (Urecholine), donepezil (Aricept), echothiophate (Phospholine Iodide), edrophonium (Enlon, Reversol, Tensilon), neostigmine (Prostigmin), physostigmine (Antilirium), pyridostigmine (Mestinon, Regonol), succinylcholine (Anectine, Quelicin), and tacrine (Cognex).

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D In vitro research suggests that calamus extract can inhibit cytochrome P450 2D6 (CYP2D6) (93975). Theoretically, use of calamus with drugs metabolized by CYP2D6 might increase drug levels and potentially increase the risk of adverse effects.  Details Some drugs metabolized by CYP2D6 include amitriptyline (Elavil), codeine, desipramine (Norpramin), flecainide (Tambocor), haloperidol (Haldol), imipramine (Tofranil), metoprolol (Lopressor, Toprol XL), ondansetron (Zofran), paroxetine (Paxil), risperidone (Risperdal), tramadol (Ultram), venlafaxine (Effexor), and others.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D In vitro research suggests that calamus inhibits cytochrome P450 3A4 (CYP3A4) (93975). Theoretically, use of calamus with drugs metabolized by CYP3A4 might increase drug levels and potentially increase the risk of adverse effects.  Details Some drugs metabolized by CYP3A4 include lovastatin (Mevacor), clarithromycin (Biaxin), indinavir (Crixivan), sildenafil (Viagra), triazolam (Halcion), and numerous others.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dong quai may increase the risk of bleeding when used with anticoagulant or antiplatelet drugs; however, research is conflicting.  Details Animal studies suggest that dong quai has antithrombin activity and inhibits platelet aggregation due to its coumarin components (6048,10057,96137). Additionally, some case reports in humans suggest that dong quai can increase the anticoagulant effects of warfarin (3526,6048,23310,48439). However, clinical research in healthy adults shows that taking 1 gram of dong quai root daily for 3 weeks does not significantly inhibit platelet aggregation or cause bleeding (96137). Until more is known, use dong quai with caution in patients taking antiplatelet/anticoagulant drugs.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, dong quai may reduce the effects of estrogens.  Details Dong quai has estrogenic effects (6180,7860,15108,15535,48459). Theoretically, concomitant use of large amounts of dong quai might interfere with hormone replacement therapy due to competition for estrogen receptors.

WARFARIN (Coumadin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Dong quai may increase the risk of bleeding when used with warfarin.  Details Case reports suggest that concomitant use of dong quai with warfarin can increase the anticoagulant effects of warfarin and increase the risk of bleeding (3526,6048,23310,48439). In one case, after 4 weeks of taking dong quai 565 mg once or twice daily, the international normalized ratio (INR) increased to 4.9. The INR normalized 4 weeks after discontinuation of dong quai (3526).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = B 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.  Details In vitro evidence suggests that ginsenoside constituents in Panax ginseng might decrease platelet aggregation (1522,11891). However, research in humans suggests that ginseng does not affect platelet aggregation (11890). Animal research indicates low oral bioavailability of Rb1 and rapid elimination of Rg1, which might explain the discrepancy between in vitro and human research (11153). Until more is known, use with caution in patients concurrently taking anticoagulant or antiplatelet drugs.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, taking Panax ginseng with antidiabetes drugs might increase the risk of hypoglycemia.  Details Clinical research suggests that Panax ginseng might decrease blood glucose levels (89740). Monitor blood glucose levels closely.

CAFFEINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, taking Panax ginseng with caffeine might increase the risk of adverse stimulant effects.  Details Panax ginseng has been shown to have stimulant effects (589,594). Theoretically, caffeine might have an additive effect on the stimulant effects of Panax ginseng.

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, Panax ginseng might decrease levels of drugs metabolized by CYP1A1.  Details In vitro research shows that Panax ginseng can induce the CYP1A1 enzyme (24104).

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, Panax ginseng might increase levels of drugs metabolized by CYP2D6. However, research is conflicting.  Details There is some evidence that Panax ginseng can inhibit the CYP2D6 enzyme by approximately 6% (1303,51331). In addition, in animal research, Panax ginseng inhibits the metabolism of dextromethorphan, a drug metabolized by CYP2D6, by a small amount (103478). However, contradictory research suggests Panax ginseng might not inhibit CYP2D6 (10847). Until more is known, use Panax ginseng cautiously in patients taking drugs metabolized by these enzymes.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, Panax ginseng might increase or decrease levels of drugs metabolized by CYP3A4.  Details 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 (89764). In contrast, Panax ginseng has been shown to increase the clearance of midazolam, another drug metabolized by CYP3A4 (89734,103478). 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% (89734). Midazolam metabolism was also increased in animals given Panax ginseng (103478). Until more is known, use Panax ginseng cautiously in combination with CYP3A4 substrates.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use of large amounts of Panax ginseng might interfere with hormone replacement therapy.  Details Laboratory research and some case reports suggest that Panax ginseng can have estrogenic effects due to competition for estrogen receptors (590,591,592,6180,10982,10983,10984). The estrogenic activity is attributed to the ginsenoside constituents of Panax ginseng (10984).

FEXOFENADINE (Allegra) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, Panax ginseng might decrease blood levels of oral or intravenous fexofenadine.  Details 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 (24101).

FUROSEMIDE (Lasix) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Panax ginseng might reduce the effects of furosemide.  Details 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 (770).

IMATINIB (Gleevec) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Panax ginseng might increase the effects and adverse effects of imatinib.  Details 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 (89764).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Theoretically, Panax ginseng use might interfere with immunosuppressive therapy.  Details Panax ginseng might have immune system stimulating properties (3122).

INSULIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, taking Panax ginseng with insulin might increase the risk of hypoglycemia.  Details Clinical research suggests that Panax ginseng might decrease blood glucose levels (89740). Insulin dose adjustments might be necessary in patients taking Panax ginseng; use with caution.

LOPINAVIR/RITONAVIR (Kaletra) Interaction Rating = Minor Be watchful with this combination. Severity = Insignificant •  Occurrence = Unlikely •  Level of Evidence = B 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.  Details 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 (89734,89764). 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 (93578).

MIDAZOLAM (Versed) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, Panax ginseng may increase the clearance of midazolam.  Details 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% (89734). Midazolam metabolism was also increased in animals given Panax ginseng (103478).

MONOAMINE OXIDASE INHIBITORS (MAOIs) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, Panax ginseng can interfere with MAOI therapy.  Details Concomitant use of Panax ginseng with phenelzine (Nardil) is associated with insomnia, headache, tremors (617), and hypomania (618,23650).

NIFEDIPINE (Procardia) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking Panax ginseng with nifedipine might increase serum levels of nifedipine and the risk of hypotension.  Details Preliminary clinical research shows that concomitant use can increase serum levels of nifedipine in healthy volunteers (22423). This might cause the blood pressure lowering effects of nifedipine to be increased when taken concomitantly with Panax ginseng.

QT INTERVAL-PROLONGING DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B 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.  Details Clinical research shows that short-term use of Panax ginseng can increase the QT interval (4322,96218). However, no changes in QT interval have been identified with prolonged use (4322).

RALTEGRAVIR (Isentress) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking Panax ginseng with raltegravir might increase the risk of liver toxicity.  Details A case report suggests that concomitant use of Panax ginseng with raltegravir can increase serum levels of raltegravir, resulting in elevated liver enzymes levels (23621).

SELEGILINE (Eldepryl) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, Panax ginseng might increase or decrease levels of selegiline, possibly altering the effects and side effects of selegiline.  Details 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 (103053). More research is needed to confirm these effects.

STIMULANT DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking Panax ginseng with stimulant drugs might increase the risk of adverse stimulant effects.  Details Panax ginseng has been shown to have stimulant effects (589,594).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Unlikely •  Level of Evidence = B Panax ginseng might affect the clearance of warfarin. However, this interaction appears to be unlikely.  Details There has been a single case report of decreased effectiveness of warfarin in a patient who also took Panax ginseng (619). 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 (2531,11890,17204,24105). However, other research in humans suggests that Panax ginseng might modestly increase the clearance of the S-warfarin isomer (15176). More evidence is needed to determine whether Panax ginseng causes a significant interaction with warfarin.

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ANTICHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, poria mushroom might decrease the clinical effects of anticholinergic drugs.  Details In animal research, poria mushroom essential oil reduces acetylcholinesterase activity (111917). This interaction has not been shown in humans.

CHOLINERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, poria mushroom might have additive effects when used with cholinergic drugs.  Details In animal research, poria mushroom essential oil reduces acetylcholinesterase activity (111917). This interaction has not been shown in humans.

CNS DEPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking poria mushroom extract may enhance the therapeutic and adverse effects of sedatives.  Details Animal research shows that poria mushroom extract has sedative properties (111916). This interaction has not been shown in humans.

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General ...Orally, nausea, vomiting, and intestinal paralysis have been reported with calamus use (33310,38458,93980). Tachycardia has also been reported (93980).

Cardiovascular ...Tachycardia has been reported as a toxic effect related to oral use of calamus oil (93980).

Gastrointestinal ...A case of gastrointestinal toxicity has been reported in a 19-year-old male who appeared to use calamus root for its euphoric effects. The man ingested a large amount of the root with water and later presented at the emergency department with continuous vomiting, paleness, and sweating. He was treated intravenously with saline and promethazine (38458). Both nausea and vomiting have been reported in patients using calamus oil orally (93980). Intestinal paralysis has also been reported with calamus use in children (33310).

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General ...Orally, dong quai is generally well-tolerated.
Most Common Adverse Effects:
Orally: Burping and flatulence.
Intravenously: Headache.

Cardiovascular ...Orally, dong quai might cause hypertension; according to one case report, a parent and breastfed infant experienced hypertension (195/85 mmHg and 115/69 mmHg, respectively) after the parent consumed a soup containing dong quai root (48428).

Dermatologic ...Dong quai contains psoralens that may cause photosensitivity and photodermatitis (10054,10057,48461).

Endocrine ...In a case report, a male developed gynecomastia after ingesting dong quai tablets (48504).

Gastrointestinal ...Orally, burping and gas may occur with dong quai (738).

Hematologic ...In one case report, a 55-year-old female with protein S deficiency and systemic lupus erythematosus (SLE) had temporary vision loss in the left eye from hemiretinal vein thrombosis three days after taking a phytoestrogen preparation containing dong quai 100 mg, black cohosh 250 mg, wild Mexican yam 276 mg, and red clover 250 mg (13155). It is unclear if dong quai contributed to this event.

Neurologic/CNS ...Dong quai given orally or by injection may be associated with headache (738,48438).

Oncologic ...Dong quai contains constituents that are carcinogenic; however, whether these constituents are present in concentrations large enough to cause cancer with long-term or high-dose use is unknown (7162).

Pulmonary/Respiratory ...A pharmacist experienced allergic asthma and rhinitis after occupational exposure to dong quai and other herbs (48435).

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General ...Orally, Panax ginseng is generally well tolerated when used for up to 6 months. There is some concern about the long-term safety due to potential hormone-like effects.
Topically, no adverse effects have been reported when ginseng is used as a single ingredient. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Insomnia.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis, arrhythmia, ischemia, Stevens-Johnson syndrome.

Cardiovascular ...Panax ginseng may cause hypertension, hypotension, and edema when used orally in high doses, long-term (3353). However, single doses of Panax ginseng up to 800 mg are not associated with changes in electrocardiogram (ECG) parameters or increases in heart rate or blood pressure (96218). There is a case report of menometrorrhagia and tachyarrhythmia in a 39-year-old female who took Panax ginseng 1000-1500 mg/day orally and also applied a facial cream topically that contained Panax ginseng. Upon evaluation for menometrorrhagia, the patient also reported a history of palpitations. It was discovered that she had sinus tachycardia on ECG. However, the patient was a habitual consumer of coffee 4-6 cups/day and at the time of evaluation was also mildly anemic. The patient was advised to discontinue taking Panax ginseng. During the 6 month period following discontinuation the patient did not have any more episodes of menometrorrhagia or tachyarrhythmia (13030). Also, a case of transient ischemic attack secondary to a hypertensive crisis has been reportedly related to oral use of Panax ginseng (89402).

Dermatologic ...Orally, Panax ginseng may cause itching or an allergic response consisting of systemic rash and pruritus (89743,89760,104953). Skin eruptions have also been reported with use of Panax ginseng at high dosage, long-term (3353). Uncommon side effects with oral Panax ginseng include Stevens-Johnson syndrome (596).
In one case report, a 6-year-old male with a previous diagnosis of generalized pustular psoriasis, which had been in remission for 18 months, presented with recurrent pustular lesions after consuming an unspecified dose of Panax ginseng. The patient was diagnosed with pityriasis amiantacea caused by subcorneal pustular dermatosis. Treatment with oral dapsone 25 mg daily was initiated, and symptoms resolved after 4 weeks (107748).
Topically, when a specific multi-ingredient cream preparation (SS Cream) has been applied to the glans penis, mild pain, local irritation, and burning have occurred (2537).

Endocrine ...The estrogenic effects of ginseng are controversial. Some clinical evidence suggests it doesn't have estrogen-mediated effects (10981). However, case reports of ginseng side effects such as postmenopausal vaginal bleeding suggest estrogenic activity (590,591,592,10982,10983).
In a 12-year-old Korean-Japanese male, enlargement of both breasts with tenderness in the right breast (gynecomastia) occurred after taking red ginseng extract 500 mg daily orally for one month. Following cessation of the product, there was no further growth or pain (89733). Swollen and tender breasts also occurred in a 70-year-old female using Panax ginseng orally (590).

Gastrointestinal ...Orally, Panax ginseng can cause decreased appetite (3353), diarrhea (3353,89734,103477), abdominal pain (89734,87984), and nausea (589,87984). However, these effects are typically associated with long-term, high-dose usage (3353).

Genitourinary ...Amenorrhea has been reported with oral use of Panax ginseng (3353).
Topically, when a specific multi-ingredient cream preparation (SS Cream) has been applied to the glans penis, sporadic erectile dysfunction and excessively delayed ejaculation have occurred (2537). Less commonly, patients can experience vaginal bleeding (591,592,3354,23630).

Hepatic ...Uncommon side effects can include cholestatic hepatitis (associated with a Panax ginseng-containing, multi-ingredient product, Prostata), such as that which occurred in a 65-year old male following oral use (598).

Immunologic ...A case of anaphylaxis, with symptoms of hypotension and rash, has been reported following ingestion of a small amount of Panax ginseng syrup (11971).

Neurologic/CNS ...Orally, one of the most common side effects to Panax ginseng is insomnia (589,89734). Headache (594,23638), vertigo, euphoria, and mania (594) have also been reported. Migraine and somnolence occurred in single subjects in a clinical trial (87984). In a case report of a 46-year-old female, orobuccolingual dyskinesia occurred following oral use of a preparation containing black cohosh 20 mg and Panax ginseng 50 mg twice daily for menopausal symptoms. The patient's condition improved once the product was stopped and treatment with baclofen 40 mg and clonazepam 20 mg daily was started (89735).

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General ...Orally, poria mushroom seems to be well tolerated. However, a thorough evaluation of safety outcomes has not been conducted.

Immunologic ...Allergic reactions have been reported rarely, including allergic rhinitis and allergic asthma (12).

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