Specific Formula Arthro Ace Capsules by Natural Health Care Development Ltd

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, in addition to conventional therapy, may improve recovery, as well as neurologic and functional scores. Details: Two meta-analyses of clinical research in patients with an ischemic stroke shows that treatment with Panax notoginseng, most commonly a specific product (Xuesaitong, Xing Zhong Pharmaceutical Co. Ltd.), 150-1080 mg intravenously daily for 10-42 days, increases the overall response rate and improvement rate by 20% to 21% when compared with conventional medicine alone (94373,109523). Treatment with Panax notoginseng also improved some measures of activities of daily living (109523). 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).

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.
• 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).
• 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 suppository containing Panax notoginseng and multiple other ingredients rectally for 3 months improves diarrhea and bloody stool symptom scores when compared with placebo. Taking the combination product also reduced recurrence by 79% when compared with placebo. Patients 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).
• 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.

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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).

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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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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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