Yunnan Paiyao by Yunnan Paiyao Group

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Chronic obstructive pulmonary disease (COPD). Oral alpinia has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-sized clinical study in adults with COPD shows that taking a combination product containing extracts of alpinia, ginger, cardamom, cinnamon, and saffron in honey 3 times daily for 8 weeks improves confidence in leaving home and the ratio of forced exploratory volume per second to forced vital capacity of the lungs (FEV1/FVC) when compared with placebo. However, the combination product does not improve most measures of respiratory function or symptoms such as cough, phlegm, chest tightness, dyspnea, reduced energy levels, sleeping disorders, or activity limitations when compared with placebo (111542). It is unclear if these effects are due to alpinia, other ingredients, or the combination.
• Male infertility. It is unclear if oral alpinia is beneficial for improving sperm function in males with infertility. Details: Preliminary clinical research in males with idiopathic infertility shows that taking alpinia extract 100 mg three times daily for 12 weeks increases sperm count and morphology when compared with placebo (102094). Whether alpinia can improve the rates of successful pregnancies is unclear.
• Mental alertness. It is unclear if oral alpinia is beneficial for improving mental alertness in healthy adults. Details: Preliminary clinical research in healthy adults with a history of moderate caffeine intake shows that taking a specific alpinia extract (EnXtra, Enovate Biolife), 300 mg orally twice daily, or the same extract plus caffeine 200 mg orally twice daily for 12 weeks, increases mental alertness three hours after the dose to a similar extent in both active groups when compared with placebo (106740).
• Minor bleeding. Oral alpinia has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Some preliminary clinical research shows that applying 4 mL of a specific product (Ankaferd blood stopper) containing alpinia, licorice, thyme, stinging nettle, and common grape vine reduces bleeding during surgery, but does not improve the surgical time for episiotomy repair, when compared with saline (31010). Other preliminary clinical research suggests that topical application of this same product reduces bleeding in postsurgical dental patients with increased bleeding tendency (31002). More evidence is needed to rate the effectiveness of alpinia for these uses.

(Read more about ALPINIA)

POSSIBLY EFFECTIVE

• Angina. Low-quality clinical research shows that oral or intravenous Panax notoginseng may improve the frequency and severity of angina symptoms. Details: Meta-analyses of low-quality clinical research in patients with angina shows that Panax notoginseng administered intravenously or orally 200-400 mg 2-3 times daily for 2-6 weeks, in addition to conventional medicine, increases the number of patients who achieve a 50% improvement in angina pectoris symptoms by approximately 1.2-fold when compared with conventional medicine alone (94321,94326,94378). Panax notoginseng also reduces angina attack frequency by about 2 attacks per week but does not reduce the incidence of intractable angina pectoris (94321).
• Intracranial hemorrhage. Low-quality clinical research shows that intravenous Panax notoginseng saponins may improve recovery and mortality in patients with intracranial hemorrhage. Details: A meta-analysis of low-quality clinical research in patients with intracranial or intracerebral hemorrhage shows that treatment with Panax notoginseng saponins 140-600 mg intravenously daily for 2-10 weeks increases the odds of improvement by 2.7-fold when compared with conventional treatment alone. A subgroup analysis also suggests that treatment within 48 hours reduces the risk of mortality by 55% when compared with conventional treatment alone (94324).
• Stroke. Low-quality clinical research in patients with ischemic stroke shows that oral or intravenous Panax notoginseng may improve recovery as well as neurologic and functional scores. Details: Three meta-analyses of clinical research in patients with ischemic stroke show that treatment with oral or injectable Panax notoginseng 150-1080 mg daily for 3 days to 6 months with or without standard treatment improves neurological status and increases the overall response rate and improvement rate by around 20% when compared with conventional medicine alone or control (94373,109523,112463). Treatment with Panax notoginseng also improved some measures of activities of daily living (109523,112463). Additionally, preliminary clinical research in patients with a recent anterior cerebral ischemic stroke shows that taking Panax notoginseng root (sanchitongtshu) extract, containing 100 mg of panaxatriol saponins, orally three times daily with aspirin 50 mg daily for 28 days improves neurological deficit scores and activities of daily living scores when compared with placebo and aspirin (17183). There is evidence that Panax notoginseng may benefit stroke sequalae beyond the acute period of symptoms. A very large clinical study in adults with mild to moderate ischemic stroke shows that taking Panax notoginseng saponins 60 mg twice daily for 3 months within 14 days of stroke symptom onset in addition to standard care increases the proportion of patients with functional independence at 3 months by 7%, the number of patients with no or minimal disability at 3 months and 12 months by 5% and 3%, respectively, and leads to greater improvements in neurological deficits and activities of daily living when compared with placebo. However, Panax notoginseng does not improve functional independence at 12 months or reduce the risk of recurrent stroke or composite cerebrovascular events when compared with placebo (112464).

POSSIBLY INEFFECTIVE

• Myocardial infarction (MI). Low-quality clinical research shows that oral Panax notoginseng may not reduce the risk of MI in patients with coronary heart disease. Details: A meta-analysis of two small clinical trials in patients with existing coronary heart disease shows that that taking a specific Panax notoginseng product (Xuesaitong soft capsule, Shenghuo Pharmaceutical Holdings) 240 mg orally twice daily along with conventional therapy for 4 weeks does not reduce the risk of MI when compared with conventional therapy alone (94321).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Atherosclerosis. Although there has been interest in using oral Panax notoginseng for atherosclerosis, there is insufficient reliable information about the clinical effects of Panax notoginseng for this purpose.
• Athletic performance. It is unclear if oral Panax notoginseng is beneficial for improving athletic performance. Details: A meta-analysis of small clinical studies in generally healthy adults shows that taking Panax notoginseng 200-1350 mg or ginsenoside Rg1, a constituent of Panax notoginseng, 5 mg orally once daily for 1-30 days before running or cycling increases exercise endurance when compared with control (109672). One clinical study of untrained adults shows that taking Panax notoginseng root powder 1350 mg daily for 30 days increases cycling endurance by at least 7 minutes when compared with baseline (94384). The validity of this study is limited by the lack of a comparator group.
• Bleeding. Although there has been interest in using oral Panax notoginseng for bleeding, there is insufficient reliable information about the clinical effects of Panax notoginseng for this purpose.
• Bruises. Although there has been interest in using topical Panax notoginseng for bruises, there is insufficient reliable information about the clinical effects of Panax notoginseng for this purpose.
• Coronary heart disease (CHD). It is unclear if oral Panax notoginseng is beneficial for improving platelet aggregation and coagulation in patients with CHD. Details: A meta-analysis of clinical studies in patients with CHD and ischemic stroke shows that taking Panax notoginseng preparations including Panax notoginseng saponins (PNS) or panaxatriol saponins (PTS) with aspirin reduces platelet aggregation rate when compared with aspirin alone. Subgroup analysis suggests that the two formulations differ in their effect on biomarkers of platelet aggregation and coagulation. PTS increases prothrombin time and prothrombin time-based international normalized ratio (PT-INR) compared with aspirin alone. Meanwhile, PNS reduces fibrinogen and D-dimer compared with aspirin alone. Neither Panax notoginseng preparation changed platelet counts when compared with aspirin alone (112462).
• Exercise-induced muscle soreness. It is unclear if oral Panax notoginseng is beneficial for reducing exercise-induced muscle soreness. Details: Preliminary clinical research in well-trained males shows that taking Panax notoginseng, 4 grams orally one hour before a downhill run, then every 4 waking hours for 48 hours, and then twice daily for 48 hours, modestly reduces delayed onset muscle soreness at 96 hours, but not at earlier time points, when compared with baseline (94320). The validity of this study is limited by the lack of a comparator group.
• Hepatitis. Although there has been interest in using oral Panax notoginseng for hepatitis, there is insufficient reliable information about the clinical effects of Panax notoginseng for this purpose.
• Hypertension. Although there has been interest in using oral Panax notoginseng for hypertension, there is insufficient reliable information about the clinical effects of Panax notoginseng for this purpose.
• Nonalcoholic steatohepatitis (NASH). Although there has been interest in using oral Panax notoginseng for NASH, there is insufficient reliable information about the clinical effects of Panax notoginseng for this purpose.
• Osteoarthritis. Oral Panax notoginseng has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults with knee osteoarthritis shows that taking two capsules, each containing 400 mg of a combination of Panax notoginseng, Siberian ginseng, and rehmannia, orally daily for 6 weeks moderately improves physical function scores, but not pain or stiffness scores, when compared with placebo (74950). It is unclear if these effects are due to Panax notoginseng, other ingredients, or the combination.
• Rheumatoid arthritis (RA). Although there has been interest in using oral Panax notoginseng for RA, there is insufficient reliable information about the clinical effects of Panax notoginseng for this purpose.
• Ulcerative colitis. Rectal Panax notoginseng has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in adults admitted to the hospital with mild to moderate ulcerative colitis lesions shows that administering a 1-gram suppository containing Panax notoginseng and multiple other ingredients rectally for 3 months improves diarrhea and bloody stool symptom scores when compared with a 0.8-gram suppository containing the same ingredients. Recurrence at 12 months occurred in approximately 10% of the patients who received the higher-dose combination product compared with 47% of patients who received the lower dose. Patients in each group received 2 suppositories twice daily for the first month, 1 suppository twice daily for the second month, and 1 suppository once daily for the third month. Each suppository contained Panax notoginseng 36 grams, cortex phellodendri 120 grams, radix Sanguisorbae 120 grams, arnebia root, 120 grams, radix pulsatillae 120 grams, rhizoma coptidis 120 grams, cortex fraxini 120 grams, rhizoma corydalis, pericarpium papaveris 72 grams, radix sophorae flavescentis 72 grams, and rhizoma bletillae 72 grams (109673). The interpretation of these results is limited by the lack of comparison to placebo or active control with known effectiveness for ulcerative colitis. Additionally, it is unclear if these effects are due to Panax notoginseng, other ingredients, or the combination.
• Venous thromboembolism (VTE). It is unclear if oral or intravenous Panax notoginseng is beneficial for the prevention of postoperative deep vein thrombosis (DVT). Details: A meta-analysis of randomized controlled trials in adults undergoing surgical treatment for a fracture shows that using a Panax notoginseng injection, alone or in combination with other anticoagulants, for 3-14 days reduces the risk of DVT by 58% when compared with active control, such as low-molecular weight heparin (LMWH) or rivaroxaban (105510). The validity of these findings is limited by the high heterogeneity of the included studies. A prospective study in post-surgical adults using LMWH shows that taking a specific Panax notoginseng tablet (Xuesaitong, Hunan Xiangya Pharmaceutical Company) 100 mg three times daily reduces the risk of DVT by 44% when compared with LMWH alone (109674). The validity of this study is limited by lack of randomization. More evidence is needed to rate Panax notoginseng for these uses.

(Read more about PANAX NOTOGINSENG)

POSSIBLY EFFECTIVE

• Acute Bronchitis. Oral Pelargonium sidoides may be beneficial in adults and children with acute bronchitis when initiated within 48 hours of symptom onset. Details: Several clinical studies and a meta-analysis of 6 small-to-moderate sized clinical studies in adults and children with acute bronchitis show that taking Pelargonium sidoides extract daily, starting within 48 hours of symptom onset, significantly reduces symptoms such as cough intensity and rales after 7 days of treatment when compared with placebo. Additionally, patients report an earlier onset of effect and increased remission of cough when compared with placebo (14258,16647,16649,16651,81557,81565,94580,110015,112124). Another meta-analysis of 6 clinical trials in children aged 6-10 years with acute bronchitis or acute tonsillopharyngitis shows that taking a specific Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 20 drops three times daily for 6 days reduces the amount of acetaminophen co-medication required to treat fever when compared with placebo (112126). However, most of the outcomes in these studies were patient-reported. Additionally, it is unclear whether any improvements are clinically significant. Various formulations of Pelargonium sidoides have been investigated. A specific liquid extract of Pelargonium sidoides containing the active ingredient EPs 7630 (Dr. Willmar Schwabe Pharmaceuticals) has been used in most studies (14258,16647,16649,16651,81557,81565,94580,110015,112124). In adults, this specific extract is administered as 30 drops of solution three times daily or in tablet form as 10-30 mg three times daily for 7 days (14258,16649,16651,81557,81565,94580). In children, this specific extract is administered as 10 drops three times daily in patients under 7 years of age or 20 drops three times daily for 7 days in those 7 years of age and older (16651,112124). In children aged 1-5 years of age, this specific extract is also available as a syrup dosed at 2.5 mL 3 times daily, which is equivalent to 10 drops of solution 3 times daily (112123). Some studies used extracts in tablet form; however, these tablet formulations have only been shown to be beneficial in adults, not in children (17417,94580).
• Chronic obstructive pulmonary disease (COPD). Oral Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) may decrease the frequency of exacerbations, improve symptoms, and reduce the need for antibiotics in patients with COPD; however, it does not seem to reduce the overall risk of exacerbations. Details: One clinical study in patients with moderate to severe COPD shows that taking Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 1.5 mL three times daily in addition to standard treatment for 24 weeks lengthens the average time to COPD exacerbation by 14 days when compared with placebo (97319). The addition of Pelargonium sidoides to standard therapy is also associated with a reduction in total COPD symptoms, antibiotic use, and missed workdays (97319,97325). However, Pelargonium sidoides does not seem to decrease the overall number of COPD exacerbations (97325).
• Common cold. Oral Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) may reduce the severity and duration of cold symptoms and improve sleep quality in adults with the common cold. Details: Some clinical research in adults with the common cold shows that taking Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 1.5 mL three times daily reduces symptoms of the common cold and increases the rate of complete resolution after 10 days of treatment, but not after 5 days of treatment, when compared with placebo (81569,94580). The same product taken at a higher dose of 3 mL three times daily reduces cold symptoms by an additional 10% and has a higher rate of complete resolution after 5 days of treatment. However, this dose is associated with a higher rate of mild to moderate adverse effects (97318). Additionally, a small uncontrolled study shows that this extract is equally effective for reducing common cold symptoms in patients testing positive for human coronavirus infection (not including COVID-19) when compared with other viruses (106648). Meta-analyses have evaluated the effects of this specific extract in adults with the common cold. One meta-analysis of 5 studies, some unpublished, using Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals)extract 1.5-3 mL three times daily, or tablets 20-40 mg three times daily, for 10 days shows that the mean reduction in a subjective, 40-point, total cold intensity score is 2.3 points at 5 days and 1.2 points at 10 days. Although it is unclear if these decreases are clinically significant, the extract was associated with fewer lost work days, lower acetaminophen consumption, and improved sleep quality when compared with placebo (103604). A separate meta-analysis of five small-to-moderate size studies, some of which were included in the previous meta-analysis, shows that taking Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) in the same formulations and doses reduces cough intensity and increases remission of cough at day 5 when compared with placebo (110015). However, all outcomes in this meta-analysis were patient-reported. Lastly, a network meta-analysis comparing 18 herbal medicines often used for the common cold suggests that Pelargonium sidoides is the most beneficial of those studied for the relief of symptoms associated with the common cold (112122). However, it is unclear whether any improvements in cold symptoms are clinically significant.

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Asthma. It is unclear if oral Pelargonium sidoides extract is beneficial in children with asthma who have an active viral upper respiratory tract infection. Details: One small clinical study in children with mild asthma and an active viral upper respiratory tract infection shows that taking 5-10 drops of a specific extract of Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) three times daily for 5 days reduces the number of children experiencing asthma attacks by 28% when compared with no treatment. It also reduces the number of children experiencing nasal symptoms by 34% and cough by 31% when compared with no treatment (94577).
• Genital herpes. Although there has been interest in using oral Pelargonium sidoides for genital herpes, there is insufficient reliable information about the clinical effects of Pelargonium sidoides for this purpose.
• Herpes labialis (cold sores). Although there has been interest in using oral Pelargonium sidoides for herpes labialis, there is insufficient reliable information about the clinical effects of Pelargonium sidoides for this purpose.
• Rhinosinusitis. Small clinical studies suggest that oral Pelargonium sidoides root extract may improve symptoms in adults with rhinosinusitis. Details: One small clinical study in adults with rhinosinusitis of unclear etiology shows that taking Pelargonium sidoides root extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 60 drops three times daily for 21 days reduces symptoms of rhinosinusitis and increases the chance of complete resolution after treatment by 57% when compared with placebo (94580). Additionally, a small open-label study in adults with acute bacterial rhinosinusitus shows that taking this same product in tablet form as 60 mg daily for 10 days reduces the total symptom score, as well as subjective measures of nasal obstruction, facial pain and pressure, impaired sense of smell, mucosal edema, and mucopurulent secretions, when compared with taking amoxicillin 1500 mg daily for 10 days (103605). Additionally, a network meta-analysis comparing 18 herbal medicines often used for acute post-viral rhinosinusitis suggests that Pelargonium sidoides is the most beneficial after cineole for the relief of symptoms (112122).
• Tonsillopharyngitis. It is unclear if oral Pelargonium sidoides extract is beneficial in children with tonsillopharyngitis. Details: A small clinical study in children aged 6-10 years with acute tonsillopharyngitis shows that taking a specific Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 20 drops three times daily for 7 days reduces symptoms such as sore throat and difficulty swallowing after 4 days of treatment when compared with placebo (14262). A meta-analysis of 6 clinical trials in children aged 6-10 years old with acute tonsillopharyngitis or acute bronchitis, including the study mentioned above, shows that taking a specific Pelargonium sidoides extract (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) 60-240 drops daily for 6 days reduces the amount of acetaminophen co-medication required to treat fever when compared with placebo (112126).
• Upper respiratory tract infection (URTI). A small clinical study suggests that oral Pelargonium sidoides root extract may improve symptoms in children with URTIs. Details: One clinical trial in children with uncomplicated URTIs shows that taking a specific Pelargonium sidoides root extract (Pelumm) three times daily for 7 days reduces total symptom scores when compared with placebo, with cough frequency and sneezing improving significantly within 3 days of treatment. The extract dose was based on patient age, with children 1-5 years of age taking 10 drops three times daily, children 5-12 years of age taking 20 drops three times daily, and children 13 years of age taking 30 drops three times daily (106646). More evidence is needed to rate Pelargonium sidoides for these uses.

(Read more about PELARGONIUM SIDOIDES)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Hereditary hemorrhagic telangiectasia (HHT). It is unclear if topical rose geranium oil is beneficial for epistaxis in patients with HHT. Details: A small clinical study in patients with HHT shows that applying 3-4 drops of a topical formulation containing rose geranium essential oil 0.17% in sesame oil into the nose twice daily for at least 3 months reduces the severity of epistaxis by 34% when compared to baseline (93881). The validity of this finding is limited by a lack of control group.
• Neuropathic pain. Although there has been interest in using oral and topical rose geranium oil for neuropathic pain, there is insufficient reliable information about the clinical effects of rose geranium oil for this purpose.
• Postherpetic neuralgia. It is unclear if topical rose geranium oil is beneficial in patients with postherpetic neuralgia. Details: A small clinical study in patients with postherpetic neuralgia shows that a single topical application of rose geranium oil 50% or 100% can significantly reduce pain when compared with placebo. Pain relief appears to be concentration-dependent. Rose geranium oil in a concentration of 100% appears to be about twice as effective as a 50% concentration (16653).
• Wound healing. Although there has been interest in using topical rose geranium oil for wound healing, there is insufficient reliable information about the clinical effects of rose geranium oil for this purpose. More evidence is needed to rate rose geranium oil for these uses.

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There is insufficient reliable information available about the effectiveness of spotted geranium.

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POSSIBLY INEFFECTIVE

• Menopausal symptoms. Topical wild yam does not seem to improve menopausal symptoms. Details: Wild yam applied topically as a cream in menopausal patients for 3 months appears to be no better than placebo for relieving vasomotor symptoms, such as hot flashes and night sweats. It also does not appear to change serum follicle stimulating hormone (FSH), estradiol, or progesterone levels (10989).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cognitive function. It is unclear if oral wild yam is beneficial for improving cognitive function in healthy adults. Details: Preliminary clinical research in healthy adults shows that taking a specific wild yam extract (Diopower 15, Anti-Aging Pro Corporation) orally, 50 mg (containing diosgenin 8 mg) daily for 12 weeks, modestly improves overall measures of cognitive function and semantic fluency when compared with placebo (96724).
• Dysmenorrhea. Although there is interest in using oral or topical wild yam for dysmenorrhea, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Gallbladder disease. Although there is interest in using oral wild yam for gallbladder disease, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Infertility. Although there is interest in using oral or topical wild yam for infertility, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Osteoporosis. Although there is interest in using oral wild yam for osteoporosis, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Postmenopausal conditions. Although there is interest in using oral wild yam for postmenopausal conditions, there is insufficient reliable information about the clinical effects of wild yam for these conditions.
• Premenstrual syndrome (PMS). Although there is interest in using oral wild yam for PMS, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Rheumatoid arthritis (RA). Although there is interest in using oral wild yam for RA, there is insufficient reliable information about the clinical effects of wild yam for this condition.
• Sexual dysfunction. Although there is interest in using oral wild yam for sexual dysfunction, there is insufficient reliable information about the clinical effects of wild yam for this condition. More evidence is needed to rate wild yam for these uses.

(Read more about WILD YAM)

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

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts (12,102094). Alpinia extract 300 mg daily has been used with apparent safety for 12 weeks (102094). There is insufficient reliable information available about the safety of alpinia when used topically.

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of alpinia when used in medicinal amounts during pregnancy and lactation; avoid using.

(Read more about ALPINIA)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Panax notoginseng has been used with apparent safety in doses of 100-400 mg 1-3 times daily for up to 6 weeks (17183,94321,94326,94378,94384,109674). ...when given as an injection, under medical supervision. Panax notoginseng extract has been used with apparent safety in doses of 400-800 mg daily for up to 10 weeks (94324,94326,94373,98976,109523). There is insufficient reliable information available about the safety of Panax notoginseng when administered rectally.

PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally (5559). Ginsenoside Rb1, an active constituent of Panax notoginseng, has teratogenic effects in animal models (10447).

(Read more about PANAX NOTOGINSENG)

LIKELY SAFE ...when used orally or appropriately, short-term. A specific extract of Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals), in doses of 4.5-9 mL daily when administered as a solution or 90 mg daily when administered as a tablet, has been safely used for up to 24 weeks (14258,16641,16647,16649,16651,17417,81557,81565,94580,97318)(97319,106647). There is insufficient reliable information available about the safety of Pelargonium sidoides when used orally, long-term.

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. A specific extract of Pelargonium sidoides (EPs 7630, Dr. Willmar Schwabe Pharmaceuticals) in doses of 3 mL daily has been used with apparent safety in children aged 6-10 years for up to 7 days (14262,16641,16651,17417,94580).

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

(Read more about PELARGONIUM SIDOIDES)

LIKELY SAFE ...when used orally in amounts commonly found in foods. Rose geranium oil has Generally Recognized as Safe (GRAS) status in the US (4912).

POSSIBLY SAFE ...when used topically and appropriately, short-term. A single application of rose geranium oil in concentrations up to 100% has been safely used in a clinical trial (16653). ...when used intranasally and appropriately, short-term. Rose geranium oil has been applied with sesame oil in the nose safely (93881). There is insufficient reliable information available about using rose geranium oil orally for medicinal purposes.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid amounts greater than those found in foods.

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There is insufficient reliable information available about the safety of spotted geranium.

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

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POSSIBLY SAFE ...when used orally. A dose of 50 mg (containing 8 mg diosgenin) has been used with apparent safety for 12 weeks (12,96724). ...when used topically. A wild yam cream has been used with apparent safety for 3 months (10989).

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

(Read more about WILD YAM)

ANTACIDS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, alpinia might decrease the effectiveness of antacids.  Details There are some reports suggesting that alpinia increases stomach acid (19).

H2-BLOCKERS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, alpinia might decrease the effectiveness of H2-blockers.  Details There are some reports suggesting that alpinia increases stomach acid (19).

INDOMETHACIN (Tivorbex) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, alpinia might reduce the levels and clinical effects of indomethacin.  Details In animals, giving an alpinia extract orally reduces systemic exposure to indomethacin, reduces its retention time in plasma, and accelerates its elimination in the bile and feces (106738). This interaction has not been reported in humans.

PROTON PUMP INHIBITORS (PPIs) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, alpinia might decrease the effectiveness of PPIs.  Details There are some reports suggesting that alpinia increases stomach acid (19).

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ASPIRIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking Panax notoginseng concomitantly with aspirin may increase the risk of adverse effects from both products.  Details Animal research shows that taking Panax notoginseng extract with aspirin increases blood levels of salicylic acid by approximately 50% and blood levels of Panax notoginseng by 75% to 196%. This effect may be due to increased absorption of both products (94322,96219).

CAFFEINE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking Panax notoginseng may decrease the levels and clinical effects of caffeine.  Details Animal research shows that administering Panax notoginseng intravenously for 7 days before intraperitoneal injection of caffeine can decrease maximal blood levels of caffeine by 37%. This interaction is attributed to the ability of Panax notoginseng to increase the activity of cytochrome P450 1A2 (CYP1A2) enzymes (94319).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking Panax notoginseng might reduce the levels and clinical effects of CYP1A2 substrates.  Details Animal research shows that administering Panax notoginseng intravenously for 7 days before intraperitoneal injection of caffeine can decrease maximal blood levels of caffeine by 37%. This interaction was attributed to the ability of Panax notoginseng to increase the activity of CYP1A2 (94319).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking Panax notoginseng concomitantly with warfarin may increase the risk of bleeding.  Details Animal research shows that taking Panax notoginseng concomitantly with warfarin increases plasma warfarin levels, prothrombin time, and international normalized ratio when compared with control. In vitro research also suggests that Panax notoginseng may downregulate expression of cytochrome P450 3A4 enzymes, which may affect warfarin metabolism (109676).

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Moderate •  Occurrence = Unlikely •  Level of Evidence = D Theoretically, Pelargonium sidoides might increase the risk of bleeding when taken with anticoagulant and antiplatelet drugs.  Details Pelargonium sidoides contains coumarin, which may reduce platelet aggregation (14259). However, in animal models, Pelargonium sidoides extract does not appear to inhibit coagulation or interact with warfarin (16648). This interaction has not been documented in humans.

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, Pelargonium sidoides might decrease the effectiveness of immunosuppressant therapy.  Details In vitro research suggests that Pelargonium sidoides has immunostimulant effects (14258,14259,16646,16650,16652).

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ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, wild yam might increase or decrease the effects of estrogen.  Details Wild yam root shows estrogenic and anti-estrogenic effects in vitro (6180,70411,96723,96725). Theoretically, wild yam might interfere with hormone therapy.

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General ...Orally and topically, alpinia seems to be well tolerated.

Gastrointestinal ...Orally, alpinia may cause gastrointestinal adverse effects. In one clinical trial, around 5% of patients taking alpinia extract 100 mg three times daily for 12 weeks discontinued treatment due to adverse gastrointestinal effects (102094).

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General ...Panax notoginseng seems to be generally well tolerated when used orally or intravenously.
Most Common Adverse Effects:
Orally: Dry mouth, flushed skin, insomnia, nausea, nervousness, rash, vomiting.
Intravenously: Headache, itching, rash.
Serious Adverse Effects (Rare):
Intravenously: Fever, pustular drug eruption.

Dermatologic ...Orally, Panax notoginseng can cause flushed skin (5558). When given orally or intravenously, rash has been reported (94321,94324,94326,94378,98976). There is a case of interstitial granulomatous drug reaction in a 73-year-old male who had been using oral Panax notoginseng extract for 2 months. The condition repeated after 5 days of intravenous use at a later time. The skin condition gradually cleared after use of the product was discontinued (94316). In a retrospective review of hospital records of 30,884 patients, a specific Xueshuantong injection (XSTI) containing Panax notoginseng saponins was associated with a 4% incidence of skin reactions, including redness, itching, and maculopapules (98976).

Gastrointestinal ...Orally and intravenously, Panax notoginseng can cause dry mouth, nausea, and vomiting (5558,94321,98976). In one case report, a patient developed a large submucosal hematoma extending from the hypopharynx to lower esophagus after taking one oral dose of an unknown quantity of Panax notoginseng and hirudin (109671). It is unclear if this event was due to Panax notoginseng, hirudin, or other factors.

Immunologic ...Intravenously, Panax notoginseng saponins have been associated with five cases of pustular drug eruption due to acute generalized exanthematous pustulosis. The skin eruption was associated with fever and an increased neutrophil count in some cases. Symptoms were deemed to be probably or likely due to the Panax notoginseng product (94327). In a retrospective review of hospital records of 30,884 patients, a specific Xueshuantong injection (XSTI) containing Panax notoginseng saponins was associated with a fever frequency of 0.2%, edema frequency of 0.1%, and anaphylactic reactions in 0.03% (98976).

Neurologic/CNS ...Orally, Panax notoginseng can cause nervousness and insomnia (5558). Intravenously, Panax notoginseng has been reported to cause headache (94326,94378). In a retrospective review of hospital records of 30,884 patients, a specific Xueshuantong injection (XSTI) containing Panax notoginseng saponins was associated with a headache frequency of 0.3% and paresthesia frequency of 0.1% (98976).

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General ...Orally, Pelargonium sidoides is generally well tolerated.
Most Common Adverse Effects:
Orally: Allergic skin rash, diarrhea, gastrointestinal upset.

Cardiovascular ...Orally, Pelargonium sidoides has been reported to cause small increases in body temperature and pulse during clinical trials (16649,17417).

Dermatologic ...Orally, Pelargonium sidoides has been associated with allergic skin rash (14262,81557).

Gastrointestinal ...Orally, Pelargonium sidoides has been associated with gastrointestinal upset and diarrhea (14262,81557,97318,97319,106647,112123).

Hematologic ...Orally, Pelargonium sidoides has been associated with epistaxis in one clinical trial (97318).

Hepatic ...Orally, Pelargonium sidoides does not appear to cause hepatotoxicity. Evaluations of hepatotoxicity cases in patients taking Pelargonium sidoides show it was only possibly associated in 4 of the 28 reported cases. In the remaining 24 cases, Pelargonium sidoides was unlikely to be the cause of hepatotoxicity, or was excluded as the cause. Other causes of hepatotoxicity in these cases included infectious disease, pre-existing liver disease, acute pancreatitis, and hepatotoxicity due to conventional medication use (94578,94579).

Immunologic ...Orally, Pelargonium sidoides has been associated with over 34 reports of allergic reactions (81567). Urticaria is the most common reaction but there were also cases of conjunctivitis, rhinitis, and systemic allergic reactions including bronchospasm, dyspnea, tachycardia, and circulatory failure (16651,81567).

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General ...Orally, rose geranium oil is well tolerated when used in food amounts. Topically, rose geranium oil seems to be well tolerated, short-term.

Dermatologic ...Topically, rose geranium oil has been associated with reports of dermatitis in hypersensitive individuals and burning sensations when applied to the face (16653).

Gastrointestinal ...When applied with droppers in the nose, rose geranium oil has been reported to cause a bad taste (93881).

Neurologic/CNS ...Topically, rose geranium oil has been associated with reports of lightheadedness and eye irritation when applied to the face (16653).

Ocular/Otic ...Topically, rose geranium oil has been associated with reports of eye irritation when applied to the face (16653).

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General ...No adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.

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General ...Orally, wild yam is generally well tolerated.
Most Common Adverse Effects:
Orally: Fever, headache, upset stomach, and vomiting.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis.

Gastrointestinal ...Orally, wild yam can cause upset stomach and vomiting, especially at higher doses (12,86450).

Hematologic ...In one case report, a 55-year-old female with protein S deficiency and systemic lupus erythematosus (SLE) had temporary vision loss in the left eye from hemiretinal vein thrombosis 3 days after taking a combination phytoestrogen product containing wild yam 276 mg, dong quai 100 mg, red clover 250 mg, and black cohosh 250 mg (13155). It is unclear if wild yam contributed to this event.

Immunologic ...There are three case reports of anaphylaxis after ingestion of cooked wild yam (96722).

Neurologic/CNS ...Orally, wild yam can cause headache and fever, especially at higher doses (86450).

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