PA(7) by High Performance Nutrition

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). It is unclear if oral astragalus is beneficial for allergic rhinitis. Details: Preliminary clinical research shows that taking a specific astragalus root extract standardized to contain 40% polysaccharides (Lectranal, Milsing d.o.o.) 160 mg orally twice daily for 3-6 weeks improves symptoms such as rhinorrhea, sneezing, and itching when compared with placebo in adults with seasonal allergic rhinitis (17355).
• Amenorrhea. Oral astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One preliminary clinical study shows that taking a liquid decoction containing astragalus 30 grams, dong quai 30 grams, zizyphus 10 fruits, horny goat weed 15 grams, dodder 30 grams, and three slices of ginger, daily in two divided doses for 3 months, can increase menstrual frequency when compared to baseline in patients with amenorrhea (33050). The validity of this finding is limited by the lack of a comparator group. Additionally, it is unclear if this effect is due to astragalus, other ingredients, or the combination.
• Angina. It is unclear if oral astragalus is beneficial for angina. Details: A preliminary clinical trial shows that taking astragalus 20 grams orally three times daily for 2 weeks can improve cardiac output, but not diastolic function, when compared to baseline in patients with angina (33063). The validity of these findings is limited by the lack of a comparator group.
• Anthracycline cardiotoxicity. It is unclear if intravenous astragalus is beneficial for preventing cardiotoxicity due to anthracyclines. Oral astragalus has not been evaluated for this use. Details: A large unblinded clinical study in patients with breast cancer or lymphoma receiving a chemotherapy regimen containing epirubicin shows that intravenous use of astragalus 500 mg daily for 14 days during 2 courses of chemotherapy modestly attenuates the decline in left ventricular ejection fraction (LVEF) and reduces the occurrence of cardiotoxicity when compared with standard care (110479). However, this study was conducted in China, which limits the generalizability of its results.
• Aplastic anemia. It is unclear if intravenous astragalus is beneficial for aplastic anemia. There is insufficient reliable information about the clinical effects of oral astragalus for this condition. Details: Preliminary clinical research in patients 15 years and older with chronic aplastic anemia shows that giving intravenous astragalus in combination with stanozolol 2 mg three times daily produces greater improvements in symptoms and blood cell counts than stanozolol alone. Astragalus was given as 80-120 grams daily for repeated 15-day courses at 7-10 day intervals for at least 4 months (32840).
• Asthma. Oral astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in children with mild asthma shows that taking a combination of astragalus, cordyceps, Radix stemonae (Bai Bu), bulbus fritillariae cirrhosae, and Baikal skullcap orally for 6 months does not improve asthma symptoms, measures of lung function, or total steroid use when compared with placebo (32935).
• Beta-thalassemia. Although there has been interest in using oral astragalus for beta-thalassemia, there is insufficient reliable information about the clinical effects of astragalus for this condition.
• Breast cancer. Although there has been interest in using oral astragalus for breast cancer, there is insufficient reliable information about the clinical effects of astragalus for this condition.
• Cervical cancer. Oral astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 19 clinical trials in adults with cervical cancer who are receiving chemotherapy shows that the use of Chinese herbal medicines containing astragalus increases tumor response (complete and partial responses) and Karnofsky performance score and reduces chemotherapy-associated adverse effects when compared with chemotherapy alone (107479). However, most studies included in the meta-analysis were low-quality, and all studies were conducted in China. Higher quality studies in other geographic locations are needed to confirm these findings. Additionally, it is unclear if any effects are due to astragalus, other ingredients, or the combination.
• Chemotherapy-induced anemia. Oral or intravenous astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of low-quality clinical trials in patients with colorectal cancer shows that oral or intravenous use of traditional Chinese medicine therapies containing astragalus and other ingredients along with conventional chemotherapy reduces the risk of anemia by 51% when compared with chemotherapy alone (102099). It is unclear if these effects are due to astragalus, the other ingredients, or the combination.
• Chemotherapy-induced diarrhea. It is unclear if oral or intravenous astragalus is beneficial for chemotherapy-induced diarrhea. Details: One preliminary clinical study shows that intravenous infusion of astragalus 40 grams in 250 mL of solution, given daily for 21 days during each of four courses of chemotherapy, reduces diarrhea by 59% when compared to chemotherapy alone (32747). Additionally, a meta-analysis of low-quality clinical trials in patients with colorectal cancer shows that oral or intravenous use of traditional Chinese medicine therapies containing astragalus and other ingredients along with conventional chemotherapy reduces the risk of diarrhea by 45% when compared with chemotherapy alone (102099). It is unclear if these effects are due to astragalus, the other ingredients, or the combination.
• Chemotherapy-induced leukopenia. Oral or intravenous astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of low-quality clinical trials in patients with colorectal cancer shows that oral or intravenous use of traditional Chinese medicine therapies containing astragalus and other ingredients along with conventional chemotherapy reduces the risk of thrombocytopenia by 41% when compared with chemotherapy alone (102099). It is unclear if these effects are due to astragalus, the other ingredients, or the combination.
• Chemotherapy-induced nausea and vomiting (CINV). Early research suggests that intravenous astragalus seems to reduce nausea and vomiting associated with chemotherapy use. It is unclear if oral astragalus is beneficial for CINV. Details: A meta-analysis of low-quality clinical research in Chinese patients with advanced non-small cell lung cancer shows that intravenous infusion of astragalus along with platinum-based chemotherapy reduces the risk of vomiting by 38% when compared with platinum-based chemotherapy alone (100698). Another preliminary clinical study shows that intravenous infusion of astragalus 40 grams in 250 mL of solution, given daily for 21 days during each of four courses of chemotherapy, reduces nausea by 36% and vomiting by 50% when compared with chemotherapy alone (32747). Higher quality studies are needed to confirm these results. The use of astragalus in combination with other ingredients for prevention of CINV has also been investigated. A meta-analysis of low-quality clinical trials in patients with colorectal cancer shows that oral or intravenous use of traditional Chinese medicine therapies containing astragalus and other ingredients along with conventional chemotherapy reduces the risk of nausea and vomiting by 44% when compared with chemotherapy alone (102099). It is unclear if these effects are due to astragalus, the other ingredients, or the combination.
• Chemotherapy-induced nephrotoxicity. Oral or intravenous astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of low-quality clinical trials in patients with colorectal cancer shows that oral or intravenous use of traditional Chinese medicine therapies containing astragalus and other ingredients along with conventional chemotherapy does not reduce the risk of nephrotoxicity when compared with chemotherapy alone (102099). The effects of astragalus when used alone are unclear.
• Chemotherapy-related fatigue. It is unclear if intravenous astragalus is beneficial for chemotherapy-related fatigue. There is insufficient reliable information about the clinical effects of oral astragalus for this condition. Details: One clinical study in patients with advanced cancer shows that treatment with an intravenous infusion of a partially purified astragalus extract (PG2, Pharmagenesis), 500 mg three times weekly for 4 weeks during chemotherapy, improves fatigue scores after one week, but not after two and four weeks, when compared with placebo (33034).
• Chronic fatigue syndrome (CFS). Oral astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One preliminary clinical study in adults with CFS shows that taking a 200 mL decoction containing astragalus 30 grams, kudzu 30 grams, codonopsis 15 grams, red sage 10 grams, aizoon stonecrop 15 grams, horny goat weed 10 grams, turmeric 10 grams, and calamus 10 grams, in two divided doses daily for 3 months improves fatigue symptoms when compared to baseline (32920). Another preliminary clinical study shows that taking 1.5 grams of a specific product (Myelophil, Samik Pharmaceutical Company) containing 66% of extracts of astragalus and danshen in a 1:1 ratio twice daily for 4 weeks improves fatigue severity when compared with placebo. However, taking 3 grams of the same product twice daily does not seem to have a benefit (32883). It is unclear if these effects are due to astragalus, the other ingredients, or the combination.
• Chronic kidney disease (CKD). It is unclear if intravenous astragalus is beneficial for CKD. There is insufficient reliable information about the clinical effects of oral astragalus for this condition. Details: A meta-analysis of preliminary clinical research in patients with CKD shows that using astragalus, usually as an injection, along with conventional treatment modestly improves creatinine clearance by 6 mL/min, serum creatinine by 0.25 mg/dL, and hemoglobin levels by 1 gram/dL when compared with conventional treatment alone (90660). However, the studies included in the meta-analysis were of low quality. Additionally, a moderate-sized clinical study in patients with CKD and type 2 diabetes shows that taking astragalus 15 grams daily for 5 days per week in combination with standard care for 48 weeks ameliorates the decline in glomerular filtration rate, but does not improve the urinary albumin to creatinine ratio, when compared with standard care alone (114803). The validity of these findings is limited by methodological flaws, including inadequate blinding. Also, it is not known if astragalus reduces mortality or attenuates the progression to kidney failure.
• Chronic obstructive pulmonary disease (COPD). Intravenous astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of low-quality clinical studies in adults with COPD shows that intravenous astragalus 10-60 mL (concentration not specified) once or twice daily for 2 weeks in combination with ambroxol hydrochloride and other conventional therapies improves COPD clinical symptoms, some measures of pulmonary function, and arterial blood gases when compared with conventional therapies alone (114688). All studies were conducted in China which may limit generalizability of the results. It is unclear if these effects are due to astragalus, ambroxol hydrochloride, or the combination.
• Cirrhosis. Intravenous astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. There is insufficient reliable information about the clinical effects of oral astragalus for this condition. Details: A meta-analysis of results from low-quality clinical studies shows that intravenous injection of a combination of astragalus and danshen for up to 90 days might decrease fibrosis when compared with control in patients with liver cirrhosis (90662). However, it is unclear if this is due to astragalus, danshen, or the combination.
• Colorectal cancer. Oral or intravenous astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of clinical trials in patients with colorectal cancer shows that oral or intravenous use of traditional Chinese medicine therapies containing astragalus and other ingredients along with conventional chemotherapy improves quality of life scores and increases the rate of tumor response by 52% when compared with chemotherapy alone (102099). It is unclear if these effects are due to astragalus, the other ingredients, or the combination.
• Diabetes. It is unclear if oral or intravenous astragalus is beneficial for diabetes. Details: A meta-analysis of preliminary clinical research in Chinese patients with type 2 diabetes shows that astragalus, given as a daily intravenous injection 40-80 grams or taken orally 40-60 grams daily as an aqueous decoction for up to 4 months, modestly improves fasting and postprandial blood glucose levels when compared to a control group. Oral astragalus seems to improve these outcomes slightly more than intravenous astragalus. Orally, astragalus also seems to improve fasting insulin levels and insulin resistance, although its effect on glycated hemoglobin (HbA1c) is inconsistent. (95909). Astragalus has also been evaluated as an adjuvant therapy to metformin. A meta-analysis of several mostly small clinical studies in adults with type 2 diabetes shows that taking astragalus 10-50 grams daily with metformin modestly reduces fasting blood glucose by approximately 12 mg/dL, 2-hour postprandial blood glucose by 12 mg/dL, and HbA1c by 0.9% when compared with metformin monotherapy (112809). A meta-analysis of mostly low-quality clinical studies in patients with diabetes shows that taking astragalus in the form of traditional Chinese medicine, with or without Western medicine, reduces fasting blood glucose, 2-hour postprandial glucose, and glycated hemoglobin when compared with Western medicine alone (114805). However, the clinical studies included in both of these meta-analyses are of low methodological quality and include only Chinese patients, which limits the reliability and generalizability of the results. Some research has evaluated astragalus in combination with other ingredients. One preliminary clinical study in adults with previously untreated type 2 diabetes shows that taking astragalus 210 mg, goldthread 350 mg, and honeysuckle 840 mg three times daily before meals for 3 months does not improve fasting blood glucose, postprandial blood glucose, or HbA1c when compared with placebo, although glucose disposal rate is modestly improved (32925).
• Diabetic nephropathy. It is unclear if intravenous astragalus is beneficial for diabetic nephropathy. Details: Meta-analyses of small, low-quality clinical studies including over 4700 patients shows that adding intravenous astragalus to routine therapy for 2-12 weeks modestly improves blood urea nitrogen, serum creatinine, creatinine clearance, urinary protein, urinary albumin, and serum albumin when compared with routine therapy alone in patients with diabetic nephropathy (33019,102100).
• Diabetic neuropathy. It is unclear if oral astragalus is beneficial for diabetic neuropathy. Details: A meta-analysis of mostly low-quality clinical studies in patients with diabetic neuropathy shows that taking astragalus in the form of traditional Chinese medicine, with or without Western medicine, modestly reduces signs and symptoms of diabetic neuropathy when compared with Western medicine alone (114805). However, this improvement may not be clinically significant. Additionally, all studies were conducted in China which may limit generalizability of the results.
• Diabetic retinopathy. It is unclear if oral astragalus is beneficial for diabetic retinopathy. Details: A meta-analysis of results from preliminary clinical research suggests that taking astragalus-containing products for up to 10 months modestly improves visual acuity and fundus manifestations when compared with control in patients with diabetic retinopathy. However, the included studies had methodological limitations, and the results were heterogeneous (90655).
• Fibromyalgia. Although there has been interest in using oral astragalus for fibromyalgia, there is insufficient reliable information about the clinical effects of astragalus for this condition.
• Gastric cancer. Oral and intravenous astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 35 randomized, controlled trials involving 2670 patients with advanced gastric cancer shows that taking either intravenous or oral traditional Chinese medicines containing astragalus in conjunction with platinum-based chemotherapy may improve objective response rate, disease control rate, 1-year survival rate, and quality of life, and may also reduce the severity of chemotherapy-associated adverse effects, when compared with chemotherapy alone (107480). The validity of this meta-analysis is limited by potential publication bias, unclear randomization methods, and substantial heterogeneity among the included studies. Additionally, it is unclear if these effects are due to astragalus, other ingredients, or the combination.
• Hearing loss. It is unclear if intravenous astragalus is beneficial for hearing loss. Details: Preliminary clinical research shows that injecting 0.5 mL/kg of solution containing astragalus 2 grams/mL daily for 10 days improves hearing in people with sudden deafness or acute acoustic trauma when compared with a control group (33028,33033).
• Heart failure. It is unclear if oral or intravenous astragalus is beneficial for heart failure. Details: A meta-analysis of small to moderate-sized low quality clinical studies in adults with heart failure with reduced ejection fraction (HFrEF) shows that oral astragalus 30 grams twice daily or intravenous astragalus 20-60 mL (concentration not specified) daily for 2-4 weeks combined with conventional treatment modestly increases left ventricular ejection fraction (LVEF), decreases brain natriuretic peptide levels, and increases 6-minute walking distance when compared with conventional treatment alone (114804). Findings are limited by significant heterogeneity. Additionally, all studies were conducted in China which may limit generalizability of the results. The conflicting nature of these results are reflected in other small studies. One preliminary clinical study in adults with CHF shows that intravenous infusion of astragalus 60 grams daily for 20 days improves LVEF and left ventricular end-diastolic volume (LVEDV) when compared with conventional treatment (32755). However, another preliminary clinical study shows that intravenous astragalus 60 grams daily for 28 days in combination with conventional treatment for CHF does not improve LVEF, LVEDV, or left ventricular end-systolic volume when compared with conventional treatment alone (32812). Other preliminary clinical research shows that taking oral astragalus 2.25-7.5 grams twice daily for 14-30 days in combination with conventional treatment improves cardiac function, LVEF, and walking distance when compared with conventional treatment alone (33018,33022). However, each of these studies has methodological problems.
• Hepatitis B. Although there has been interest in using oral astragalus for hepatitis B, there is insufficient reliable information about the clinical effects of astragalus for this condition.
• HIV/AIDS. Oral astragalus 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 containing mainly Baikal skullcap root, glossy privet fruit, astragalus root, and Eupolyphaga et polyphage (Ailing granules) 20 grams twice daily for 4 months improves HIV/AIDS symptoms and CD4 cell counts (32824). However, taking a different combination containing licorice, yin chen, white mulberry, astragalus, and safflower orally for 12 weeks is associated with only a slight decline in viral load and no change in CD4 cell counts (32795). The effects of astragalus alone are unclear.
• IgA nephropathy. Although there has been interest in using intravenous astragalus for IgA nephropathy, there is insufficient reliable information about the clinical effects of oral or intravenous astragalus for this condition.
• Lung cancer. Early research suggests that oral or intravenous astragalus seems to increase the effectiveness of platinum-based chemotherapy or radiotherapy in patients with advanced non-small cell lung cancer (NSCLC). Details: One meta-analysis in patients with advanced NSCLC shows that intravenous administration of astragalus along with platinum-based chemotherapy increases the rate of one-year survival by 40% when compared with platinum-based chemotherapy alone (100698). Other meta-analyses in these patients show that use of oral or intravenous astragalus-containing herbal products appears to reduce the risk of death at six months by 42%, at one year by 33%, at two years by 27% to 33%, and at three years by 15% to 24% when compared with platinum-based chemotherapy or radiotherapy alone (15001,90656). Additionally, a network meta-analysis of clinical research in patients with NSCLC ranks intravenous administration of astragalus along with a combination of docetaxel and cisplatin as the most effective of various Chinese herbal medicine injection and docetaxel and cisplatin combinations (114689). However, most studies included in the meta-analyses were low-quality, and all studies were conducted in China. Higher quality studies in other geographic locations are needed to confirm these findings.
• Membranous nephropathy. Oral astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of 48 small, low-quality clinical studies in adults with idiopathic membranous nephropathy conducted in China shows that taking astragalus 20-90 grams per day in combination with a variety of other supplements, in addition to conventional therapy, modestly improves the rate of complete or partial renal remission when compared with conventional therapy (e.g. angiotensin-converting enzyme inhibitors, immunosuppression). Adding astragalus combinations to conventional therapy also modestly reduces proteinuria and serum creatinine (112010). However, the interpretation of these findings is limited by the heterogeneity of the included studies and variable definitions of complete and partial renal remission. Additionally, it is unclear if these effects are due to astragalus, other ingredients, or the combination.
• Menopausal symptoms. Oral astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One preliminary clinical study shows that taking Dang Gui Buxue Tang, an herbal decoction containing astragalus and dong quai extract, 3 grams daily for 6 months does not reduce the incidence of menopausal hot flashes (32857). However, another preliminary clinical study shows that taking Dang Gui Buxue Tang 3-6 grams daily for 12 weeks reduces hot flash frequency by up to 40% and night sweat frequency up to 53% when compared to baseline (90659). Each 1.5 grams of Dang gui Buxue Tang contains extract prepared from dong quai 1.5 grams and astragalus 7.5 grams (90659). Another small clinical study in females with moderate or severe menopausal symptoms shows that taking a tablet containing astragalus and Rubus coreanus extract 1000 mg twice daily for 12 weeks modestly improves symptom and quality of life scores when compared with placebo (110478). However, the validity of these findings is limited by a high rate of study participant discontinuation.
• Myocardial infarction (MI). Although there has been interest in using intravenous astragalus for MI, there is insufficient reliable information about the clinical effects of oral or intravenous astragalus for this purpose.
• Myocarditis. It is unclear if oral or injectable astragalus is beneficial for viral myocarditis. Details: A meta-analysis of 13 mostly small, low-quality clinical studies in adults and children with viral myocarditis shows that astragalus injection may improve the total effective rate and reduce markers of inflammation when compared with conventional treatment (110477). However, most studies included in the meta-analysis were low-quality, dosing was variable, and all studies were conducted in China. Higher quality studies in other geographic locations are needed to confirm these findings. Several clinical studies report improvements in cardiac enzymes, cardiac function, or viral load in peripheral leukocytes with the use of astragalus preparations, but results are inconsistent and the methodological quality of these studies is low (33084,33105,33217,33218,33220,33221,33223). Doses demonstrating benefit include intramuscular astragalus extract, equivalent to 8 grams daily for 3-4 months (33105) and intravenous astragalus extract 40 grams daily for 2 weeks (33218,33221). It is unclear if astragalus speeds recovery or reduces the risk of mortality due to myocarditis.
• Nephrotic syndrome. It is unclear if oral astragalus is beneficial for preventing infections in patients with nephrotic syndrome. Details: A meta-analysis of results from two preliminary clinical studies shows that taking astragalus 7.5-15 grams twice daily for 3-6 months reduces the risk of infection by 38% when compared to control in children with nephrotic syndrome (33036).
• Obesity. Oral astragalus 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 astragalus, rhubarb, turmeric, red sage root, ginger, and gallic acid concurrently with a reduced-calorie diet does not improve weight loss when compared with a reduced-calorie diet alone in adults who are overweight or obese (20347).
• Post-stroke fatigue. It is unclear if oral astragalus is beneficial for post-stroke fatigue. Details: A preliminary clinical study shows that taking astragalus extract (Sun Ten Pharmaceutical Co. Ltd.) 2.8 grams three times daily for 28 days improves fatigue and some quality of life measures such as social functioning, role functioning, and physical functioning, when compared with placebo in patients experiencing fatigue following a recent stroke (95908).
• Systemic lupus erythematosus (SLE). It is unclear if intravenous astragalus is beneficial for lupus nephritis. There is insufficient reliable information about the clinical effects of oral astragalus for this condition. Details: A preliminary clinical study in adults with lupus nephritis shows that intravenous infusions of astragalus 40 grams daily for 12 consecutive days monthly for 3 months, in combination with corticosteroids and cyclophosphamide once monthly as an intravenous drip, can improve symptoms, reduce infections, and reduce urinary protein excretion when compared to treatment with corticosteroids and cyclophosphamide alone (32838).
• Tinnitus. It is unclear if intravenous astragalus is beneficial for tinnitus. Details: Preliminary clinical research shows that injecting 0.5 mL/kg of solution containing astragalus 2 grams/mL daily for 10 days reduces tinnitus in patients with acute acoustic trauma when compared to a control group (33028).
• Upper respiratory tract infection (URTI). Although there has been interest in using oral astragalus for URTI prevention, there is insufficient reliable information about the clinical effects of astragalus for this purpose.
• Urinary Tract Infections (UTIs). Oral astragalus has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A moderate-size clinical study in females aged 18-45 with uncomplicated UTIs shows that taking a supplement containing astragalus root extract 100 mg, d-mannose, citric acid, dandelion, and prebiotics as a sachet dissolved in water twice daily for 5 days improves complete resolution of UTI symptoms and clearance of bacteriuria at days 6 and 35 when compared with placebo (111757). However, it is unclear if these effects are due to astragalus, other ingredients, or the combination.
• Wound healing. Although there has been interest in using topical astragalus for wound healing, there is insufficient reliable information about the clinical effects of astragalus for this purpose. More evidence is needed to rate astragalus for these uses.

(Read more about ASTRAGALUS)

POSSIBLY EFFECTIVE

• Hepatic encephalopathy. Oral and intravenous BCAAs improve symptoms and nutritional status in patients with hepatic encephalopathy, especially in those not tolerating protein supplementation. Details: Taking BCAAs 240 mg/kg (up to 25 grams) daily in 3 divided doses for up to 3 months can improve symptoms, liver function tests, and nitrogen balance in patients with chronic hepatic encephalopathy (68,69,82,690,92643,97531). Oral BCAAs are recommended for malnourished patients with chronic hepatic encephalopathy who cannot tolerate protein supplementation (69,4274). When the enteral route is unavailable and when patients cannot tolerate general purpose amino acid solutions, intravenous solutions with BCAAs can be used for nutritional support; however, most patients can tolerate standard amino acid mixtures (4274). Some clinical research also suggests that taking BCAAs orally improves psychomotor function, attention, intelligence, and driving ability in patients with latent hepatic encephalopathy (684,685,37131,97531). However, not all studies show a positive effect of BCAAs on psychometric outcomes (37135). There is also some preliminary evidence that intravenous BCAAs might be helpful for reversing coma in acute hepatic encephalopathy, although findings are conflicting (66,81,686,687,688,689,4274,37134). BCAAs do not appear to reduce the risk of mortality or improve quality of life in patients with hepatic encephalopathy (92643,97531).
• Tardive dyskinesia. Oral BCAAs might reduce symptoms of tardive dyskinesia precipitated by antipsychotic drugs. Details: Taking BCAAs orally seems to reduce symptoms of tardive dyskinesia (72,10146,13307). Clinical research in adult and pediatric patients who are taking antipsychotic drugs shows that taking a drink containing BCAAs 222 mg/kg three times daily for 3 weeks reduces tardive dyskinesia movements by 30% to 60% when compared with placebo (10146,13307).

POSSIBLY INEFFECTIVE

• Liver cancer. Oral BCAAs do not seem to improve outcomes or reduce the risk for recurrence in patients with liver cancer. Details: A meta-analysis of the available clinical research, as well as individual clinical studies, in patients with hepatocellular carcinoma show that consuming up to 50 grams of BCAAs twice daily for up to 4 years does not improve survival, reduce tumor recurrence, or reduce the risk of complications such as ascites following liver resection when compared with a control group receiving no intervention (37143,92646,97532,105578). However, one small clinical study suggests that BCAAs may be beneficial in patients recently diagnosed with hepatocellular carcinoma that does not require surgery. Taking two packets of a specific supplement (Aminoleban EN) daily containing a total of L-leucine 4 grams, L-isoleucine 3.8 grams, and L-valine 3.2 grams, starting two weeks before receiving transcatheter arterial chemoembolization and radiofrequency ablation and continuing for up to 5 years, reduces recurrence of liver cancer and increases event-free survival when compared with placebo (97533). However, the validity of these findings is limited by the high withdrawal rate in this study.

LIKELY INEFFECTIVE

• Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). Overall, oral BCAAs are not beneficial and might even lead to worsened outcomes in patients with ALS. Details: Although early studies have indicated that taking BCAAs might be beneficial in ALS, more recent studies show no benefit and a possible increased loss of pulmonary function and higher rate of mortality among patients using BCAAs (678,679,680,681,37154).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. It is unclear if dietary BCAAs prevent Alzheimer disease. Details: Observational research has found that higher blood levels of BCAAs are associated with an 11% to 13% lower risk of Alzheimer disease; however, when research was adjusted for mortality, body mass index, and concomitant cholesterol-lowering medications, the association was no longer significant (100469).
• Athletic performance. Small clinical trials suggest that although oral BCAAs may not enhance athletic performance, they may modestly reduce perceived exertion and fatigue with some forms of exercise. Details: In most studies, taking BCAAs orally does not enhance athletic performance (692,1135,37080,37094,37106,37123,37141,37142,37151,92641). For instance, BCAAs do not appear to improve strength or work power or to reduce completion times for long-distance running or cycling trials (692,37106,37112,37141,37142,92641). However, most research shows that BCAAs are beneficial for reducing exercise-induced fatigue and perceived exertion after prolonged or intense exercise, exercise in the heat, or exercise following glycogen depletion (692,37112,37124,37144,92642,92644,92645,92648,97529,97530)(97535,105582). In many cases, this improvement is observed when BCAAs are taken in combination with arginine, citrulline, or green tea powder (37124,92642,92645,92648,97529,100462). However, some conflicting evidence exists (1135,37080,37094). Overall, the validity of these findings is limited because most studies differ widely in the amount and type of product consumed. For example, studied doses included BCAAs 0.17-0.3 mg/kg daily; or valine 0.5-1.7 grams, leucine 1-3.5 grams, and isoleucine 0.48-2.1 grams given before and/or after exercise (37108,37123,92642,92644,92645). Other limitations include variability in the studied endpoints and control comparisons used.
• Bipolar disorder. It is unclear if oral BCAAs are beneficial in patients with bipolar disorder. Details: One small clinical study shows that consuming a tyrosine-free amino acid drink containing 60 grams of the BCAAs leucine, isoleucine, and valine in a ratio of 3:3:4, reduces acute manic symptoms within 6 hours when compared with placebo. When taken daily for 7 days, it seems to continue to improve symptoms over a 2-week period (10117).
• Cachexia. Small clinical studies suggest that oral BCAAs are beneficial in patients with cachexia from various causes. Details: Preliminary clinical research in elderly malnourished patients receiving hemodialysis shows that taking a combination of BCAAs 4 grams three times daily improves appetite and caloric intake and increases plasma albumin levels and anthropometric measurements when compared with placebo (10147). Also, small clinical studies in adults with cachexia due to cancer or cirrhosis show that taking oral BCAAs 2.4 grams twice daily for 1 year or 4.8 grams 3 times daily for 1 week might be helpful when compared to baseline (71,37090). This finding is limited by the lack of a comparator group. A small clinical study in adults with congestive heart failure who have lost at least 7.5% of dry weight over the past 6 months or have a body mass index below 20 kg/m² shows that taking BCAAs 10 grams every evening at bedtime for 8 weeks improves physical and emotional quality of life scores, appetite, and fatigue when compared with placebo. Patients taking melatonin 20 mg nightly in addition to BCAA supplementation observed greater improvements in appetite and fatigue when compared with placebo (108478). However, a statistical comparison of outcomes between the groups taking BCAA alone or BCAA with melatonin was not provided.
• Cancer. It is unclear if dietary BCAA consumption improves cancer-related mortality. Details: Observational research in adults has found that consuming BCAAs 19 grams or more daily as part of the diet is not associated with a reduced risk of cancer-related mortality when compared with a lower dietary BCAA intake of less than 7.8 grams daily (108467). The validity of this finding is limited due to unclear reporting; additionally, dietary intake was recorded from a single survey.
• Cardiovascular disease (CVD). It is unclear if dietary BCAA consumption reduces the risk of CVD-related mortality. Details: Observational research in adults has found that CVD-related mortality is not associated with dietary BCAA intake or with individual leucine, isoleucine, or valine intake (108467). The validity of this meta-analysis is limited due to unclear reporting; additionally dietary intake was recorded from a single survey.
• Chronic obstructive pulmonary disease (COPD). It is unclear if oral BCAAs can improve physical performance in adults with COPD. Details: A clinical study in adults with stable, stage 2 or 3 COPD undergoing a pulmonary rehabilitation program shows that taking a BCAA powder 4.3 grams, diluted in water and consumed once daily for 4 weeks, may improve recovery after exercise, but does not impact maximal exercise capacity, functional and muscular performance, or quality of life when compared with placebo (108464). The validity of these findings is limited due to the short duration of treatment.
• Cirrhosis. Most small studies suggest that BCAAs may modestly improve certain measures in some patients with liver cirrhosis. Details: One small clinical study shows that although taking BCAAs 14.4 grams daily for 12 months does not improve survival or liver function in patients with advanced liver cirrhosis, the number of hospitalizations and prevalence of cachexia are reduced and quality of life is improved when compared with control or whey protein (37090). A clinical study in patients with sarcopenia and liver cirrhosis shows that taking BCAAs 7.2 grams for 6 months decreases bilirubin levels and improves Child-Turcotte-Pugh and model for end-stage liver disease (MELD) scores when compared with baseline (108468). Although the study enrolled a control group (whey protein), the investigators did not provide a statistical comparison of outcomes between groups. In addition, a small study in Japanese patients with cirrhosis shows that taking BCAAs 12.45 grams daily for at least 12 months improves liver function and reduces liver complications by 50% to 60% over 3-5 years when compared with control (37120). Also, taking a specific product (Livact, Samil Pharmaceutical) providing the same dose for 11-22 months improves liver function by a small to moderate amount over a 24-month period when compared with not taking BCAAs. There was also a moderate reduction in the rate of developing or worsening major complications such as ascites or hepatic encephalopathy (103351). However, some research providing BCAAs as part of a late evening snack has found no benefit. In one small study, consuming BCAAs as part of a late evening snack in an undefined dose for 3 months does not seem to improve quality of life when compared with a late evening snack without BCAAs (37101). Also, a very small clinical study in patients with abnormal glucose metabolism related to cirrhosis shows that consuming BCAAs in an undefined dose as part of a late evening snack for 1 week does not improve glycemic control when compared with baseline. Instead, glucose levels increased in some patients (103348). It is possible that the doses provided in these latter studies were lower than those used in the studies showing benefit. Additionally, these very small studies may not have been adequately powered to detect a difference between groups.
• Colorectal cancer. It is unclear if dietary BCAAs are beneficial or harmful in patients with colorectal cancer. Details: An observational study in Italy has found that increased dietary intake of BCAAs is associated with a lower risk of developing sigmoid colon cancer, but not overall colorectal cancer risk, when compared with lower intake (105584). However, there's some concern that increased dietary BCAAs may have negative effects in patients who have been diagnosed with colorectal cancer. Observational research in patients living in the US has found that higher dietary intake of BCAAs is associated with a slightly higher risk of all-cause mortality when compared with lower intake (105581).
• Dementia. It is unclear if dietary BCAAs help to prevent dementia. Details: Observational research has found that higher blood levels of BCAAs are associated with a 13% to 17% lower risk of dementia. The lowered risk was maintained when research was adjusted for mortality, body mass index, and concomitant cholesterol-lowering medications (100469).
• Diabetes. It is unclear if dietary BCAAs reduce the risk for developing diabetes. Details: Some population research in Japanese females has found a decreased risk of diabetes associated with higher intake of BCAAs (97543). However, other observational research in people from the US has found that increased dietary intake of BCAAs is associated with an increased risk of diabetes (97536). Reasons for the conflicting finding are not entirely clear. Some evidence suggests that the dietary pattern of BCAA intake, rather than the total intake, may influence the risk of diabetes. Also, there is some speculation that differences in gut microbiota may attribute to the observed differences in diabetes risk associated with BCAA intake (100465). Prospective clinical research is needed to determine whether this association is causal or correlative.
• Exercise-induced muscle damage. Small studies suggest that BCAAs might reduce some, but not all, markers of muscle damage caused by exercise. Details: A meta-analysis of small clinical studies shows that supplementation with BCAAs reduces creatine kinase (CK) levels 24 hours post-exercise, but not 48 hours post-exercise. Additionally, this analysis shows that lactate dehydrogenase (LDH) levels are not affected by BCAA supplementation (97534). The validity of this analysis was limited because baseline dietary protein consumption was not taken into consideration as a potential confounder. A separate meta-analysis of clinical research in trained male athletes performing various resistance exercises shows that taking BCAAs 0.2-1.76 grams/kg for 1-28 days improves CK levels immediately following exercise, and at 24 and 48 hours post-exercise, but does not reduce LDH levels at any timepoint, when compared with placebo or control (108469). Most doses of BCAAs studied consisted of a 2:1:1 ratio of leucine, isoleucine, and valine, respectively. The validity of these findings is limited due to the short duration of treatment and various doses studied. Small individual clinical trials show that taking BCAAs does not affect urinary myoglobin after a marathon nor plasma myoglobin or CK levels after isotonic muscular exercise (37123,92641,100471). The benefits of BCAAs might depend on baseline protein consumption. A small clinical study in resistance trained males shows that adding BCAAs 0.22 grams/kg (MusclePharm BCAA) daily for 8 days to a high daily protein consumption of 1.2 grams/kg does not attenuate muscle damage or improve muscle recovery when compared with placebo (100471). Conversely, a meta-analysis of clinical research in adults completing various exercises shows that taking BCAAs consisting of any combination of valine, leucine, and isoleucine ratios modestly reduces CK, LDH, and myoglobin 24 and 48 hours post-exercise, but does not improve muscle recovery or muscle force after exercise, when compared with placebo (108471). The validity of these findings is limited due to unclear reporting.
• Exercise-induced muscle soreness. Limited evidence suggests that oral BCAAs may modestly attenuate exercise-induced muscle soreness. Details: One meta-analysis shows that taking BCAAs does not reduce delayed-onset muscle soreness after exercise when assessed at the individual time points of 24, 48, or 72 hours (97534). However, when results of all time points are pooled together in two separate meta-analyses, supplementation modestly reduces soreness after exercise (97534,103353). Most, but not all, individual trials also show that taking BCAAs in various doses, such as 0.087 grams/kg or 5-10 grams before and/or after exercise, modestly reduces muscle soreness after exercise (37108,37123,37124,92648,97530,97535,100467,100471,103346,108471). The validity of these individual trials is limited by their small sample sizes, variable dosing regimens, and enrolled populations, which were mainly limited to young untrained adult males (97534,103353). A separate meta-analysis of clinical research in trained male athletes performing various resistance exercises shows that taking BCAAs 0.2-1.76 grams/kg for 1-28 days may improve muscle soreness during the first 24 hours after exercise, but not at 24 or 48 hours post-exercise, when compared with placebo or control (108469). The validity of these findings is limited due to the short duration of treatment and various doses studied. Also, it is not clear whether taking BCAAs before or after a workout may be more beneficial. Some research found a nonsignificant trend toward reduced muscle soreness when consuming a specific product (Aminofeel, Seikatsu Bunkasya Co. Ltd.) containing BCAAs 3.2 grams three times daily starting 3 days before working out and continuing 3 days after, when compared to control (100467). More research is needed to determine the best dosing regimen and which populations, if any, may benefit.
• Heart failure. It is unclear if oral BCAAs are beneficial in patients with heart failure. Details: A small clinical study in patients with heart failure and hypoalbuminemia shows that taking a specific packet of BCAA granules (LIVACT, Ajinomoto Co) containing L-valine 1144 mg, L-leucine 1904 mg, and L-isoleucine 952 mg, three times daily for at least 7 days and stopping after discharge from the hospital, does not affect serum albumin or cardiothoracic ratio (CTR) when compared with placebo (100470). It is possible that this study was underpowered to detect differences between groups. Another small clinical study in adults with chronic heart failure participating in a cardiac rehabilitation program shows that taking a specific oral supplement (Meiji Mei Balance Rehasupport Mini; Meiji Group) containing BCAAs 2.5 grams and various vitamins, minerals, and whey protein, twice daily for 12 weeks increases fat mass, but has no effect on peak oxygen uptake, 6-minute walking distance, or strength parameters, when compared with no supplementation (108470). It is unclear if these effects are due to BCAAs, the other ingredients, or the combination.
• Hepatitis. It is unclear if oral BCAAs are beneficial in patients with hepatitis. Details: Preliminary clinical research in patients with alcoholic hepatitis shows that taking BCAAs 20 grams daily orally or enterally for 3 weeks or until discharge, in combination with a controlled diet, does not reduce the risk of mortality when compared with conventional protein or a controlled diet alone (37133).
• Inflammatory myopathies. It is unclear if oral BCAAs are beneficial in patients with polymyositis and dermatomyositis. Details: A small clinical study in adults with suspected or confirmed polymyositis or dermatomyositis who are receiving standard corticosteroid therapy shows that a BCAA-specific product containing L-isoleucine 952 mg, L-leucine 1904 mg, and L-valine 1144 mg for 12-28 weeks, taken as two packages three times daily for a total daily dose of 24 grams, does not improve manual muscle test scores or clinical response at 12 and 28 weeks when compared with placebo (108477).
• Obesity. It is unclear of oral BCAAs can reduce the likelihood of developing obesity or improve weight loss in adults with overweight or obesity. Details: Some observational research has found that higher dietary intake of BCAAs is associated with lower odds of obesity when compared with a lower intake (100466). Conversely, a large observational study in adults in Iran, including those who are overweight or obese, has found that the highest dietary intake of BCAAs is associated with a 24% higher likelihood of general obesity in males, but not in females, when compared with the lowest dietary BCAA intake (108465). This study did not report ranges for highest and lowest BCAA intake, limiting the validity of this study. BCAAs have also been evaluated in adults with overweight or obesity. A small clinical study in obese females that underwent a 4-week calorie-restricted diet shows that taking 6 caplets daily containing a total of L-leucine 3 grams, L-isoleucine 1.5 grams, and L-valine 1.5 grams in addition to vitamin B6 40 mg daily for 4 weeks does not further reduce weight, but may slightly preserve lean body mass, when compared with placebo (100464). Another small clinical study in overweight and obese adults shows that taking BCAAs 0.1 gram/kg daily in addition to starting a low-calorie diet for 16 weeks does not improve weight loss, but may preserve lean muscle mass, when compared with taking placebo while following the low-calorie diet (105583).
• Overall mortality. It is unclear if dietary BCAA consumption reduces the risk of all-cause mortality. Details: Observational research in adults has found that total BCAA intake, as well as isoleucine intake, is associated with a reduced risk of all-cause mortality, particularly in those with higher serum triglyceride concentrations (108467). However, this association was not present for leucine or valine intake. The validity of this meta-analysis is limited due to unclear reporting; additionally dietary intake was recorded from a single survey.
• Pancreatic cancer. The association between dietary BCAA intake and pancreatic cancer risk is unclear. Details: Observational research in adults in Italy has found that consuming BCAAs as part of the diet in quantities greater than 18 grams daily is associated with a 2-fold increased risk of pancreatic cancer when compared with less than 12 grams daily. This relationship was stronger in younger males, those with higher body mass indexes, and in those who smoke or have high alcohol intake (108476). Dietary information was recorded from a single, weekly consumption questionnaire.
• Phenylketonuria (PKU). It is unclear if oral BCAAs are beneficial in patients with PKU. Details: A small clinical trial in adolescents and young adults with PKU shows that taking BCAAs, consisting of valine 150 mg/kg, isoleucine 150 mg/kg, and leucine 200 mg/kg, with meals and at bedtime for up to 6 months seems to improve attention and processing when compared with a control group (37127).
• Physical performance. It is unclear if oral BCAAs are beneficial for improving physical function and muscle strength in older adults. Details: In malnourished elderly individuals, preliminary clinical research shows that taking a supplement providing BCAAs 5000 mg daily, in addition to other amino acids, vitamin B6, and vitamin B1 (Aminotrofic) for 2 months, does not improve muscle mass, muscle strength, or physical function to a greater extent than dietary advice intended to maximize nutritional intake from food and drink (103349). Similarly, a clinical study in middle aged and elderly adults shows that a specific product (Sarcojoint; Orient Euro Pharma, Inc) containing leucine 1 gram, arginine, vitamin D3, glucosamine, chondroitin, and calcium, taken twice daily in addition to regular resistance exercise for 12 weeks, does not improve muscle strength, muscle mass, or physical performance when compared with taking an unspecified vitamin B supplement twice daily with regular exercise (108472). Conversely, one small clinical study in older adults who have had a hip replacement shows that taking BCAAs 1.2 grams and lysine 1.8 grams (Amino-aile, Ajinomoto Co., Inc.) daily for one month after undergoing exercise therapy sessions modestly increases the strength of both legs and arms when compared with taking starch. However, there was no effect on hip abductor strength of the operated leg or on grip strength or measures of independence (103347).
• Postoperative infection. There is limited evidence on the intravenous and oral use of BCAAs for reducing infection after oncologic surgery. Details: A meta-analysis of 6 small heterogeneous clinical trials in patients after oncologic surgery, mostly for liver cancer, suggests that receiving oral or intravenous BCAAs reduces the risk of postoperative infection by 38% when compared with control (105577).
• Postoperative recovery. There is limited evidence on the intravenous and oral use of BCAAs for improving postoperative recovery after oncologic surgery. Details: A meta-analysis of small heterogeneous clinical trials in patients after oncologic surgery, mostly for liver cancer, suggests that receiving oral or intravenous BCAAs reduces hospital stay by about 2 days, but does not reduce mortality or post-operative complications, when compared with control (105577).
• Psychological well-being. It is unclear if oral BCAAs are beneficial for psychological well-being. Details: A cross-sectional observational study has found that higher dietary consumption of BCAAs is associated with a lower risk of anxiety and depression when compared with lower consumption (105579).
• Sarcopenia. It is unclear if oral BCAAs are beneficial in patients with primary sarcopenia or in those with sarcopenia related to liver cirrhosis. Details: A small clinical study in postmenopausal adults at risk for sarcopenia shows that consuming BCAAs 9 grams daily for 8 weeks in addition to resistance training increases strength and muscle mass when compared with baseline, but is no different than resistance training plus a placebo (105576). Another small clinical study in adults 65 years or older with sarcopenia shows that taking a supplement containing BCAAs 2500 mg, vitamin D 500 IU, protein, and other vitamins daily for 8 weeks in addition to resistance training does not improve physical function when compared with resistance training alone. The supplement did seem to slightly improve handgrip strength and body mass when compared with no supplementation (100468). However, overall the study was inadequately powered to detect smaller effects on physical function and muscle mass. There is also interest in using BCCAs in patients with sarcopenia and liver cirrhosis. A clinical study in this population shows that taking BCAAs 7.2 grams (containing 1.2 grams of L-leucine, 600 mg of L-isoleucine, and 600 mg of L-valine) daily for 6 months improves handgrip strength, gait speed, and muscle mass when compared with baseline (108468). Although the study enrolled a control group (whey protein), the investigators did not provide a statistical comparison of outcomes between groups. A separate meta-analysis of low-quality clinical research in this population shows that taking BCAAs has no effect on handgrip strength when compared with no supplementation (108473). Although other outcomes were evaluated, results are inconclusive due to the limited number of studies available for each outcome.
• Spinocerebellar ataxia (SCA). It is unclear if oral BCAAs are beneficial in patients with SCA. Details: Although there is some preliminary clinical evidence that oral BCAAs might have a beneficial effect on symptoms of SCA (73), a small clinical crossover study shows that taking a particular BCAA compound (Livact) 4.5-18 grams daily for 4 weeks does not improve ataxia in patients with SCA when compared with placebo (37088).
• Stroke. It is unclear if oral BCAAs are beneficial in patients recovering from stroke. Details:A small nonblinded, clinical study in elderly patients with subacute stroke and sarcopenia currently undergoing intensive inpatient rehabilitation therapy shows that administering a specific product (Seniup; Enterogenomics Co) containing BCAAs 6 grams, given twice daily orally or by feeding tube for 1 month, modestly improves skeletal muscle index, dysphagia, gait, balance, and handgrip strength, and may attenuate muscle loss in affected upper and lower extremities, when compared with rehabilitation alone (108474). The validity of these findings is limited by the short duration of treatment. Other research has compared BCAA dosing regimens. A small study in stroke patients taking part in exercise sessions shows that taking BCAAs 3.5 grams (Hepas, Clinico Co. Ltd) daily for 2 months with breakfast is more effective for improving leg strength and balance than when taken post-exercise in the mid-afternoon. However, there were no differences in most measures of strength or in skeletal muscle mass (103352). More evidence is needed to rate BCAAs for these uses.

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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.

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POSSIBLY SAFE ...when used orally and appropriately. Doses of astragalus up to 60 grams daily for up to 4 months have been used without reported adverse effects (32920,33038,95909,114804). ...when used intravenously. Infusion of doses up to 80 grams daily for up to 4 months under the supervision of a medical professional have been used with apparent safety (32811,32812,32828,95909,114688,114804). There is insufficient reliable information available about the safety of astragalus when used topically.

PREGNANCY AND LACTATION:
There is insufficient reliable information in humans. However, astragaloside, a constituent of astragalus, has maternal and fetal toxic effects in animals (32881). Avoid using.

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LIKELY SAFE ...when used orally and appropriately. BCAAs 12 grams daily have not been associated with significant adverse effects in studies lasting for up to 2 years (68,72,73,74,10117,10146,10147,37120,92643,97531,103351,103352). ...when used intravenously and appropriately. BCAAs are an FDA-approved injectable product (13309).

CHILDREN: LIKELY SAFE
when used orally in dietary amounts of 71-134 mg/kg daily (11120,13308).

CHILDREN: POSSIBLY SAFE
when larger, supplemental doses are used orally and appropriately for up to 6 months (13307,13308,37127).

PREGNANCY:
Insufficient reliable information available; avoid using amounts greater than those found in food. Although adverse effects have not been reported in humans, some animal research suggests that consumption of supplemental isoleucine, a BCAA, during the first half of pregnancy may have variable effects on birth weight, possibly due to abnormal placental development (103350).

LACTATION:
Insufficient reliable information available; avoid using amounts greater than those found in food. Although the safety of increased BCAA consumption during lactation is unclear, some clinical research suggests that a higher concentration of isoleucine and leucine in breastmilk during the first 6 months postpartum is not associated with infant growth or body composition at 2 weeks, 2 months, or 6 months (108466).

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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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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = A Theoretically, taking astragalus with antidiabetes drugs might increase the risk of hypoglycemia.  Details Clinical research in humans shows that astragalus might have hypoglycemic effects (95909,112809,114805). Theoretically, taking astragalus, especially in combination with other hypoglycemic agents, might increase the risk of hypoglycemia.

CYCLOPHOSPHAMIDE Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, astragalus might interfere with cyclophosphamide therapy.  Details Evidence regarding the effect of astragalus on immunosuppression caused by cyclophosphamide is conflicting. Some animal research suggests that astragalus reverses cyclophosphamide-induced immunosuppression (3713). However, other animal research shows no effect (418).

IMMUNOSUPPRESSANTS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, astragalus might interfere with immunosuppressive therapy.  Details Astragalus seems to stimulate immune function (303,10777). Theoretically, taking astragalus might decrease the effects of immunosuppressive therapy.

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, astragalus might increase levels and adverse effects of lithium.  Details Animal research suggests that astragalus has diuretic properties (15103). Theoretically, due to this diuretic effect, astragalus might reduce excretion and increase levels of lithium.

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ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, BCAAs might alter the effects of antidiabetes medications.  Details Some evidence suggests that BCAAs might stimulate insulin release (10105,10110,10113,10114,10118). However, a small clinical study in adults with liver cirrhosis and high nocturnal levels of blood glucose suggests that BCAAs might increase blood glucose levels (103348).

LEVODOPA Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B BCAAs in large doses can reduce the effects of levodopa.  Details BCAAs may compete with levodopa for transport systems in the intestine and brain and decrease the effectiveness of levodopa (66,2719). Small clinical studies how that concomitant ingestion of protein or high doses of leucine or isoleucine (100 mg/kg) and levodopa can exacerbate tremor, rigidity, and the "on-off" syndrome in patients with Parkinson disease (3291,3292,3293,3294).

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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 ...Orally and intravenously, astragalus root seems to be well tolerated. Topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: A case report raises concerns about liver and kidney cysts with astragalus use.

Cardiovascular ...Orally, astragalus has reportedly been associated with lacunar angina in one clinical trial. However, this may not have been caused by astragalus (17355). In addition, rapid intravenous administration of astragalus has resulted in temporary palpitations (32812).

Dermatologic ...Intravenously, astragalus may cause rash, eczema, and pruritus (33034).

Gastrointestinal ...Orally, astragalus has reportedly been associated with enterocolitis and nausea in one clinical trial. However, these effects may not have been caused by astragalus (17355).

Genitourinary ...Orally, astragalus has reportedly been associated with vulvitis in one clinical trial. However, this effect may not have been caused by astragalus (17355).

Hepatic ...A case of high serum CA19-9 levels and small liver and kidney cysts has been reported for a 38-year-old woman who drank astragalus tea daily for one month. Levels returned to normal after one month, and cysts disappeared after ten months. Both symptoms returned following a resumption of astragalus use. The authors state that astragalus was the likely cause given the temporal relationship (90658).

Musculoskeletal ...Orally, astragalus has been associated with reports of musculoskeletal pain in one clinical trial. However, these effects may not have been caused by astragalus (114803).

Neurologic/CNS ...Intravenously, administration of astragalus has been associated with temporary dizziness in patients with heart failure in clinical research (32812,114804). Orally, astragalus has also been associated with dizziness in one clinical study. However, these effects may not have been caused by astragalus (114803).

Pulmonary/Respiratory ...Orally, astragalus has reportedly been associated with rhinosinusitis and pharyngitis in one clinical trial. However, these effects may not have been caused by astragalus (17355).

Renal ...A case of high serum CA19-9 levels and small liver and kidney cysts has been reported for a 38-year-old woman who drank astragalus tea daily for one month. Levels returned to normal after one month, and cysts disappeared after ten months. Both symptoms returned following a resumption of astragalus use. The authors state that astragalus was the likely cause given the temporal relationship (90658).

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General ...Orally or intravenously, BCAAs are generally well tolerated.
Most Common Adverse Effects:
Orally: Abdominal distension, diarrhea, nausea, vomiting.
All routes of administration: High doses can lead to fatigue and loss of motor coordination.

Cardiovascular ...Orally, a single case of hypertension following the use of BCAAs has been reported (37143).

Dermatologic ...Orally, a single case of skin blanching following the use of BCAAs has been reported (681). It is not known if this effect was due to use of BCAAs or other factors.

Gastrointestinal ...Orally, BCAAs can cause nausea, vomiting, diarrhea, and abdominal distension. Nausea and diarrhea has been reported to occur in about 10% of people taking BCAAs (10117,37143,92643,97531).

Neurologic/CNS ...Orally and intravenously, BCAAs can cause fatigue and loss of motor coordination due to increased plasma ammonia levels (693,694,10117). Short-term use of 60 grams of BCAAs containing leucine, isoleucine, and valine for 7 days in patients with normal metabolic function seems to increase levels of ammonia, but not to toxic plasma levels (10117). However, liver function should be monitored with high doses or long-term use (10117). Due to the potential of increased plasma levels of ammonia and subsequent fatigue and loss of motor coordination, BCAAs should be used cautiously before or during activities where performance depends on motor coordination (75). Orally, BCAAs may also cause headache, but this has only been reported in one clinical trial (681).

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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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