Ginkgo Supreme by Gaia Herbs

Genital herpes. Oral eleuthero root extract might help to prevent and reduce the severity of genital herpes outbreaks. Details: One clinical study in patients with recurrent genital herpes infections shows that taking a specific eleuthero root extract (Elagen) 400 mg, standardized to contain eleutheroside 0.3%, daily for at least 3 months reduces the frequency, severity, and duration of outbreaks when compared with placebo (730).

Athletic performance. Small clinical studies suggest that oral eleuthero root is not beneficial for improving athletic performance. Details: One study in trained distance runners shows that a specific eleuthero root liquid extract, standardized to eleutherosides B and E content, taken as 3.4 mL daily for 6 weeks, does not affect endurance, performance, or psychological, cardiac, or respiratory parameters when compared with placebo (7522). Small studies in trained athletes or healthy adults show that taking eleuthero 800-1200 mg daily (Endurox) for 1-6 weeks does not seem to have any effect on cycling performance time, respiration, lactate production, or heart rate recovery during cycling, stair-stepping exercise, treadmill, or cycle ergometry when compared with placebo (2335,7600,7601,8994). However, there has been some speculation that a longer duration of supplementation is needed for benefit. One study in recreationally trained athletes shows that taking a specific powdered eleuthero root product 400 mg twice daily for 8 weeks increased cycling endurance time by 23% and maximal oxygen consumption by 12% when compared with placebo. This product was standardized to contain eleutheroside B 0.11% and eleutheroside E 0.12% (17186).
Bipolar disorder. It is unclear if oral eleuthero root is beneficial for bipolar disorder. Details: A small clinical study in Chinese adolescents aged 12-17 years with bipolar disorder shows that taking eleuthero root 750 mg orally three times daily, in conjunction with lithium for 6 weeks, induces similar response rates and remission rates when compared with lithium plus fluoxetine 20 mg (75028). It is not clear how this response rate compares to the use of lithium alone.
Cardiovascular disease (CVD). It is unclear if oral eleuthero fruit is beneficial for preventing the development of CVD. Details: One small clinical study in healthy adults with at least two cardiovascular risk factors shows that taking an aqueous extract of eleuthero fruit 500 mg daily for 12 weeks seems to modestly reduce systolic blood pressure and arterial stiffness, as measured by brachial-ankle pulse wave velocity, when compared with placebo. It did not affect diastolic blood pressure, flow-mediated dilation, or carotid intima-media thickness. Also, taking a higher 1000 mg dose of the same eleuthero extract daily did not have significant effects on any measured parameters (105025).
Chronic fatigue syndrome (CFS). It is unclear if oral eleuthero root is beneficial for CFS. Details: One clinical study in adults with CFS shows that taking eleuthero root extract 2 grams daily for 2 months improves fatigue severity and duration when compared to baseline, but not when compared with placebo (11099).
Cognitive function. It is unclear if oral eleuthero is beneficial for cognitive function. Details: A very small clinical study in middle-aged people shows that taking eleuthero 325 mg twice daily might improve selective memory when compared with placebo (2574). Another very small study in healthy adults shows that taking a combination product containing extracts of eleuthero leaf 203 mg and Drynaria fortunei 20 mg daily for 12 weeks improves figure recall, but not immediate memory or attention, when compared with placebo (102316). It is unclear if this effect is due to eleuthero, Drynaria fortunei, or the combination.
Common cold. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some clinical research shows that taking capsules of a specific combination product containing eleuthero plus andrographis (Kan Jang, Swedish Herbal Institute) orally improves symptoms of the common cold when started within 72 hours of symptom onset. Some symptoms can improve after 2 days of treatment; however, it typically takes 4-5 days of treatment for maximal symptom relief (5784,10795,12380). Some research shows the combination of eleuthero and andrographis relieves cold symptoms better than echinacea or placebo in children (12381). It is unclear if this effect is due to eleuthero, andrographis, or the combination.
Coronavirus disease 2019 (COVID-19). Oral eleuthero extract has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults with a history of COVID-19 infection and current symptoms of long COVID-19 shows that taking a specific combination product containing eleuthero extract 78 mg, rhodiola extract 90 mg, and schisandra extract 300 mg (ADAPT-232/Chisan, Swedish Herbal Institute) twice daily for 2 weeks increases exercise capacity by about 13 minutes but does not reduce the duration of cough, fatigue, headache, pain, or other respiratory problems when compared with placebo (109635). It is unclear if these findings are due to eleuthero, other ingredients, or the combination.
Diabetes. It is unclear if oral eleuthero is beneficial for improving glycemic control in type 2 diabetes. Details: One small clinical study in adults with type 2 diabetes shows that taking a specific eleuthero extract, standardized to contain eleutherosides E and B 1.12%, as 480 mg daily for 3 months, decreases fasting glucose by a mean of 36 mg/dL, postprandial blood glucose by a mean of 35 mg/dL, glycated hemoglobin (HbA1c) by a mean of 0.8%, triglycerides by a mean of 106 mg/dL, and total cholesterol by a mean of 21 mg/dL when compared with placebo (91509).
Diabetic neuropathy. It is unclear if oral eleuthero is beneficial for diabetic neuropathy. Details: One small clinical study in adults with type 2 diabetes shows that taking a specific eleuthero extract, standardized to contain eleutherosides E and B 1.12%, as 480 mg daily for 3 months, modestly improves subjective symptoms of diabetic neuropathy when compared with placebo (91509).
Dry eye. Oral eleuthero root has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in adults with dry eye disease shows that taking a specific combination product containing eleuthero root 50 mg, zinc 10 mg, L-carnitine 50 mg, elderberry fruit extract 300 mg, and currant 100 mg (Meramirt CM) once daily improves dry eye symptom scores when compared with no intervention. Contrast sensitivity scores also improved when compared to baseline in the treated group, but not in the control group (111295). It is unclear if these effects are due to eleuthero, other ingredients, or the combination.
Familial Mediterranean fever. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in children ages 3-15 years with familial Mediterranean fever shows that taking a specific combination product (ImmunoGuard, Inspired Nutritionals) containing eleuthero, andrographis, schisandra, and licorice for one month reduces the duration, frequency, and severity of disease recurrence when compared with placebo (12382). It is unclear if this effect is due to eleuthero, other ingredients, or the combination.
Fibromyalgia. Although there is interest in using oral eleuthero for fibromyalgia, there is insufficient reliable information about the clinical effects of eleuthero for this condition.
Hangover. It is unclear if oral eleuthero root is beneficial for hangovers. Details: One small clinical study in healthy males shows that consuming one bottle of a powdered polysaccharide-rich extract of eleuthero root before and after consuming alcohol modestly reduces the severity of hangover as measured by the Acute Hangover Scale questionnaire score when compared with placebo (91508). However, the validity of these findings is brought into question due to the incomplete study information provided.
Influenza. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with influenza shows that taking a specific combination product containing eleuthero 20-30 mg plus andrographis 178-266 mg (Kan Jang, Swedish Herbal Institute) three times daily for 3-5 days relieves symptoms more quickly than amantadine. This combination product also reduced the risk of post-influenza complications, such as sinusitis or bronchitis, when compared with amantadine (10441). It is unclear if these effects are due to eleuthero, andrographis, or the combination.
Osteoarthritis. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking two capsules each containing 400 mg of a combination of eleuthero, Panax pseudoginseng, and rehmannia daily for 6 weeks improves physical function in individuals with knee osteoarthritis when compared with placebo. However, the combination does not seem to reduce pain or stiffness when compared with placebo (74950). It is unclear if this effect is due to eleuthero, other ingredients, or the combination.
Osteoporosis. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A very small clinical study in postmenopausal patients shows that taking low-dose calcium and vitamin D3 in combination with a 250 mg blend of rehmannia root and eleuthero stem bark extracts twice daily for 12 months attenuates the loss of spine and femur bone mineral density when compared with placebo or high-dose calcium and vitamin D (75036). It is unclear if this effect is due to eleuthero, rehmannia, or the combination.
Pneumonia. Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with acute, nonspecific pneumonia shows that taking a specific combination product (ADAPT-232), containing eleuthero, rhodiola, and schisandra, as 20 mL twice daily for 10-15 days in conjunction with conventional treatment, reduces the duration of antibiotic treatment and improves quality of life when compared with conventional treatment alone (71152).
Quality of life. It is unclear if oral eleuthero root improves quality of life in older healthy adults. Details: A small clinical study in elderly volunteers shows that taking eleuthero 300 mg daily improves social functioning and mental well-being after 4 weeks of treatment when compared with placebo. However, this improvement was not maintained after 8 weeks of treatment (15586).
Rheumatoid arthritis (RA). Although there is interest in using oral eleuthero for RA, there is insufficient reliable information about the clinical effects of eleuthero for this condition.
Stress. It is unclear if oral eleuthero root is beneficial for stress. Details: One clinical study in adults 30-50 years of age with symptoms of stress shows that taking a specific eleuthero root extract (WS 1070) 120 mg daily for 8 weeks does not improve fatigue, exhaustion, cognitive alertness, or measures of stress when taken alone or in conjunction with stress management training (91510). However, another small clinical study in healthy females 20-68 years of age who have experienced stress for a prolonged period of time shows that taking 270 mg of a combination agent (ADAPT-232) containing eleuthero, rhodiola, and schisandra improves attention and cognitive speed and accuracy when compared with placebo (19289). It is unclear if these effects are due to eleuthero, other ingredients, or the combination.
Upper respiratory tract infection (URTI). Oral eleuthero has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults with an uncomplicated URTI shows that taking 30 mL of a combination product (Kan Jang, Swedish Herbal Institute) containing extracts of eleuthero root (eleutherosides B and E 0.03 mg/mL), echinacea root, and malabar nut leaf daily does not reduce the severity or frequency of cough by a clinically meaningful amount after 3-4 days of treatment when compared with bromhexine hydrochloride or placebo (95648). However, a non-blinded clinical study shows that taking 30 mL of this same product three times daily for 6 days improves the severity and frequency of coughing and the degree of nasal congestion when compared with bromhexine. Additionally, patients taking the combination product recovered two days sooner, on average, than those taking bromhexine (48569). The reason for these conflicting findings is unclear but may be due to an inadequate duration of treatment in the first study and/or lack of blinding in the second study. Also, it is unclear if any benefit is due to eleuthero, other ingredients, or the combination. Other research has evaluated a capsule formulation of Kan Jang (Swedish Herbal Institute), with each capsule containing eleuthero root 11.4 mg and andrographis 195 mg. One small clinical study in patients with an uncomplicated URTI shows that taking this product as two capsules three times daily for 5 days reduces the median number of sick leave days to 2 days, compared with 3 days in the placebo group. It also increases the total number of recovered patients on day 3 to 75%, compared with 55% of those taking placebo (107471). More evidence is needed to rate eleuthero for these uses.

Age-related cognitive decline. Oral fo-ti has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with mild age-related cognitive decline shows that taking a combination product containing fo-ti root and Panax ginseng as five capsules three times daily for 3 months improves memory when compared to baseline (50720). The validity of these findings is limited by a lack of placebo control group.
Aging. Although there has been interest in using oral fo-ti for aging, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
Alopecia areata. Although there has been interest in using oral fo-ti for alopecia areata, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
Alzheimer disease. Although there has been interest in using oral fo-ti for Alzheimer disease, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
Androgenic alopecia. Although there has been interest in using oral fo-ti for androgenic alopecia, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
Cardiovascular disease (CVD). Although there has been interest in using oral fo-ti for CVD, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
Dyslipidemia. Oral fo-ti has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in adults in China with dyslipidemia shows that taking four capsules of a specific combination product (Blood Fat Droplets, Vita Green Pharmaceutical Ltd.), containing extracts of fo-ti 43 mg, hawthorn 129 mg, Asian water plantain 86 mg, corn silk 86 mg, reishi mushroom 43 mg, and white mulberry 43 mg, twice daily for 12 weeks decreases low-density lipoprotein (LDL) cholesterol by 12 mg/dL, or around 9%, but does not improve total cholesterol, high-density lipoprotein (HDL) cholesterol, or triglyceride levels, when compared with placebo (99854).
Insomnia. Although there has been interest in using oral fo-ti for insomnia, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
Osteoarthritis. Although there has been interest in using oral fo-ti for osteoarthritis, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
Osteoporosis. Although there has been interest in using oral fo-ti for osteoporosis, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
Parkinson disease. Although there has been interest in using oral fo-ti for Parkinson disease, there is insufficient reliable information about the clinical effects of fo-ti for this purpose.
Wrinkled skin. Although there has been interest in using topical fo-ti for wrinkled skin, there is insufficient reliable information about the clinical effects of fo-ti for this purpose. More evidence is needed to rate fo-ti for these uses.

Anxiety. Oral ginkgo seems to modestly reduce anxiety symptoms. Details: Clinical research shows that taking a specific ginkgo extract called EGb 761 (Dr. Willmar Schwabe Pharmaceuticals) for 4 weeks can modestly reduce symptoms of anxiety in a greater percentage of adults with generalized anxiety disorder or adjustment disorder with anxious mood when compared with placebo. After 4 weeks of treatment, a reduction in anxiety rating score of at least 50% was seen in 44% of patients treated with 480 mg daily, 39% of patients treated with 240 mg daily, and 22% of patients treated with placebo (15578). It is unclear whether these effects would persist when taken for longer than 4 weeks. This study was also included in a meta-analysis that performed indirect comparisons of multiple herbs for the treatment of anxiety. This analysis suggests that taking ginkgo may reduce anxiety scores modestly more than kava (110711). However, the interpretation of these results is limited by the small amount of data available for ginkgo.
Dementia. Oral ginkgo 240 mg seems to improve symptoms of various types of dementia, but lower doses are not always effective. Oral ginkgo does not seem to prevent or slow down the progression of dementia. Details: Most evidence shows that higher doses of a specific ginkgo extract (EGb761) modestly improve symptoms of Alzheimer, vascular, or mixed dementias. Meta-analyses of clinical research in patients with dementia show that taking ginkgo, usually 240 mg daily for 24 weeks, modestly improves cognition and activities of daily living when compared with placebo. When analyses pooled studies testing low-dose (120 mg) and high-dose (240 mg) ginkgo together, the benefit was not always present (87855,87819,87851,87866,88006,89713,102183,102185,102186,103572)(111333). Although most clinical trials show benefit, there are some clinical trials with conflicting findings, suggesting inconsistent and unpredictable effects (16637,87726). There has been some debate about whether ginkgo is more effective in dementia patients who have neuropsychiatric symptoms. Most clinical research shows that this is not the case. However, high-dose ginkgo 240 mg daily seems to modestly relieve most neuropsychiatric symptoms other than psychosis (17717,87794,87897,102185,102187). Few clinical studies compare ginkgo leaf extract to conventional drugs such as cholinesterase inhibitors. Some preliminary comparative studies show that taking a specific ginkgo leaf extract called EGb 761 (Dr. Willmar Schwabe Pharmaceuticals) 160-240 mg daily for 22-24 weeks seems to be comparable to donepezil (Aricept) 5-10 mg daily for mild to moderate Alzheimer disease (14499,87826). Similarly, a clinical study in patients with Alzheimer disease or mild cognitive impairment shows that taking ginkgo extract 150 mg three times daily for 6 months seems to be comparable to donepezil 5 mg daily for improvement of cognitive scores (106611). However, indirect comparisons suggest that ginkgo leaf extract might be less effective than the conventional drugs donepezil, tacrine (Cognex), rivastigmine (Exelon), and other cholinesterase inhibitors (6224,6490,11981,89710). Also, some studies show that taking ginkgo in combination with conventional medications for 12-24 weeks does not improve cognitive scores by a clinically meaningful extent when compared with conventional medications alone (95902,106611). However, a meta-analysis of 17 mostly small, low quality clinical studies in patients with Alzheimer disease, that includes some of these studies, shows that taking ginkgo in combination with donepezil for 3-9 months modestly improves cognitive scores when compared with donepezil alone. Adding ginkgo may also improve activities of daily living scores (111332). Another meta-analysis of mostly small clinical studies in adults with vascular dementia also shows that taking ginkgo extract orally or intravenously daily for 4-12 weeks, in addition to donepezil, moderately improves cognitive scores and functional scores when compared with donepezil alone (114767). However, the validity of these findings is limited by the heterogeneity of the included studies, which utilized various doses and forms of ginkgo. Ginkgo does not appear to be beneficial for preventing or slowing the progression of dementia. Epidemiologic research shows that taking ginkgo extract is not associated with a decreased risk of developing dementia in elderly patients with memory impairment (14812). Three large-scale clinical trials also show that taking ginkgo extract 120 mg twice daily does not reduce the risk of developing all-cause dementia or Alzheimer disease in elderly patients with normal cognitive function or in those with mild cognitive impairment (16634,87848,87904). In addition, taking ginkgo extract does not seem to prevent disease progression in Alzheimer patients (89713). Most of the clinical studies on the effectiveness of ginkgo leaf for dementia have used the standardized extracts EGb 761 (Dr. Willmar Schwabe Pharmaceuticals and Ipsen) and LI 1370 (Lichtwer Pharma). These two extracts are similar and prepared to contain approximately 24% to 25% flavone glycosides and 6% terpene lactones. Other products with similar ingredients include Ginkai (Lichtwer Pharma), Ginkgo 5 (Pharmline), Ginkgold and Ginkgo (Nature's Way), and Quanterra Mental Sharpness (Warner-Lambert).
Hearing loss. Intravenous ginkgo appears to improve hearing loss when used in conjunction with corticosteroids. The effectiveness of oral ginkgo is unclear. Details: A meta-analysis of randomized controlled trials (RCTs) in adults with sudden hearing loss shows that using intravenous ginkgo leaf extract 40-175 mg daily, in addition to corticosteroids, for 5-14 days increases clinical cure rates by 1.3 times that of corticosteroids alone. Ginkgo leaf in combination with corticosteroids also improved hearing sensitivity (107360). Another meta-analysis of 27 mostly low-quality RCTs in patients with sudden hearing loss, that includes some of the same studies as the prior analysis, shows that adding ginkgo extract to usual care for 1-14 days leads to improvement or no further deterioration in 91% of patients when compared with 75% of patients receiving usual care (111339). However, the interpretation of these results is limited by unclear ginkgo dosing and inclusion of studies that administered ginkgo orally, as an injection, or unknown route. In addition, usual care treatments were not described. In addition, one clinical study in patients with short-term idiopathic hearing loss shows that oral ginkgo leaf extract 120 mg twice daily for 8 weeks might improve hearing recovery rates when compared with ginkgo leaf extract 12 mg twice daily (8543). However, there was a high spontaneous recovery rate in both groups, so it is unclear how much benefit, if any, can be attributed to ginkgo leaf extract.
Premenstrual syndrome (PMS). Oral ginkgo seems to reduce symptoms of PMS. Details: Taking ginkgo leaf extract orally 80 mg twice daily or 40 mg three times daily seems to produce significant relief in breast tenderness and other physical and psychological symptoms associated with PMS when started during the 16th day of the menstrual cycle and continued until the 5th day of the following cycle for up to two cycles (6229,87839). Specific ginkgo leaf extracts that have been assessed for this condition include Ginko T.D. (Tolidaru Pharmaceuticals) and EGb 761, which is an ingredient in several commercial products including Tebonin (Dr. Willmar Schwabe Pharmaceuticals), Tanakan (Ipsen), and Quanterra Mental Sharpness (Warner-Lambert).
Schizophrenia. Oral ginkgo seems to reduce total and negative symptoms of schizophrenia, and may be beneficial for reducing antipsychotic-associated adverse effects. Details: Taking a standardized ginkgo leaf extract EGb 761 (Yi Kang Ning, Yang Zi Jiang Pharmaceuticals Ltd.), 120-360 mg orally daily in addition to standard antipsychotic medications (such as olanzapine, clozapine, or haloperidol) for 8-16 weeks, can reduce total and negative symptoms of schizophrenia when compared to treatment with antipsychotic medications alone (87844,95901). Guidelines from The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce state that ginkgo extract at doses of 120-360 mg daily is weakly recommended for adjunctive use in schizophrenia, primarily for negative symptoms (110318). Treatment with ginkgo leaf extract might also reduce anticholinergic side effects such as thirst and constipation and adverse behavioral, cardiovascular, and nerve symptoms associated with antipsychotic treatment (87708,95901). Additional clinical research is needed to determine the role of ginkgo on antipsychotic-associated adverse effects.
Stroke. Oral and intravenous ginkgo seem to improve recovery from stroke; intravenous ginkgo might be more effective. Details: While some individual studies show conflicting results, meta-analyses of small, low-quality clinical trials in patients recovering from ischemic stroke show that oral or intravenous ginkgo extract along with conventional therapy seems to improve neurologic function and activities of daily living scores, but does not improve quality of life or reduce the risk of recurrent stroke or death, when compared with conventional therapy alone (14435,102883,102884,107452). However, the overall methodological quality of the meta-analyses is described as critically low, with a high risk of bias (113783). One meta-analysis shows that intravenous ginkgo extract is associated with greater improvements in these measures than oral ginkgo extract (102884). Ginkgo diterpene lactone meglumine (GDLM) is a derivative of ginkgo composed of active ingredients ginkgolides A, B, and K that has been investigated for the treatment of acute ischemic stroke both as monotherapy and in combination with thrombolysis. Large clinical trials in adults with moderate acute ischemic stroke show that giving an intravenous infusion of GDLM 25 mg daily, initiated within 48 hours of symptom onset and continuing for up to 14 days, increases the proportion of patients achieving a favorable outcome, defined as a score of 0 or 1 on the modified Rankin Scale (mRS) on day 90, by 15% when compared with placebo. About 62% of patients treated with GDLM show clinically significant improvement in Montreal Cognitive Assessment scores, compared with 56% of those on placebo. The most significant improvements occur in measures of language and visuo-spatial and executive function (111693,113784). Additionally, a meta-analysis shows that combination therapy with GDLM and tissue plasminogen activator (rTPA) is associated with greater improvements than conventional treatments alone or other traditional Chinese herbal medicines that contain ginkgo (i.e. ginaton, danhong, xueshuantong, and shuxuening injections). This specific formulation also appears to be more effective than intravenous ginkgolides or ginkgolide B; however, investigators did not provide a statistical comparison of outcomes between groups, limiting the validity of this finding (108610). Another meta-analysis shows that intravenous administration of ginkgo leaf extract plus dipyridamole 10-40 mL daily for 14-30 days along with conventional therapy also improves neurologic function and activities of daily living when compared with conventional therapy alone (102882). In patients not treated with thrombolytics, a small clinical study in adults in China shows that administering ginkgo diterpene lactone meglumine 25 mg intravenously daily for 14 days, starting within 48 hours after an ischemic stroke, in addition to aspirin 100 mg daily for 90 days, led to improvement in scores related to stroke severity or the degree of disability at 90 days in 94% of patients when compared with 83% of patients treated with aspirin alone (111340). However, the patients in this study had minor or moderate strokes; these results may not apply to patients with more severe strokes. In patients with hemorrhagic stroke, preliminary clinical research shows that daily intravenous administration of ginkgo extract (Taiwan Jisheng Chemical Pharmaceutical Co., Ltd.) 17.5 grams for 2 weeks, in conjunction with routine treatment and intravenous oxiracetam 6 grams, reduces cerebral edema and bleeding and modestly improves recovery of neurological and cognitive function and activities of daily living when compared with oxiracetam plus routine care or routine care alone (103573). A meta-analysis of 19 Chinese clinical trials in patients with hemorrhagic stroke shows that treatment with ginkgo leaf extracts for 7-20 days in combination with standard treatment is associated with lower NIH and Chinese stroke scale scores, lower residual hematoma and cerebral edema volumes, lower serum levels of inflammatory factors, and higher cognitive function and activity of daily living scores, when compared with standard treatment alone, although with considerable heterogeneity in the results (113781).
Tardive dyskinesia. Oral ginkgo seems to reduce the severity of tardive dyskinesia in schizophrenic patients being treated with antipsychotic medications. Details: Clinical research shows that taking a specific ginkgo extract called EGb 761 (Yi Kang Ning, Yang Zi Jiang Pharmaceuticals Ltd.) 80 mg three times daily for 12 weeks can reduce the severity of tardive dyskinesia by at least 30% when compared with placebo in schizophrenic patients being treated with antipsychotic medications (87864).
Vascular dementia. Oral ginkgo extract seems to modestly improve scores related to cognitive function in patients with this condition. Details: A meta-analysis of small randomized controlled trials in adults with vascular dementia shows that taking ginkgo extract orally or intravenously daily for 4-12 weeks, in addition to donepezil, moderately improves cognitive scores and functional scores when compared with donepezil alone (114767). However, the results of this study are limited by high heterogeneity. In addition, these trials do not report standard doses of ginkgo. A small clinical study in patients with vascular dementia shows that taking a specific extract of ginkgo EGb 761 (Dr. Willmar Schwabe Pharmaceuticals) 240 mg daily for 24 weeks modestly improves scores related to cognitive function, neuropsychiatric symptoms, and activities of daily living when compared with placebo (17191). A preliminary open-label clinical study in patients aged 50 years or older in China shows that taking the same ginkgo extract 240 mg daily for 24 weeks, starting within 7-14 days after an ischemic stroke, modestly improves scores related to cognitive function and mental health, but not neuropsychiatric symptoms, when compared with standard care (111335). However, the patients in this study had minor strokes; these results may not apply to patients with more severe strokes. Ginkgo has also been evaluated in combination with other ingredients to treat vascular dementia. A small clinical study in patients aged 60 years or older with vascular dementia shows that taking a supplement containing extracts of ginkgo, Panax ginseng, and saffron 60 mg three times daily for 16 weeks modestly improves some cognitive function scores, caregiver assessed activities of daily living, and patient-reported quality of life. However, these effects were not maintained after patients stopped taking the supplement (111336).
Vertigo. Oral ginkgo seems to improve symptoms of vertigo in people with vestibular disorders. It is unclear if it is beneficial for vertigo caused by cerebral arteriosclerosis. Details: Taking ginkgo leaf extract 120-160 mg daily orally seems to improve symptoms of vertigo and equilibrium disorders (5721,6220,6221,107359,108608). There is evidence from two clinical studies that ginkgo leaf extract (EGb 761) for 3 months is significantly more effective than placebo (6220), and possibly as effective as betahistine, for improving vertigo and dizziness caused by vascular vestibular disorders and vestibular disorders of unknown origin (6220,6221). However, adding balance training to treatment with ginkgo leaf extract (EGb 761) orally 80 mg twice daily for 3 months is no better than taking ginkgo leaf extract alone (107359). Ginkgo has also been evaluated in patients with vertigo caused by mild cerebral arteriosclerosis. A clinical study in this population shows that taking oral ginkgo leaf extract (Zhejiang Jiu Xu Pharmaceutical Co, Ltd) 40 mg three times daily for 6 weeks improves scores of traditional Chinese medicine symptom pattern, specifically dizziness, blurry vision, headache, and amnesia, but does not impact Dizziness Handicap Inventory scores, when compared with naoxinqing (NXQ), a standardized herbal product that contains Japanese persimmon leaf extract (108608). The validity of this study is limited due to the lack of comparison to placebo or an accepted conventional treatment.

POSSIBLY INEFFECTIVE

Age-related cognitive decline. Most research shows that oral ginkgo does not improve symptoms of age-related cognitive impairment. Details: While some preliminary clinical research shows a modest benefit of ginkgo leaf extract on memory and cognitive function in patients with age-related memory or thinking impairment (5717,6216,89712), most clinical research shows that taking ginkgo leaf extract orally does not improve memory or attention in elderly individuals with normal mental function (5718,8586,8587,8588,87848). Clinical research also shows that taking a standardized ginkgo leaf extract (Thorne Research Inc.) 240 mg daily for 3.5 years does not reduce the risk of developing age-related cognitive impairment in elderly patients aged 85 years and older who have normal cognitive function (16635).
Antidepressant-induced sexual dysfunction. Most research shows that oral ginkgo does not improve symptoms of sexual dysfunction in people using antidepressants. Details: Although some preliminary clinical research shows that taking ginkgo leaf extract orally might help sexual dysfunction caused by antidepressant therapy (3965,3967), subsequent research indicates that it not likely to be beneficial (207,3966,3969,10893,14383).
Cardiovascular disease (CVD). Oral ginkgo does not seem to prevent CVD. Details: A large-scale randomized trial shows that taking a specific ginkgo leaf extract called EGb 761 (Dr. Willmar Schwabe Pharmaceuticals) 240 mg daily orally for an average of 6.1 years does not reduce the risk of myocardial infarction, angina, stroke, CVD-related hospitalization, or mortality in elderly patients when compared with placebo (17402).
Chemotherapy-related cognitive impairment. Oral ginkgo does not seem to improve symptoms of cognitive impairment in people using chemotherapy. Details: Clinical research shows that taking a specific ginkgo leaf extract called EGb 761 (Dr. Willmar Schwabe Pharmaceuticals) 60 mg twice daily, starting prior to the second cycle of chemotherapy and continuing until one month after chemotherapy completion, does not prevent chemotherapy-related cognitive dysfunction when compared with placebo in chemotherapy-naïve breast cancer patients (89701).
Hypertension. Oral ginkgo does not seem to reduce blood pressure in older, hypertensive patients. Details: A meta-analysis of low-quality research in subjects with hypertension shows that taking ginkgo orally daily for 4-26 weeks modestly improves systolic and diastolic blood pressure when compared with control (114766). However, the validity of this study is limited by high heterogeneity, differing co-interventions, including known antihypertensives, and differing controls. Other clinical research shows that taking a standardized ginkgo leaf extract called EGb 761 (Dr. Willmar Schwabe Pharmaceuticals) 240 mg daily for up to 6 years does not reduce blood pressure when compared with placebo in hypertensive patients aged 75 years or older (87853).
Multiple sclerosis (MS). Most research shows that oral ginkgo does not improve symptoms of MS. Details: Most clinical research shows that taking ginkgo leaf extract or ginkgolide B, a constituent of ginkgo leaf extract, does not improve cognition or disability in patients with MS (87739,87787,87903,87947). However, a single preliminary clinical study shows that taking a standardized ginkgo leaf extract called EGb 761 (Dr. Willmar Schwabe Pharmaceuticals) may improve processing speed when compared with placebo in patients with multiple sclerosis (89705).
Tinnitus. Most research shows that oral ginkgo does not improve symptoms of tinnitus. Details: Taking ginkgo leaf extract orally does not seem to improve symptoms of tinnitus. Although some studies have shown benefit, the majority of the clinical evidence indicates that ginkgo leaf extract is not consistently effective for patients with tinnitus (221,910,5721,6218,6219,9871,87754,87901,110093,111337)(111513).

Age-related macular degeneration (AMD). It is unclear if oral ginkgo is beneficial in AMD. Details: Preliminary clinical research suggests that taking a specific ginkgo leaf extract (EGb 761) 60-240 mg orally in divided doses for up to 6 months might improve symptoms of AMD (6227,6228,11797). There is limited evidence that ginkgo leaf extract might significantly improve distance vision in patients with AMD (6227).
Aging. Although there has been interest in using oral ginkgo for aging, there is insufficient reliable information about the clinical effects of ginkgo for this condition.
Allergic rhinitis (hay fever). Topical ginkgo has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with seasonal allergic conjunctivitis shows that applying two drops of specific eye drops (Trium, SOOFT) containing ginkgo extract 0.05% and hyaluronic acid 0.15%, three times daily for one month can decrease redness by 80%, discharge by 40%, and swelling by 10% when compared to using eye drops with hyaluronic acid alone (87829).
Altitude sickness. Research on the use of oral ginkgo for altitude sickness is conflicting. Details: Some research shows that taking ginkgo extract 80-120 mg twice daily for 4 days before the ascent to an altitude of 4300-5400 meters significantly reduces the occurrence of symptoms of acute altitude sickness, including headache, fatigue, dyspnea, nausea, and vomiting, when compared with placebo (6230,87827). A standardized ginkgo leaf extract called EGb 761, 160 mg in two divided doses daily, was used in one of these studies (6230). However, a large-scale trial using a different ginkgo extract (GK501, Pharmaton Natural Health Products) 120 mg twice daily for 1-2 days before the climb from an altitude of 4280 meters to 4928 meters, shows that ginkgo extract has no effect on preventing altitude sickness (11766). Also, another small study suggests that taking ginkgo extract 120 mg twice daily for 3 days before an ascent does not reduce altitude sickness when compared with placebo (87827). The conflicting results may be due to differences in starting baseline altitudes before ascent, duration of the pre-treatment period, or the source of the ginkgo product.
Angina. Some low-quality evidence suggests that oral ginkgo may reduce angina symptoms when taken in addition to standard of care. Details: A large meta-analysis of variable-quality studies in patients with unstable angina shows that taking ginkgo orally or intravenously for up to 12 weeks modestly improves angina symptoms when compared with control (114768). However, the results of this study are limited by the heterogeneity of included studies, including different control treatments. A small clinical study in patients with stable angina shows that taking ginkgo extract formulated with a polyethylene glycol matrix to improve bioavailability, 315 mg three times daily with standard therapy for 12 weeks, does not improve the overall Seattle Angina Questionnaire score when compared with placebo, although there is a trend towards a reduction in angina attack frequency (113782).
Asthma. Oral ginkgo has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that a taking two capsules of a specific combination product (AKL1, AKL International Ltd.) containing ginkgo extract 130 mg/capsule, ginger 100 mg/capsule, and Picrorhiza 270 mg/capsule twice daily for 12 weeks does not improve lung function, respiratory symptoms, or quality of life when compared with placebo in adult patients with asthma (87786).
Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral ginkgo is beneficial in ADHD. Details: One clinical study shows that taking a standardized ginkgo extract (Ginko T.D., Tolidaru Pharmaceuticals) 80-120 mg daily for 6 weeks is less effective than methylphenidate 20-30 mg daily in children aged 6-14 years with newly diagnosed ADHD. Only 8% of children taking ginkgo extract had at least a 40% improvement in a teacher/parent ADHD rating scale, compared with 64% in children taking methylphenidate (17112). Another clinical study in children aged 6-12 years with ADHD shows that taking the same standardized ginkgo extract 80-120 mg daily in combination with methylphenidate 20-40 mg daily for 6 weeks does not improve parent- or teacher-rated ADHD scores by a clinically meaningful amount when compared with methylphenidate alone (95669). However, one preliminary clinical study shows that taking a specific combination product (AD-fX, CV Technologies) containing ginkgo leaf extract 100 mg, in combination with American ginseng extract 400 mg, in two divided doses for 4 weeks might significantly improve ADHD symptoms such as anxiety, hyperactivity, and impulsivity in children aged 3-17 years (8235). Guidelines from The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce state that ginkgo extract at doses of 80-120 mg daily is not currently recommended for monotherapy or adjunctive use in children with ADHD due to mixed evidence (110318).
Autism spectrum disorder. It is unclear if oral ginkgo is beneficial in children with autism. Details: A small clinical trial shows that taking a specific ginkgo extract (Ginko T.D., Tolidaru Pharmaceuticals) 80-120 mg daily for 10 weeks along with risperidone 1-3 mg daily does not improve symptoms of autism when compared with risperidone alone in children aged 4-12 years (89708).
Bronchitis. Although there has been interest in using oral ginkgo for bronchitis, there is insufficient reliable information about the clinical effects of ginkgo for this condition.
Chronic fatigue syndrome (CFS). Oral ginkgo has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with CFS shows that taking ginkgo leaf 120-180 mg in combination with Cistanche tubulosa root 300-450 mg orally daily for 60 days improves fatigue scores by 16% to 19% when compared with placebo. Taking this combination also improved quality of life scores when compared with placebo (107361).
Chronic kidney disease (CKD). There is limited evidence on the intravenous use of ginkgo leaf extract in adults with hypertensive nephropathy. It has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small meta-analysis in patients with hypertensive nephropathy shows that intravenous administration of 20-30 mL of ginkgo leaf extract and dipyridamole injection once daily for 3-4 weeks along with conventional antihypertensive therapy improves levels of 24-hour urinary total protein, serum creatinine, and blood urea nitrogen by 0.6 grams/dL, 33 mg/dL, and 7 mg/dL, respectively (106610). It is unclear if these effects are due to ginkgo, dipyridamole, or the combination.
Chronic obstructive pulmonary disease (COPD). Oral ginkgo has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that taking two capsules of a specific combination product (AKL1, AKL International Ltd.) containing ginkgo extract, ginger, and Picrorhiza twice daily for 8 weeks does not improve respiratory symptoms when compared with placebo in patients with COPD (89702).
Cocaine dependence. It is unclear if oral ginkgo is beneficial for maintenance of abstinence from cocaine. Details: A small clinical trial shows that taking a standardized ginkgo leaf extract called EGb 761 in a dose of 120 mg twice daily for 10 weeks does not help maintain abstinence from cocaine use when compared with placebo in cocaine-dependent patients (87723).
Cognitive function. It is unclear if oral ginkgo is beneficial for cognitive function. Details: Clinical research in healthy adults shows that taking ginkgo leaf extract daily for up to 12 weeks might improve some measures of cognitive function, such as working and long term memory, attention based tasks, speed of information processing, executive function, immediate and delayed recall, and recognition (6214,6215,8236,8544,8585,8588,9759,16635,87788,87879,95668). Doses used in these studies include single doses of ginkgo extract 240-600 mg (6215,8236), a standardized ginkgo extract called EGb 761, 120-240 mg taken once daily or in 2-3 divided doses daily for 4-24 weeks (5717,6216,8585,8588,87879,95668), or another specific ginkgo extract called LI 1370 (Lichtwer Pharma), 120-300 mg daily in three divided doses for 2 days (6214). However, other clinical studies and one clinical review show no significant effect of ginkgo on gait ability, attention, memory, or executive function regardless of participant age, dose, or formulation used (87907,5718,8586,8587,8588,87907,95667). Due to the small number of study participants, significant differences in baseline cognitive function between groups, and variability in outcome measures, no definitive conclusions can be drawn. Larger scale studies are needed to determine the effect of ginkgo on cognitive function in healthy individuals. There is also conflicting evidence about the effect of ginkgo on cognitive function when taken in combination with other products. Some research suggests that taking ginkgo in combination with Panax ginseng or codonopsis enhances memory in healthy young or middle-aged adults, and the combinations might be more effective than the individual products (8591,9759,87758). These studies have used a specific combination product (Ginkoba M/E, Pharmaton SA) containing ginkgo extract 100-600 mg and Panax ginseng 60-360 mg, taken as a single dose or once daily for 12 weeks (8591,9759) or two capsules of a product containing ginkgo extract 40 mg/capsule and Codonopsis 75 mg/capsule daily (87758). However, other clinical research shows that taking ginkgo combined with Panax ginseng (Gincosan, Pharmaton Natural Health Products) or bacopa extract (Ginkgo Brahmi, Blackmore's Ltd.) for up to 12 weeks does not improve cognition when compared with placebo in healthy adults (87767,87748). Similarly, a moderate-sized clinical study in healthy adults aged 40-65 years shows that taking a supplement containing ginkgo leaf, bacopa, and B vitamins twice daily for 12 weeks does not improve memory or attention when compared with placebo (111334).
Cognitive impairment. It is unclear if ginkgo is beneficial for cognitive impairment. Details: A clinical study of 500 patients with mild cognitive impairment that is abnormal for their age shows that taking a specific ginkgo standardized extract (EGb761, Tanakan) 40 mg three times daily for 24 months improves scores for cognitive decline, memory, activities of daily living, and depression when compared with baseline (105530). However, it is not clear if these improvements are clinically significant and the validity of the study is limited by the lack of a control group. Cognitive impairment is common side effect of electroconvulsive therapy (ECT). A small clinical study in patients aged 18-60 years with psychiatric disorders undergoing ECT in Iran shows that taking ginkgo (Vitarmonil Co., France) 200 mg after meals, starting 48 hours before initiation of ECT and continuing until the end of ECT sessions, modestly improves scores related to cognitive impairment and memory when compared with placebo (111338). However, it is unclear if these improvements are clinically significant.
Colorectal cancer. Intravenous ginkgo has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that adding intravenous ginkgo extract (EGb 761 ONC), 350 mg over 30 minutes on days 1-6 of every 3-week cycle to treatment with 5-fluorouracil 500 mg/m2 daily on days 2-6 of every 3-week cycle for 4 courses of treatment, might reduce disease progression in some patients with metastatic colorectal cancer (9872). However, since the study did not include a control group, it is unclear if the effects of treatment were greater than the effects of 5-fluorouracil alone.
Cough. Although there has been interest in using oral ginkgo for cough, there is insufficient reliable information about the clinical effects of ginkgo for this condition.
Depression. It is unclear if oral ginkgo is beneficial in depression. Details: Preliminary clinical research in elderly patients shows that taking an unknown dose of a specific ginkgo extract (Harbin HaoBo Pharmaceutical Co., Ltd.) in conjunction with citalopram 20 mg daily for 12 weeks improves depression scores by 75% or more in an additional 3% of patients when compared with taking citalopram alone. Taking ginkgo extract with citalopram also produces a faster onset of action when compared to taking citalopram alone. However, it is not clear if these improvements are clinically significant (98811). A meta-analysis of 21 mainly Chinese studies shows that adding ginkgo preparations in various doses to conventional treatment for depression improves Hamilton Depression Scale scores and increases serotonin levels when compared with conventional treatment alone, but there is high heterogeneity in the results (113779).
Diabetes. Research on the use of oral ginkgo in type 2 diabetes is conflicting. Details: In patients with uncontrolled type 2 diabetes taking metformin, preliminary clinical research shows that taking ginkgo extract (EGb 761) 120 mg for 90 days reduces glycated hemoglobin (HbA1c) levels from an average of 8.6% at baseline to an average of 7.7%. Fasting serum glucose and insulin were also reduced, when compared with baseline, by approximately 20% and 28%, respectively (103574). However, a meta-analysis of 7 clinical studies shows that taking ginkgo is associated with an increase in HbA1c levels, with no effect on fasting serum glucose levels. The only beneficial effect identified in this analysis was an increase in high density lipoprotein (HDL) cholesterol levels (105529). Another meta-analysis of mainly Chinese studies, shows that adding various ginkgo preparations to metformin for 1-3 years does not improve fasting serum glucose, HbA1c, or cholesterol levels, but does reduce blood viscosity and hematocrit while improving dorsalis pedis artery blood flow and ankle brachial index, suggesting a beneficial effect on peripheral arterial disease associated with diabetes (113780).
Diabetic retinopathy. It is unclear if oral ginkgo is beneficial for this condition. Details: Preliminary clinical research shows that taking a specific ginkgo leaf extract called EGb 761 120 mg daily orally for 6 months improves measures of color vision when compared with placebo in patients with early diabetic retinopathy (6175).
Dry eye. Ginkgo eye drops have only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A nonblinded clinical study in adults undergoing cataract surgery and receiving standard treatment shows that applying a specific, preservative-free eye drop (Trium Free; SOOFT) containing ginkgo extract 0.05% and hyaluronic acid 0.15%, three times daily, beginning the first day after surgery and continued for 4 weeks, reduces dry eye severity and symptoms when compared with standard treatment alone. After 4 weeks, 50% of patients in the standard treatment group reported dry eye symptoms, compared with 16% of patients using ginkgo (108609). The effects of ginkgo in patients with chronic dry eye or dry eye caused by other factors is unclear.
Dyslexia. It is unclear if oral ginkgo is beneficial for dyslexia in children. Details: Preliminary clinical research shows that taking a standardized ginkgo leaf extract (EGb 761) 80 mg daily for an average of 34 days can help reduce dyslexia when compared to baseline in children aged 5-16 years (87790). The validity of this finding is limited by the lack of a comparator group.
Fibromyalgia. Oral ginkgo has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking tablets containing ginkgo extract (Bio-Biloba, Pharma Nord) 200 mg daily in conjunction with capsules containing coenzyme Q10 (Bio Quinone Q10, Pharma Nord) 200 mg daily orally for 84 days improves patient-reported quality of life, such as physical fitness levels, emotional feelings, social activities, overall health, and pain, when compared to baseline (17716). The validity of these findings is limited by the lack of a comparator group.
Gastric cancer. It is unclear if oral ginkgo is beneficial in gastric cancer. Details: Preliminary clinical research shows that taking carbohydrates from the outer layer of ginkgo fruit 250 mg orally twice daily for 30 days may reduce tumor size in patients with gastric cancer when compared with pre-treatment (87742).
Glaucoma. It is unclear if oral ginkgo is beneficial in glaucoma. Details: A small observational study has found that taking ginkgo leaf extract 80 mg twice daily for up to 12.3 years is associated with reduced progression of visual field damage in patients with normal tension glaucoma (87900). Furthermore, a small clinical study in patients with normal tension glaucoma shows that taking ginkgo leaf extract 40 mg three times daily for up 4 weeks might improve pre-existing damage and reduce the progression of damage to the visual field (10378). However, conflicting evidence exists. Another small study in patients with newly diagnosed normal tension glaucoma shows that taking a specific ginkgo extract (Ginaton, Dr. Willmar Schwabe Pharmaceuticals) 40 mg three times daily for 4 weeks does not improve damage or progression of glaucoma (89707). Reasons for the discrepancies may be due to the formulation of ginkgo leaf extract used or the severity of glaucoma at baseline.
Hemorrhoids. Oral ginkgo has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study shows that taking a combination of ginkgo extract, troxerutin, and heptaminol for one week may decrease some symptoms of hemorrhoids, including bleeding, pain, feelings of incomplete defecation, and discharge when compared to baseline (87751). The validity of these findings is limited by the lack of a comparator group. Additionally, it is unclear if these effects are due to ginkgo, other ingredients, or the combination.
Hypercholesterolemia. Although there has been interest in using oral ginkgo for hypercholesterolemia, there is insufficient reliable information about the clinical effects of ginkgo for this condition.
Intestinal parasite infection. Although there has been interest in using oral ginkgo for intestinal parasite infection, there is insufficient reliable information about the clinical effects of ginkgo for this condition.
Lyme disease. Although there has been interest in using oral ginkgo for cognitive dysfunction associated with Lyme disease, there is insufficient reliable information about the clinical effects of ginkgo for this condition.
Migraine headache. Oral ginkgolide B, a constituent of ginkgo biloba extract, has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that ginkgolide B (BN52021), a constituent of ginkgo extract, along with coenzyme Q10, riboflavin, and magnesium, taken twice daily for 3 months, may help prevent migraines in school-aged children when compared to baseline (44181,87876). Also, a specific product (Migrasoll, Pharmaval Srl) containing ginkgolide B 60 mg, coenzyme Q10 11 mg, and vitamin B2 8.7 mg, taken twice daily for 4 months, may help prevent migraines in females when compared to baseline (44103). The validity of the findings from these studies is limited by the lack of a comparator group.
Ovarian cancer. It is unclear if oral ginkgo is beneficial in preventing ovarian cancer. Details: Epidemiological evidence found that use of ginkgo extract for 6 months is associated with a decreased risk for developing ovarian cancer (14813).
Pancreatic cancer. Intravenous ginkgo has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that adding a specific intravenous ginkgo extract called EGb 761 ONC 350 mg on days 1-6 of every 3-week cycle to treatment with 5-fluorouracil 500 mg/m2 daily on days 2-6 of every 3-week cycle until disease progression might slow the progression of pancreatic cancer in some patients (87699). However, since the study did not include a control group, it is unclear if the effects of treatment were greater than the effects of 5-fluorouracil alone.
Parkinson disease. It is unclear if oral ginkgo is beneficial for drug-induced Parkinsonism. Details: Preliminary clinical research in patients with psychiatric diagnoses treated with antipsychotic drugs shows that taking dried ginkgo extract, 80 mg three times daily orally for 3 months, reduces resting tremors, rigidity, bradykinesia, and the severity of motor symptoms when compared with placebo (112945).
Peripheral arterial disease (PAD). It is unclear if oral ginkgo is beneficial in PAD. Details: Some small clinical studies show that taking a specific ginkgo leaf extract called EGb 761 (Dr. Willmar Schwabe Pharmaceuticals and Ipsen) orally increases pain-free walking distance in patients with Fontaine's IIb peripheral arterial occlusive disease and intermittent claudication and might decrease overall peripheral vascular disease (PVD) event incidence, such as surgery or amputation, in elderly patients (3461,6211,6212,6213,17402). Significant benefit has been found with doses as low as 120-160 mg daily (6211). However, there is some evidence that a higher dose of 240 mg daily might be more beneficial in some patients (3461,6212). Although some research is positive, other research shows that taking a specific ginkgo leaf extract called EGb 761 (Dr. Willmar Schwabe Pharmaceuticals) 300 mg daily for 16 weeks does not significantly improve maximum treadmill walking time when compared with placebo in patients with PAD (16638). A reason for this discrepancy may be due to the duration of treatment. A meta-analysis of clinical research shows that taking ginkgo leaf extract does not improve maximum treadmill walking distance when compared with placebo in patients with Fontaine stage II PVD and intermittent claudication when administered for 6-8 weeks or 12-16 weeks, but does increase maximum treadmill walking distance by about 85 meters when administered for at least 24 weeks (89440).
Pulmonary hypertension. It is unclear if intravenous ginkgo is beneficial in patients with pulmonary hypertension and cor pulmonale. Details: A meta-analysis of 28 small, low-quality clinical trials, including nearly 2500 Chinese patients with pulmonary hypertension and cor pulmonale, shows that intravenous administration of ginkgo leaf extract plus dipyridamole 15-40 mL daily for 1-4 weeks along with conventional therapy increases the total effective rate by 28% and improves various blood gas measures when compared with conventional therapy alone (102881). It is unclear if these effects are due to ginkgo, dipyridamole, or the combination. Large, high-quality clinical trials are needed to confirm these results.
Quality of life. Some preliminary clinical studies suggest that oral ginkgo might improve quality of life in elderly individuals. Details: A large survey-based study shows that taking a standardized ginkgo leaf extract called LI 1370 (Lichtwer Pharma) 120 mg daily for 4-10 months may improve quality of life measures such as activities of daily living, mood, sleep, and alertness in elderly individuals when compared with control (87715,87760).
Radiation exposure. It is unclear if intravenous ginkgo is beneficial in people who have been exposed to radiation. Details: Preliminary clinical research shows that taking a standardized ginkgo leaf extract called EGb 761 (Tanakan, Ipsen) 120 mg daily for 2 months might reduce clastogenic factors in the blood of patients who had previously been irradiated. The reduction in clastogenic factors was observed for at least 7 months after initiation of ginkgo in most patients (17719).
Radiation dermatitis. Topical ginkgo has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying a specific cream product (Radioskin 2, Herbalab di Perazza Massimiliano Company) containing ginkgo extract, Aloe vera, and metal esculetina, along with another specific cream product (Radioskin 1) containing alga atlantica and ethylbisiminomethylguaicolo manganese cloruro, may improve skin hydration and reduce skin toxicity associated with radiation therapy in patients with breast cancer (89727). The creams were applied topically 2-3 times daily at least 3 hours before and after radiation treatment from 15 days prior to radiation until one month after completion. It is unclear if these effects are due to ginkgo, other ingredients, or the combination.
Raynaud syndrome. Evidence for the use of oral ginkgo for flare reduction is conflicting. Details: Some research shows that taking a standardized ginkgo extract (Seredrin, Health Perception Ltd.) 120 mg orally three times daily for 10 weeks can decrease the number of painful attacks per week in patients with Raynaud syndrome (11363). However, other research shows that ginkgo extract is no different than placebo in decreasing the number of attacks in these patients (87888). Also, another study shows that taking ginkgo extract 120 mg daily is less effective than nifedipine SR 30 mg daily orally in decreasing Raynaud syndrome flares (87818).
Scabies. Although there has been interest in using topical ginkgo for scabies, there is insufficient reliable information about the clinical effects of ginkgo for this condition.
Seasonal affective disorder (SAD). It is unclear if oral ginkgo is beneficial for SAD. Details: One small clinical study shows that taking ginkgo leaf extract orally does not seem to prevent winter depression symptoms in patients with SAD when compared with placebo (8233).
Sexual dysfunction. It is unclear if oral ginkgo is beneficial for sexual dysfunction in females. Details: Some clinical research shows that taking a ginkgo leaf extract 300 mg daily for 8 weeks does not significantly improve sexual function in females with sexual arousal disorder when compared with placebo (16640). However, 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 self-report sexual dysfunction (46933). It is unclear if these effects are due to ginkgo, other ingredients, or the combination.
Venous thromboembolism (VTE). Although there has been interest in using oral ginkgo for thrombosis, there is insufficient reliable information about the clinical effects of ginkgo for this condition.
Vitiligo. It is unclear if oral ginkgo is beneficial for reducing vitiligo progression. Details: Preliminary clinical research shows that taking a specific ginkgo extract (Ginkgo Plus, Seroyal) 120 mg in two divided doses daily for up to 6 months reduces the progression of vitiligo vulgaris and lesion size when compared to baseline (17718,87728). The validity of these findings is limited by the lack of a comparator group.
Wound healing. Although there has been interest in using topical ginkgo for healing of skin sores or chilblains, there is insufficient reliable information about the clinical effects of ginkgo for these conditions. More evidence is needed to rate ginkgo for these uses.

Burns. Topical gotu kola seems to improve the rate of burn healing. Details: Clinical research shows that applying a cream containing gotu kola 3% once daily to second degree burns increases the rate of re-epithelialization and complete healing by about 7 days when compared with silver sulfadiazine (SSD) 1% cream. Gotu kola cream also seems to reduce dryness, itching, irritation, and scar severity when compared with SSD (97027). Other research in adults with second degree burns shows that applying a gauze dressing containing gotu kola 5% and aloe 2.5%, covered with absorbent cotton wool and changed every 3 days, reduces time to healing by 1.5 days and length of hospital stay by 1.7 days when compared with the use of a gauze dressing containing chlorhexidine acetate 0.5% (97028).
Venous insufficiency. Oral gotu kola seems to improve symptoms of venous insufficiency. Details: Clinical research shows that taking gotu kola or a specific extract of gotu kola (Centellase) 60-180 mg daily orally for 4-8 weeks seems to improve measures of circulation and decrease symptoms such as edema in patients with venous insufficiency (6887,9786,11063,11064,11066,11070,52894,52909).

POSSIBLY INEFFECTIVE

Cognitive function. Oral gotu kola does not seem to be beneficial for cognitive function. Details: A meta-analysis of a small number of generally moderate quality clinical trials shows that taking a single dose of gotu kola, alone or in combination with other ingredients, does not improve cognitive function when compared with placebo (105334). In one study, gotu kola was taken in combination with ginkgo and docosahexaenoic acid (DHA) for 4 months by healthy, cognitively intact older adults (52880).
Radiation dermatitis. Topical gotu kola does not seem to reduce symptoms of radiation dermatitis. Details: Clinical research in females undergoing radiotherapy for breast cancer shows that applying a cream containing gotu kola extract 7% once daily during and up to 4 weeks following radiotherapy does not reduce the severity of dermatitis when compared with no treatment or applying a moisturizing cream (102792).

Aging skin. Oral gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in healthy, middle-aged females shows that applying a topical emulsion containing extracts of gotu kola 3% and Indian gooseberry 3% twice daily for 60 days improves skin hydration, some measures of skin wrinkles, and elasticity of the cheek (but not the eye) when compared with placebo (111571). It is unclear if these effects are due to gotu kola, Indian gooseberry, or the combination.
Alzheimer disease. Although there is interest in using oral gotu kola for Alzheimer disease, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
Anal fissures. It is unclear if topical gotu kola is beneficial for anal fissures. Details: In patients with chronic anal fissures who are using standard dietary and hygiene treatments, preliminary clinical research shows that taking gotu kola extract 60 mg twice daily for 8 weeks and locally applying an ointment containing gotu kola does not reduce the mean time to bleeding cessation when compared with standard treatments alone. However, pain may be modestly improved. Also, gotu kola was less effective than an unspecified flavonoid mixture used both orally and topically (105332).
Atherosclerosis. It is unclear if oral gotu kola is beneficial for slowing the progression of atherosclerotic plaques. Details: Some preliminary clinical research shows that taking gotu kola extract 60 mg orally three times daily for 12 months helps stabilize low-density atherosclerotic plaques when compared with placebo (11062,11069). Gotu kola has also been evaluated in combination with a specific maritime pine bark product (Pycnogenol, Horphag Research). A non-randomized clinical trial shows that taking gotu kola 225 mg and Pycnogenol 150 mg in two divided doses daily for 3 months reduces plaque height and length and increases plaque echogenicity and stability when compared to control (97030). Another non-randomized clinical study in adults with atherosclerotic plaques and no other cardiovascular risk factors shows that taking gotu kola extract 100 mg and Pycnogenol 100 mg daily for up to 4 years reduces plaque progression and increases plaque echogenicity when compared with Pycnogenol alone or no treatment at all. Taking gotu kola and Pycnogenol is also associated with a reduced rate of clinical vascular events, including angina, myocardial infarction, minor transient ischemic attacks (TIAs), and minor strokes when compared with taking Pycnogenol alone or receiving no treatment at all (97029). It is unclear how these outcomes would compare to the use of gotu kola alone.
Attention deficit-hyperactivity disorder (ADHD). Although there is interest in using oral gotu kola for ADHD, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
Atopic dermatitis (eczema). Topical gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that applying an ointment containing 5% each of the extracts of heart's ease, gotu kola, and Oregon grape twice daily for 4 weeks does not improve eczema when compared with a base cream. However, patients with eczema on skin exposed to cold weather might experience some improvement (67372).
Depression. Although there is interest in using oral gotu kola for depression, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
Diabetic foot ulcers. Topical gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In patients with deep diabetic foot ulcers, preliminary clinical research shows that applying a cream (WH-1 cream) containing 1.25% of gotu kola and Plectranthus amboinicus extracts in a 4:1 ratio twice daily for 2 weeks after surgical debridement is as effective as the use of a standard hydrocolloid fiber wound dressing for improving wound size. However, when compared with baseline, changes in wound size were not statistically significant (105335).
Diabetic microangiopathy. It is unclear if oral gotu kola is beneficial for diabetic microangiopathy. Details: Preliminary clinical research shows that taking gotu kola extract 60 mg orally twice daily for 6-12 months helps increase measures of circulation and decrease edema in patients with diabetic microangiopathy (11065,11068,52917).
Dry skin. It is unclear if topical gotu kola is beneficial for dry skin. Details: In patients with dry skin associated with type 2 diabetes, clinical research shows that topical application with 0.25 grams of a gotu kola 1% ointment twice daily, either alone or with oral gotu kola 1100 mg twice daily, for 28 days does not improve dry skin when compared with placebo. However, in a sub-group of patients with well-controlled diabetes, the combination of oral and topical gotu kola modestly improved dry skin (105329). Additionally, a small clinical study in individuals with dry skin due to working with synthetic and natural dyes shows that application of a gotu kola 2% ceramide-based cream to the hands and arms twice daily for 4 weeks improves skin barrier hydration, as measured by hydration of the stratum corneum and skin acidity, when compared to baseline. These improvements were similar to those seen with a ceramide 5% cream (109554). As the gotu kola cream was formulated with ceramide, it is unclear if these findings are due to gotu kola, ceramide, or the combination.
Epilepsy. Although there is interest in using oral gotu kola for epilepsy, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
Generalized anxiety disorder (GAD). It is unclear if oral gotu kola is beneficial for GAD. Details: In patients with GAD, preliminary clinical research shows that taking gotu kola extract 500 mg twice daily for 60 days reduces symptoms of anxiety, depression, and stress by 22% to 26% when compared with baseline (105333). The validity of these findings is limited by the lack of a comparator group.
Hemorrhoids. It is unclear if topical gotu kola is beneficial for hemorrhoids. Details: Preliminary clinical research in patients with chronic hemorrhoids, as well as patients with acute symptoms following a hemorrhoidectomy or surgical treatment for hemorrhoidal thrombosis, shows that taking gotu kola extract (Centella complex) 60 mg twice daily for 15 weeks and locally applying an ointment (Proctocella) containing gotu kola, arnica, and aloe, in conjunction with standard treatments, does not reduce the mean time to bleeding cessation when compared with standard treatments alone. Anal irritation was modestly improved in the patients with chronic hemorrhoids and in those undergoing treatment for hemorrhoidal thrombosis, but not in those that had undergone a hemorrhoidectomy (105336).
Herpes zoster (shingles). Although there is interest in using oral gotu kola for shingles, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
Hypertension. It is unclear if oral gotu kola is beneficial for hypertension. Details: Preliminary clinical research in patients with hypertension shows that drinking a tea made by boiling gotu kola 4 grams in 250 mL water three times daily for 3 days modestly reduces systolic and diastolic blood pressure when compared with baseline. After consuming the tea, about 40% of patients had normal or high-normal systolic blood pressure and 77% had optimal or normal diastolic blood pressure, compared with 0% and 45%, respectively, prior to consumption (105330). The validity of these findings is limited by the lack of a comparator group.
Hypertrophic scars. Topical gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research shows that topical use of a specific silicone gel (Bangkok Botanica) containing 15% extracts of gotu kola, onion, aloe, and paper mulberry, starting 2 weeks after surgery and continuing for 6 months, moderately improves the height and pliability of the post-surgical hypertrophic scar when compared with a silicone placebo gel. There was no effect on pigmentation or vascularity (102793). It is unknown whether any benefit is related to gotu kola, other ingredients, or their combination.
Idiopathic interstitial pneumonia. Oral gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small observational registry study in males less than 65 years old with idiopathic interstitial pneumonia has found that taking a specific gotu kola extract (Centellicum; Horphag Research) 225 mg three times daily in combination with a standardized extract of maritime pine bark (Pycnogenol, Horphag Research) 50 mg three times daily for 8 months is associated with a modest improvement in Karnofsky Performance Scale scores and a reduction in fatigue when compared with pirfenidone (108862). However, the validity of these findings is limited by the unblinded, non-randomized nature of the study.
Keloids. It is unclear if oral or topical gotu kola are beneficial for keloids. Details: There is some early evidence that applying a specific extract of gotu kola (Madecassol) topically might help reduce keloids and hypertrophic scarring (13558). Gotu kola has also been taken orally for keloids. Preliminary clinical research in patients at high risk for keloids shows that taking a specific extract of gotu kola (Centellicum, Horphag Research Ltd) 450 mg daily for 4 weeks starting on the second week after surgery seems to improve scar homogeneity and regularity (99756). However, the reliability of these results is limited because patients in this study were not randomized or blinded to different interventions.
Laser skin resurfacing. It is unclear if topical gotu kola is beneficial for recovery from laser skin resurfacing. Details: A small clinical trial shows that applying a gel containing gotu kola extract (ECa 233) 0.05% four times daily for 7 days, then twice daily for 3 months, improves wound healing following laser resurfacing for facial acne. Redness returned to baseline levels by day 7, in contrast to day 28 on the side treated with a placebo gel. The general wound appearance and crusting were also improved on the side on which the gotu kola extract gel was applied (102794).
Osteoarthritis. Topical gotu kola has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A large, single-blind clinical study in adults with knee osteoarthritis causing moderate pain shows that applying a specific cream (TMP-4) containing extracts of gotu kola leaf, sesame seed, soybean, and mangosteen peel four times daily for 4 weeks provides similar improvement in pain scores when compared with diclofenac 1% gel. Topical TMP-4 cream also seems to improve knee stiffness, stair climbing, and mobility similarly to diclofenac gel. However, patient impression of overall improvement was higher with diclofenac (110128). The validity of this study is limited by inadequate blinding.
Scarring. It is unclear if topical gotu kola is beneficial for scarring or tenderness from scarring. Details: Preliminary clinical research in patients without a history of keloid formation suggests that applying a specific cream (Alpha Centella, not available in the US) containing gotu kola and Bulbine frutescens extracts twice daily for 6-8 weeks following suture removal might help to reduce scarring (11072). Also, a large clinical study in adults who underwent carpal tunnel release surgery shows that applying gotu kola cream 1% three times daily for 6 months after suture removal marginally improves self-reported scar tenderness pain when compared with control, and modestly improves scarring scores when compared to baseline (112425). However, the interpretation of these findings is limited by patient-reported outcomes and insufficient validity of the scar scoring tool in this population.
Skin grafts. Although there is interest in using topical gotu kola for skin graft recovery, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
Stretch marks (striae distensae). It is unclear if oral gotu kola is beneficial for stretch marks; topical gotu kola has only been evaluated in combination with other ingredients. Details: Preliminary clinical research in females with stretch marks shows that taking a specific extract of gotu kola (Centellicum, Horphag Research Ltd) 225 mg three times daily for 6 weeks increases skin thickness, elasticity, and perfusion when compared with a stretch mark minimizer cream (Clarins) and regular control cream (99757). The validity of these results is limited by the fact that patients were not randomized or blinded to the different interventions. Gotu kola has also been evaluated topically in combination with other ingredients. Preliminary clinical research shows that applying a specific mixture of gotu kola, vitamin E, and collagen-elastin hydrolysates in a cream (Trofolastin, not available in the US) daily during the second and third trimesters reduces stretch marks when compared with a placebo cream (13559). Another small clinical study shows that applying a specific mixture of gotu kola, vitamin E, essential fatty acids, hyaluronic acid, elastin, and menthol in an ointment (Verum, not available in the US) helps decrease the formation of stretch marks during pregnancy when compared with placebo (11073). Other preliminary clinical research in patients without previous striae shows that applying a specific formula containing hydroxyprolisilane C, rosehip oil, gotu kola triterpenes, and vitamin E (Velastisa Antiestrías, ISDIN) twice daily, beginning at week 10-14 and continuing throughout pregnancy, decreases the severity of both new and old stretch marks and the incidence of stretch marks when compared with placebo (92507). It is unclear if the effects seen in these studies are due to gotu kola, other ingredients, or the combinations.
Systemic lupus erythematosus (SLE). Although there is interest in using oral gotu kola for SLE, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
Tonsillitis. Although there is interest in using oral gotu kola for tonsillitis, there is insufficient reliable information about the clinical effects of gotu kola for this condition.
Venous thromboembolism (VTE). It is unclear if oral gotu kola is beneficial for VTE prevention. Details: Preliminary clinical research shows that gotu kola decreases edema and improves measures of circulation in patients traveling on airplanes for more than 3 hours when compared to a control group receiving no treatment (11067). However, it is unknown if these changes reduce the incidence of clots.
Wound healing. Although there is interest in using topical gotu kola for wound healing, there is insufficient reliable information about the clinical effects of gotu kola for this purpose.
Wrinkled skin. It is unclear if topical gotu kola is beneficial for wrinkled skin. Details: Small, low-quality studies in healthy adults suggest that topical formulations of gotu kola extract or the constituent asiaticoside 0.1% or 0.2% applied 1-3 times daily have shown modest benefit for wrinkled skin. Cream or gel formulations were used for 12 weeks for periorbital wrinkles and a lipstick was used for 8 weeks for lip wrinkles. However, the extent of benefit is not clear and meta-analyses are limited to a very small number of studies with varied comparator groups, including placebo, vehicle, tretinoin 0.02%, and Pueraria mirifica extract (106639). More evidence is needed to rate gotu kola for these uses.

OATS (organic Oats (Avena sativa) milky seed extract)

LIKELY EFFECTIVE

Coronary heart disease (CHD). A diet high in soluble fiber, such as that found in oats, reduces the risk of CHD. Details: Clinical research shows that a diet containing foods high in fiber, such as oats, oat bran, or whole oat flour, reduces the risk of CHD (2737,4960,4962,4963,4964,4965,4966,4967,4968). In 1993, the US Food and Drug Administration (FDA) approved a health claim stating that consuming at least 3 grams of soluble fiber per day, as part of a diet low in saturated fat and cholesterol, may reduce the risk of CHD (102336). However, clinical studies show that at least 3.6 grams of soluble fiber daily is needed to reduce the risk of CHD (5786,5787,5788,5794,5795,5796).
Dyslipidemia. A diet rich in soluble fiber, such as that found in oats, can reduce cholesterol by a moderate amount. Details: Oats, oat bran, and other soluble fibers can modestly reduce total and low-density lipoprotein (LDL) cholesterol, especially when consumed as part of a diet low in saturated fat. Consuming 56-150 grams of whole oat products such as oatmeal and oat bran, containing 3.6-10 grams of soluble fiber daily, can significantly lower total and LDL cholesterol levels. For each gram of soluble fiber consumed, total cholesterol decreases by about 1.4 mg/dL and LDL by about 1.2 mg/dL. Eating 3-10 grams of soluble fiber daily can reduce total cholesterol by about 4-14 mg/dL (4976,4977,5786,5788,5792,5794,5795,8521,107749,113488,113495). For example, eating 3 bowls of oatmeal (28 gram servings) daily, providing a total of 3 grams of soluble fiber daily, can decrease total cholesterol by about 5 mg/dL (5788). However, consuming more than 10 grams of soluble fiber daily doesn't seem to increase effectiveness (5788). A meta-analysis comparing the effects of oats and isolated beta-glucans shows that both products similarly impact lipid profiles, suggesting that the bioactive component of oats are beta-glucans (113488). Oat bran products, such as oat bran muffins and oat bran flakes, may vary in their ability to lower cholesterol, depending on the total soluble fiber content and other dietary variables (6188). Whole oat products might be more effective for lowering LDL and total cholesterol than foods containing oat bran plus soluble fiber (10145). Although oats are shown to lower total and LDL cholesterol, a meta-analysis and a small clinical study in adults with and without dyslipidemia shows that consuming oatmeal or oat products does not reduce triglycerides or increase high-density lipoprotein (HDL) cholesterol when compared with controls (113488,113495).

Diabetes. A diet rich in whole grains, such as oats, may help prevent diabetes or improve blood glucose control in patients with type 1, type 2, or gestational diabetes. Details: Population research shows that for every 16 gram daily serving of whole grains, including oats, there is a 7% to 11% lower risk of developing type 2 diabetes (100622). There is also evidence that consuming oats can decrease blood glucose and insulin levels, as well as lipid levels, in patients with diabetes. The glycemic effects of oats depend on the level of processing of the oat products. Consuming intact oat kernels or thick-cut oats (>0.6 mm) reduces postprandial blood glucose and insulin, but consuming thin-cut, or "quick", oats has no effect (105536). Clinical research shows that consuming oats and oat bran for 4-8 weeks decreases pre-prandial blood glucose, 24-hour plasma glucose, glycated hemoglobin (HbA1c), insulin levels, and low-density lipoprotein (LDL) cholesterol in people with type 2 diabetes (4980,4982,6266,103345). Various doses have been used, including 3 grams of soluble fiber daily, or bread providing 34 grams of total fiber daily (9 grams of soluble fiber) (4961,4980). Additional clinical research in obese adults with type 2 diabetes shows that eating whole grain oats 50-100 grams daily in place of other carbohydrates reduces postprandial blood glucose by 19-27 mg/dL when compared with other carbohydrates in a healthy diet. After 1 year, the groups consuming 50 grams and 100 grams of oats had an additional 0.48% and 0.64% reduction in HbA1c, respectively, when compared with the regular healthy diet group (97520). There is also some evidence that consuming oats 50 grams daily, containing 25 grams of soluble fiber, might be more effective for improving glycemic control and decreasing hyperinsulinemia than the standard moderate fiber diet recommended by the American Diabetes Association (ADA) (6266). Oats have also been evaluated in adolescents with type 1 diabetes. One very small clinical study shows that taking 50 grams of a specific oat product (Betaglucare), providing beta-glucans 6 grams, in three divided doses daily for one week is beneficial for glycemic control and variability when compared with a standard diet without beta-glucans or with taking only 25 grams of the product daily. Maximal, mean, and pre- and post-meal blood glucose levels were modestly lower, and minimal blood glucose levels were modestly higher. Most measures of glycemic variability were statistically different, although there were no differences in the duration of hypoglycemia or hyperglycemia between groups (105261). Oats have also been evaluated in patients with gestational diabetes. A randomized, controlled trial shows that taking 30 grams of a specific oat bran product (OAB; Golden Light Cup Company) orally twice daily at lunch and dinner for 4 weeks improves mean fasting blood glucose and two-hour postprandial glucose when compared with a control group. After 4 weeks, the mean fasting blood glucose and 2-hour postprandial glucose in the treatment group were 85 mg/dL and 104 mg/dL, respectively, compared with 93 mg/dL and 117 mg/dL, respectively, in the control group (107751). The validity of this study is limited by the short treatment duration and lack of follow-up.
Gastric cancer. A diet rich in soluble fiber, such as that found in oats, might reduce the risk of gastric cancer. Details: Observational research has found that consuming a diet that includes cereal fiber, such as oats and oat bran, might reduce the incidence of gastric cancer (10435).

POSSIBLY INEFFECTIVE

Colorectal cancer. Regular consumption of oats does not seem to reduce the risk of colorectal cancer. Details: Observational research has found that consuming oat bran or oats orally doesn't seem to reduce the risk of colon cancer. Additionally, consuming fiber, including oat-bran fiber, is not associated with a reduction in the risk for recurrence of colorectal adenomas (4820,5104).

Acne. Although there is interest in using topical oats for acne, there is insufficient reliable information about the clinical effects of oats for this purpose.
Anxiety. Although there is interest in using oral oats for anxiety, there is insufficient reliable information about the clinical effects of oats for this purpose.
Atopic dermatitis (eczema). Topical colloidal oatmeal cream may be beneficial in patients with atopic dermatitis. Details: Preliminary clinical research shows that applying a cream containing colloidal oatmeal 1% daily for 2 weeks moderately reduces the severity of atopic dermatitis when compared with baseline (103344). The validity of this finding is limited by the lack of a comparator group. Other research suggests that colloidal oatmeal may be beneficial when used in combination with topical steroids. Clinical research shows that the benefits obtained from applying an ointment containing fluocinolone 0.025% to the hands for 2 weeks were better maintained in the patients who also used a cream containing colloidal oatmeal 1% during this time period and for an additional 4 weeks when compared with patients using fluocinolone and the cream base without colloidal oatmeal. Quality of life was also improved in the patients using colloidal oatmeal (103340).
Breast cancer. Observational research suggests that regular oatmeal intake may be associated with reduced mortality from breast cancer. Details: Population research in postmenopausal patients has found that those who have eaten 50 grams of oatmeal daily prior to a breast cancer diagnosis have a 20% reduced risk of all-cause mortality in the 7 years following the diagnosis when compared with patients who have not eaten oatmeal. However, no benefit was seen when post-diagnostic oatmeal intakes were examined (103343).
Burns. Although there is interest in using topical oats for burns, there is insufficient reliable information about the clinical effects of oats for this purpose.
Chronic fatigue syndrome (CFS). Although there is interest in using oral oats for CFS, there is insufficient reliable information about the clinical effects of oats for this purpose.
Cognitive function. It is unclear if oral oats are beneficial in healthy adults with mild memory impairment. Details: Preliminary clinical research in healthy middle-aged adults with self-reported memory decline shows that consuming a specific wild green-oats extract (Neuravena, Frutarom) 800 mg as a single dose improves overall speed, but not overall accuracy, of cognitive performance when compared with placebo. However, a higher dose of 1600 mg was ineffective (97519).
Dry skin. It is unclear if applying lotion containing colloidal oat extract improves dry skin to a greater extent than other lotion products. Details: Preliminary clinical research shows that applying a lotion containing colloidal oat extract (Aveeno Active Naturals Skin Relief 24Hr Moisturizing Lotion, Johnson & Johnson) twice daily for 2 weeks improves itchiness, cracking, scaling, dryness, and roughness when compared to baseline in females with dry skin (91458). Additional preliminary clinical research shows that applying a colloidal oatmeal lotion to the legs twice daily for three weeks reduces skin dryness and improves skin integrity when compared to baseline in adults with dry skin (97518). The validity of these findings is limited by the lack of a comparator group.
Exercise-induced muscle soreness. It is unclear if oral oats are beneficial for exercise-induced muscle soreness. Details: A small clinical trial shows that eating two cookies containing oat flour 60 grams daily for 8 weeks reduces muscle soreness 48 or 72 hours after downhill running when compared with baseline (103341).
Fat redistribution syndrome. It is unclear if oral oats are beneficial for fat redistribution syndrome. Details: Consumption of a high fiber diet, including oats, with adequate energy and protein might prevent fat deposition in patients with HIV. A one-gram increase in total dietary fiber may decrease the risk of fat deposition by 7% (12517).
Gallbladder disease. Although there is interest in using oral oats for gallbladder disease, there is insufficient reliable information about the clinical effects of oats for this purpose.
Hypertension. It is unclear if oral oats are beneficial for hypertension. Details: A meta-analysis of 21 clinical studies in healthy adults and those with a variety of metabolic conditions including hypertension shows that consumption of oat products reduces systolic blood pressure (SBP) by 3 mmHg but has no effect on diastolic blood pressure (DBP) when compared with control. Subgroup analysis suggests that consuming oat products reduces SBP by 10 mmHg in patients with hypertension at baseline. An additional subgroup analysis suggests that consuming at least 5 grams of beta-glucan-enriched oats daily or consuming oats for a duration at least 8 weeks reduces SBP and DBP (113494). Observational research has found that consumption of oats as oatmeal or oat cereal does not seem to reduce DBPor SBP in males with minor elevations in blood pressure or patients with dyslipidemia (2956,113495). A randomized, controlled trial in patients with stage 1 hypertension receiving dietary guidance shows that taking 30 grams of oat bran, providing 8.9 grams of dietary fiber, once daily with breakfast or in between meals for 3 months improves various blood pressure measures when compared with dietary guidance alone. After 3 months of treatment, 24-hour maximum SBP and DBP decreased by 14 mmHg and 11 mmHg, respectively, and office SBP and DBP decreased by 15 mmHg and 10 mmHg, respectively. Oat consumption may also have impacted antihypertensive medication use. Two patients in the control group increased doses of antihypertensive medications, whereas 6 patients in the treatment group decreased doses and 1 patient discontinued use (107750). The effect of oral oat bran on patients with stage 2 hypertension or pre-hypertension is unknown.
Irritable bowel syndrome (IBS). Although there is interest in using oral oats for IBS, there is insufficient reliable information about the clinical effects of oats for this purpose.
Metabolic syndrome. Limited research suggests that oats may not be beneficial for metabolic syndrome. Details: Preliminary clinical research in adults with metabolic syndrome shows that adding oat bran 40 grams daily for 6 weeks to a low-calorie diet does not reduce the incidence of metabolic syndrome. Oat bran also does not improve body weight, blood pressure, low-density lipoprotein (LDL) cholesterol, triglycerides, or blood glucose levels when compared with a low-calorie diet alone in patients with metabolic syndrome (103342).
Osteoarthritis. Although there is interest in using oral oats for osteoarthritis, there is insufficient reliable information about the clinical effects of oats for this condition.
Pruritus. Applying oat lotion topically may improve some types of pruritus. Details: Preliminary clinical research shows that applying an oat lotion (Espanol) twice daily for up to 2 weeks can decrease itching intensity by about 20% when compared to baseline in patients with pruritus associated with chronic kidney disease (uremic pruritus). This decrease is similar to the effects of applying vinegar 5% solution or taking hydroxyzine 10 mg orally. However, applying the oat lotion does not appear to decrease the frequency of itching (91457).
Psoriasis. Although there is interest in using topical oats for psoriasis, there is insufficient reliable information about the clinical effects of oats for this purpose.
Rheumatoid arthritis (RA). Although there is interest in using oral oats for RA, there is insufficient reliable information about the clinical effects of oats for this purpose.
Stroke. It is unclear if oral oats are beneficial for reducing the risk of stroke. Details: Population research suggests that consuming oatmeal for breakfast once weekly might reduce the incidence of stroke by a small amount when compared with consuming white bread or eggs for breakfast (103337).
Ulcerative colitis. Oral oats have only been evaluated in combination with other ingredients; their effect when used alone is unclear. Details: Preliminary clinical research shows that taking a specific oat-based product (Profermin, Nordisk Rebalance) containing fermented oat flour, Lactobacillus plantarum, barley malt flour, and lecithin, 250 mL orally twice daily for 8 weeks, reduces disease activity and increases remission in about two-fold more patients with relapsing ulcerative colitis, when compared with treatment with a specific nutritional beverage (Fresubin Original, Fresenius Kabi) (90271).
Wound healing. Although there is interest in using topical oats for wound healing, there is insufficient reliable information about the clinical effects of oats for this purpose. More evidence is needed to rate oats for these uses.

LIKELY EFFECTIVE

Irritable bowel syndrome (IBS). Oral enteric-coated peppermint oil is conditionally recommended by the American College of Gastroenterology (ACG) for the relief of global IBS symptoms, such as abdominal pain. Details: The ACG conditionally recommends the use of peppermint for the relief of global IBS symptoms. This recommendation is based on an available meta-analysis of generally low-quality clinical research (105124). Several clinical trials and meta-analyses show that taking enteric-coated peppermint oil 1-2 capsules orally two to four times daily reduces abdominal pain, distention, flatulence, and bowel movements in patients with IBS. Each capsule provides approximately 0.2 mL of peppermint oil or 180-225 mg peppermint oil. Most trials have used specific products (Colpermin, Tillotts Pharma; Mintoil, Cadigroup; Ibgard, IM HealthScience, Tempocol) (3802,3803,4469,11778,11779,17681,17682,68467,68515,68522)(68603,68604,68605,96360,99493,109980). The most recent meta-analysis to date shows that four patients would need to take peppermint oil to prevent one patient from having persistent IBS symptoms, and seven patients would need to take peppermint oil to prevent one patient from having abdominal pain. However, the individual studies included in the analysis lasted no more than 12 weeks (109980); any long-term effects are unclear. Although most studies have shown benefit for reducing symptoms, some older studies have found no significant effect (11777,11789) or only short-term benefits (68620). Also, a well-designed study shows that taking peppermint oil capsules designed for either small intestinal release (enteric-coated) or ileocolonic release does not increase the number of people with at least a 30% decrease in abdominal pain over a period of 4 weeks, although symptoms are modestly reduced when compared with placebo (102602). Another clinical trial in patients with moderate to severe IBS shows that taking a specific enteric-coated formulation of peppermint oil (Pepogest; Nature's Way) 180 mg three times daily for 6 weeks does not further improve symptom severity when compared with placebo. However, both groups experienced a large improvement on the IBS-Severity Scoring System (IBS-SSS) and the IBS Global Improvement Scale (107955). The validity of these findings is limited due to lost data and inconsistent follow-up; additionally, adverse effects occurred more frequently in the peppermint oil group. The reasons for these negative findings are unclear but may include short treatment durations and the use of different formulations; additionally, IBS is comprised of various subtypes and symptoms that can range in severity and presentation, which may alter treatment response. Some clinical research has also evaluated a specific combination product (Atrantil, KBS Research) containing peppermint leaf, red quebracho extract, and conker tree extract. Taking this product as needed for 2 weeks seems to reduce constipation and bloating when compared to baseline in patients with constipation-predominant IBS (95429,95430). It is unclear if the effects of this product are due to peppermint, the other ingredients, or the combination.

Barium enema-related colonic spasm. Rectal peppermint, as part of barium enema preparations, seems to reduce colonic spasms during examination. Oral peppermint also seems to be beneficial. Details: Rectal use of peppermint oil, added as an ingredient in barium enema preparations, seems to relax the colon during barium enema examination and reduce the percentage of patients who experience colonic spasms by about 25% to 30% (6739,6749,12009). Adding peppermint oil to the barium enema seems to be at least as effective as using systemic scopolamine (Buscopan). Adding peppermint oil to the barium solution also does not seem to impair image quality (12009). Some clinical research also shows that taking peppermint oil orally before the start of a double-contrast barium enema examination decreases spasms and might also increase diagnostic quality (14467).
Chemotherapy-induced nausea and vomiting (CINV). Oral and inhaled peppermint seem to reduce nausea and vomiting in patients with CINV. Details: Clinical research shows that adding peppermint oil, 40 drops in 20 mL water, every 8 hours following chemotherapy treatment to treatment with standard antiemetics reduces the severity of nausea, vomiting, and anorexia by moderate to large amounts over 48 hours when compared with a plain water placebo (105123). The use of peppermint oil aromatherapy has also been investigated. Clinical research shows that adding 2 drops of peppermint oil to a cool, damp washcloth for use on the neck as aromatherapy for about 30 minutes helps relieve chemotherapy-induced nausea by a small amount when compared with a washcloth without peppermint oil (102603). Additional clinical research in patients receiving standard antiemetics after chemotherapy shows that applying one drop of peppermint oil below the nose three times daily for 5 days reduces the severity of nausea and the frequency of nausea, vomiting, and retching by a moderate to large amount when compared with the antiemetics alone. These parameters were not improved following treatment with cisplatin (105122). A meta-analysis of 3 randomized controlled trials in adults receiving chemotherapy also shows that peppermint oil aromatherapy moderately improves nausea and vomiting when compared with control. However, the results of this analysis are limited by heterogenous application methods, doses, and durations of peppermint therapy (114761). In children with acute leukemia, a small clinical study shows that aromatherapy with 2 drops of peppermint oil and 3 drops of lemon oil in 80 mL of water diffused 30 minutes prior to and 2 and 4 hours after chemotherapy once weekly for 4 weeks decreases the severity of nausea, vomiting, and retching, and improves quality of life scores when compared with diffused water or no intervention (112015). The validity of these findings is limited by the use of patient-reported outcomes. Another small clinical trial in children receiving chemotherapy for acute leukemia shows that aromatherapy with peppermint oil 2%, 0.2 mL inhaled over 3 minutes immediately prior to 3 consecutive chemotherapy sessions, added to standard care (e.g. antiemetic medications), reduces overall incidence of nausea by 40%, and improves nausea and vomiting severity scores, when compared with no additional interventions. These results were similar to those receiving Swedish massage prior to chemotherapy sessions (114759).
Dyspepsia. Oral peppermint, in combination with caraway and possibly other ingredients, seems to reduce symptoms of dyspepsia. It is unclear if oral peppermint alone is beneficial. Details: Some clinical research shows that taking specific products containing peppermint and caraway oil (Enteroplant, Dr Willmar Schwabe Pharmaceuticals; Menthacarin, Dr Willmar Schwabe GmbH & Co.) improves quality of life and reduces symptoms of dyspepsia, including feelings of fullness, pain, and mild gastrointestinal spasms (6740,6741,10075,96344,102600). A meta-analysis of three of these clinical studies shows that taking this combination product 2-3 times daily for 4 weeks modestly reduces abdominal pain when compared with placebo (110091). Taking this combination twice daily for 4 weeks also improves postprandial distress syndrome and epigastric pain syndrome, two subtypes of dyspepsia, when compared with placebo (96344). The combination of enteric-coated peppermint oil 90 mg and caraway oil 50 mg appears to be comparable to cisapride for relieving dyspepsia when taken 2-3 times daily for up to 4 weeks (6740,6741,10075). However, most trials investigating this combination are small and/or of overall low quality (102600). A specific combination product containing peppermint leaf (Iberogast, Steigerwald Arzneimittelwerk GmbH) also seems to improve symptoms of dyspepsia. The combination includes peppermint leaf plus clown's mustard plant, German chamomile, caraway, licorice, milk thistle, angelica, celandine, and lemon balm (7049). A meta-analysis of studies using this combination product shows that taking 1 mL orally three times daily over a period of 4 weeks reduces the severity of acid reflux, epigastric pain, cramping, nausea, and vomiting when compared with placebo (13089). A similar combination product containing extracts from peppermint leaf, clown's mustard plant, German chamomile flower, caraway, licorice root, and lemon balm (STW 5-II, Steigerwald Arzneimittelwerk GmbH) 1 mL taken three times daily for up to 8 weeks eliminates gastrointestinal symptoms in 40% more dyspepsia patients when compared with placebo (12724).
Endoscopy-associated adverse effects. Intraluminal peppermint seems to reduce spasticity during an endoscopy. It is unclear if oral peppermint is beneficial for reducing adverse effects related to endoscopy. Details: A meta-analysis of four clinical trials show that peppermint oil, administered orally or intraluminally, reduces the incidence of spasticity by about 41% when compared with placebo in patients undergoing endoscopy, with severe spasticity occurring at about 30% the rate of those taking placebo. However, there was no effect on subjective pain (102604). Individual clinical studies show that intraluminal peppermint oil can reduce both pain and spams in patients undergoing endoscopy (18220,68371,68395,68445,68532). However, there are limitations with this form of administration, including cost and practicality, which has led to interest in the use of oral formulations (104221). Studies evaluating oral extended-release peppermint have been conflicting. While one study shows that a specific extended-release peppermint oil product (Colpermin) 187 mg or 0.2 mL taken orally 4 hours prior to a colonoscopy reduces procedure time, pain, and spasticity (68532), a study using another specific extended-release peppermint oil (IBGard) did not show an effect on colonic spasms, procedure time, or adenoma detection rate when compared with placebo (104221). These differing outcomes may be due to timing of administration. The study that showed benefit administered the treatment 4 hours prior to endoscopy, whereas the study showing no benefit administered the treatment only 1 hour prior. This suggests that extended-release peppermint may need to be administered at least 4 hours prior to the procedure to allow for adequate colonic release (68532,102604,104221).
Nipple fissures. Topical peppermint seems to reduce cracked skin and pain in the nipples due to breastfeeding. Details: Clinical research shows that topical application of peppermint oil in gel or water reduces cracked skin and pain in the nipple area from breastfeeding when compared with using placebo, lanolin, or the expressed breast milk technique (68454,68462). Other research shows that applying peppermint oil in cream immediately after breastfeeding for 2 weeks decreases pain and trauma in the nipple area similarly to the topical application of dexpanthenol or lanolin (96365).
Pressure ulcers. Topical peppermint seems to reduce the risk of pressure ulcers. Details: Clinical research in bedridden patients shows that prophylactic application of a topical gel containing peppermint oil 0.2% three times daily for up to 14 days results in pressure injuries in about 23% of patients compared with 77% of those given a placebo gel (102605).
Tension headache. Topical peppermint seems to relieve tension headaches. Details: Clinical research shows that topical application of peppermint oil 10% relieves tension headaches when compared with placebo (3801,6190).

Abdominal pain. Although there has been interest in using oral peppermint for abdominal pain, there is insufficient reliable information about the clinical effects of peppermint for this condition.
Anxiety. It is unclear if inhaled peppermint oil is beneficial for reducing anxiety. Details: A clinical trial in patients presenting to the emergency department for an acute coronary syndrome event shows that placing 3 drops of peppermint oil on a cotton ball and inhaling for 1 hour improves anxiety and respiratory rate when compared with baseline or placebo (107958). Due to the single-dose nature of this study, the effects of repeated inhalation of peppermint oil are unclear.
Athletic performance. It is unclear if oral peppermint oil is beneficial for athletic performance. Details: Preliminary clinical research in trained adult runners shows that taking peppermint essential oil, 0.05 mL diluted in 500 mL of water, orally once 30 minutes before exercise improves running time to exhaustion by 11% when compared with placebo (112742). Another very small clinical study in elite soccer athletes shows that use of a specific peppermint essential oil (doTERRA), 1 drop rubbed into hands and inhaled with 5 deep breaths, does not improve jump performance metrics when compared with placebo (114760).
Breast cancer-related hot flashes. It is unclear if topical peppermint is beneficial for reducing hot flashes in patients with breast cancer. Details: Preliminary clinical research shows that using a spray containing a combination of peppermint and neroli hydrolat does not alleviate hot flashes in most patients receiving chemotherapy for breast cancer when compared with using a plain water spray (68481).
Cognitive function. It is unclear if inhaled peppermint oil is beneficial for improving cognitive function. Details: Preliminary clinical research shows that inhalation of peppermint oil slightly improves memory and the performance of cognitive tasks such as typing, alphabetization, and ordering, but not attention and speed of task completion, when compared with control (56954,68416,68466).
Common cold. Although there has been interest in using oral, topical, or inhaled peppermint for the common cold, there is insufficient reliable information about the clinical effects of peppermint for this condition.
Dental plaque. Topical peppermint has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that rinsing the mouth for one minute with 10 mL of a specific combination product (HiOra, Himalaya Herbal Healthcare) containing peppermint oil and numerous other ingredients twice daily for two days reduces plaque index or plaque area when compared with placebo; however, it was not as effective as chlorhexidine 0.2% solution (68530). It is unclear if these effects are due to peppermint oil, other ingredients, or the combination.
Diffuse esophageal spasm. It is unclear if oral peppermint oil is beneficial for diffuse esophageal spasm. Details: A small exploratory study in adults with diffuse esophageal spasm shows that drinking a solution of peppermint oil, 5 drops in 10 mL of water, can resolve esophageal contractions when compared with baseline (13415). The validity of this finding is limited by the lack of a comparator group.
Dysmenorrhea. It is unclear if oral peppermint oil is beneficial for reducing menstrual pain. Details: Preliminary clinical research shows that taking three capsules of peppermint oil (Colpermin; Tillotts Company or Razak company) daily for 3 days, starting on the first day of menstruation, is as effective as mefenamic acid 250 mg three times daily for reducing pain, and more effective for reducing nausea and vomiting, associated with dysmenorrhea. However, mefenamic acid was more effective for reducing bleeding and analgesic use (105125).
Fatigue. It is unclear if inhaled peppermint oil improves fatigue in patients with cardiac disease. Details: A clinical trial in hospitalized patients with various forms of cardiac disease shows that placing 3 drops of peppermint oil on a cotton ball and inhaling for 20 minutes nightly for 7 days improves fatigue scores when compared with placebo. These improvements were similar to those seen with lavender oil inhalation. Fatigue scores decreased by 24 and 21 points in the peppermint and lavender groups, respectively, compared with a 2-point reduction in the placebo group (107959). The validity of these findings is limited due to the short duration of treatment.
Halitosis. Peppermint has only been evaluated in combination with other ingredients as a mouthwash; its effect when used alone is unclear. Details: Preliminary clinical research shows that rinsing the mouth with a specific combination of tea tree oil, peppermint, and lemon essential oil once for three minutes improves breath smell when compared with placebo or benzydamine hydrochloride (19177). Other preliminary clinical research in elderly adults with dementia who require oral care assistance shows that cleaning the mouth with a mixture of peppermint oil, tea tree oil, and lemon essential oils diluted to 0.5%, applied via gauze, twice daily for 7 days improves halitosis scores and oral condition scores when compared with placebo (112957).
Insomnia. It is unclear if inhaled peppermint oil is beneficial for insomnia. Details: Preliminary clinical research in cancer patients shows that receiving aromatherapy as three drops of peppermint oil applied to a cotton ball and attached to the collar for 20 minutes at bedtime for one week improves sleep when compared with baseline. However, it seems to be no better than using lavender oil aromatherapy or using a control of lavender oil 1% (103063).
Menopausal symptoms. It is unclear if inhaled peppermint oil is beneficial for menopausal symptoms. Details: Preliminary clinical research in adults with menopausal symptoms shows that receiving aromatherapy as 2 drops of peppermint oil with upper extremity massage and for 30 minutes twice weekly for 4 weeks moderately improves menopause symptom scores, including both somatic symptoms and urogenital symptoms, when compared with placebo (112745).
Migraine headache. It is unclear if intranasal or inhaled peppermint oil is beneficial for migraine headache. Details: Preliminary clinical research shows that using 1-2 doses of intranasal peppermint oil 1.5% (Poursina Company) at the start of migraine pain is as effective as intranasal lidocaine 4%, and more effective than placebo, for reducing migraine headache intensity. Approximately 42% of those using peppermint oil indicated a high level of headache reduction, compared with 42% of those using lidocaine and 5% of those using placebo. Also, pain relief was felt within 5 minutes in more patients using peppermint than placebo (105126). However, it is unclear if participants were truly blinded to the use of peppermint oil. Other preliminary clinical research in pediatric patients with migraine or other chronic headaches shows that receiving aromatherapy with peppermint oil over 10 minutes during a footbath does not improve pain or anxiety scores when compared with control (112746).
Mosquito repellent. Although there has been interest in using topical peppermint oil as a mosquito repellent, there is insufficient reliable information about the clinical effects of peppermint for this purpose.
Myalgia. Although there has been interest in using topical peppermint oil for myalgia, there is insufficient reliable information about the clinical effects of peppermint for this condition.
Oral mucositis. Topical peppermint has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults undergoing stem cell transplantation shows that using an oral rinse containing peppermint oil and German chamomile three times daily, in addition to standard treatment with sodium chloride and chlorhexidine, reduces the duration and severity of mucositis and the use of narcotic analgesics when compared with placebo and standard treatment. However, this oral rinse does not reduce or delay the occurrence of mucositis or affect the duration of hospitalization (96363). Another small clinical study in adults with head and neck cancers undergoing radiation shows that rinsing with 5 mL of a polyherbal mouthwash containing peppermint oil, German chamomile, aloe vera, and honey for 1 minute 3 times daily for 6 weeks reduces oral mucositis incidence, severity, and pain when compared with chlorhexidine 0.2% and placebo (111291). Clinical research in adults receiving treatment with 5-fluorouracil shows that using an oral rinse containing peppermint, sage tea, and thyme in addition to basic oral care, starting on the first day of chemotherapy and continuing for 14 days, delays the onset of mucositis, but not the rate or severity of mucositis, when compared with basic oral care alone (96364). It is unclear if these effects are due to peppermint oil, other ingredients, or the combinations.
Osteoarthritis. Although there has been interest in using topical peppermint oil for osteoarthritis, there is insufficient reliable information about the clinical effects of peppermint for this condition.
Pain (acute). It is unclear if inhaled or topical peppermint oil is beneficial for acute pain. Details: Preliminary clinical research in cardiac patients shows that peppermint oil aromatherapy reduces pain associated with intravenous catheterization by a small amount when compared with a distilled water control (102601). Another small open-label study in adults undergoing venipuncture for dialysis shows that topical application of peppermint gel 5 mL reduces pain scores by approximately 50% when compared with no intervention. These results were similar to using a cold compress (114758). Additionally, a small open-label study in children undergoing a dental procedure, shows that topical application of peppermint oil 0.2% , moderately improves pain scores after a buccal injection when compared with lidocaine spray 15% (114757).
Postherpetic neuralgia. Although there has been interest in using topical peppermint oil for postherpetic neuralgia, there is insufficient reliable information about the clinical effects of peppermint for this condition.
Postoperative ileus. It is unclear if oral peppermint oil is beneficial for the prevention of postoperative ileus. Details: Clinical research shows that taking a specific peppermint oil product (Colpermin, Tillotts Pharma) as two capsules three times daily for 5 days after routine gynecological surgery does not prevent postoperative abdominal distension and dyspepsia when compared with placebo (68602). Conversely, a small clinical study in patients undergoing elective cesarean section shows that taking 20 drops of peppermint oil 4 hours after surgery and then hourly for a total of three doses reduces the time to first bowel sounds by around 3.3 hours, first flatulence by 4.4 hours, and first stool by 5 hours when compared with placebo (110092).
Postoperative nausea and vomiting (PONV). Some preliminary clinical studies suggest that inhaled peppermint may be beneficial for PONV. However, it is unclear if the benefit is due to aromatherapy or improved breathing patterns. Details: Some preliminary clinical research shows that using peppermint aromatherapy helps relieve postoperative nausea (3804,13415,68524,104219,104220,115149). Inhaling peppermint oil 10% and 30% as aromatherapy reduces the severity of nausea when compared with placebo, with no significant difference between concentrations (104219). However, one small clinical trial shows improvement in PONV only within the first 4 hours after surgery, with a diminishing effect beyond 4 hours (104220). Other preliminary clinical research shows that peppermint oil aromatherapy is no more effective for reducing postoperative nausea than inhaling isopropyl alcohol or saline (13416,68529). It is possible that any relief of postoperative nausea observed with peppermint aromatherapy results from improved breathing patterns after surgery rather than peppermint oil itself (13416,90512). One small study shows that inhaling peppermint oil while practicing controlled breathing does not appear to relieve PONV better than practicing controlled breathing alone (90512). Some preliminary clinical research shows that inhaling vapors from a mixture of peppermint, ginger, spearmint, and cardamom essential oils reduces symptoms of postoperative nausea in approximately 15% more patients when compared with inhaling ginger essential oils alone, and in approximately 43% more patients when compared with inhaling saline (89888). However, it is not clear if the effect is due to peppermint, the other oils, or the combination. In contrast, a small clinical trial in adults undergoing port catheter placement shows that application of a specific aromatherapy patch containing peppermint and lavender (Elequil Aromatabs, Beekley Medical) preoperatively does not reduce PONV rescue treatment when compared with placebo (114623). Another small clinical trial in adults with anxiety undergoing total hip or knee arthroplasty shows that application of the same patch containing peppermint and lavender every 12 hours for 6 doses does not reduce overall PONV when compared with placebo (114622).
Postoperative pain. It is unclear if inhaled peppermint oil is beneficial for postoperative pain. Details: Preliminary clinical research in adults undergoing open heart cardiac surgery shows that receiving aromatherapy with peppermint oil 10%, 0.1 mL, three times daily for 7 doses moderately improves pain scores when compared with placebo (112747). Other preliminary clinical research in adults undergoing lumbar discectomy surgery shows that receiving aromatherapy with peppermint oil 5 drops once postoperatively modestly improves pain scores and anxiety scores when compared with no intervention (112744). A small clinical trial in adults undergoing port catheter placement shows that application of a specific aromatherapy patch containing peppermint and lavender (Elequil Aromatabs, Beekley Medical) preoperatively does not improve pain scores or reduce opioid rescue treatment in the immediate post-operative period when compared with placebo (114623). Another small clinical trial in adults with anxiety undergoing total hip or knee arthroplasty shows that application of the same patch containing peppermint and lavender every 12 hours for 6 doses modestly reduceses opioid consumption on postoperative day 2, but not day 1, 7, or 30, when compared with placebo (114622). However, these changes are unlikely to be clinically relevant. In addition, it is unclear if any potential effects are due to peppermint, lavender, or the combination.
Postoperative recovery. Inhaled peppermint has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in adults undergoing port catheter placement shows that application of a specific aromatherapy patch containing peppermint and lavender (Elequil Aromatabs, Beekley Medical) preoperatively does not shorten postoperative length of stay when compared with placebo (114623).
Postoperative sleep disturbance. It is unclear if inhaled peppermint oil is beneficial for postoperative sleep disturbance. Details: Preliminary clinical research in adults undergoing open heart cardiac surgery shows that receiving aromatherapy with peppermint oil 10%, 0.1 mL, three times daily for 7 doses modestly improves sleep scores when compared with placebo (112747).
Pre-procedural anxiety. It is unclear if inhaled peppermint oil is beneficial for reducing anxiety prior to a medical procedure. Details: Preliminary clinical research in cardiac patients shows that peppermint oil aromatherapy does not reduce anxiety associated with intravenous catheterization when compared with a distilled water control (102601).
Pregnancy-induced nausea and vomiting. Inhaled peppermint oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that aromatherapy with a mixture of 5% lemon and 5% peppermint essential oils modestly reduces the intensity of nausea and vomiting on days 2-4, but not day 1, when compared with placebo aromatherapy. When nauseated, patients placed three drops of the essential oil mixture (Barij Essence Co.) onto a cotton ball held 3 cm from the nose. This action could be repeated after 5 minutes if needed (105121).
Pruritus. Some preliminary clinical studies suggest that topical peppermint oil improves itching of various etiologies. Details: Preliminary clinical research in adults with renal, hepatic, or diabetic pruritus shows that topical application of peppermint oil 5% in petrolatum twice daily for 2 weeks improves symptoms of pruritus when compared with petrolatum alone (96361). Preliminary clinical research in patients with severe or intractable pruritus secondary to burn scars shows that applying a specific product (Chongqing No.1, CQ-01, MJ Medical Gel Systems Ltd.) containing peppermint oil 3.6%, menthol 1.4%, and methyl salicylate 2.5%, covered with gauze for 24 hours, reduces the severity of pruritus for up to 7 days after application when compared with hydrogel covered with gauze or with gauze alone (96362). Preliminary clinical research in females experiencing itchy skin due to intrahepatic cholestasis of pregnancy also shows that applying peppermint oil 0.5% in sesame oil twice daily for 2 weeks reduces pruritus severity approximately 1.8-fold when compared with sesame oil alone (89478).
Small intestinal bacterial overgrowth (SIBO). Although there has been interest in using oral peppermint for SIBO, there is insufficient reliable information about the clinical effects of peppermint for this condition.
Stress. It is unclear if inhaled peppermint oil is beneficial for stress. Details: Clinical research shows that peppermint aromatherapy decreases physical and perceived levels of stress when compared with baseline (68422,68517). A small clinical study in adults undergoing a virtual reality (VR) driving scenario to test road rage shows that exposure to peppermint oil (Pure Essential Oil of Peppermint, Tisserand Aromatherapy) 5 drops via fan diffuser improves aggressive driving behavior scores but does not seem to improve self-reported stress, aggression, alertness, happiness, or calmness when compared with controls that did not receive aromatherapy during the VR session (112017).
Toothache. Although there has been interest in using topical peppermint oil for toothache, there is insufficient reliable information about the clinical effects of peppermint for this condition.
Urticaria. Although there has been interest in using topical peppermint oil for urticaria, there is insufficient reliable information about the clinical effects of peppermint for this condition. More evidence is needed to rate peppermint for these uses.

Memory. Oral rosemary seems to improve memory in young adults. It is unclear if rosemary aromatherapy improves memory. Details: Clinical research in healthy adults shows that taking rosemary 500 mg orally twice daily for one month improves memory by approximately 14% when compared with placebo (98536). Other preliminary clinical research shows that applying four drops of pure rosemary essential oil (Tisserand Aromatherapy) to an aromatherapy diffuser pad 5 minutes before a single test period can improve the quality, but not the speed, of memory recall, and increase alertness and contentment more than lavender aromatherapy or no aroma (18323). Rosemary aromatherapy has also been evaluated for improving memory in adults with kidney failure. A small clinical study in patients (mean age 53 years) undergoing hemodialysis shows that aromatherapy with rosemary essential oil three times weekly for 1 month does not improve medication adherence or measures of prospective and retrospective memory when compared with a control group. In this study, five drops of rosemary essential oil were applied to gauze, which was then placed 10 cm from the patient's nose for 30 minutes starting 1 hour after hemodialysis (109559).

Abortion. Although there has been interest in the use of oral rosemary as an abortifacient, there is insufficient reliable information about the clinical effects of rosemary for this purpose.
Age-related cognitive decline. It is unclear if oral rosemary is beneficial for age-related cognitive decline. Details: A small clinical study in healthy individuals aged 65-90 years shows that a single 750 mg dose of powdered rosemary leaf in tomato juice may improve memory speed. However, higher single doses of 1500-6000 mg seem to have a deleterious effect on memory speed. For other measures of attention and memory, there were no clear benefits across the range of doses from 750-6000 mg (18246). Oral rosemary has also been evaluated in combination with other ingredients. A small clinical study in healthy adults aged 62 years or younger shows that taking a combination product containing equal parts rosemary, lemon balm, and sage twice daily for 2 weeks modestly improves word recall when compared with placebo. However, it does not appear to have benefit in adults aged 63 years and older (97277). It is unclear if any benefit is due to rosemary, other ingredients, or the combination.
Alopecia areata. Topical rosemary oil has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that rosemary oil 114 mg, in combination with lavender oil 108 mg, thyme oil 88 mg, and cedarwood oil 94 mg, mixed with jojoba oil 3 mL and grapeseed oil 20 mL and applied topically to the scalp, improves hair growth in 44% of patients, compared with 15% of those receiving placebo. This combination was massaged into the scalp for a minimum of 2 minutes, followed by wrapping the head in a warm towel, every night for 7 months (5177).
Androgenic alopecia. It is unclear if topical rosemary is beneficial for androgenic alopecia. Details: Preliminary clinical research shows that applying rosemary oil (Barij Essence Pharmaceutical Company) 1 mL to the scalp twice daily for 6 months is as effective as minoxidil 2% for increasing hair count in patients with androgenic alopecia (91729).
Depression. It is unclear if oral rosemary is beneficial for major depressive disorder. Details: A small clinical trial among adults newly diagnosed with major depressive disorder and recent initiation of antidepressant medication shows that taking rosemary dried leaf extract 650 mg twice daily for 8 weeks might reduce some symptoms of depression and anxiety when compared with placebo (112141). However, the validity of these findings is limited by differences in baseline depression symptom scores between groups.
Diabetes. It is unclear if oral rosemary is beneficial for improving glycemic control in patients with type 2 diabetes. Details: In patients with type 2 diabetes, preliminary clinical research shows that taking rosemary tea daily for 90 days decreases glycated hemoglobin levels by 15% and waist and hip circumference by 6% and improves insulin resistance. However, there was no effect on fasting blood glucose, lipid profile, body weight, or body mass index (BMI). The tea was made by adding rosemary 2 grams to a liter of boiling water for 3 minutes and then passing through a sieve (105323). Other preliminary clinical research in adults with type 2 diabetes shows that taking rosemary powder 3 grams daily for 4 weeks does not reduce fasting blood glucose levels or improve lipid profile when compared with baseline. These endpoints were improved in a group of healthy adults (105327). The validity of the findings from these studies is limited by the lack a comparator group.
Diabetic nephropathy. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a specific combination product (Canephron N, Bionorica) containing 18 mg each of rosemary leaf, centaury herb, and lovage root per tablet, as two tablets three times daily for 6 months along with standard antidiabetes treatment and enalapril (Vasotec), decreases microalbuminuria by 73%, decreases albumin:creatinine ratio by 46%, increases high-density lipoprotein (HDL) cholesterol by 25%, and lowers triglyceride levels by 43%, but does not improve glomerular filtration rate, when compared to baseline. Improvements were greater in those taking the combination product than in those treated only with standard antidiabetes therapy and enalapril. However, the combination product does not appear to improve reductions in total cholesterol or low-density lipoprotein (LDL) cholesterol (91726).
Dysmenorrhea. It is unclear if oral rosemary is beneficial for dysmenorrhea. Details: In patients with moderate primary dysmenorrhea, clinical research shows that taking rosemary extract 220 mg every 8 hours for the first three days of the menstrual cycle, repeated for two menstrual cycles, is as effective as mefenamic acid for reducing average pain and bleeding when compared with two baseline cycles (105328).
Fatigue. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in healthy young adults with below-average energy levels shows that taking a single dose of a mixture of rosemary from Albania (Rosmarinus officinalis) and Morocco (Rosmarinus eriocalyx) 1.7 grams does not consistently improve sustained attention, motivation to perform cognitive tasks, mental energy, or mental fatigue when compared with placebo (91731).
Fibromyalgia. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with fibromyalgia shows that taking an oral product containing rosemary leaf extract, oleanolic acid from olive leaf, and rho iso-alpha acids from hops (Meta050, Metagenics), at a dose of 440 mg three times daily for 4 weeks, then 880 mg twice daily for 4 weeks, does not improve symptoms when compared to baseline (18327).
Gingivitis. A mouth rinse containing rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with mild to moderate gingivitis and mild plaque shows that rinsing the mouth with 10 mL of mouthwash containing 5% v/v of a combined alcoholic extract of rosemary, calendula, and ginger for 30 seconds twice daily after meals for 2 weeks decreases plaque formation, gingival inflammation, and gingival bleeding similarly to chlorhexidine gluconate 0.2% mouthwash and better than a placebo mouthwash (93555).
Hypertension. Although there is interest in using oral rosemary for hypertension, there is insufficient reliable information about the clinical effects of rosemary for this condition.
Hypotension. It is unclear if oral rosemary is beneficial for hypotension. Details: Preliminary clinical research in patients with primary hypotension shows that taking rosemary essential oil (Metapharmaceutical) 1 mL every 8 hours for 44 weeks increases systolic blood pressure by 13 mmHg and diastolic blood pressure by 7 mmHg when compared to baseline. However, blood pressure returned to near baseline values after treatment discontinuation (91730).
Mental alertness. It is unclear if rosemary aromatherapy is beneficial for improving mental alertness. Details: Preliminary clinical research in nurses working on a night shift shows that placing one drop of rosemary oil on a surgical mask that is worn for 2 hours with a 10-minute on/15-minute off cycle modestly increases alertness and reduces sleepiness when compared with a water drop control (105324).
Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral rosemary leaf is beneficial in patients with NAFLD. Details: A small clinical study in patients with NAFLD shows that taking rosemary leaf powder 2 grams twice daily for 8 weeks, in conjunction with diet and exercise recommendations, does not improve measures of liver function, glycemic control, cholesterol, or body weight when compared with placebo (109561).
Opioid withdrawal. It is unclear if oral rosemary is beneficial for opioid withdrawal when used in combination with methadone. Details: Preliminary clinical research shows that taking rosemary leaf along with methadone for 2 weeks improves symptoms of opioid withdrawal and the ability to sleep when compared with methadone alone after 3 and 7 days of treatment, but not after 2 weeks. Rosemary leaf was provided in capsules containing 300 mg each (Barij Essence Pharmaceutical Company) at a dose of 16 capsules daily for the first 3 days, 12 capsules daily for the next 4 days, and eight capsules daily for the next 7 days, in divided doses (91727).
Osteoarthritis. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows subjective reductions in pain associated with osteoarthritis when oral formulations containing rosemary leaf extract, oleanolic acid from olive leaf, and rho iso-alpha acids from hops (NG440-2, Metagenics; Meta050, Metagenics) are used (18326,18327). The formulation used in one of these studies (Meta050, Metagenics) was taken in a dose of 440 mg three times daily for 4 weeks, then 880 mg twice daily for 4 weeks (18327). The formulation used in the other study, which was taken daily for 4 weeks, contained rosemary leaf extract 112.5 mg, oleanolic acid from olive leaf 1 mg, and rho iso-alpha acids from hops 225 mg per tablet (18326).
Raynaud syndrome. It is unclear if topical rosemary essential oil is beneficial in patients with Raynaud syndrome. Details: A very small, open-label study in patients with Raynaud syndrome caused by systemic scleroderma shows that applying 10 drops of rosemary 10% essential oil to the hands does not increase skin temperature or improve warmth perception when compared with olive oil (109560). However, this study may have been inadequately powered to detect a difference between groups.
Rheumatoid arthritis (RA). Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows subjective decreases in pain associated with RA when oral formulations containing rosemary leaf extract, oleanolic acid from olive leaf, and rho iso-alpha acids from hops (NG440-2, Metagenics; Meta050, Metagenics) are used (18326,18327). The formulation used in one of these studies (Meta050, Metagenics) was taken in a dose of 440 mg three times daily for 4 weeks, then 880 mg twice daily for 4 weeks (18327). The formulation used in the other study, which was taken daily for 4 weeks, contained rosemary leaf extract 112.5 mg, oleanolic acid from olive leaf 1 mg, and rho iso-alpha acids from hops 225 mg per tablet (18326).
Stress. It is unclear if rosemary aromatherapy is beneficial for stress. Details: Preliminary clinical research on the use of rosemary aromatherapy for anxiety and stress is conflicting. In a group of graduate nursing students, perceived stress associated with taking a test was lower when inhalers containing rosemary or lavender oil were used. Three drops of rosemary essential oil were added to an inhaler and inhaled before and during the test. Pulse rates, but not blood pressure, were also reduced (18324). In contrast, a small clinical study in adults aged 18-30 years shows that the aroma from diluted rosemary essential oil applied to the wrist during timed crossword puzzle completion actually increases subjective feelings of anxiety and tension when compared with placebo (18325).
Sunburn. Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking a combination of rosemary and grapefruit extracts in a 1:1 ratio (NutroxSun, Monteloeder, Inc.), 250 mg orally once daily for 12 weeks, increases the amount of UV radiation needed to cause sunburn by 34% after 8 weeks and 56% after 12 weeks when compared to baseline (91728). The validity of these findings is limited by the lack of a comparator group.
Upper respiratory tract infection (URTI). Oral rosemary has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial among healthy adults shows that taking a combination product containing rosemary leaf extract, aloe gel powder, and poria mushroom extract daily for 8 weeks does not reduce the frequency, duration, or severity of URTI-related symptoms when compared with placebo. However, in patients receiving an influenza vaccine midway through the study, this product does seem to improve some immune response biomarkers when compared with placebo (111921). The amount of rosemary leaf extract in the supplement was not disclosed.
Wound healing. It is unclear if topical rosemary cream is beneficial for wound healing. Details: A moderate-sized clinical trial among primiparous adults with medio-lateral episiotomy shows that applying a cream containing rosemary extract to the wound twice daily for 10 days improves episiotomy wound healing and reduces redness and discharge when compared with placebo cream (112143). More evidence is needed to rate rosemary for these uses.

ELEUTHERO (Eleuthero extract, Eleuthero (Eleutherococcus senticosus) root extract)

Safety view details

Below is general information about the safety of the known ingredients contained in the product Ginkgo Supreme. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

LIKELY SAFE ...when used orally and appropriately, short-term. Eleuthero root extract 300-2000 mg has been used safely in clinical trials lasting up to 3 months (730,1427,2574,7522,11099,15586,91509). There is insufficient reliable information available about the safety of eleuthero when used long-term.

CHILDREN: POSSIBLY SAFE
when used orally in adolescents aged 12-17 years, short-term. Eleuthero 750 mg three times daily was used for 6 weeks with apparent safety in one clinical trial (75028). There is insufficient reliable information available about the safety of eleuthero in children or adolescents when used long-term.

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

POSSIBLY UNSAFE ...when used orally. Fo-ti has been linked to several cases of liver damage (7626,7627,14327,14347,14482,16459,17192,50711,50727,50729) (92892,92895,112231).

CHILDREN: POSSIBLY UNSAFE
when used orally. Fo-ti has been linked to several cases of liver damage in adults and at least one case in a 5-year-old child (14339,92895).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Fo-ti contains anthraquinone constituents, which can exert a stimulant laxative effect. Bulk-forming or emollient laxatives are preferred in pregnancy (272). Fo-ti has also been linked to several cases of liver damage (7626,7627,14327). There is insufficient reliable information available about the safety of fo-ti when used topically during pregnancy.

LACTATION: POSSIBLY UNSAFE
when used orally. Anthraquinone constituents can cross into breast milk and might cause loose stools in some breast-fed infants (272). Fo-ti has also been linked to several cases of liver damage (7626,7627,14327). There is insufficient reliable information available about the safety of fo-ti when used topically during lactation.

LIKELY SAFE ...when used orally and appropriately. Standardized ginkgo leaf extracts have been used safely in trials lasting for several weeks up to 6 years (1514,1515,3461,5717,5718,6211,6212,6213,6214,6215)(6216,6222,6223,6224,6225,6490,14383,14499,16634,16635)(16636,16637,17402,17716,17718,87794,87819,87826,87848,87864)(87888,87897,87901,87904,89701,89707,107359,107360). There have been some reports of arrhythmias associated with ginkgo leaf extract. However, it is not yet clear if ginkgo might cause arrhythmia (105253,105254). There is some concern about toxic and carcinogenic effects seen in animals exposed to a ginkgo leaf extract containing 31.2% flavonoids, 15.4% terpenoids, and 10.45 ppm ginkgolic acid, in doses of 100 to 2000 mg/kg five times per week for 2 years (18272). However, the clinical relevance of this data for humans, using typical doses, is unclear. The content of the extract used is not identical to that commonly used in supplement products, and the doses studied are much higher than those typically used by humans. A single dose of 50 mg/kg in rats is estimated to be equivalent to a single dose of about 240 mg in humans (18272).

POSSIBLY SAFE ...when used intravenously, short-term. A standardized ginkgo leaf extract called EGb 761 ONC has been safely administered intravenously for up to 14 days (9871,9872,107360,107452). A Chinese preparation containing ginkgo leaf extract and dipyridamole has been safely administered intravenously for up to 30 days (102881,102882). ...when applied topically, short-term. There was no dermal irritation during a 24-hour patch test using the leaf extract, and no sensitization with repeat applications (112946). When used topically in cosmetics, extracts of ginkgo leaves are reported to be safe, but there is insufficient data to determine the safety of nut and root extracts, and isolated biflavones and terpenoids (112946).

POSSIBLY UNSAFE ...when the roasted seed or crude ginkgo plant is used orally. Consuming more than 10 roasted seeds per day can cause difficulty breathing, weak pulse, seizures, loss of consciousness, and shock (8231,8232). Crude ginkgo plant parts can exceed concentrations of 5 ppm of the toxic ginkgolic acid constituents and can cause severe allergic reactions (5714).

LIKELY UNSAFE ...when the fresh ginkgo seed is used orally. Fresh seeds are toxic and potentially deadly (11296).

PREGNANCY: POSSIBLY UNSAFE
when used orally. There is concern that ginkgo might have labor-inducing and hormonal effects. There is also concern that the antiplatelet effects of ginkgo could prolong bleeding time if taken around the time of labor and delivery (15052). Theoretically, ginkgo might adversely affect pregnancy outcome; avoid using during pregnancy.

LACTATION:
Insufficient reliable information available; avoid using.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term (87790,89708). A specific ginkgo dried extract (Ginko T.D., Tolidaru Pharmaceuticals), has been safely used in doses of 80-120 mg daily for 6 weeks in children aged 6-14 years (17112,95669). Another specific combination product containing ginkgo leaf extract and American ginseng extract (AD-FX, CV Technologies, Canada) has also been safely used in children aged 3-17 years for up to 4 weeks (8235).

CHILDREN: LIKELY UNSAFE
when ginkgo seed is used orally. The fresh seeds have caused seizures and death in children (8231,11296).

POSSIBLY SAFE ...when used topically and appropriately. Gotu kola has been used safely in a cream or ointment for up to 10 weeks (11072,11073,67372,102792,105329,105335). An emulsion containing gotu kola extract 3% and other ingredients has been applied safely to the skin twice daily for up to 60 days (111571). ...when used orally and appropriately. Gotu kola extract has been used with apparent safety in doses of up to 180 mg daily for up to 12 months or 1000 mg daily for 60 days. Dried gotu kola has been used with apparent safety in doses of up to 2200 mg daily for 4 weeks (6887,11062,11063,11064,11065,11066,11067,11068,11069,11070)(11071,99756,99757,99758,105329,105332,105333). A specific gotu kola extract (Centellicum, Horphag Research Ltd) 450-675 mg daily has been used with apparent safety for up to 6 weeks (99756,99757).

PREGNANCY: POSSIBLY SAFE
when used topically and appropriately (11073,13559). There is insufficient reliable information available about the safety gotu kola when used orally during pregnancy; avoid using.

LACTATION:
Insufficient reliable information available; avoid using.

OATS (organic Oats (Avena sativa) milky seed extract)

LIKELY SAFE ...when used orally and appropriately in food amounts (4960,4969,5792,5797). Oat bran has Generally Recognized as Safe (GRAS) status in the US (4912). Whole grain oats 50-100 grams daily have been used for up to 1 year without serious adverse effects (97520).

POSSIBLY SAFE ...when used topically and appropriately (12). Lotion containing colloidal oat 1% has been used topically without adverse effects for up to 6 weeks (97518,103340). There is insufficient reliable information available about the safety of oats when used orally in medicinal amounts.

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in food amounts (5792,5797).

LIKELY SAFE ...when peppermint oil is used orally, topically, or rectally in medicinal doses. Peppermint oil has been safely used in multiple clinical trials (3801,3804,6190,6740,6741,10075,12009,13413,14467,17681)(17682,68522,96344,96360,96361,96362,96363,96364,96365,99493).

POSSIBLY SAFE ...when peppermint leaf is used orally and appropriately, short-term. There is some clinical research showing that peppermint leaf can be used safely for up to 8 weeks (12724,13413). The long-term safety of peppermint leaf in medicinal doses is unknown. ...when peppermint oil is used by inhalation as aromatherapy (7107). There is insufficient reliable information available about the safety of using intranasal peppermint oil.

CHILDREN: POSSIBLY SAFE
when used orally for medicinal purposes. Enteric-coated peppermint oil capsules have been used with apparent safety under medical supervision in children 8 years of age and older (4469).

PREGNANCY AND LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (96361). There is insufficient information available about the safety of using peppermint in medicinal amounts during pregnancy or lactation; avoid using.

LIKELY SAFE ...when used orally in amounts typically found in foods. Rosemary has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when the leaf is used orally and appropriately in medicinal amounts (18). Powdered rosemary leaf has been used with apparent safety as a single dose of up to 1.5 grams (18246,91731) or at a dose of 1-4 grams daily for up to 8 weeks (91727,98536,105327,109561). ...when the essential oil is used topically and appropriately for up to 7 months (5177,91729,109560). ...when the essential oil is used by inhalation as aromatherapy, short-term (7107,18323,105324,109559).

LIKELY UNSAFE ...when the essential oil or very large quantities of rosemary leaf are used orally. Ingestion of undiluted rosemary oil or very large quantities of rosemary leaf can cause serious adverse effects (18,515).

PREGNANCY: POSSIBLY UNSAFE
when used orally in medicinal amounts. Rosemary might have uterine and menstrual flow stimulant effects (4,12,18), and might increase metabolism of estradiol and estrone (18331); avoid using. There is insufficient reliable information available about the safety of rosemary when used topically during pregnancy.

LACTATION:
There is insufficient reliable information available about the safety of using rosemary in medicinal amounts during lactation; avoid using.

ELEUTHERO (Eleuthero extract, Eleuthero (Eleutherococcus senticosus) root extract)

Interactions with Drugs view details

Below is general information about the interactions of the known ingredients contained in the product Ginkgo Supreme. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, eleuthero may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Details

In vitro and animal research shows that a constituent of eleuthero, dihydroxybenzoic acid, appears to inhibit platelet aggregation (7592,74976). Concomitant use with anticoagulant or antiplatelet drugs might increase the risk of bleeding. This effect has not been reported in humans.

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, eleuthero might have additive effects when used with antidiabetes drugs.

Details

Animal research suggests that certain constituents of eleuthero have hypoglycemic activity in both healthy and diabetic animals (7591,73535,74932,74956,74988,74990). A small study in adults with type 2 diabetes also shows that taking eleuthero for 3 months can lower blood glucose levels (91509). However, one very small study in healthy individuals shows that taking powdered eleuthero 3 grams, 40 minutes prior to a 75-gram oral glucose tolerance test, significantly increases postprandial blood glucose levels when compared with placebo (12536). These contradictory findings might be due to patient-specific variability and variability in active ingredient ratios.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, eleuthero might increase levels of drugs metabolized by CYP1A2.

Details

In vitro and animal research suggest that standardized extracts of eleuthero inhibit CYP1A2 (7532). This effect has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, eleuthero might increase levels of drugs metabolized by CYP2C9.

Details

In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2C9 (7532). This effect has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

Severity = Moderate • Occurrence = Unlikely • Level of Evidence = B

Theoretically, eleuthero might increase levels of drugs metabolized by CYP2D6.

Details

In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2D6. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP2D6 drug metabolism (7532,10400).

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

Severity = Moderate • Occurrence = Unlikely • Level of Evidence = B

Theoretically, eleuthero might increase levels of drugs metabolized by CYP3A4.

Details

In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP3A4. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP3A4 drug metabolism (7532,10400).

DIGOXIN (Lanoxin)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Unlikely • Level of Evidence = D

Eleuthero might increase serum digoxin levels and increase the risk of side effects.

Details

In one case report, a 74-year-old male who was stabilized on digoxin presented with an elevated serum digoxin level after starting an eleuthero supplement, without symptoms of toxicity. After stopping the supplement, serum digoxin levels returned to normal (543). It is not clear whether this was due to a pharmacokinetic interaction or to interference with the digoxin assay (15585). Although the product was found to be free of digoxin and digitoxin (543), it was not tested for other contaminants (797).

IMMUNOSUPPRESSANTS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, eleuthero might interfere with immunosuppressive drugs because of its immunostimulant activity.

Details

Animal and in vitro research shows that eleuthero extracts have immunomodulatory effects, including increasing cellular and humoral activity (74887,74915).

ORGANIC ANION-TRANSPORTING POLYPEPTIDE SUBSTRATES (OATP)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = D

Theoretically, eleuthero might decrease levels of drugs metabolized by OATP.

Details

In vitro research suggests that eleuthero inhibits OATP2B1, which might reduce the bioavailability of oral drugs that are substrates of OATP2B1 (35450). Due to the weak inhibitory effect identified in this study, this interaction is not likely to be clinically significant.

P-GLYCOPROTEIN SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, eleuthero might increase levels of P-glycoprotein substrates.

Details

In vitro research suggests that eleuthero can inhibit the multi-drug transporter protein, P-glycoprotein (22639,91509). However, it is too soon to tell if this is clinically important. This interaction has not been reported in humans.

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, fo-ti might increase the risk of hypoglycemia when taken with antidiabetes drugs.

Details

Fo-ti reportedly has hypoglycemic effects (5,19).

CONTRACEPTIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = D

Theoretically, taking large amounts of fo-ti might interfere with contraceptive drugs due to competition for estrogen receptors.

Details

In vitro research suggests that fo-ti extract has estrogenic activity (10143,16061,50710).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, fo-ti might increase or decrease the levels and clinical effects of drugs metabolized by CYP1A2.

Details

In vitro research suggests that fo-ti might inhibit CYP1A2 (12479,112351). Additionally, in vitro research suggests that the degree of CYP1A2 inhibition depends on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts) (112351). However, in an animal study, an aqueous extract of fo-ti inhibited CYP1A2 while an alcoholic extract of fo-ti induced CYP1A2 (92898). Induction or inhibition of CYP1A2 by fo-ti has not been reported in humans.

CYTOCHROME P450 2B6 (CYP2B6) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, fo-ti might increase the levels and clinical effects of drugs metabolized by CYP2B6.

Details

Animal research suggests that fo-ti might inhibit CYP2B6 (92898). One in vitro study suggests that the degree of CYP2B6 inhibition may depend on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts) (112351). However, this interaction has not been reported in humans.

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, fo-ti may increase the levels and clinical effects of drugs metabolized by CYP2C19.

Details

Animal and in vitro research suggests that fo-ti may inhibit CYP2C19 (12479,92898,112351). An in vitro study suggests that the degree of CYP2C19 inhibition may depend on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts) (112351). However, this interaction has not been reported in humans.

CYTOCHROME P450 2C8 (CYP2C8) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, fo-ti might increase the levels and clinical effects of drugs metabolized by CYP2C8.

Details

In vitro research suggests that fo-ti might inhibit CYP2C8 (112351). However, this interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, fo-ti may increase the levels and clinical effects of drugs metabolized by CYP2C9.

Details

Animal and in vitro research suggests that fo-ti may inhibit CYP2C9 (12479,92898,112351). However, this interaction has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, fo-ti may increase the levels and clinical effects of drugs metabolized by CYP2D6.

Details

Animal research suggests that fo-ti might inhibit CYP2D6 (92898). Additionally, an in vitro study suggests that the degree of CYP2D6 inhibition may depend on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts) (112351). However, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, fo-ti might increase the levels and clinical effects of drugs metabolized by CYP3A4.

Details

In vitro research suggests that fo-ti might inhibit CYP3A4 (12479,112351). One in vitro study suggests that the degree of CYP3A4 inhibition may depend on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts) (112351). However, this evidence conflicts with animal research suggesting that fo-ti does not inhibit CYP3A4 (92898). This interaction has not been reported in humans.

DIGOXIN (Lanoxin)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, fo-ti, particularly raw fo-ti root, might increase the risk of hypokalemia and cardiotoxicity when taken with digoxin.

Details

Raw fo-ti root contains anthraquinone derivatives, which might have stimulant laxative effects (5,16459). In vitro research shows that fermented and processed fo-ti root have reduced laxative effects compared with raw fo-ti root (99855).

DIURETIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, fo-ti, particularly raw fo-ti root, might increase the risk of hypokalemia when taken with diuretic drugs.

Details

Raw fo-ti root contains anthraquinone derivatives, which might have stimulant laxative effects and compound diuretic-induced potassium loss (5,16459). In vitro research shows that fermented and processed fo-ti root have reduced laxative effects compared with raw fo-ti root (99855).

ESTROGENS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = D

Theoretically, taking large amounts of fo-ti might interfere with hormone replacement therapy through competition for estrogen receptors.

Details

In vitro research suggests that fo-ti extract has estrogenic activity (10143,16061,50710).

HEPATOTOXIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, fo-ti might increase the risk of liver damage when taken with hepatotoxic drugs.

Details

Fo-ti has been linked to liver damage in many reports (7626,7627,14327,14339,14347,14482,16459,17192,50711,50727,50729,92892,92895).

STIMULANT LAXATIVES

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, fo-ti, particularly raw fo-ti root, might increase the risk of fluid and electrolyte depletion when taken with stimulant laxatives.

Details

Raw fo-ti root contains anthraquinone derivatives, which might have stimulant laxative effects (5,16459). However, in vitro research shows that fermented and processed fo-ti root have reduced laxative effects compared with raw fo-ti root (99855).

SULINDAC (Clinoril)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, fo-ti might increase or decrease the levels and clinical effects of sulindac.

Details

Animal research suggests that the type of fo-ti extract might affect the levels of sulindac differently; the raw plant may increase levels, but processed parts may decrease levels (112351). Induction or inhibition of CYP1A2 by fo-ti has not been reported in humans.

WARFARIN (Coumadin)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, fo-ti might increase the effects and adverse effects of warfarin.

Details

Fo-ti may have stimulant laxative effects and cause diarrhea, especially when the raw or unprocessed fo-ti root is used (5,12,16459,50733,99855). Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding. Also, fo-ti has been linked to cases of acute liver failure which can decrease clotting factor production and increase the effects of warfarin. In one case, a patient who had been stable on warfarin presented with acute hepatitis and an INR elevated to 14.98. The patient had been taking fo-ti for 90 days prior to admission. Discontinuation of warfarin and fo-ti lead to a decrease in the INR and full recovery (17192).

ALPRAZOLAM (Xanax)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Mild • Occurrence = Probable • Level of Evidence = B

Theoretically, ginkgo might decrease the levels and clinical effects of alprazolam.

Details

In clinical research, ginkgo extract (Ginkgold) 120 mg twice daily seems to decrease alprazolam levels by about 17%. However, ginkgo does not appear to decrease the elimination half-life of alprazolam. This suggests that ginkgo is more likely to decrease absorption of alprazolam rather than induce hepatic metabolism of alprazolam (11029).

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = A

Ginkgo has been shown to increase the risk of bleeding in some people when taken with warfarin. Theoretically, ginkgo might increase the risk of bleeding if used with other anticoagulant or antiplatelet drugs.

Details

Several pharmacodynamic studies suggest that ginkgo inhibits platelet aggregation. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation (6048,9760). Several case reports have documented serious bleeding events in patients taking ginkgo (244,578,579,8581,13002,13135,13179,13194,14456,87868). However, population and clinical studies have produced mixed results. Some evidence shows that short-term use of ginkgo leaf does not significantly reduce platelet aggregation and blood clotting (87732). A study in healthy males who took a specific ginkgo leaf extract (EGb 761) 160 mg twice daily for 7 days found no change in prothrombin time (12114). An analysis of a large medical record database suggests that ginkgo increases the risk of a bleeding adverse event by 38% when taken concurrently with warfarin (91326). It has been suggested that ginkgo has to be taken for at least 2-3 weeks to have a significant effect on platelet aggregation (14811). However, a meta-analysis of 18 studies using standardized ginkgo extracts, 80-480 mg daily for up to 32 weeks, did not find a significant effect on platelet aggregation, fibrinogen concentration, or PT/aPTT (17179). In addition, a single dose of ginkgo plus clopidogrel (14811) or ticlopidine does not seem to significantly increase bleeding time or platelet aggregation (17111,87846). Also, taking ginkgo leaf extract daily for 8 days in conjunction with rivaroxaban does not affect anti-factor Xa activity; however, this study did not evaluate bleeding time (109526).

ANTICONVULSANTS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, ginkgo might reduce the effectiveness of anticonvulsants.

Details

Ginkgo seeds contain ginkgotoxin. Large amounts of ginkgotoxin can cause neurotoxicity and seizure. Ginkgotoxin is present in much larger amounts in ginkgo seeds than leaves (8232). Ginkgo leaf extract contains trace amounts of ginkgotoxin. The amount of ginkgotoxin in ginkgo leaf and leaf extract seems unlikely to cause toxicity (11296). However, there are anecdotal reports of seizure occurring after use of ginkgo leaf both in patients without a history of seizure disorder and in those with previously well-controlled epilepsy (7030,7090).

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, taking ginkgo with antidiabetes drugs might alter the response to antidiabetes drugs.

Details

Ginkgo leaf extract seems to alter insulin secretion and metabolism, and might affect blood glucose levels in people with type 2 diabetes (5719,14448,103574). The effect of ginkgo seems to differ depending on the insulin and treatment status of the patient. In diet-controlled diabetes patients with hyperinsulinemia, taking ginkgo does not seem to significantly affect insulin or blood glucose levels. In patients with hyperinsulinemia who are treated with oral hypoglycemic agents, taking ginkgo seems to decrease insulin levels and increase blood glucose following an oral glucose tolerance test. Researchers speculate that this could be due to ginkgo-enhanced hepatic metabolism of insulin. In patients with pancreatic exhaustion, taking ginkgo seems to stimulate pancreatic beta-cells, resulting in increased insulin and C-peptide levels, but with no significant change in blood glucose levels in response to an oral glucose tolerance test (14448).

ATORVASTATIN (Lipitor)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Mild • Occurrence = Probable • Level of Evidence = B

Theoretically, ginkgo might decrease the levels and clinical effects of atorvastatin.

Details

In humans, intake of ginkgo extract appears to increase atorvastatin clearance, reducing the area under the curve of atorvastatin by 10% to 14% and the maximum concentration by 29%. However, this interaction does not appear to affect cholesterol synthesis and absorption (89706). Further, a model in rats with hyperlipidemia suggests that administering ginkgo extract does not impact blood levels of atorvastatin and leads to lower total cholesterol, low-density lipoprotein cholesterol, and triglycerides when compared with rats given atorvastatin alone (111331).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, ginkgo might increase levels of drugs metabolized by CYP1A2.

Details

Laboratory research suggests that ginkgo leaf extract can mildly inhibit CYP1A2 enzymes (1303,6423,6450). However, clinical research suggests ginkgo might not affect CYP1A2 (10847). Until more is known, use ginkgo cautiously in patients taking drugs metabolized by these enzymes.

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Probable • Level of Evidence = B

Theoretically, ginkgo might decrease levels of drugs metabolized by CYP2C19.

Details

Some clinical research shows that a specific ginkgo leaf extract (Remembrance, Herbs Product LTD) 140 mg twice daily can induce CYP2C19 enzymes and potentially decrease levels of drugs metabolized by these enzymes (13108). However, other clinical research shows that taking ginkgo 120 mg twice daily for 12 days has no effect on levels of drugs metabolized by CYP2C19 (87824).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, ginkgo might increase levels of drugs metabolized by CYP2C9.

Details

In vitro, a specific standardized extract of ginkgo leaf (EGb 761) inhibits CYP2C9 activity (11026,12061,14337). The terpenoid (ginkgolides) and flavonoid (quercetin, kaempferol, etc.) constituents seem to be responsible for this effect. Most ginkgo extracts contain some amount of these constituents. Therefore, other ginkgo leaf extracts might also inhibit the CYP2C9 enzyme. However, clinical research suggests that ginkgo might not have a significant effect on CYP2C9 in humans. Ginkgo does not seem to significantly affect the pharmacokinetics of CYP2C9 substrates diclofenac or tolbutamide.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, ginkgo might decrease levels of drugs metabolized by CYP3A4.

Details

There is conflicting evidence about whether ginkgo induces or inhibits CYP3A4 (1303,6423,6450,11026,87800,87805,111330). Ginkgo does not appear to affect hepatic CYP3A4 (11029). However, it is not known if ginkgo affects intestinal CYP3A4. Preliminary clinical research suggests that taking ginkgo does not significantly affect levels of donepezil, lopinavir, or ritonavir, which are all CYP3A4 substrates (11027,87800,93578). Other clinical research also suggests ginkgo does not significantly affect CYP3A4 activity (10847). However, there are two case reports of decreased efavirenz concentrations and increased viral load in patients taking ginkgo. It is suspected that terpenoids from the ginkgo extract reduced drug levels by inducing cytochrome P450 3A4 (CYP3A4) (16821,25464).

EFAVIRENZ (Sustiva)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, ginkgo might decrease the levels and clinical effects of efavirenz.

Details

There are two case reports of decreased efavirenz concentrations and increased viral load in patients taking ginkgo. In one case, an HIV-positive male experienced over a 50% decrease in efavirenz levels over the course of 14 months while taking ginkgo extract. HIV-1 RNA copies also increased substantially, from less than 50 to more than 1500. It is suspected that terpenoids from the ginkgo extract reduced drug levels by inducing cytochrome P450 3A4 (CYP3A4) (16821). In another case report, a patient stable on antiviral therapy including efavirenz for 10 years, had an increase in viral load from <50 copies/mL to 1350 copies/mL after 2 months of taking a combination of supplements including ginkgo. After stopping ginkgo, the viral load was again controlled with the same antiviral therapy regimen (25464).

IBUPROFEN (Advil, others)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, ginkgo might increase the risk of bleeding when used with ibuprofen.

Details

Ginkgo might have antiplatelet effects and has been associated with several case reports of spontaneous bleeding. In one case, a 71-year-old male had taken a specific ginkgo extract (Gingium, Biocur) 40 mg twice daily for 2.5 years. About 4 weeks after starting ibuprofen 600 mg daily he experienced a fatal intracerebral hemorrhage (13179). However, the antiplatelet effects of ginkgo have been questioned. A meta-analysis and other studies have not found a significant antiplatelet effect with standardized ginkgo extracts, 80 mg to 480 mg taken daily for up to 32 weeks (17179).

NIFEDIPINE (Procardia)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = B

Theoretically, taking ginkgo with oral, but not intravenous, nifedipine might increase levels and adverse effects of nifedipine.

Details

Animal research and some clinical evidence suggests that taking ginkgo leaf extract orally in combination with oral nifedipine might increase nifedipine levels and cause increased side effects, such as headaches, dizziness, and hot flushes (87764,87765). However, taking ginkgo orally does not seem to affect the pharmacokinetics of intravenous nifedipine (87765).

OMEPRAZOLE (Prilosec)

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = B

Theoretically, taking ginkgo with omeprazole might decrease the levels and clinical effects of omeprazole.

Details

Clinical research shows that a specific ginkgo leaf extract (Remembrance, Herbs Product LTD) 140 mg twice daily can induce cytochrome P450 (CYP) 2C19 enzymes and decrease levels of omeprazole by about 27% to 42% (13108).

P-GLYCOPROTEIN SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = B

Theoretically, taking ginkgo with P-glycoprotein substrates might increase the levels and adverse effects of these substrates.

Details

A small clinical study in healthy volunteers shows that using ginkgo leaf extract 120 mg orally three times daily for 14 days can increase levels of the P-glycoprotein substrate, talinolol, by 36% in healthy male individuals. However, single doses of ginkgo do not have the same effect (87830).

RISPERIDONE (Risperdal)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, taking ginkgo with risperidone might increase the levels and adverse effects of risperidone.

Details

A single case of priapism has been reported for a 26-year-old male with schizophrenia who used risperidone 3 mg daily along with ginkgo extract 160 mg daily (87796). Risperidone is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4. CYP3A4 activity might be affected by ginkgo. Theoretically, ginkgo may inhibit the metabolism of risperidone and increase the risk of adverse effects.

ROSIGLITAZONE (Avandia)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, ginkgo might decrease the levels and clinical effects of rosiglitazone.

Details

Animal research shows that ginkgo leaf extract orally 100 or 200 mg/kg daily for 10 days alters the pharmacodynamics of rosiglitazone in a dose-dependent manner. The 100 mg/kg and 200 mg/kg doses reduce the area under the concentration time curve (AUC) of rosiglitazone by 39% and 52%, respectively, and the half-life by 28% and 39%, respectively. It is hypothesized that these changes may be due to induction of cytochrome P450 2C8 by ginkgo (109525).

SEIZURE THRESHOLD LOWERING DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, taking ginkgo with drugs that lower the seizure threshold might increase the risk for convulsions.

Details

SIMVASTATIN (Zocor)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Mild • Occurrence = Probable • Level of Evidence = B

Theoretically, ginkgo might decrease the levels and clinical effects of simvastatin.

Details

Clinical research shows that taking ginkgo extract can reduce the area under the curve and maximum concentration of simvastatin by 32% to 39%. However, ginkgo extract does not seem to affect the cholesterol-lowering ability of simvastatin (89704).

SOFOSBUVIR (Sovaldi)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, ginkgo might increase the levels and clinical effects of sofosbuvir.

Details

Animal research in rats shows that giving a ginkgo extract 25 mg/kg orally daily for 14 days increases the area under the concentration time curve (AUC) after a single sofosbuvir dose of 40 mg/kg by 11%, increases the half-life by 60%, and increases the plasma concentration at 4 hours by 38%. This interaction appears to be related to the inhibition of intestinal P-glycoprotein by ginkgo (109524).

TACROLIMUS (Prograf)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, ginkgo might increase the blood levels of tacrolimus.

Details

In vitro evidence suggests that certain biflavonoids in ginkgo leaves (i.e. amentoflavone, ginkgetin, bilobetin) may inhibit the metabolism of tacrolimus by up to 50%. This interaction appears to be time-dependent and due to inhibition of cytochrome P450 (CYP) 3A4 by these bioflavonoids. In rats given tacrolimus 1 mg/kg orally, amentoflavone was shown to increase the area under the concentration time curve (AUC) of tacrolimus by 3.8-fold (111330).

TALINOLOL

Interaction Rating = Major Do not take this combination.

Severity = High • Occurrence = Probable • Level of Evidence = B

Taking ginkgo with talinolol seems to increase blood levels of talinolol.

Details

There is some evidence that using ginkgo leaf extract 120 mg orally three times daily for 14 days can increase levels of talinolol by 36% in healthy male individuals. However, single doses of ginkgo do not seem to affect talinolol pharmacokinetics (87830).

TRAZODONE (Desyrel)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, ginkgo might increase the levels and clinical effects of trazodone.

Details

In a case report, an Alzheimer patient taking trazodone 20 mg twice daily and ginkgo leaf extract 80 mg twice daily for four doses became comatose. The coma was reversed by administration of flumazenil (Romazicon). Coma might have been induced by excessive GABA-ergic activity. Ginkgo flavonoids are thought to have GABA-ergic activity and act directly on benzodiazepine receptors. Ginkgo might also increase metabolism of trazodone to active GABA-ergic metabolites, possibly by inducing cytochrome P450 3A4 (CYP3A4) metabolism (6423).

WARFARIN (Coumadin)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = B

Ginkgo has been shown to increase the risk of bleeding in some people when taken with warfarin.

Details

Several pharmacodynamic studies suggest that ginkgo inhibits platelet aggregation. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation (6048,9760). Several case reports have documented serious bleeding events in patients taking ginkgo (244,576,578,579,8581,13002,13135,13179,13194,14456,87868). Information from a medical database suggests that when taken concurrently with warfarin, ginkgo increases the risk of a bleeding adverse event by 38% (91326). There is also some evidence that ginkgo leaf extract can inhibit cytochrome P450 2C9, an enzyme that metabolizes warfarin. This could result in increased warfarin levels (12061). However, population and clinical research has produced mixed results. Clinical research in healthy people suggests that ginkgo has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin (12881,15176,87727,87889). A meta-analysis of 18 studies using standardized ginkgo extracts, 80 mg to 480 mg daily for up to 32 weeks, did not find a significant effect on platelet aggregation, fibrinogen concentration, or PT/aPTT (17179). There is also some preliminary clinical research that suggests ginkgo might not significantly increase the effects of warfarin in patients that have a stable INR (11905).

CNS DEPRESSANTS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, taking gotu kola might increase the sedative effects of CNS depressants.

Details

In vitro research suggests that gotu kola may have sedative effects via binding of GABA receptors (6887,11071).

HEPATOTOXIC DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, taking gotu kola with hepatotoxic drugs might have additive adverse effects.

Details

There are at least four case reports of hepatotoxicity associated with the use of gotu kola. However, more information is needed to determine if gotu kola was the causative factor in these cases (13182,92506).

OATS (organic Oats (Avena sativa) milky seed extract)

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, oats may have additive effects with antidiabetic agents and might increase the risk of hypoglycemia.

Details

Consuming oats can decrease blood glucose in patients with diabetes (4980,4982,6266,103345). In those who require insulin, taking oats 100 grams daily for 2 days reduces the insulin dose required to achieve metabolic control (103336).

INSULIN

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Concomitant use of oats and insulin might increase the risk of hypoglycemia.

Details

In patients with insulin-dependent type 2 diabetes, taking oats 100 grams daily for 2 days reduces the insulin dose required to achieve metabolic control (103336).

CYCLOSPORINE (Neoral, Sandimmune)

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, peppermint oil might increase the levels and adverse effects of cyclosporine.

Details

In animal research, peppermint oil inhibits cyclosporine metabolism and increases cyclosporine levels. Inhibition of cytochrome P450 3A4 (CYP3A4) may be partially responsible for this interaction (11784). An interaction between peppermint oil and cyclosporine has not been reported in humans.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

Severity = Mild • Occurrence = Possible • Level of Evidence = B

Theoretically, peppermint might increase the levels of CYP1A2 substrates.

Details

In vitro and animal research shows that peppermint oil and peppermint leaf inhibit CYP1A2 (12479,12734). However, in clinical research, peppermint tea did not significantly affect the metabolism of caffeine, a CYP1A2 substrate. It is possible that the 6-day duration of treatment may have been too short to identify a difference (96359).

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, peppermint might increase the levels of CYP2C19 substrates.

Details

In vitro research shows that peppermint oil inhibits CYP2C19 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, peppermint might increase the levels of CYP2C9 substrates.

Details

In vitro research shows that peppermint oil inhibits CYP2C9 (12479). So far, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, peppermint might increase the levels of CYP3A4 substrates.

Details

Clinical research in healthy volunteers shows that a single dose of peppermint oil 600 mg inhibits CYP3A4 enzymes and increases the AUC of felodipine, a CYP3A4 substrate (11783). However, in vitro research suggests that peppermint oil only inhibits CYP3A4 at very high concentrations (12479).

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = High • Occurrence = Possible • Level of Evidence = D

Theoretically, rosemary may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.

Details

In vitro and animal research suggests that rosemary inhibits platelet aggregation (18334,18335,18336,18337).

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = B

Theoretically, taking rosemary with antidiabetes drugs might increase the risk of hypoglycemia.

Details

Animal research shows that rosemary extract can decrease blood glucose levels in diabetic models (71821,71923). However, research in humans is conflicting. Although rosemary powder decreased blood glucose levels in healthy adults (105327), no change in blood glucose levels was seen in adults with type 2 diabetes, most of whom were taking antidiabetes drugs (105323,105327).

ASPIRIN

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, rosemary might have additive effects with salicylate-containing drugs such as aspirin.

Details

Rosemary is reported to contain salicylates (18330).

CHOLINE MAGNESIUM TRISALICYLATE (Trilisate)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, rosemary might have additive effects with salicylate-containing drugs such as choline magnesium trisalicylate.

Details

Rosemary is reported to contain salicylate (18330).

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

Severity = Moderate • Occurrence = Unlikely • Level of Evidence = D

Theoretically, rosemary might decrease the levels and clinical effects of CYP1A1 substrates.

Details

In vitro research shows that rosemary induces CYP1A1 enzymes (18332,18333). This effect has not been reported in humans.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Minor Be watchful with this combination.

Severity = Moderate • Occurrence = Unlikely • Level of Evidence = D

Theoretically, rosemary might decrease the levels and clinical effects of CYP1A2 substrates.

Details

In vitro research shows that rosemary induces CYP1A2 enzymes (18332,18333). This effect has not been reported in humans.

SALSALATE (Disalcid)

Interaction Rating = Moderate Be cautious with this combination.

Severity = Moderate • Occurrence = Possible • Level of Evidence = D

Theoretically, rosemary might have additive effects with salicylate-containing drugs such as salsalate.

Details

Rosemary is reported to contain salicylate (18330).

Report an Adverse Reaction to Ginkgo Supreme

Adverse Effects view details

Below is general information about the adverse effects of the known ingredients contained in the product Ginkgo Supreme. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

ELEUTHERO (Eleuthero extract, Eleuthero (Eleutherococcus senticosus) root extract)

General ...Orally, eleuthero root is generally well tolerated when used short-term.
Most Common Adverse Effects:
Orally: Diarrhea, dyspepsia, gastrointestinal upset, headache, nausea, and urticaria.

Cardiovascular ...Orally, increased blood pressure has been reported in children with hypotension taking eleuthero in one clinical study (74980). Eleuthero has been reported to cause tachycardia, hypertension, and pericardial pain in patients with rheumatic heart disease or atherosclerosis. It is unclear if these effects were caused by eleuthero, or by the cardioglycoside-containing herb, silk vine (Periploca sepium), which is a common adulterant found in eleuthero products (12,797,6500).

Dermatologic ...Orally, eleuthero has been reported to cause rash in some clinical studies (75013,75028).

Gastrointestinal ...Orally, eleuthero has been reported to cause dyspepsia, nausea, diarrhea, and gastrointestinal upset in some patients (74938,75028,91510).

Genitourinary ...Orally, mastalgia and uterine bleeding were reported in 7. 3% of females taking eleuthero 2 grams daily in one clinical study (6500,11099). These adverse effects seem to be more likely with higher doses.

Neurologic/CNS ...Orally, headaches have been reported in 9. 8% of people taking eleuthero in one clinical study (11099).
In one case report, a 53-year-old female developed spontaneous subarachnoid hemorrhage associated with the use of an herbal supplement containing red clover, dong quai, and eleuthero (70419). It is unclear if this event was related to the use of eleuthero, the other ingredients, the combination, or another cause entirely.

Psychiatric ...Orally, nervousness has been reported in 7. 3% of people taking eleuthero in one clinical study (11099). Eleuthero has also been reported to cause slight anxiety, irritability, and melancholy in some patients (6500,11099). These adverse effects seem to be more likely to occur with higher doses.

General ...Orally, fo-ti may be unsafe.
Most Common Adverse Effects:
Orally: Abdominal pain, diarrhea, nausea, and vomiting with use of unprocessed fo-ti.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity with processed or unprocessed fo-ti.

Dermatologic ...Orally, one case of a fine maculopapular rash was reported in a patient taking the herbal product known as Shen-Min, which contains fo-ti. Symptoms resolved within three weeks after discontinuing the product (14482). It is unclear if the rash was due to fo-ti or other ingredients in the herbal product.

Gastrointestinal ...Orally, unprocessed fo-ti may cause diarrhea, abdominal pain, nausea, and vomiting (12,50733).

Hematologic ...Orally, one case of mild eosinophilia was reported in a patient taking the herbal product known as Shen-Min, which contains fo-ti. Symptoms resolved within three weeks after discontinuing the product (14482). It is unclear if this reaction was due to fo-ti or other ingredients in the herbal product. A case of agranulocytosis was reported in a 65-year-old female taking fo-ti 30 grams/day for 17 days. The patient recovered gradually following a 15-day hospitalization, which included treatment with intravenous steroids and granulocyte colony-stimulating factor (112231).

Hepatic ...Orally, cases of liver damage due to both processed and unprocessed fo-ti have been well documented in the medical literature. (7626,7627,14327,14339,14347,14482,16459,17192,50711,50726)(50727,50729,92892,92895,112231).
In a systematic review, around 450 cases of hepatitis associated with fo-ti were identified. These cases occurred in patients 5-78 years of age. Liver damage occurred at a wide range of doses, formulations, and durations of intake. The type of liver injury ranged from hepatocellular, to cholestatic, or mixed. Outcomes ranged from full recovery to cirrhosis, liver transplantation, and/or death. The evidence suggests that when the daily fo-ti dose is less than 12 grams, the median time to occurrence of liver damage is 60 days. When the daily fo-ti dose is more than 12 grams, the median time to liver damage is 30 days (92895). Presenting signs and symptoms may include jaundice, abdominal pain, nausea, fatigue, loss of appetite, dark urine, myalgias, and elevations in liver function tests (LFTs), ferritin, transferrin, prothrombin time, and INR (17192,92892). Other manifestations may include fever, skin rash, thrombocytopenia, pancytopenia, and arthralgias. Symptoms and increased LFTs usually seem to resolve within a month after discontinuing fo-ti (7626,7627,14339,14347,14482,16459). In one case series, liver enzymes began to normalize 48 hours after discontinuation of fo-ti and treatment with S-adenosylmethionine, compound glycyrrhizin injection, polyene phosphatidylcholine, and reduced glutathione. All patients were eventually discharged home in stable condition (92892). Rechallenge with fo-ti should not be attempted. A patient who had recovered from hepatitis associated with fo-ti use presented with myalgias and markedly elevated LFTs after a single dose of the herb (17192).
It is thought that this idiosyncratic reaction leading to liver damage is at least partially related to genetic polymorphisms. Cytochrome P450 1A2 (CYP1A2) is the predominant enzyme involved in biotransformation of emodin, a constituent of fo-ti thought to play a role in liver damage. In one genetic study, the frequency of CYP1A2*1C mutation in fo-ti induced drug-induced liver injury patients was 46.5%, which is significantly higher than the 27.9% frequency of liver injury reported in healthy patients without the mutation. Patients with a CYP1A2*1C mutation may have decreased activity of the CYP1A2 enzyme, which could inhibit the metabolism of fo-ti, causing an accumulation of toxic substances (92897).

General ...Orally, ginkgo leaf extract is generally well tolerated when used for up to 6 years. However, the seed and crude plant contain toxic constituents and should be avoided.
Intravenously, ginkgo leaf extract seems to be well tolerated when used for up to 30 days.
Topically, no adverse effects have been reported with ginkgo as a single ingredient. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Dizziness, gastrointestinal symptoms, headache.
Serious Adverse Effects (Rare):
Orally: Arrhythmia, bleeding, Stevens-Johnson syndrome.

Cardiovascular ...Cardiac arrhythmias suspected to be related to ginkgo have been reported. Internationally, there are at least 162 reports from 18 countries, with 34% of cases considered serious, involving five deaths and four life-threatening events. Additionally, a report from Canada found that 10 out of 15 cases of arrhythmia were considered serious. Ginkgo was the only suspect ingredient in 57% of all international reports, with symptoms generally presenting within days of initiation. The most common symptoms included palpitations, tachycardia, bradycardia, syncope, and loss of consciousness. Most cases were reported to be related to oral use of ginkgo leaf products; however, some cases were associated with oral use of the seed, and others with intravenous or intramuscular use of the leaf. Documented discontinuation of ginkgo led to recovery in approximately 84% of cases where ginkgo was the sole suspect. Despite these findings, ginkgo cannot be confirmed as the causal agent. It is possible that these reports are confounded by underlying co-morbidities. Of the reported cases, the main reason for ginkgo use was tinnitus, a symptom commonly associated with pre-existing arrhythmias (105253,105254). Despite this large number of reports, only three cases of cardiac arrhythmia have been published in the literature (105253,105254). In one case, frequent nocturnal episodes of paroxysmal atrial fibrillation were reported for a 35-year-old female taking ginkgo extract 240 mg daily orally for 2 months. Arrythmias ceased following discontinuation of ginkgo (87884).
Increases in blood pressure were commonly reported with ginkgo in a safety database analysis; however, information on the magnitude of the increase was limited, and reports included both oral and intravenous administration (115628).
In one clinical trial, the rate of ischemic stroke and transient ischemic attacks was significantly higher in patients taking ginkgo extract orally when compared with placebo (16635). It is unclear if these events were due to ginkgo, other factors, or a combination.

Dermatologic ...Topically, ginkgo fruit pulp can cause contact dermatitis, with intense itching, edema, papules, and pustules which take 7-10 days to resolve after stopping contact (112946).

Gastrointestinal ...Orally, ginkgo extract may cause mild gastrointestinal discomfort or pain (3965,8543,17112,87818,87858), nausea and vomiting (8543,17112,87728,87844,87858), diarrhea (87844), dry mouth (17112), and constipation (5719,87787). However, post-market surveillance suggests that the incidence of these events is relatively low, occurring in less than 2% of patients (88007).
Fresh ginkgo seeds can cause stomach ache, nausea, vomiting, or diarrhea. Ingesting roasted seeds in amounts larger than the normal food amounts of 8-10 seeds per day, or long-term, can also cause these same adverse reactions (8231,8232).

Genitourinary ...Orally, ginkgo extract has been reported to cause blood in the urine (87858,115628).

Hematologic ...Spontaneous bleeding is one of the most concerning potential side effects associated with ginkgo. There are several published case reports linking ginkgo to episodes of minor to severe bleeding; however, not all case reports clearly establish ginkgo as the cause of bleeding. In most cases, other bleeding risk factors were also present including taking other medications or natural medicines, old age, liver cirrhosis, recent surgery, and other conditions. In most cases, bleeding occurred after several weeks or months of taking ginkgo (13135). Large-scale clinical trials and a meta-analysis evaluating standardized ginkgo leaf extracts show that the incidence of bleeding in patients taking ginkgo is not significantly higher than in those taking placebo (16634,16635,17179,17402).
There are several case reports of intracerebral bleeding. Some of these cases resulted in permanent neurological damage and one case resulted in death (244,578,8581,13135,13179,14456,87868,87977).
There are at least 4 cases of ocular bleeding including spontaneous hyphema (bleeding from the iris into the anterior part of the eye) and retrobulbar hemorrhage associated with ginkgo use (579,10450,13135).
There are also cases of surgical and post-surgical complications in patients using ginkgo. Retrobulbar hemorrhage (bleeding behind the eye) during cataract surgery has been associated with ginkgo use (10450). Excessive postoperative bleeding requiring transfusion has also occurred following laparoscopic surgery in a patient who had been taking ginkgo leaf extract (887). There have also been two cases of excessive bleeding during surgery and post-surgical hematoma in patients undergoing rhytidoplasty and blepharoplasty (13002). In another case, an elderly patient taking ginkgo experienced excessive postoperative bleeding following total hip arthroplasty (13194). In another case, use of ginkgo following liver transplantation surgery was associated with subphrenic hematoma requiring evacuation by laparotomy. The patient also subsequently experienced vitreous hemorrhage (14315). In another case, an elderly patient who had taken ginkgo chronically experienced excessive post-operative bleeding following an ambulatory surgical procedure (14453).
In another case, an elderly man experienced nose bleeds and ecchymosis following use of ginkgo. One case of diffuse alveolar hemorrhage in a female taking ginkgo and ginseng for over one year has been reported (95670). These instances of bleeding stopped when ginkgo was discontinued, and recurred when the patient started taking ginkgo again (13135).
Persistent bleeding has also occurred following dental surgery (87862) and laparoscopic cholecystectomy (88000). Nosebleed has also been reported as an adverse effect in a clinical trial (87813).

Immunologic ...Orally, ginkgo leaf extract can cause allergic skin reactions in some patients (14449,15578,112946). In one case, a patient developed acute generalized exanthematous pustulosis 48 hours after taking a single-ingredient ginkgo product. The rash resolved within 10 days after discontinuing ginkgo (14449). In another case, progressive erythema of the face, neck, trunk, and extremities occurred after two 60 mg oral doses of ginkgo extract (112946). There is also a case of Stevens-Johnson syndrome following a second administration of a preparation containing ginkgo leaf extract, choline, vitamin B6, and vitamin B12 (208). In another case, systemic edema and severe arthralgia was reported after contact with a ginkgo tree nut and manifested as multifocal lymphadenopathy associated with an allergic reaction on PET/CT scan imaging (95672).

Musculoskeletal ...Edema has been reported for three patients treated with ginkgo extract 40 mg orally three times daily (87818).

Neurologic/CNS ...Orally, ginkgo extract may cause headache (6220,8543,87818), dizziness (5719,87818), increased desire to sleep (87839,115628), and sedation (10893) in some patients. In addition, although ginkgo leaf and ginkgo leaf extract contain only small amounts of ginkgotoxin, there are anecdotal reports of seizure occurring after use of ginkgo leaf preparations both in patients without a history of seizure disorder and in those with previously well-controlled epilepsy (7030,7090,11296,14281).

Ocular/Otic ...Orally, ginkgo may cause tinnitus is some patients (8543,115628).
Topically, eye drops containing ginkgo extract and hyaluronic acid may cause stinging sensations in some people (87829).

Psychiatric ...Orally, ginkgo has been associated with a single case of mood dysregulation. A 50-year-old female with schizophrenia developed irritability, difficulty controlling anger, and agitation after one week of taking ginkgo 80 mg twice daily. The mood changes resolved within 2-3 days of discontinuation. When ginkgo was re-trialed at a later date, the same symptoms reappeared, and again dissipated after discontinuation of the ginkgo product. The relationship between ginkgo and mood dysregulation was considered to be "probable" based on the Naranjo adverse drug reaction probability scale (96763); however, the exact mechanism by which ginkgo may have affected mood regulation is unknown.

General ...Orally and topically, gotu kola seems to be well tolerated.
Most Common Adverse Effects:
Orally: Gastric irritation and nausea.
Topically: Eczema.
Serious Adverse Effects (Rare):
Orally: Hepatotoxicity.

Dermatologic ...Topically, gotu kola may cause eczema (10277,10278). Also, gotu kola can cause allergic contact dermatitis, characterized by erythema, itching, papules, and a burning sensation (4,6887,9789,52875,52887,52896,52902). One specific gotu kola product (Blasteostimulina,Almirall, S. A.) has been reported to cause allergic contact dermatitis. However, not all patients with reactions to this product are sensitive to gotu kola; some patients are sensitive to neomycin, another ingredient in the product (52875). Madecassol ointment (Rona Laboratories Limited) is another gotu kola product that has resulted in allergic contact dermatitis. Controlled testing suggests that this product can cause this adverse effect in about 8% of patients (9789). Centellase cream has also caused allergic contact dermatitis in at least two cases (52887,52888).

Gastrointestinal ...In some patients, gotu kola can extract cause gastrointestinal upset and nausea (780,6887,52894).

Hepatic ...There is concern that gotu kola may cause liver toxicity in some patients. There are at least four case reports of hepatotoxicity associated with gotu kola; however, hepatotoxic contaminants cannot be ruled out, as laboratory analysis was not conducted on the products used. Additionally, the doses of gotu kola used in these cases were not reported (13182,92506). In a clinical trial where liver function was monitored, taking gotu kola 120 mg daily for 6 months was not associated with changes in liver function (11065).
In one case of hepatotoxicity, a 61-year-old female developed elevated liver transaminase and total bilirubin levels after taking gotu kola tablets for 30 days. Liver biopsy showed granulomatous acute hepatitis. Months later, the patient took gotu kola again and developed elevated liver transaminases after 2 weeks. In another case, a 52-year-old female developed symptoms of hepatitis and increased liver transaminases after taking gotu kola for 3 weeks. Biopsy indicated chronic hepatitis and granulomas, areas of necrosis, and cirrhotic transformation. Liver function normalized after discontinuation of gotu kola. In a third case, a 49-year-old female developed symptoms of hepatitis after taking gotu kola for 2 months. Biopsy revealed granulomatous hepatitis. Liver function normalized after discontinuation of gotu kola (13182). In a fourth case, a 15-year-old female taking an unknown dose of gotu kola and lymecycline for 6 weeks for acne experienced acute liver failure with abdominal pain and vomiting, as well as elevated liver transaminases, bilirubin, international normalized ratio (INR), and prothrombin. Liver function returned to normal after both products were discontinued (92506).

Immunologic ...Topically, gotu kola can cause allergic contact dermatitis, characterized by erythema, itching, papules, and a burning sensation (4,6887,9789,52875,52887,52896,52902). One specific gotu kola product (Blasteostimulina, Almirall, S. A.) has been reported to cause allergic contact dermatitis in some patients. However, not all patients who react to this product are sensitive to gotu kola; some are sensitive to neomycin, another ingredient in the product (52875). Madecassol ointment (Rona Laboratories Limited) is another gotu kola product that has resulted in allergic contact dermatitis. Controlled testing suggests that this product can cause this adverse effect in about 8% of patients (9789). Centellase cream has also caused allergic contact dermatitis in at least two cases (52887,52888).

Psychiatric ...A case of night eating syndrome has been reported for a 41-year-old female who had been taking a gotu kola tincture (dose not specified) for 2 years. Symptoms resolved after gotu kola use was discontinued (52878).

OATS (organic Oats (Avena sativa) milky seed extract)

General ...Orally, oats are well tolerated.
Most Common Adverse Effects:
Orally: Abdominal distension, bloating, flatulence, and unpleasant taste.
Topically: Burning, contact dermatitis, itching, and redness.

Dermatologic ...Topically, oat-containing preparations can cause contact dermatitis (12515). Redness, burning, and itchiness have also been reported (103340).

Gastrointestinal ...When consumed orally, oats provide fiber. Increasing fiber in the diet can cause flatulence, bloating, abdominal distention, and unpleasant taste. To minimize side effects, doses should be slowly titrated to the desired level. These adverse effects usually subside with continued use (12514).
In patients who have difficulty chewing food, or those with conditions that decrease small bowel motility, oat bran may cause bezoars (concretions) and intestinal obstruction. Oats and oat bran are unlikely to cause obstruction without other causative factors (4979,4985).

Immunologic ...In a case report, a 45-year-old male developed acute generalized urticaria, facial angioedema, and dyspnea immediately after consuming oat flour. The reaction resolved after emergency care for anaphylaxis. Further investigation revealed an IgE-mediated hypersensitivity reaction to oat proteins (113490).

General ...Orally, topically, or rectally, peppermint oil is generally well tolerated. Inhaled, peppermint oil seems to be well tolerated. Intranasally, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted. Orally, peppermint leaf seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal pain, anal burning, belching, diarrhea, dry mouth, heartburn, nausea, and vomiting.
Topically: Burning, dermatitis, irritation, and redness.

Dermatologic ...Topically, peppermint oil can cause skin irritation, burning, erythema, and contact dermatitis (3802,11781,31528,43338,68473,68457,68509,96361,96362). Also, a case of severe mucosal injury has been reported for a patient who misused an undiluted over the counter mouthwash that contained peppermint and arnica oil in 70% alcohol (19106).
In large amounts, peppermint oil may cause chemical burns when used topically or orally. A case of multiple burns in the oral cavity and pharynx, along with edema of the lips, tongue, uvula, and soft palate, has been reported for a 49-year-old female who ingested 40 drops of pure peppermint oil. Following treatment with intravenous steroids and antibiotics, the patient's symptoms resolved over the course of 2 weeks (68432). Also, a case of chemical burns on the skin and skin necrosis has been reported for a 35-year-old male who spilled undiluted peppermint oil on a previous skin graft (68572). Oral peppermint oil has also been associated with burning mouth syndrome and chronic mouth ulceration in people with contact sensitivity to peppermint (6743). Also, excessive consumption of mint candies containing peppermint oil has been linked to cases of stomatitis (13114).

Gastrointestinal ...Orally, peppermint oil can cause heartburn, nausea and vomiting, anal or perianal burning, abdominal pain, belching, dry mouth, diarrhea, and increased appetite (3803,6740,6741,6742,10075,11779,11789,17682,68497,68514)(68532,68544,96344,96360,102602,107955). Enteric-coated capsules might help to reduce the incidence of heartburn (3802,4469,6740,11777). However, in one clinical study, a specific enteric-coated formulation of peppermint oil (Pepogest; Nature's Way) taken as 180 mg three times daily was associated with a higher rate of adverse effects when compared with placebo (48% versus 31%, respectively). Specifically, of the patients consuming this product, 11% experienced belching and 26% experienced heartburn, compared to 2% and 12%, respectively, in the placebo group (107955). A meta-analysis of eight small clinical studies in patients with irritable bowel syndrome shows that taking enteric-coated formulations of peppermint oil increases the risk of gastroesophageal reflux symptoms by 67% when compared with a control group (109980). Enteric-coated capsules can also cause anal burning in people with reduced bowel transit time (11782,11789).

Genitourinary ...Orally, a sensitive urethra has been reported rarely (102602).

Hepatic ...One case of hepatocellular liver injury has been reported following the oral use of peppermint. Symptoms included elevated liver enzymes, fatigue, jaundice, dark urine, and signs of hypersensitivity. Details on the dosage and type of peppermint consumed were unavailable (96358).

Immunologic ...One case of IgE-mediated anaphylaxis, characterized by sudden onset of lip and tongue swelling, tightness of throat, and shortness of breath, has been reported in a 69-year-old male who consumed peppermint candy (89479). An allergic reaction after use of peppermint oil in combination with caraway oil has been reported in a patient with a history of bronchial asthma (96344). It is not clear if this reaction occurred in response to the peppermint or caraway components.

Neurologic/CNS ...Orally, headache has been reported rarely (102602).

Ocular/Otic ...Orally, peppermint has been reported to cause blurry vision (3803).

General ...Orally, rosemary seems to be well tolerated when used in appropriate medicinal amounts. Undiluted rosemary oil or very large quantities of rosemary leaf should not be consumed. Topically and as aromatherapy, rosemary seems to be well tolerated.

Dermatologic ...Topically, rosemary use can lead to photosensitivity, erythema, dermatitis, and cheilitis in hypersensitive individuals (4,6).

Immunologic ...Topically, allergic reactions can occur. When used in the mouth, lip and gum edema have occurred (101173). When used on the skin, allergic contact dermatitis has occurred, likely due to the constituent carnosol (71715,71924,71926).
Rosemary might also cause occupational asthma. A case of occupational asthma caused by several aromatic herbs including thyme, rosemary, bay leaf, and garlic has been reported. The diagnosis was confirmed by inhalation challenges. Although all of the herbs caused immediate skin reactivity, a radioallergosorbent test (RAST) showed that garlic was the most potent allergen by weight, with rosemary and the other herbs showing less reactivity (783).

Neurologic/CNS ...Orally, the undiluted oil, as well as the camphor constituent of rosemary, might cause seizures (4,5,6,12868).

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