OsteoV SC [Discontinued] by NuMedica

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)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral black pepper for allergic rhinitis, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Asthma. Although there has been interest in using oral black pepper for asthma, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Athletic performance. Oral black pepper has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial in untrained males shows that taking a supplement containing black pepper extract 10 mg, caffeine 400 mg, capsicum extract 66.7 mg, and niacin 40 mg as a single dose prior to exercise does not improve strength, time to exhaustion, or maximal oxygen consumption when compared with placebo (37873).
• Depression. Although there has been interest in using oral black pepper for depression, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Diarrhea. Although there has been interest in using oral black pepper for diarrhea, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Dysmenorrhea. Although there has been interest in using oral black pepper for dysmenorrhea, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Dyspepsia. Although there has been interest in using oral black pepper for dyspepsia, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Fall prevention. It is unclear if inhaling black pepper oil as aromatherapy is beneficial for fall prevention in older adults. Details: One small clinical study in older adults shows that applying black pepper oil near the right side of the nose as an olfactory stimulant improves stability while the eyes are closed during a one-minute trial when compared with the application of water. The improvement with black pepper oil is comparable to the improvement seen with the application of lavender oil (29160). It is unclear if any benefit persists after inhalation of black pepper oil.
• Fatigue. It is unclear if oral black pepper is beneficial in patients with fatigue. Details: One small clinical trial in adults with below-average energy levels shows that taking black pepper 2 grams as a single dose does not improve sustained attention, motivation to perform cognitive tasks, or feelings of mental energy and mental fatigue when compared with placebo (91731).
• Flatulence. Although there has been interest in using oral black pepper for flatulence, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Headache. Although there has been interest in using oral black pepper for headache, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Insect bite. Topical black pepper has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial shows that applying a specific product (Trikatu) containing black pepper, long pepper, and ginger, as well as camphor, eucalyptus oil, and menthol, directly to mosquito bites does not reduce papule size, erythema, edema, or pruritis when compared with a control compound containing the same base ingredients but without the pepper and ginger components (89893).
• Obesity. Although there has been interest in using oral black pepper for obesity, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Pain (chronic). Although there has been interest in using topical black pepper for chronic pain related to various etiologies, including osteoarthritis, postherpetic neuralgia, and peripheral neuropathy, there is insufficient reliable information about the clinical effects of black pepper for these conditions.
• Rhinosinusitis. Although there has been interest in using oral black pepper for rhinosinusitis, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Sexual desire. Although there has been interest in using oral black pepper for increasing sexual desire, there is insufficient reliable information about the clinical effects of black pepper for this purpose.
• Smoking cessation. It is unclear if inhaling black pepper essential oil as aromatherapy is effective for smoking cessation. Details: One small clinical trial in adult male smokers who were deprived from smoking overnight shows that inhaling a vapor from the essential oil of black pepper, as needed over a 3-hour period, reduces cigarette cravings, negative feelings, and anxiety when compared with a placebo vapor (29159). Another small clinical study in patients addicted to dipping, chewing, or smoking tobacco shows that placing a drop of black pepper essential oil on tissue paper and inhaling for 2 minutes at least three times a day for 3 days reduces nicotine cravings when compared to baseline (90502).
• Swallowing dysfunction. It is unclear if inhaling black pepper oil as aromatherapy is beneficial in patients with swallowing dysfunction. Details: One small clinical study in post-stroke residents of nursing homes shows that one minute of olfactory stimulation with black pepper oil before each meal for 30 days decreases swallowing reflex latency by 11 seconds and increases the number of swallowing movements by 3.3 when compared to baseline (29161). A small clinical trial in children with neurological disorders who were on long-term enteral nutrition shows that applying black pepper oil to the nostrils or nasal cavity for one minute improves the amount of oral intake and swallowing movement in 63% of patients. Although oral intake increased, the need for enteral nutrition was not eliminated (29162).
• Vitiligo. It is unclear if topical piperine oil, a constituent of black pepper, is beneficial in patients with vitiligo. Details: A small clinical study in patients with vitiligo shows that applying piperine oil 1% daily in addition to receiving narrowband ultraviolet B (NB-UVB) light therapy every other day for 3 months improves repigmentation more rapidly when compared with using NB-UVB alone (103820). More evidence is needed to rate black pepper for these uses.

(Read more about BLACK PEPPER)

POSSIBLY EFFECTIVE

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

POSSIBLY INEFFECTIVE

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

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

(Read more about PANAX NOTOGINSENG)

EFFECTIVE

• Dental hypersensitivity. Brushing with strontium-containing toothpaste improves dental hypersensitivity. Details: Several clinical studies show that topical use of strontium acetate 8% and strontium chloride 10% in toothpaste relieves the pain of sensitive teeth (11745,11746,32177,76519,76570,76590). Best results are obtained with twice daily brushing (11756,32177,76590).
• Painful bony metastases. Intravenous strontium-89 improves pain associated with bony metastases. Details: Several clinical studies show that intravenous administration of strontium-89 chloride reduces metastatic bone pain (11749,11750,11751,11752,76608).

LIKELY EFFECTIVE

• Osteoporosis. Oral strontium ranelate seems to increase bone mineral density (BMD) and reduce fracture risk to a clinically significant degree in females and males with osteoporosis; however, safety concerns limit its use. Details: Several clinical studies and a meta-analysis in postmenopausal individuals with osteoporosis show that taking strontium ranelate reduces the risk of vertebral fractures by around 40% in patients with a history of vertebral fracture. There is some evidence that it might increase BMD in these patients by 14% at the lumbar spine and 8% at the femoral neck. Taking strontium ranelate also appears to reduce the risk of nonvertebral fractures by 31% (11392,11393,11395,76597,94010). In patients with or without a history of vertebral fracture, taking strontium ranelate for up to 10 years also reduces the risk of nonvertebral fractures by 15% to 38% and vertebral fractures by 24% to 35%. BMD at the lumbar spine, femoral neck, and total hip also continues to increase over the first 5 years of treatment (76527,76562,94012). In postmenopausal individuals over the age of 80 years, taking strontium ranelate 2 grams daily for 4 years reduces the relative risk of vertebral fractures by 31%, nonvertebral fractures by 33%, major nonvertebral fractures by 27%, and hip fractures by 24% when compared with placebo (94011). A large clinical trial in males with osteoporosis also shows that taking strontium ranelate 2 grams daily for 2 years significantly increases lumbar spine, femoral neck, and total hip BMD when compared with placebo (94002). There is conflicting evidence about the efficacy of strontium ranelate in patients previously treated with bisphosphonates. A moderate sized clinical study in postmenopausal individuals with osteoporosis suggests that prior treatment with bisphosphonate therapy might blunt the BMD response in patients taking strontium ranelate 2 grams daily for 2 years. In bisphosphonate naïve patients, treatment with strontium lead to increases in BMD at the spine, hip, and heel. In patients with prior bisphosphonate therapy, treatment with strontium lead to increases in BMD at the spine and hip, but not the heel. (94009). Based on the benefits of strontium ranelate on BMD and fracture risk, it was approved in Europe in 2004 for the treatment of severe osteoporosis in postmenopausal patients, and later granted market authorization for males with osteoporosis. However, its use is associated with cardiac events and thromboembolism; it is therefore contraindicated in patients with a history or risk of venous thromboembolism, uncontrolled hypertension, ischemic heart disease, peripheral heart disease, and/or cerebrovascular disease. Because of its limited use in patients with osteoporosis, the manufacturers of prescription strontium ranelate (Protelos) discontinued its manufacturing in August 2017 (95698). Strontium ranelate is not approved for use in the US.

POSSIBLY EFFECTIVE

• Osteoarthritis. Large clinical trials suggest that oral strontium ranelate is beneficial for the prevention of spinal osteoarthritis progression and the treatment of knee osteoarthritis. Details: Analysis of data from two large clinical trials in postmenopausal individuals with a history of vertebral fracture shows that taking strontium ranelate daily for 3 years appears to improve back pain and reduce the risk of spinal osteoarthritis progression by 42% when compared with placebo (76558). Additionally, two large clinical trials in patients with knee osteoarthritis show that taking strontium ranelate 1-2 grams daily for 3 years reduces joint space narrowing by 0.1-0.14 mm, improves overall symptoms and pain symptoms, and may improve stiffness and physical function when compared with placebo (94006,94007). The dose of 2 grams daily seems to be more effective than a lower dose of 1 gram daily (94007,94008).
• Prostate cancer. Some clinical research suggests that intravenous strontium-89 chloride slows the progression of prostate cancer. Details: Two clinical trials show that intravenous administration of strontium-89 chloride seems to slow the progression of treatment-resistant prostate cancer and to relieve pain associated with prostate cancer (11747,11748). However, it appears to be less effective when compared with local radiation therapy (111748).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Cancer. Although there has been interest in using oral strontium for metastatic cancer, there is insufficient reliable information about the clinical effects of strontium for this purpose.
• Dental caries. Although there has been interest in using oral strontium for the prevention of dental caries, there is insufficient reliable information about the clinical effects of strontium for this purpose.
• Fractures. It is unclear if oral strontium is beneficial in patients with wrist fractures. Details: A small clinical study in patients over 60 years of age with a wrist fracture shows that taking strontium ranelate 2 grams daily for 3 months, in addition to calcium and vitamin D, does not improve or accelerate wrist fracture healing when compared with calcium and vitamin D alone (94005).
• Pruritus. It is unclear if topical strontium is beneficial for the prevention of pruritus. Details: A small clinical study in healthy individuals shows that topical application of strontium chloride 4% gel (TriCalm, Cosmederm Bioscience) 15 minutes prior to itch induction with cowhage reduces itch intensity and duration when compared with placebo. It also seems to decrease itch intensity more than topical hydrocortisone 1% or diphenhydramine 2% (94004). More evidence is needed to rate strontium for these uses.

(Read more about STRONTIUM)

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.

(Read more about ASTRAGALUS)

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

POSSIBLY SAFE ...when black pepper oil is applied topically. Black pepper oil is nonirritating to the skin and is generally well tolerated (11). ...when black pepper oil is inhaled through the nose or as a vapor through the mouth, short-term. Black pepper oil as a vapor or as an olfactory stimulant has been used with apparent safety in clinical studies for up to 3 days and 30 days, respectively (29159,29160,29161,90502). There is insufficient reliable information available about the safety of black pepper when used orally in medicinal amounts.

CHILDREN: LIKELY SAFE
when used orally in amounts commonly found in foods (11).

CHILDREN: POSSIBLY UNSAFE
when used orally in large amounts. Fatal cases of pepper aspiration have been reported in some patients (5619,5620). There is insufficient reliable information available about the safety of topical pepper oil when used in children.

PREGNANCY: LIKELY SAFE
when used orally in amounts commonly found in foods (11).

PREGNANCY: LIKELY UNSAFE
when used orally in large amounts. Black pepper might have abortifacient effects (11,19); contraindicated. There is insufficient reliable information available about the safety of topical pepper when used during pregnancy.

LACTATION: LIKELY SAFE
when used orally in amounts commonly found in foods (11). There is insufficient reliable information available about the safety of black pepper when used in medicinal amounts during breast-feeding.

(Read more about BLACK PEPPER)

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

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

(Read more about PANAX NOTOGINSENG)

LIKELY SAFE ...when consumed orally in food amounts. Strontium has not been linked to toxicity when consumed in dietary amounts, which are typically about 0.5-1.5 mg daily (14554,14560). ...when strontium-89 chloride is used intravenously and appropriately. Strontium-89 chloride is an FDA-approved product (4948). ...when strontium chloride is used topically and appropriately as a toothpaste. Strontium chloride hexahydrate (Sensodyne-SC) is an FDA-approved product (9).

POSSIBLY SAFE ...when strontium ranelate is used orally and appropriately. Strontium ranelate 2 grams daily, providing elemental strontium 680 mg daily, seems to be safe when used for up to 10 years (11392,11393,11395,14549,94012).

POSSIBLY UNSAFE ...when used orally in high doses. Very high doses may adversely affect bone structure, although data in humans is limited (11394,11399,14554,14556). Until more is known, advise patients to avoid doses of elemental strontium above 680 mg/day. There is insufficient reliable information available about the safety of strontium chloride, the form most commonly used in dietary supplements, when used orally.

PREGNANCY AND LACTATION: LIKELY SAFE
when consumed orally in food amounts. Strontium has not been linked to toxicity when consumed in dietary amounts, which are typically about 0.5 mg to 1.5 mg/day (14554,14560). ...when strontium chloride is used topically and appropriately as a toothpaste (9). Strontium chloride hexahydrate (Sensodyne-SC) is an FDA approved product.

PREGNANCY AND LACTATION: LIKELY UNSAFE
when strontium-89 chloride is used during pregnancy or lactation. Strontium-89 chloride is a radioactive isotope which may cause fetal harm. It is FDA pregnancy risk category D; avoid using (11755). Since strontium behaves similarly to calcium in the body, strontium-89 is likely to be excreted into breast milk; avoid using during lactation (11755). There is insufficient reliable information about the safety of oral strontium when used in amounts exceeding typical dietary intake during pregnancy or lactation; avoid using.

(Read more about STRONTIUM)

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.

(Read more about ASTRAGALUS)

AMOXICILLIN (Amoxil, Trimox) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase the effects and side effects of amoxicillin.  Details Animal research shows that taking piperine, a constituent of black pepper, with amoxicillin increases plasma levels of amoxicillin (29269). This has not been reported in humans.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase the risk of bleeding when taken with antiplatelet or anticoagulant drugs.  Details In vitro research shows that piperine, a constituent of black pepper, seems to inhibit platelet aggregation (29206). This has not been reported in humans.

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase the risk of hypoglycemia when taken with antidiabetes drugs.  Details Animal research shows that piperine, a constituent of black pepper, can reduce blood glucose levels (29225). Monitor blood glucose levels closely. Dose adjustments might be necessary.

ATORVASTATIN (Lipitor) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase blood levels of atorvastatin.  Details Animal research shows that taking piperine, a constituent of black pepper, 35 mg/kg can increase the maximum serum concentration of atorvastatin three-fold (104188). This has not been reported in humans.

CARBAMAZEPINE (Tegretol) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, black pepper might increase blood levels of carbamazepine, potentially increasing the effects and side effects of carbamazepine.  Details One clinical study in patients taking carbamazepine 300 mg or 500 mg twice daily shows that taking a single 20 mg dose of purified piperine, a constituent of black pepper, increases carbamazepine levels. Piperine may increase carbamazepine absorption by increasing blood flow to the GI tract, increasing the surface area of the small intestine, or inhibiting cytochrome P450 3A4 (CYP3A4) in the gut wall. Absorption was significantly increased by 7-10 mcg/mL/hour. The time to eliminate carbamazepine was also increased by 4-8 hours. Although carbamazepine levels were increased, this did not appear to increase side effects (16833). In vitro research also shows that piperine can increase carbamazepine levels by 11% in a time-dependent manner (103819).

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase the effects and side effects of cyclosporine.  Details In vitro research shows that piperine, a constituent of black pepper, increases the bioavailability of cyclosporine (29282). This has not been reported in humans.

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase levels of drugs metabolized by CYP1A1.  Details In vitro research suggests that piperine, a constituent of black pepper, inhibits CYP1A1 (29213). This has not been reported in humans.

CYTOCHROME P450 2B1 (CYP2B1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase levels of drugs metabolized by CYP2B1.  Details In vitro research suggests that piperine, a constituent of black pepper, inhibits CYP2B1 (29332). This has not been reported in humans.

CYTOCHROME P450 2D6 (CYP2D6) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase levels of drugs metabolized by CYP2D6.  Details In vitro research suggests that some constituents of black pepper inhibit CYP2D6 (29207,29212,38375). This has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.  Details In vitro research shows that piperine, a constituent of black pepper, as well as the pepper fruit seem to inhibit CYP3A4 (14375,29212). This has not been reported in humans.

LITHIUM Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, black pepper might increase blood levels of lithium due to its diuretic effects. The dose of lithium might need to be reduced.  Details Black pepper is thought to have diuretic properties (11).

NEVIRAPINE (Viramune) Interaction Rating = Moderate Be cautious with this combination. Severity = Mild •  Occurrence = Probable •  Level of Evidence = D Black pepper might increase blood levels of nevirapine.  Details Clinical research shows that piperine, a constituent of black pepper, increases the plasma concentration of nevirapine. However, no adverse effects were observed in this study (29209).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase levels of P-glycoprotein substrates.  Details In vitro research shows that piperine, a constituent of black pepper, seems to inhibit P-glycoprotein (14375,29281,29283).

PENTOBARBITAL (Nembutal) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, black pepper might increase the sedative effects of pentobarbital.  Details Animal research shows that piperine, a constituent of black pepper, increases pentobarbital-induced sleeping time (29214).

PHENYTOIN (Dilantin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Black pepper might increase blood levels of phenytoin.  Details Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption, slow elimination, and increase levels of phenytoin (537,14442). Taking a single dose of black pepper 1 gram along with phenytoin seems to double the serum concentration of phenytoin (14375). Consuming a soup with black pepper providing piperine 44 mg/200 mL of soup along with phenytoin also seems to increase phenytoin levels when compared with consuming the same soup without black pepper (14442).

PROPRANOLOL (Inderal) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Black pepper might increase blood levels of propranolol.  Details Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of propranolol (538).

RIFAMPIN (Rifadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = B Black pepper might increase blood levels of rifampin.  Details Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and serum levels of rifampin (14375,29284).

THEOPHYLLINE Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Black pepper might increase blood levels of theophylline.  Details Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of theophylline (538).

(Read more about BLACK PEPPER)

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).

(Read more about PANAX NOTOGINSENG)

ANDROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, androgens might reduce the excretion of strontium, potentially increasing its effects and adverse effects.  Details A small clinical study suggests that treatment with androgens such as testosterone, nandrolone, oxandrolone, and oxymetholone for 5-6 weeks might decrease urinary strontium excretion (11405). The clinical significance of this interaction is unknown.

ANTACIDS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Antacids can reduce the absorption of strontium, potentially decreasing its effectiveness.  Details Aluminum hydroxide and magnesium hydroxide can reduce absorption of strontium ranelate by 20% to 25%. Calcium can reduce its absorption to 60% to 70%. Avoid taking antacids within 2 hours of a dose of strontium ranelate (14549,25056). This interaction has also been reported with orally-administered radioactive strontium-85 (14554). It will likely also occur with other forms of strontium.

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, estrogens might reduce the excretion of strontium, potentially increasing its effects and adverse effects.  Details A small clinical study suggests that treatment with estrogens for 5-6 weeks might decrease urinary strontium excretion (11405). The clinical significance of this interaction is unknown.

QUINOLONE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, strontium might decrease the absorption of quinolone antibiotics.  Details Strontium is a divalent cation with similar properties to calcium. It is likely to form complexes with quinolones in the gastrointestinal (GI) tract, preventing absorption of the antibiotic (14549). Recommend taking strontium supplements at least 2 hours before or after quinolones to avoid an interaction.

TETRACYCLINE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = D Theoretically, strontium might decrease the absorption of tetracycline antibiotics.  Details Strontium is a divalent cation with similar properties to calcium. It is likely to form complexes with tetracyclines in the gastrointestinal (GI) tract, preventing absorption of the antibiotic (14549). Recommend taking strontium supplements at least 2 hours before or after tetracyclines to avoid an interaction.

(Read more about STRONTIUM)

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).

(Read more about ASTRAGALUS)

General ...Orally, black pepper seems to be well tolerated when used in the amounts found in food or when taken as a medicine as a single dose. Topically and as aromatherapy, black pepper oil seems to be well tolerated.
Most Common Adverse Effects:
Orally: Burning aftertaste, dyspepsia, and reduced taste perception.
Inhalation: Cough.
Serious Adverse Effects (Rare):
Orally: Allergic reaction in sensitive individuals.

Gastrointestinal ...Orally, black pepper can cause a burning aftertaste (5619) and dyspepsia (38061). Single and repeated application of piperine, the active constituent in black pepper, to the tongue and oral cavity can decrease taste perception (29267). By intragastric route, black pepper 1.5 grams has been reported to cause gastrointestinal microbleeds (29164). It is not clear if such an effect would occur with oral administration.

Immunologic ...In one case report, a 17-month-old male developed hives, red eyes, facial swelling, and a severe cough following consumption of a sauce containing multiple ingredients. Allergen skin tests were positive to both black pepper and cayenne, which were found in the sauce (93947).

Ocular/Otic ...Topically, ground black pepper can cause redness of the eyes and swelling of the eyelids (5619).

Pulmonary/Respiratory ...When inhaled through the nose as an olfactory stimulant, black pepper oil has been reported to cause cough in one clinical trial (29162).

(Read more about BLACK PEPPER)

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).

(Read more about PANAX NOTOGINSENG)

General ...Orally, strontium ranelate seems to be well tolerated when used in doses up to 2 grams (680 mg elemental strontium) daily, long-term.
Most Common Adverse Effects:
Orally: Atopic dermatitis, diarrhea, headache, nausea.
Serious Adverse Effects (Rare):
Orally: Myocardial infarction, osteomalacia, venous thromboembolism.

Cardiovascular ...Orally, clinical research shows that strontium ranelate increases the relative risk of venous thromboembolism and pulmonary embolism by about 50% compared with placebo (14561,14562). The reason for this is unknown. Strontium ranelate also seems to increase the risk of myocardial infarction by about 1.6-fold in patients with osteoporosis (95699).

Dermatologic ...Orally, common side effects of strontium ranelate can include dermatitis and eczema (11392,11393,11395,14549).

Gastrointestinal ...Orally, strontium ranelate can cause stomach pain, diarrhea, and nausea, particularly at higher doses (14561,76541,94010,94012).

Hematologic ...Intravenously, strontium-89 causes bone marrow toxicity, particularly affecting platelet and white blood cell counts. Platelet levels fall by about 30% and the nadir is generally 12 to 16 weeks after injection. The effect on white blood cells is variable. Blood cell counts generally recover slowly over a period of about 6 months (11752,11755).

Musculoskeletal ...There is some concern that doses of strontium higher than those used in clinical trials may adversely affect bone by impairing mineralization and reducing calcium absorption, leading to abnormal skeletal development and reduced bone quality (11394,11399,14554,14557). This would manifest as rickets if it occurs during bone growth, and as osteomalacia after growth is complete (14556). The concern is mainly based on animal data, although strontium-related rickets has been observed in children eating plant-derived foods grown in locations with high soil strontium levels (>350 ppm), especially if they also have inadequate protein, calcium, and vitamin D intake (11399,14554,14556,14557). Accumulation of strontium has also been reported in people with end-stage renal disease, especially those on dialysis, and has been linked to osteomalacia in such patients. Elevated serum and bone strontium levels seem to occur more commonly in patients with osteomalacia than in those with other types of renal osteodystrophy or no bone changes. Strontium is thought to accumulate due to reduced renal excretion and also the presence of strontium in dialysis fluids (14554,14555,14557,14559).

Neurologic/CNS ...Orally, strontium ranelate has reportedly caused altered consciousness, memory loss, and seizures on occasion (14549).

(Read more about STRONTIUM)