ageLOC Vitality [Discontinued] by Pharmanex

POSSIBLY INEFFECTIVE

• Athletic performance. Taking cordyceps orally does not seem to improve athletic performance in adults. Details: One small clinical study in endurance-trained cyclists shows that taking a specific mycelial fermentation product of cordyceps (CordyMax Cs-4) 3.15 grams daily for 5 weeks does not improve endurance time trials or aerobic capacity when compared with placebo (12095). Another small study in healthy elderly adults shows that taking the same cordyceps preparation (CordyMax Cs-4) 3 grams daily for 12 weeks does not improve exercise performance when compared with placebo (46120). Research also shows that taking combination products containing cordyceps and other ingredients does not improve athletic performance when compared with control. These products have combined cordyceps (CordyMax Cs-4) 1000 mg with rhodiola 300 mg (46091) or cordyceps (CordyMax Cs-4) 2000 mg with roseroot 600 mg (Optygen, First Endurance) (15573); liquid and powdered cordyceps formulations with reishi mushroom, shiitake mushroom, bamboo, and honey (Fohow oral liquid and Fohow lingzhi capsules, FOHOW Technology Investment Group Co. Ltd.) (98686); and cordyceps (form unknown) 1.2 grams with a 930 mg mixture of extracts of ashwagandha root, green tea leaf, rhodiola root, and astragalus root (Shroom Tech Sport, Onnit Labs) (105079).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Arrhythmia. Although there is interest in using oral cordyceps for arrhythmia, there is insufficient reliable information about the clinical effects of cordyceps for this condition.
• Asthma. Oral cordyceps has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in children with asthma shows that a 619 mg capsule containing equal weights of the dried aqueous extracts of cordyceps, astragalus, skullcap, Radix stemonae, and Bulbus fritillariae daily for 6 months does not reduce the need for medication or improve symptoms when compared with placebo (32935).
• Chronic kidney disease (CKD). Small clinical studies suggest that oral cordyceps may modestly improve biomarkers in some patients with CKD. Details: A meta-analysis of clinical research in patients in China with CKD shows that taking cordyceps 0.6-2 grams orally three times daily, along with standard treatment, seems to decrease serum creatinine levels by 0.6 mg/dL and increase creatinine clearance by 9.2 mL/min when compared with standard treatment alone (92829). Another meta-analysis of clinical studies in patients in China with diabetic kidney disease shows that taking cordyceps 0.5-2 grams orally three times daily along with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) decreases blood urea nitrogen by 2 mg/dL and decreases serum creatinine levels by 0.1 mg/dL when compared with ACEI/ARB treatment alone (92830). Most individual studies in these analyses used Bailing (Cs-C-Q80) or Jinshuibao (Cs-4), fermented cordyceps mycelial products (92829,92830). Both of these analyses are limited by the low methodological quality and short duration (usually 1-6 months) of most of the included studies.
• Chronic obstructive pulmonary disease (COPD). Preliminary clinical studies suggest that oral cordyceps may modestly improve symptoms of COPD. Details: A meta-analysis of preliminary clinical research in patients with moderate or severe COPD shows that taking cordyceps alone or as part of a formulation containing other products for up to 12 months improves lung function and reduces the incidence of an acute exacerbation by a small amount. Also, the distance walked in 6 minutes is increased by about 45 meters, which was considered clinically meaningful. Most individual studies in this analysis used Bailing (Cs-C-Q80) or Jinshuibao (Cs-4), fermented cordyceps mycelial products, in combination with conventional treatments with conventional treatments alone (109705). This analysis is limited by the low methodological quality of the included studies.
• Contrast induced nephropathy. Small clinical studies suggest that oral cordyceps may modestly reduce contrast induced nephropathy. Details: A preliminary clinical study in patients with diabetic nephropathy shows that taking a specific cordyceps mycelial product (Corbrin; CS-C-Q80) 2-3 grams orally three times daily for 3 days before and after angiography reduces the risk of contrast induced nephropathy by about 48% to 66% when compared to standard treatment (92827). However, other preliminary clinical research in patients with stable angina pectoris shows that taking the same cordyceps product 3 grams orally three times daily for 3 days before and after angioplasty does not decrease the prevalence of contrast induced nephropathy when compared to standard therapy (92826). Reasons for these discrepancies are not clear but may relate to the small size and heterogenous populations in these studies.
• Diabetic nephropathy. Early research suggests that oral cordyceps may modestly improve kidney function in patients with diabetic kidney disease. Details: A meta-analysis of low to moderate quality clinical research in patients with diabetic kidney disease shows that taking cordyceps as adjunctive therapy to angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for 2-24 weeks modestly improves kidney function when compared to these medications alone. Kidney function was based on markers such as blood creatinine and urea nitrogen, as well as urinary albumin and total protein. There were also modest improvements in systolic and diastolic blood pressure, triglycerides, and low-density lipoprotein (LDL) cholesterol. There was no effect on glycemic indices. The effect of cordyceps on disease progression or cardiovascular events is unclear (111903).
• Cough. Although there is interest in using oral cordyceps for cough, there is insufficient reliable information about the clinical effects of cordyceps for this purpose.
• Fatigue. Although there is interest in using oral cordyceps for fatigue, there is insufficient reliable information about the clinical effects of cordyceps for this purpose.
• Hepatitis B. Although there is interest in using oral cordyceps for hepatitis B, there is insufficient reliable information about the clinical effects of cordyceps for this condition.
• Hypercholesterolemia. Although there is interest in using oral cordyceps for hypercholesterolemia, there is insufficient reliable information about the clinical effects of cordyceps for this condition.
• Kidney failure. Small clinical studies suggest that oral cordyceps may improve inflammatory markers in patients on hemodialysis. Details: A meta-analysis of small clinical trials in patients in China on hemodialysis suggests that adding cordyceps to standard treatment does not seem to improve serum creatinine levels but may improve certain markers of inflammation, such as C-reactive protein, when compared with placebo. Most individual studies in this analysis used Bailing (Cs-C-Q80) or Jinshuibao (Cs-4), fermented cordyceps mycelial products (105076).
• Kidney transplant. Small clinical studies suggest that oral cordyceps is no better than standard treatment in patients with kidney transplant. Details: A meta-analysis of 4 heterogeneous clinical trials evaluating patients in China immediately post-kidney transplant or patients with complications post-kidney transplant suggests that adding cordyceps to standard therapy with cyclosporine and steroids is no better than adding azathioprine 50-150 mg for improving overall survival or graft survival or reducing rejection risk. However, there was a non-significant trend to reduced risk of graft rejection in the cordyceps group (95905). A higher quality systematic review, which determined the available studies were too heterogeneous to pool together in a meta-analysis, suggests that adding cordyceps 3-6 grams to standard therapy daily is no better than azathioprine or cyclosporine for improving organ rejection, kidney function, or survival in patients after kidney transplant (92828). All individual studies in these analyses used Bailing (Cs-C-Q80) fermented cordyceps mycelial product (95905,92828).
• Sexual dysfunction. It is unclear if oral cordyceps is beneficial in patients with sexual dysfunction. Details: Preliminary clinical research shows that taking a specific mycelial fermentation product of cordyceps (CordyMax Cs-4) approximately 3 grams daily for 40 days can improve symptoms of hyposexuality in 66% of patients, compared with 32% of patients taking natural cordyceps and 24% of patients taking placebo (46145).
• Tinnitus. Although there is interest in using oral cordyceps for tinnitus, there is insufficient reliable information about the clinical effects of cordyceps for this condition. More evidence is needed to rate cordyceps for these uses.

(Read more about CORDYCEPS)

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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POSSIBLY EFFECTIVE

• Hypertension. Oral pomegranate juice seems to modestly reduce blood pressure. Details: Most clinical research evaluating pomegranate juice for reducing systolic blood pressure (SBP) and diastolic blood pressure (DBP) shows modest benefits (8310,13023,13691,69372,69373,69374). A meta-analysis of results from eight clinical studies including 574 patients shows that pomegranate juice reduces SBP by about 5 mmHg, but does not affect DBP, when compared with placebo. Doses of pomegranate juice ranged from 43-330 mL daily for 2 weeks to 18 months. Changes in SBP and DBP were not related to the dose or duration of pomegranate juice consumption (96247).

POSSIBLY INEFFECTIVE

• Diabetes. Most oral pomegranate products do not seem to be beneficial for diabetes. It is unclear if pomegranate seed powder is beneficial. Details: A meta-analysis of clinical research shows that taking pomegranate has no effect on glycated hemoglobin (HbA1c) or plasma levels of insulin, lipids, or fasting glucose when compared with placebo in patients with type 2 diabetes. Various formulations, including juice, fruit extract, peel extract, and seed oil, were used in these studies (105265). However, a more recent clinical trial shows that drinking a beverage twice daily for 8 weeks, made by soaking a 'tea bag' containing pomegranate seed powder 5 grams in hot water for 10 minutes, modestly reduces levels of fasting blood glucose, HbA1c, total cholesterol, and triglycerides when compared with placebo. Fasting blood glucose levels were reduced by approximately 4%, compared with a 6% increase in the placebo group (105270).
• Hyperlipidemia. Oral pomegranate does not seem to be beneficial for hyperlipidemia. Details: Most clinical research shows that taking pomegranate does not increase high-density lipoprotein (HDL) cholesterol levels or reduce total cholesterol, low-density lipoprotein (LDL) cholesterol, or triglyceride levels when compared with placebo (13022,13023,13690,69142,69168,69276). A meta-analysis of results from 12 clinical studies including 545 patients with or without hyperlipidemia shows that taking pomegranate daily for at least 10 days and up to 1 year does not improve blood lipid levels when compared with placebo. Pomegranate formulations evaluated in these studies include juice, seed oil, whole fruit, extract, and vinegar beverage; no specific form or dose of pomegranate was associated with improvements in cholesterol or triglyceride levels (96248). One preliminary clinical study has evaluated pomegranate juice in combination with other fruits. Results from the study show that taking a specific pomegranate-containing combination product (Radical Fruits, Garden of Life) 900 mg orally three times daily before meals reduces total and LDL cholesterol and increases HDL cholesterol in males with hypercholesterolemia (69170). However, it is unclear if these benefits are due to pomegranate, other ingredients, or the combination.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atherosclerosis. It is unclear if oral pomegranate juice is beneficial for preventing atherosclerosis. Details: Preliminary clinical research shows that drinking pomegranate juice 50 mL daily reduces intima-media thickness of the carotid artery by up to 35% after one year when compared to baseline in patients with atherosclerosis and carotid artery stenosis (13023).
• Athletic performance. It is unclear if oral pomegranate extract is beneficial for athletic performance. Details: Preliminary clinical research in trained male cyclists shows that taking pomegranate extract (POM Wonderful LLC) 15 mg/kg daily for 8 days moderately reduces the amount of oxygen needed to perform submaximal exercise when compared with placebo. However, pomegranate extract does not improve performance in a timed trial (99100). Other preliminary clinical research in regionally competitive male cyclists shows that taking pomegranate extract (Pomanox P30, Euromed S.A.) 750 mg daily for 15 days increases the time to exhaustion by 94 seconds after a prolonged submaximal effort, as well as the time to reach the anaerobic threshold by about 55 seconds, when compared with placebo. There was no effect on the restoration of force or on oxygen consumption (101881).
• Chronic obstructive pulmonary disease (COPD). It is unclear if oral pomegranate juice is beneficial for COPD. Details: A small clinical trial shows that drinking pomegranate juice 400 mL daily for 5 weeks does not improve symptoms or respiratory function in patients with COPD when compared with placebo (13692).
• Coronary heart disease (CHD). It is unclear if oral pomegranate juice is beneficial for patients with CHD. Details: Some preliminary clinical research shows that drinking pomegranate juice (POM Wonderful Pomegranate Juice, POM Wonderful LLC) 240 mL daily for 3 months decreases stress-induced myocardial ischemia in patients with CHD. The average improvement in myocardial perfusion was about 17% with pomegranate juice, compared with an 18% worsening of myocardial perfusion in patients taking placebo (13691). However, other preliminary clinical research in patients with moderate CHD risk shows that drinking the same pomegranate juice product 240 mL daily for 18 months does not improve carotid intima-media thickness when compared to control (17329). It is not known if drinking pomegranate juice can prevent or reduce the risk of a myocardial infarction or other cardiovascular outcomes.
• Dental plaque. It is unclear if rinsing the mouth with pomegranate extract is beneficial for reducing dental plaque. Details: Preliminary clinical research shows that rinsing with pomegranate extract mouthwash for one minute once or twice daily reduces dental plaque in patients with or without fixed orthodontic appliances. The antiplaque activity of pomegranate extract is similar to that of chlorhexidine (69171,69316).
• Erectile dysfunction (ED). It is unclear if oral pomegranate juice is beneficial for ED. Details: In patients with mild-to-moderate ED, preliminary clinical research shows that drinking pomegranate juice daily for 4 weeks does not improve symptoms of ED when compared with placebo (69175).
• Exercise-induced muscle soreness. It is unclear if oral pomegranate juice is beneficial for reducing exercise-induced muscle soreness. Details: Preliminary clinical research shows that drinking pomegranate juice (POM Wonderful Pomegranate Juice, POM Wonderful LLC) 250 mL twice daily for 15 days reduces post-exercise muscle soreness in elbow flexor, but not knee extensor, muscles in resistance-rained males when compared with placebo (69355). However, in non-resistance trained males, drinking the same pomegranate juice 250 mL twice daily for 9 days does not reduce exercise-induced muscle damage or delayed onset soreness of elbow flexor muscles when compared with placebo (101880).
• HIV/AIDS. Although there has been interest in using oral pomegranate for HIV/AIDS, there is insufficient reliable information about the clinical effects of pomegranate for this condition.
• Influenza. Although there has been interest in using oral pomegranate for influenza prevention, there is insufficient reliable information about the clinical effects of pomegranate for this purpose.
• Intrauterine growth restriction (IUGR). It is unclear if oral pomegranate juice is beneficial for preventing brain injury in IUGR neonates. Details: In patients with an IUGR pregnancy, clinical research shows that drinking pomegranate juice 8 ounces daily from 24-34 weeks' gestation until delivery reduces the risk of an MRI-diagnosed gray matter brain injury in the infant by approximately 28%. There was no effect on brain volume or white matter injury (105267).
• Kidney failure. It is unclear if oral pomegranate juice is beneficial for patients on hemodialysis; the available research is conflicting. Details: Some preliminary clinical research shows that taking pomegranate juice (Nutrafood) 100 mL during the first dialysis treatment hour three times weekly for one year reduces antihypertensive medication requirements and the rate of second hospitalization due to infection when compared with placebo. Consuming pomegranate juice also increases high-density lipoprotein (HDL) cholesterol in patients with baseline levels of 40 mg/dL or less and reduces triglycerides in patients with baseline levels of at least 200 mg/dL (91698,91699). Preliminary clinical research also shows that taking pomegranate juice 100 mL immediately after dialysis three times weekly for 8 weeks reduces triglycerides by approximately 20%, as well as systolic and diastolic blood pressure by 5% and 7%, respectively, when compared with baseline. HDL cholesterol was also increased by approximately 23%. These changes were significant when compared with placebo (101882). However, pomegranate juice did not affect total cholesterol, low-density lipoprotein (LDL) cholesterol, liver enzymes, or incidence of cardiovascular events when compared with placebo (91698,91699,101882). Other preliminary clinical research shows that drinking pomegranate juice (POM Wonderful Pomegranate Juice, POM Wonderful LLC) 100 mL or taking pomegranate juice extract tablets (POM Wonderful LLC) 1050 mg daily prior to each dialysis session for 4 weeks does not improve blood pressure, lipids, or markers of inflammation and oxidative stress when compared to baseline in patients receiving maintenance hemodialysis (91697). Although the reason for these conflicting findings is not clear, it may have to do with the timing of consumption. The evidence suggests that offering pomegranate during dialysis or after completion of dialysis might be more effective than prior to dialysis.
• Menopausal symptoms. It is unclear if oral pomegranate seed oil or pomegranate extract is beneficial for menopausal symptoms. Details: Preliminary clinical research shows that taking a specific pomegranate seed oil (Delima, Pekana Naturheilmittel GmbH) 30 mg orally twice daily for 12 weeks does not reduce the frequency of hot flashes when compared with placebo in postmenopausal adults experiencing at least 5 hot flashes per day. However, pomegranate seed oil might improve sleep in some patients with sleep disturbances attributed to menopause (91685). A clinical study in healthy, perimenopausal and menopausal adults with untreated menopausal symptoms shows that taking pomegranate extract 3 mL three times daily for 4 weeks reduces symptoms, including hot flashes and vertigo, and improves physical and mental quality of life when compared with placebo. Additionally, these improvements were sustained 3 weeks after discontinuing treatment (108484). The validity of this study is limited by the short duration of treatment.
• Metabolic syndrome. It is unclear if oral pomegranate juice is beneficial for metabolic syndrome. Details: Preliminary clinical research shows that drinking pomegranate juice 240 mL daily for one month improves endothelial dysfunction in adolescents with metabolic syndrome when compared with drinking grape juice 240 mL daily (53174,69362).
• Muscle strength. It is unclear if oral pomegranate juice is beneficial for increasing muscle strength. Details: Preliminary clinical research shows that taking a specific pomegranate extract (POMx, POM Wonderful LLC) 480 mL twice daily modestly improves recovery of strength 2-3 days after eccentric exercise but does not reduce muscle soreness after exercise when compared with placebo (69261).
• Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral pomegranate seed oil or pomegranate extract improves anthropometric measures in adults with NAFLD. Details: A small clinical study in overweight and obese adults with NAFLD shows that taking a dried pomegranate extract, standardized to contain 90 mg of ellagic acid, twice daily for 12 weeks reduces body mass index and body weight when compared with placebo. A 5 kg weight reduction occurred in the pomegranate group, compared to a small increase in weight in the placebo group. Pomegranate also improved diastolic blood pressure, as well as lipid and glycemic parameters; however, the patients included in this study had normal baseline parameters, limiting the validity of this finding (108481). Pomegranate has also been evaluated in combination with other ingredients. One small clinical crossover study in obese females with NAFLD shows that taking a specific combination product (Xanthigen, Polinat) containing pomegranate seed oil 300 mg and brown marine algae 300 mg (standardized to fucoxanthin 2.4 mg) modestly reduces body weight and liver fat content when compared with placebo (69257).
• Obesity. It is unclear if oral pomegranate is beneficial for obesity. Most evidence suggests that it is not beneficial, although some studies have yielded conflicting findings. Details: A meta-analysis of 513 participants shows that taking pomegranate extract, juice, or concentrate for 2-26 weeks does not reduce body weight, body mass index, waist circumference, or body fat percentage when compared with placebo or other control (101883). However, most of these studies were not designed to investigate weight as the primary outcome, and some preliminary clinical research in overweight or obese individuals suggests that some pomegranate products might have some benefit. Drinking pomegranate juice 120 mL daily for one month helps these individuals maintain weight when compared with placebo, although it does not appear to improve glucose, insulin secretion, or insulin sensitivity (91693).
• Oropharyngeal candidiasis. It is unclear if topical pomegranate peel extract is beneficial for oropharyngeal candidiasis. Details: Preliminary clinical research in patients with candidiasis associated with denture stomatitis shows that applying a gel containing the extract of pomegranate fruit peel to the gums three times daily for 15 days seems to be as effective as miconazole gel for improving symptoms of candidiasis (13689).
• Polycystic ovary syndrome (PCOS). It is unclear if oral pomegranate juice is beneficial for PCOS. Details: In patients with PCOS, preliminary clinical research shows that taking pomegranate juice 45 mL daily for 8 weeks reduces systolic and diastolic blood pressures by 10 and 4 mmHg, respectively, when compared with a control group not taking pomegranate juice. Triglyceride and high-density lipoprotein (HDL) cholesterol levels were also modestly improved. However, there was no effect on glycemic measures, and low-density lipoprotein (LDL) cholesterol levels increased by 6 mg/dL (105266). Another clinical trial in patients with PCOS shows that taking synbiotic pomegranate juice containing inulin and lactobacillus as 2 liters weekly for 8 weeks improves insulin sensitivity, body mass index, waist circumference, and testosterone levels when compared with baseline or a control juice. However, patients consuming a drink containing only the synbiotic ingredients experienced the same improvements, whereas patients consuming only regular pomegranate juice experienced no benefits, suggesting that pomegranate was not responsible for these changes (101884).
• Prostate cancer. It is unclear if oral pomegranate extract or juice is beneficial for prostate cancer. Details: Preliminary clinical research shows that pomegranate might slow prostate cancer progression in some patients after surgery or radiation for prostate cancer. The length of time to doubling of prostate specific antigen (PSA) was longer in those who took a specific pomegranate extract (POMx, POM Wonderful LLC) 1-3 grams daily, as well as those who drank 8 ounces of pomegranate juice daily, for up to 24 months (14137,14388,91695). However, the results from a large well-designed study do not support these findings. This study shows that taking 8 ounces of a pomegranate liquid extract does not increase the length of time to doubling of PSA (105271). In patients with favorable-risk localized prostate cancer, a small clinical trial also shows that taking pomegranate fruit extract (POMx, POM Wonderful) 1000 mg daily for 12 months does not affect the length of time to doubling of PSA, although there were some changes in tumor markers of DNA damage (105269). Pomegranate has also been evaluated in combination with other ingredients. Preliminary clinical research in patients with localized prostate cancer shows that taking a combination supplement containing pomegranate powder 100 mg, broccoli powder 100 mg, turmeric powder 100 mg, and green tea extract 20 mg daily for 6 months slows the increase in PSA levels when compared with placebo (89730). It is not clear if this effect is due to pomegranate, the other ingredients, or the combination.
• Rheumatoid arthritis (RA). It is unclear if oral pomegranate extract is beneficial for RA. Details: Preliminary clinical research shows that taking a specific pomegranate extract (POMx, POM Wonderful LLC) 5 mL twice daily for 12 weeks decreases disease activity and reduces tender joint count by 62% when compared to baseline in patients with RA (91686). The validity of these findings is limited by the lack of a control group.
• Rhinosinusitis. It is unclear if intranasal pomegranate extract is beneficial for chronic rhinosinusitis. Details: A clinical study in adults with chronic rhinosinusitis or rhinitis persisting longer than 12 weeks, with or without the presence of nasal polyps, shows that using a nasal spray containing pomegranate extract in an unknown dose twice daily for 30 days does not improve objective or subjective nasal or sinus symptoms when compared with placebo nasal spray. In a subgroup of patients with chronic rhinitis, including allergic and nonallergic rhinitis, improvement in thick nasal discharge is also observed in those receiving the pomegranate nasal spray; however, the study does not report outcomes for each subtype of rhinitis (108480).
• Stroke. Although there has been interest in using oral pomegranate for stroke recovery, there is insufficient reliable information about the clinical effects of pomegranate for this purpose.
• Sunburn. It is unclear if oral pomegranate extract is beneficial for sunburn prevention. Details: A small clinical study shows that taking pomegranate extract standardized to contain ellagic acid 100-200 mg daily for 4 weeks does not reduce skin pigmentation caused by UV light exposure when compared with placebo (69172). However, this study was not adequately powered to detect a difference between treatments.
• Trichomoniasis. It is unclear if oral pomegranate extract is beneficial for trichomoniasis. Details: A very small clinical study in patients with vaginal Trichomoniasis suggests that taking pomegranate extract might help to eradicate Trichomonas vaginalis infection (69286). The validity of this finding is limited by the small study size, unclear reporting, and lack of a control group. More evidence is needed to rate pomegranate for these uses.

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POSSIBLY SAFE ...when used orally and appropriately. Cordyceps has been used with apparent safety in doses of 3-6 grams daily for up to 1 year (12,12095,92828,95905,105076,111903).

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

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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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LIKELY SAFE ...when pomegranate fruit or fruit juice is used orally and appropriately. Pomegranate juice has been safely used in studies lasting up to 3 years (4912,8310,13022,13023,13690,14137,14388,17329,91693).

POSSIBLY SAFE ...when pomegranate extract is taken orally and appropriately. A specific pomegranate ellagitannin-enriched polyphenol extract (POMx, POM Wonderful) 1-3 grams daily has been safely used for up to 18 months (17729,69261,91686,91695,91697,99100,105269). ...when pomegranate seed oil is used orally and appropriately. Pomegranate seed oil 60 mg daily has been used with apparent safety for up to 12 weeks (91685). ...when a hot water extract of pomegranate seed powder is used orally and appropriately. Pomegranate seed powder 5 grams daily has been used with apparent safety for up to 8 weeks (105270). ...when pomegranate extract is used topically on oral mucosa (13689).

POSSIBLY UNSAFE ...when the pomegranate root, stem, and peel are used orally in large amounts. Bark of the pomegranate root and stem contains the piperidine alkaloids pelletierine, pseudopelletierine, isopelletierine, and methyl isopelletierine. These alkaloids have muscle relaxant properties that have been associated with paralysis and death in animals (13687,13694,13695). Dried pomegranate peel may contain aflatoxin, which is a potent hepatocarcinogen and toxin (92018).

PREGNANCY AND LACTATION: POSSIBLY SAFE
when the fruit or fruit juice is consumed orally and appropriately (13686,105267). There is insufficient reliable information available regarding the safety of using other forms of pomegranate or other parts of the plant during pregnancy or lactation; avoid using.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, cordyceps may increase the risk of bleeding when used with antiplatelet or anticoagulant drugs.  Details In vitro and animal research suggests that cordyceps extract inhibits platelet aggregation and function (3429,46112). However, this interaction has not been reported in humans.

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, concurrent use of cordyceps might interfere with immunosuppressive therapy.  Details Animal and in vitro research suggests that cordyceps stimulates the immune system (3403,3404,3414,3431,3432). However, limited clinical research suggests that taking cordyceps may lower the necessary therapeutic dose of the immunosuppressant cyclosporine (92828), which suggests that cordyceps may have an immunosuppressive effect.

TESTOSTERONE Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, concurrent use of cordyceps and testosterone might have additive effects.  Details Animal research suggests that cordyceps can increase testosterone levels (46087). The clinical significance of this finding is unclear.

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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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ACE INHIBITORS (ACEIs) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking pomegranate with ACEIs might increase the risk of adverse effects.  Details Pomegranate juice is thought to have ACE inhibitor-like effects (8310).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, taking pomegranate with antihypertensive drugs might increase the risk of hypotension.  Details Consuming pomegranate juice can modestly lower blood pressure (8310,13023,69373,69374).

CARBAMAZEPINE (Tegretol) Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, taking pomegranate with carbamazepine might increase the risk of adverse effects, although research suggests this interaction is unlikely to be clinically significant.  Details Animal research shows that pomegranate juice may inhibit cytochrome P450 3A4 (CYP3A4) metabolism of carbamazepine and increase levels of carbamazepine by 1.5 times without prolonging the elimination half-life. This suggests that pomegranate juice inhibits intestinal CYP3A4, but might not inhibit hepatic CYP3A4 (13188). However, some human research suggests that pomegranate does not significantly inhibit CYP3A4 drug metabolism in humans (16711,16712,17326).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, pomegranate might increase levels of drugs metabolized by CYP2C9.  Details Some animal and in vitro research shows that pomegranate juice inhibits intestinal, but not hepatic, CYP2C9 isoenzyme activity (17327). However, clinical research shows that neither pomegranate juice nor pomegranate extract have a significant effect on CYP2C9 activity in humans (91694).

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, pomegranate might increase levels of drugs metabolized by CYP2D6.  Details In vitro, pomegranate juice inhibits CYP2D6 (13703). However, the clinical significance of this potential interaction in humans is not known.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = B Theoretically, pomegranate might increase levels of drugs metabolized by CYP3A4, but most research suggests this interaction is unlikely to be clinically significant.  Details Pomegranate contains several polyphenols that have individually been shown to inhibit CYP3A4. However, there is contradictory evidence about the effect of whole pomegranate juice on CYP3A4 activity. In vitro, pomegranate juice significantly inhibits the CYP3A4 enzyme, with comparable inhibition to grapefruit juice (13188,16711,17326). In an animal model, pomegranate juice inhibits CYP3A4 metabolism of carbamazepine and increases levels of carbamazepine by 1.5 times (13188); however, in human volunteers, drinking a single glass of pomegranate juice 240 mL or taking 200 mL daily for 2 weeks does not significantly affect levels of the CYP3A4 substrate midazolam after oral or intravenous administration (16711,17730). Another study in healthy volunteers shows that consuming pomegranate juice 300 mL three times daily for three days also does not significantly affect levels of simvastatin, a CYP3A4 substrate (16712,91696) This suggests that pomegranate is unlikely to significantly affect levels of CYP3A4 substrates in humans (17326).

ROSUVASTATIN (Crestor) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking pomegranate with rosuvastatin might increase the risk of adverse effects.  Details In one case, a patient taking rosuvastatin 5 mg every other day in combination with ezetimibe 10 mg daily developed rhabdomyolysis after drinking pomegranate juice 200 mL twice weekly for 3 weeks. This patient had a history of elevated creatine kinase levels while not receiving any statin treatment. This suggests a possible underlying myopathy and predisposition to rhabdomyolysis (14465).

TOLBUTAMIDE (Orinase) Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, pomegranate might increase levels of tolbutamide, although research suggests this interaction is unlikely to be clinically significant.  Details Animal research shows that pomegranate juice inhibits the cytochrome P450 2C9 (CYP2C9) metabolism of tolbutamide. Pomegranate juice increased tolbutamide levels by 1.2 times without prolonging the elimination half-life. This suggests that pomegranate juice inhibits intestinal CYP2C9, but might not inhibit hepatic CYP2C9 (17327). Despite this evidence, clinical research shows that neither pomegranate juice nor pomegranate extract have a significant effect on CYP2C9 activity in humans (91694). This interaction does not appear to be clinically significant in humans.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, pomegranate might increase warfarin levels and increase the risk of bleeding. Also, discontinuing regular consumption of pomegranate juice might decrease warfarin levels.  Details In one case report, a patient had a stable, therapeutic bleeding time, as measured by international normalized ratio (INR), while taking warfarin in combination with pomegranate juice 2-3 times per week. The patient became subtherapeutic within about 10 days after discontinuing pomegranate juice, which required a warfarin dose increase (17328). In another case report, a patient with a stable INR for over one year presented with an INR of 14. The patient noted no changes to medications or diet but did report consuming around 3 liters of pomegranate juice over the previous week. The patient's INR stabilized upon moderation of pomegranate juice consumption (24273). The mechanism of this potential interaction is unclear.

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General ...Orally, cordyceps seems to be generally well tolerated when used for up to 1 year.
Most Common Adverse Effects:
Orally: Abdominal discomfort, constipation, diarrhea.

Gastrointestinal ...Orally, cordyceps has been associated with diarrhea, constipation, abdominal discomfort, dry mouth, and throat discomfort in clinical research. However, these events were uncommon, and in some cases symptoms could be reduced by taking cordyceps after eating (92829,105076,109705).

Hematologic ...Two cases of lead poisoning, characterized by loss of appetite and other symptoms, have been reported for patients taking cordyceps powder. After discontinuing cordyceps supplementation, both patients were treated with chelating agents (46135).

Hepatic ...There is a case report of acute cholestatic hepatitis probably associated with the use of a product containing cordyceps. The 64-year-old male was asymptomatic except for jaundice and laboratory markers and recovered once the supplement was stopped. However, it is unclear whether the hepatitis is associated with the cordyceps or with an unknown contaminant (109704).

Renal ...One case of a mild increase in serum creatinine level (< 30%) has been reported (95905).

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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, pomegranate fruit juice is generally well tolerated. Pomegranate fruit extract and seed oil seem to be well tolerated. Pomegranate root, stem, and peel should not be used orally in large amounts. Topically, pomegranate fruit extract seems to be well tolerated.
Most Common Adverse Effects:
Oral: Diarrhea, flatulence.

Cardiovascular ...In one clinical trial, 2% of patients experienced hyperlipidemia and hypertension after consumption of pomegranate juice (69175). However, most clinical research shows that pomegranate does not increase cholesterol or blood pressure and may actually improve these parameters in some patients (8310,13022,13023,69168,69373,69374).

Dermatologic ...Topically, pomegranate may cause urticaria (hives) in some patients (8445).

Gastrointestinal ...Orally, pomegranate may cause mild gastrointestinal adverse effects. In one clinical study, drinking pomegranate juice 8 ounces daily caused diarrhea and flatulence in 2% of patients (69175). In another clinical study, taking pomegranate extract (POMx, POM Wonderful LLC) 3000 mg daily caused diarrhea in 10% of patients. This dose of pomegranate extract also caused nausea, abdominal pain, constipation, gastrointestinal upset, and vomiting in a small number of patients (91695).

Immunologic ...Orally, pomegranate fruit or seeds may cause allergic reactions. These allergic reactions occur more commonly in people who are allergic to other plants (7674). In rare cases, pomegranate fruit can cause angioedema. Angioedema seems to occur without warning and in people who have eaten pomegranate for many years. Patients should be told to stop eating pomegranate if swelling of the tongue or face develops (7673). In one report, a patient experienced pomegranate-dependent, exercise-induced anaphylaxis. The patient developed widespread urticaria (hives) and lip edema after eating pomegranate seeds and then exercising (17331). In another report, an atopic patient experienced an allergic reaction to pomegranate fruit. Symptoms included urticaria (hives), facial angioedema, and hypotension (91692).
Topically, pomegranate may cause contact hypersensitivity characterized by urticaria (hives), angioedema, rhinorrhea, red itchy eyes, and dyspnea arising within a few minutes of exposure (8445).

Pulmonary/Respiratory ...Orally, pomegranate juice may cause nasal congestion, but this event is rare. In one clinical study, pomegranate juice was associated with nasal congestion in 2% of patients (69175). There is also one case report of a 7-year-old asthmatic child who developed bronchospasm moments after ingesting several pomegranate seeds (69149).

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