NO3 Drive Capsules by ProSupps USA, LLC

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Ingredients hide details

Three capsules contain: No3 Drive brand Vasolialation Matrix 700 mg: L-Citrulline , Agmatine Sulfate (AGMAPURE brand), Gynostemma pentaphyllum extract (std. min. 90% Gypenoside) (whole herb), Rutaecarpine • GPLC Matrix 527 mg: GlycoPro brand ( Propionyl L-Carnitine HCl Glycine complex), GlycoCarn brand ( Glycine Propionyl L-Carnitine HCl ) • Enhanced Nutrient Absorbtion Matrix 110 mg: AstraGin brand Proprietary Blend of Panax notoginseng (root) and Astragalus membranaceous (root), AstraGin brand Proprietary Blend of Panax notoginseng (whole plant) and Rosa Roxburghii (fruit) • PteroPro brand ( D-Pinitol , Pterostilbene , Resveratrol , Piceid ). Other Ingredients: Maltodextrin, Hypromellose, L-Carnitine Fumarate, Silica, Magnesium Stearate, Stearic Acid, Titanium Dioxide.

Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.

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Effectiveness view details

Below is general information about the effectiveness of the known ingredients contained in the product NO3 Drive Capsules. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

AGMATINE (Agmatine Sulfate)

INSUFFICIENT RELIABLE EVIDENCE to RATE

Alcohol use disorder. Although there has been interest in using oral agmatine for alcohol use disorder, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Alzheimer disease. Although there has been interest in using oral agmatine for Alzheimer disease, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Anxiety. Although there has been interest in using oral agmatine for anxiety, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Athletic performance. Although there has been interest in using oral agmatine for improving athletic performance, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Autism spectrum disorder. Although there has been interest in using oral agmatine for autism spectrum disorder, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Bipolar disorder. Although there has been interest in using oral agmatine for bipolar disorder, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Depression. Although there has been interest in using oral agmatine for depression, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Epilepsy. Although there has been interest in using oral agmatine for epilepsy, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Herniated disc. It is unclear if oral agmatine is beneficial in patients with herniated disc. Details: A small clinical study in patients with radicular pain associated with lumbar disc herniation shows that taking agmatine sulfate 890 mg three times daily for 14 days decreases pain scores by around 20% and increases health-related quality of life scores by around 50% when compared with placebo (94736).
Muscle strength. Although there has been interest in using oral agmatine for increasing muscle strength, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Parkinson disease. Although there has been interest in using oral agmatine for Parkinson disease, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Peripheral neuropathy. It is unclear if oral agmatine is beneficial in patients with peripheral neuropathy. Details: A small, open-label study in patients with peripheral neuropathy of mixed etiologies shows that taking a specific agmatine sulfate product (AgmaSet, Gilad&Gilad LLC) 2.67 grams daily, in divided doses, for 2 months reduces pain intensity by around 46% and improves symptom scores for burning, numbness, and tingling when compared to baseline (111144). The validity of these findings is limited by a lack of comparator group.
Schizophrenia. Although there has been interest in using oral agmatine for schizophrenia, there is insufficient reliable information about the clinical effects of agmatine for this purpose.
Stroke. Although there has been interest in using oral agmatine for neuroprotection against stroke, there is insufficient reliable information about the clinical effects of agmatine for this purpose. More evidence is needed to rate agmatine for these uses.

(Read more about AGMATINE)

ASTRAGALUS

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.

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JIAOGULAN (Gynostemma pentaphyllum)

POSSIBLY EFFECTIVE

Diabetes. Oral jiaogulan extract powder may improve glycemic control in patients newly diagnosed with type 2 diabetes when used alone or with diabetes medications. Details: A meta-analysis of two small clinical trials in adults with newly diagnosed type 2 diabetes shows that taking jiaogulan whole plant extract powder, 1.5 grams dissolved in 60 mL of room temperature water, twice daily before meals for 8-12 weeks reduces glycated hemoglobin by 1%, fasting blood glucose by 29 mg/dL, and post-prandial blood glucose by 80 mg/dL when compared with green tea (111503). In one of the trials, both the jiaogulan and the placebo groups were also started on a sulfonylurea 4 weeks prior to the study and remained on it throughout the trial (95519). In the other trial no participants were taking diabetes medications (95520). Additionally, a very small cross-over trial that was not included in the aforementioned meta-analysis shows this same jiaogulan protocol reduces fasting blood glucose and improves insulin sensitivity at 4 weeks when compared with green tea in adults newly diagnosed with type 2 diabetes (94054). The washout period was 2 weeks, and switching to placebo reversed the improvements in glycemic control. All three clinical trials above were conducted in Vietnam by the same research group with the same jiaogulan extract product and protocol (94054,95519,95520). The validity of these findings may be limited by the use of a potentially non-inert green tea placebo, as green tea itself has been studied for its effects on preventing and treating diabetes.

INSUFFICIENT RELIABLE EVIDENCE to RATE

Aging. Although there has been interest in using oral jiaogulan for aging, there is insufficient reliable information about the clinical effects of jiaogulan for this purpose.
Athletic performance. Although there has been interest in using oral jiaogulan for athletic performance, there is insufficient reliable information about the clinical effects of jiaogulan for this purpose.
Cancer. Although there has been interest in using oral jiaogulan for preventing or treating cancer, there is insufficient reliable information about the clinical effects of jiaogulan for this purpose.
Cardiovascular disease (CVD). Although there has been interest in using oral jiaogulan for CVD, there is insufficient reliable information about the clinical effects of jiaogulan for this purpose.
Hypercholesterolemia. Small clinical studies suggest that oral jiaogulan extract may lower cholesterol levels in patients with hypercholesterolemia. Details: Two small clinical studies in patients with hypercholesterolemia show that taking jiaogulan extract can decrease total cholesterol and increase the high-density lipoprotein (HDL)/total cholesterol ratio (7069,7070). The dose of jiaogulan extract used in one study was 10 mg three times daily (7069).
Hypertension. Although there has been interest in using oral jiaogulan for hypertension, there is insufficient reliable information about the clinical effects of jiaogulan for this purpose.
Memory. Although there has been interest in using oral jiaogulan for memory, there is insufficient reliable information about the clinical effects of jiaogulan for this purpose.
Nonalcoholic fatty liver disease (NAFLD). It is unclear if oral jiaogulan extract is beneficial in patients with NAFLD. Details: One small clinical study in patients with NAFLD shows that taking jiaogulan extract three times daily for 4 months in conjunction with controlled dieting does not improve markers of liver function, body mass index, cholesterol levels, kidney function, or glucose levels when compared with placebo (57056).
Obesity. Small clinical studies suggest that oral jiaogulan extract may slightly reduce body weight in patients who are overweight or obese. Details: Two small clinical studies in adult patients who are overweight or obese show that taking jiaogulan extract 225 mg twice daily for 12-16 weeks reduces body weight by 1.3 kg and body mass index (BMI) by around 0.4 kg/m2 when compared with placebo (94058,106651).
Respiratory tract infections. Although there has been interest in using oral jiaogulan for various respiratory tract infections, including bronchitis, rhinosinusitis, and the common cold, there is insufficient reliable information about the clinical effects of jiaogulan for these conditions.
Stress. It is unclear if oral jiaogulan extract is beneficial in patients with chronic stress. Details: One small clinical study in healthy adults with self-perceived chronic stress and anxiety at baseline, but without a confirmed diagnosis of anxiety, depression, or other mental health disorders, shows that taking jiaogulan extract 200 mg twice daily for 8 weeks while being exposed to repetitive stressful tasks decreases anxiety scores by almost 17% when compared with placebo. While no subjective assessments of stress were included, salivary cortisol levels and other stress markers did not improve with jiaogulan when compared with placebo (100961). More evidence is needed to rate jiaogulan for these uses.

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L-CITRULLINE

POSSIBLY EFFECTIVE

Athletic performance. Small studies show that taking a single oral dose of L-citrulline before anaerobic resistance exercise might reduce exhaustion and improve some performance measures. It is unclear if L-citrulline improves aerobic exercise performance; results are conflicting. Details: A meta-analysis of small clinical trials in healthy trained and untrained adults shows that taking L-citrulline prior to mostly anaerobic exercise marginally reduces perceived exhaustion and muscle soreness when compared with placebo (105965). Another meta-analysis including some of the same clinical studies shows that taking L-citrulline malate before exercise modestly increases performance on resistance exercises by an average of 6% when compared with placebo (105968). Individual studies show mixed benefit and mostly use a single dose of L-citrulline malate 8 grams 1 hour before exercise; other studies used L-citrulline 3.3-6 grams mixed in watermelon juice or sucrose water or L-citrulline malate 12 grams given 1-2 hours before exercise (94966,94957,97395,105965). L-citrulline has also been evaluated for use with aerobic exercise. A small study in healthy young adults taking L-citrulline 9 grams in 3 divided doses over 24 hours or as a single dose of 3 grams 3 hours before a treadmill test does not improve performance, but might reduce time to exhaustion, when compared with placebo (16473). Another small clinical study in healthy adults shows that taking about 6.8 grams (100 mg/kg) of L-citrulline daily for 5 days prior to a cycling trial does not improve time to exhaustion, oxygen uptake, or lactate levels when compared with taking 3 grams of glucose as placebo (105964). However, two small clinical trials in healthy males show that taking L-citrulline 2.4-6 grams daily for 7 days prior to a cycling test improves peak power by 9%, total work by 7%, and cycling time trial performance by 1.5% when compared with placebo (94954,94965). Differences in methods of testing athletic performance, the form and dose of L-citrulline used, and/or the duration of supplementation may explain the mixed results. L-citrulline has also been evaluated in combination with L-arginine. Research in male soccer players shows that taking L-citrulline 1.2 grams and L-arginine 1.2 grams daily for 7 days increases total power output over a 10-minute cycling test and improves subjective perceptions of exertion when compared with placebo (100956).

POSSIBLY INEFFECTIVE

Sarcopenia. Oral L-citrulline does not seem beneficial for muscle strength in older adults when added to structured exercise. Details: Two small clinical studies in older adults show that taking L-citrulline in conjunction with structured exercise does not improve measures of strength, endurance, speed, or balance when compared with placebo and structured exercise (110146,110148). One study evaluated otherwise healthy adults aged 60-73 years taking L-citrulline 3 grams daily for 6 weeks (110146). The other study evaluated older adults with obesity and an average age of 68.5 years taking a specific L-citrulline product (Citrage) 10 grams daily for 12 weeks (110148).

INSUFFICIENT RELIABLE EVIDENCE to RATE

Cardiovascular disease (CVD). Although there is interest in using oral L-citrulline for CVD, there is insufficient reliable information about the clinical effects of L-citrulline for this condition.
Dementia. Although there is interest in using oral L-citrulline for dementia, there is insufficient reliable information about the clinical effects of L-citrulline for this condition.
Diabetes. It is unclear if oral L-citrulline is beneficial in patients with diabetes. Details: A small clinical study in adults with diabetes who are taking metformin and sulfonylureas shows that adding L-citrulline (Bulk Supplements Co., Ltd.) 3 grams daily before breakfast for 8 weeks reduces average fasting blood glucose levels by 22 mg/dL and glycated hemoglobin by 0.7%, but does not affect lipid levels, when compared with taking a microcrystalline cellulose placebo (105963).
Erectile dysfunction (ED). It is unclear if oral L-citrulline is beneficial in patients with ED. Details: A small non-randomized crossover study in adults with mild ED shows that taking L-citrulline 1.5 grams daily for one month improves erection hardness from "mild dysfunction" to "normal function" in 50% of patients, compared with only 8% of patients taking placebo (94956). L-citrulline has also been evaluated in combination with other ingredients. A clinical study in middle-aged males with ED shows that taking a specific combination product (Revactin, MD Concepts LLC) containing L-citrulline, muira puama, ginger root, and guarana twice daily for 3 months improves scores related to erectile function and intercourse satisfaction, but does not improve sexual desire or orgasmic function scores, when compared to baseline (103224). The validity of this study is limited by the lack of a placebo control, the use of per-protocol analysis, and a high dropout rate. In fact, 44% of patients withdrew in order to resume use of phosphodiesterase type 5 (PDE5) inhibitors. Another small clinical study in adults with ED living in Japan and using PDE5 inhibitors as needed shows that taking an adjunct 50 mL drink containing L-citrulline 800 mg, a specific fenugreek extract (Testofen) 600 mg, resveratrol 300 mg, and caffeine 40 mg daily for 14 days modestly improves erectile function and satisfaction with intercourse and orgasm when compared with a placebo drink (105966). The validity of this finding may be confounded by the "as needed" use of PDE5 inhibitors, which was not reported throughout the study. Further, in both combination studies, it is unclear if these effects are due to L-citrulline, other supplement ingredients, or the combination.
Heart failure. Small clinical studies suggest that oral L-citrulline might be beneficial in patients with heart failure. Details: A very small clinical study in patients with heart failure with preserved ejection fraction (HFpEF) shows that taking L-citrulline malate 3 grams daily for 2 months decreases systolic pulmonary arterial pressure by 16% and improves the right ventricular ejection fraction after a stress test by 27% when compared to baseline (94962). The validity of this finding is limited by the lack of a control group. Another small open-label clinical study in patients with heart failure with reduced ejection fraction (HFrEF) shows that taking L-citrulline 3 grams daily for 4 months increases left ventricular ejection fraction by about 20% at rest and 13% during the stress test, and increases the right ventricular ejection fraction by about 15%, both at rest and with the stress test, when compared with no supplementation. This improved the heart failure functional class in 35% of patients (94955).
Hypertension. It is unclear if oral L-citrulline is beneficial for lowering blood pressure. Details: A small clinical trial in adults with prehypertension shows that taking L-citrulline 2 grams with grape and cranberry polyphenols 548 mg daily for 6 weeks does not reduce mean ambulatory blood pressure when compared with a cellulose placebo (105969). A small crossover study in postmenopausal females with hypertension shows that taking L-citrulline 6 grams as a single dose does not improve systolic or diastolic blood pressure at rest or during 5 minutes of plantar flexion exercise when compared with placebo (110147). The effects of using L-citrulline regularly or in other patients with diagnosed hypertension is unclear.
Lysinuric protein intolerance. Although there is interest in using oral L-citrulline for lysinuric protein intolerance, there is insufficient reliable information about the clinical effects of L-citrulline for this condition.
Muscle strength. It is unclear if oral L-citrulline can improve muscle strength when used in conjunction with resistance training. Details: A clinical study in healthy resistance-trained adults shows that taking L-citrulline malate 2 grams daily for 8 weeks in conjunction with resistance training does not further increase lean mass or muscle strength, measured by leg and bench presses, when compared with a cellulose placebo and resistance training (97394).
Muscular dystrophy. It is unclear if oral L-citrulline is beneficial in patients with Duchenne muscular dystrophy. Details: A small clinical study in adults with Becker muscular dystrophy, a milder form of Duchenne muscular dystrophy (DMD), shows that taking L-citrulline 5 grams with or without metformin 500 mg three times daily for 6 weeks improves 6-minute walking distance and decreases markers of muscle necrosis when compared to baseline (100975). A small clinical study in males aged 6.5-10 years with DMD shows that taking L-citrulline 2.5 grams with metformin 250 mg three times daily for 26 weeks does not appear to slow decline in motor function when compared with placebo. However, this combination seems to slow decline in children with more stable disease, defined as those who can walk at least 350 meters in 6 minutes (100976). The reasons for these disparate results are unclear, but they may be due to the different patient populations, disease severities, doses, and durations of therapy being studied.
Postoperative pulmonary hypertension. It is unclear if oral citrulline prevents postoperative hypertension in children undergoing heart surgery. Details: A small clinical study in children 6 years of age and younger undergoing congenital heart surgery shows that higher blood levels of L-citrulline might protect against the incidence of postoperative hypertension. L-citrulline blood levels of at least 37 micromol/L immediately after surgery, and at 12, 24, and 36 hours postoperatively, protects against its development. However, supplementation with 1.9 grams/m2 during induction of anesthesia is not necessarily protective (16467).
Post-polio syndrome. It is unclear if oral L-citrulline is beneficial for patients with this condition. Details: A small clinical study in adults with post-polio syndrome shows that taking L-citrulline 5 grams three times daily for 24 weeks does not improve 6-minute walking distance, motor function scores, muscle strength, or quality of life when compared with placebo (110149).
Pulmonary hypertension. It is unclear if oral L-citrulline is beneficial in patients with pulmonary hypertension. Details: A very small clinical study in patients with idiopathic arterial pulmonary hypertension or pulmonary hypertension due to Eisenmenger syndrome shows that taking L-citrulline malate 1 gram three times daily for 2 weeks increases 6-minute walking distance by 44 meters and reduces mean pulmonary arterial pressure by 5% when compared with baseline (94963). The validity of these findings is limited by the small study size and the lack of a comparator group.
Reye syndrome. Although there is interest in using oral L-citrulline for Reye syndrome, there is insufficient reliable information about the clinical effects of L-citrulline for this condition.
Sickle cell disease. It is unclear if oral L-citrulline is beneficial in patients with sickle cell disease. Details: A small clinical study in children ages 10-18 years shows that taking L-citrulline 90-130 mg/kg daily in 2 divided doses for up to 9 months might reduce neutrophilia and other symptoms when compared with baseline (16463). The validity of these findings is limited by the small study size and the lack of a comparator group. More evidence is needed to rate L-citrulline for these uses.

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PANAX NOTOGINSENG

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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PROPIONYL-L-CARNITINE (Propionyl L-Carnitine, Glycine Propionyl L-Carnitine HCl)

POSSIBLY EFFECTIVE

Angina. Oral propionyl-L-carnitine may improve myocardial ischemia and exercise capacity in patients with chronic, stable angina. Details: In patients with chronic, stable angina, taking propionyl-L-carnitine 500 mg three times daily orally for 4-6 weeks seems to produce small improvements in myocardial ischemia and exercise capacity (1579,1580,1581). In one study, exercise duration was increased by 5% when compared with placebo. However, angina attacks were not affected (1580). In another study, the number of angina attacks was reduced by approximately 67% when compared with placebo, although there was no change in nitroglycerin use (1581).
Cardiovascular disease (CVD). Intravenous propionyl-L-carnitine may improve left ventricular function and decrease myocardial ischemia. Details: In patients with chronic myocardial ischemia, intravenous administration of single doses of propionyl-L-carnitine 15 mg/kg may improve left ventricular function and cardiac output, as well as decrease myocardial ischemia (1571,1572,1573). In one study, left ventricular fraction increased by 18% when compared with placebo (1573).
Congestive heart failure (CHF). Oral propionyl-L-carnitine may improve left ventricular function and exercise capacity in patients with class II or III CHF. Details: In patients with class II or III CHF, taking propionyl-L-carnitine 500 mg three times daily for up to 6 months seems to improve left ventricular function and exercise capacity (1575,1582,1583). Some research has found that exercise time increases by up to approximately 26% (1575,1583) or by an additional minute when compared with placebo (1582). Also, ejection fraction is improved by 13% when compared with placebo (1583).
Intermittent claudication. Oral and intravenous propionyl-L-carnitine may improve walking capacity and quality of life in some patients with intermittent claudication and peripheral vascular disease. Details: A meta-analysis, as well as individual clinical trials, suggest that taking oral propionyl-L-carnitine 1-4 grams daily in divided doses increases walking distance by up to 45 meters when compared with placebo (1434,1435,1436,1576,10456,94439,94446). One study suggests an increase in walking time of 1.33 minutes (94446). Taking propionyl-L-carnitine 1-3 grams daily over 6 months also seems to improve quality of life when compared with placebo. Oral propionyl-L-carnitine might be more effective in individuals with the ability to walk shorter distances, specifically less than 250 meters, at baseline (1436). One small clinical study failed to show a benefit when propionyl-L-carnitine 2 grams daily was added to exercise; however, it may not have been adequately powered to detect a difference between groups (94443). Intravenous propionyl-L-carnitine also increases claudication distance and maximal walking distance when given as a single dose of 600 mg or daily doses of 600 mg for 4 days. Maximal walking distance increases by 28% to 42% when compared with placebo (1437).
Ulcerative colitis. Oral propionyl-L-carnitine may improve clinical response and remission rates in patients with mild to moderate ulcerative colitis. Details: In patients with mild to moderate ulcerative colitis receiving conventional therapy, clinical research shows that taking colonic-release propionyl-L-carnitine tablets 0.5-1 gram twice daily for 4 weeks improves clinical response and remission rates (94447,94448,94449). Clinical response and clinical remission occur in 55% to 72% of patients treated with propionyl-L-carnitine when compared with baseline or placebo (94447,94448). In one study, propionyl-L-carnitine increases the rate of clinical response by 44% when compared with placebo. However, a significant difference in remission rate when compared with placebo was lacking (94448).

INSUFFICIENT RELIABLE EVIDENCE to RATE

Age-related testosterone deficiency. Oral propionyl-L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in older males shows that taking propionyl-L-carnitine 2 grams, in combination with acetyl-L-carnitine 2 grams, daily for 6 months seems to attenuate symptoms of androgen decline. The combination appears to be similar to testosterone for improving sexual dysfunction, depression, and fatigue (12353). It is unclear if these findings are due to propionyl-L-carnitine, acetyl-L-carnitine, or the combination.
Athletic performance. It is unclear if oral glycine propionyl-L-carnitine is beneficial for improving athletic performance in young resistance-trained males; the available research is mixed. Details: Some clinical research shows that taking a specific ingredient called glycine propionyl-L-carnitine (GlycoCarn, Sigma Ta Health Sciences, S.p.A.) 4.5 grams as a single dose 90 minutes before testing improves peak anaerobic power by 4% to 16% in repeated cycling sprints when compared with placebo (94444). However, taking 1.5, 3, or 4.5 grams of this product daily for 28 days does not improve anaerobic performance of repeated high speed high intensity bouts when compared with placebo. Additionally, preliminary research shows that taking 3 grams or 4.5 grams daily might actually be detrimental to performance. However, the study size was too small for definitive conclusions (94445). The reason for the discrepancy between studies is not clear. However, it is possible that a single dose prior to exercise is more effective than repeated dosing.
Androgenic alopecia. Topical propionyl-L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in males and females with androgenic alopecia shows that applying 1 mL of a combination lotion (TRINOV Lozione Anticaduta Uomo/Donna, Fidia Farmaceutici s.p.a.) containing undisclosed quantities of propionyl-L-carnitine, gamma-linolenic acid, and S-equol to the scalp daily for 6 months increases total hair count and the proportion of actively growing hair to senescent hair, but not hair diameter, when compared with baseline (100348). The validity of these findings is limited by the lack of a comparator group. Also, it is unclear if these effects are due to propionyl-L-carnitine, the other ingredients, or the combination.
Crohn disease. It is unclear if oral propionyl-L-carnitine is beneficial in patients with mild to moderate Crohn disease. Details: A small clinical study in patients with mild to moderate Crohn disease receiving conventional therapy shows that taking colonic-release propionyl-L-carnitine tablets 1 gram twice daily for 4 weeks results in clinical remission in 75% of patients (94447). The validity of this study is limited by the lack of a comparator group.
Chronic fatigue syndrome (CFS). It is unclear if oral propionyl-L-carnitine is beneficial in patients with CFS. Details: Preliminary clinical research in patients with CFS shows that taking propionyl-L-carnitine 2 grams daily for 6 months improves general fatigue in up to 63% of patients when compared with baseline. The combination of propionyl-L-carnitine and acetyl-L-carnitine appears to be less effective than either supplement alone, with only 37% of patients taking this combination achieving improvement when compared with baseline (11788).
Erectile dysfunction (ED). Oral propionyl-L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: In males with ED and diabetes, combination therapy with propionyl-L-carnitine and sildenafil may improve erectile function better than sildenafil alone. In males unresponsive to 8 uses of sildenafil, adding propionyl-L-carnitine 2 grams daily to continued twice weekly doses of sildenafil 50 mg seems to improve erections and successful intercourse attempts more than sildenafil alone (12682). Also, preliminary clinical research in adults with ED shows that taking a specific combination of propionyl-L-carnitine 250 mg, niacin 20 mg, and arginine 2500 mg daily (Ezerex, Sigma-Tau) for 3 months substantially improves erections in 46% of patients and modestly improves sexual function in 37% of patients (94442). It is unclear if these findings are due to propionyl-L-carnitine, other ingredients, or the combination.
Peyronie disease. Oral propionyl-L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with advanced or resistant Peyronie disease shows that receiving the combination of oral propionyl-L-carnitine 2 grams daily with injectable verapamil for 3 months improves erectile function by 42% compared with no change in a group receiving oral tamoxifen with injectable verapamil. The need for surgery was reduced from 27% in the tamoxifen group to 2% in the propionyl-L-carnitine group. Pain was reduced in 97% of all patients (12683). It is unclear if these findings are due to propionyl-L-carnitine, verapamil, or the combination. More evidence is needed to rate propionyl-L-carnitine for these uses.

RESVERATROL

POSSIBLY EFFECTIVE

Allergic rhinitis (hay fever). Intranasal resveratrol seems to be beneficial for reducing allergic rhinitis symptoms in adults and children. Details: Some clinical research shows that intranasal resveratrol with carboxymethyl-beta-glucan can improve symptoms of allergic rhinitis (91332,97339). One clinical study in adults with allergic rhinitis shows that using an intranasal spray containing resveratrol 0.1% three times daily for 4 weeks reduces nasal symptoms and improves quality of life scores when compared with placebo (97339). A study in children aged 4-17 years with pollen-induced allergic rhinitis shows that using an intranasal spray containing resveratrol 0.05% three times daily for 2 months improves itching, sneezing, runny nose, and nasal obstruction and reduces use of rescue medication when compared with placebo (91332).
Obesity. Oral resveratrol seems to be beneficial for weight loss in individuals with overweight or obesity. However, it is unlikely to be beneficial for improving most metabolic parameters in this population. Details: A meta-analysis of 28 clinical trials shows that taking resveratrol decreases body weight by 0.5 kg, body mass index (BMI) by 0.17 kg/m2, and waist circumference by 0.8 cm when compared with placebo or no intervention. This analysis included studies of individuals with normal weight, overweight, and obesity, with or without type 2 diabetes, metabolic syndrome, non-alcoholic fatty liver disease, or other chronic conditions. A subgroup analysis suggests that individuals with obesity have a greater response to resveratrol. In these individuals, taking resveratrol 8-3000 mg daily resulted in an average weight reduction of 1.15 kg and a BMI reduction of 0.3 kg/m2 when compared with placebo. The greatest impact on body weight and BMI occurred with resveratrol doses of no more than 500 mg daily and treatment durations of at least 3 months (100696). One clinical trial also shows that taking resveratrol 150 mg daily for 6 months reduces glycated hemoglobin (HbA1c) by a small amount when compared with placebo in individuals with overweight or obesity but has no effect on insulin sensitivity, fat mass, or levels of fasting blood glucose, lipids, or liver enzymes (105183). Also, meta-analyses of clinical research show that resveratrol is unlikely to be beneficial for improving blood pressure or blood lipids when compared with placebo in individuals with overweight or obesity (102513,105181).

POSSIBLY INEFFECTIVE

Cardiovascular disease (CVD). Oral resveratrol does not seem to be beneficial for CVD prevention. Details: Population research suggests that a higher dietary intake of resveratrol is not associated with a reduced risk of CVD when compared with a lower dietary intake (91334). Also, a meta-analysis of clinical research shows that taking resveratrol for up to 6 months does not improve any measures of plasma lipids, including total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, or triglycerides in patients at high risk for CVD (91333). While one preliminary clinical study shows that taking resveratrol 10 mg daily for 3 months improves left ventricular function by about 1% and endothelial function when compared to baseline in patients with a history of myocardial infarction and coronary artery disease, the improvements are very small and blood pressure and markers of inflammation do not appear to be improved (91330).
Hypercholesterolemia. Oral resveratrol does not seem to be beneficial for hypercholesterolemia. Details: A meta-analysis of clinical research shows that resveratrol is unlikely to be beneficial for improving blood lipids when compared with placebo in patients with hypercholesterolemia. In the meta-analysis, studied populations included people who are overweight or obese, as well as patients with hypertension, type 2 diabetes, metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), angina, and dyslipidemia (105181). Although there was a small reduction in total cholesterol levels of approximately 7 mg/dL, resveratrol did not improve levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, or triglycerides (105181). Also, an analysis of results from clinical research shows that taking resveratrol for up to 6 months does not improve any measures of plasma lipids, including total cholesterol, HDL cholesterol, LDL cholesterol, or triglycerides in patients at high risk for cardiovascular disease (91333). Also, clinical research in healthy humans shows that taking resveratrol 500 mg orally daily for 30 days increases levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and apolipoprotein B (112944). Another meta-analysis identified more promising results; however, any effect on blood lipids may not be considered clinically significant. This meta-analysis included 17 clinical studies enrolling 968 participants with dyslipidemia, type 2 diabetes, coronary artery disease, overweight or obesity, or stroke. Resveratrol reduced total cholesterol by approximately 10 mg/dL, LDL by approximately 6 mg/dL, and triglycerides by approximately 9 mg/dL, but did not improve HDL, when compared with placebo. However, most of the included studies were small and utilized heterogenous dosing regimens, with doses ranging from 10-3000 mg daily for 4-48 weeks (110020).
Metabolic syndrome. Oral resveratrol does not seem to be beneficial for metabolic syndrome. Details: A meta-analysis of clinical research shows that taking resveratrol does not improve blood pressure when compared with placebo in patients with metabolic syndrome or related disorders (102513). A similar meta-analysis shows that taking resveratrol does not improve levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, or liver enzymes. There was a small reduction in total cholesterol levels of approximately 7 mg/dL (105181). However, only 3-4 of the papers included in these meta-analyses, which included 28-31 publications, evaluated patients with metabolic syndrome. The remainder included patients with related conditions, such as overweight/obesity, type 2 diabetes, or nonalcoholic fatty liver disease (NAFLD). The mainly small or preliminary clinical studies that did evaluate patients with metabolic syndrome all show that taking resveratrol 100-1000 mg daily for 12-16 weeks does not improve blood pressure, glucose control, or plasma lipids (91331,95828,102513,105181). However, one preliminary clinical trial shows that taking resveratrol 500 mg three times daily for 3 months reduces body weight by about 4 kg, body mass index (BMI) by 1.3 kg/m2, fat mass by 2.4 kg, and waist circumference by 4 cm when compared to baseline (91331). The validity of these findings is limited by the lack of a comparator group. Also, a moderate-sized clinical trial of adults with metabolic syndrome shows that taking resveratrol 300 mg and delta-tocotrienols 500 mg daily for 24 weeks improves body weight, waist circumference, blood pressure, fasting blood glucose, triglycerides, total and HDL cholesterol, and markers of inflammation and oxidative stress when compared with placebo (112144). It is unclear if these effects are due to resveratrol, delta-tocotrienols, or the combination.
Nonalcoholic fatty liver disease (NAFLD). Oral resveratrol does not seem to be beneficial for most metabolic symptoms of NAFLD. It is unclear if oral resveratrol is beneficial for improving steatosis. Details: Although some individual studies disagree, meta-analyses reviewing 4-6 preliminary clinical studies show that taking resveratrol does not affect liver enzyme levels, insulin resistance, blood pressure, blood lipids, body mass index (BMI), or abdominal size when compared with placebo in patients with NAFLD (95826,99048,105184). Most trials have studied doses of 300-3000 mg daily for 2-3 months; one study used resveratrol 500 mg 3 times daily for 6 months (95826,98911,99048,105184). However, one meta-analysis shows that taking resveratrol might have a small effect on levels of the inflammatory mediators C-reactive protein and tumor necrosis factor (TNF)-alpha (105184). It is not clear if resveratrol might reduce steatosis in patients with NAFLD. One preliminary clinical study shows that taking resveratrol 3000 mg daily in two divided doses for 8 weeks does not improve steatosis when compared to baseline in males with NAFLD (91327). However, another preliminary clinical study in adults with NAFLD shows that taking resveratrol 500 mg daily for 3 months, while following an energy-balanced diet and exercising, improves steatosis, but not fibrosis, insulin resistance, lipid levels, or body composition, when compared with lifestyle modifications alone (91328). The difference in these findings might be due to small study sizes, the duration of therapy, or the gender of the included patients.

INSUFFICIENT RELIABLE EVIDENCE to RATE

Acne. It is unclear if topical resveratrol is beneficial for acne. Details: Preliminary clinical research shows that applying a gel containing trans-resveratrol 1 mcg per gram to facial skin for 60 days reduces the severity of acne by about 54%, compared to only 6% for control gel (71064).
Age-related cognitive decline. It is unclear if oral resveratrol is beneficial for age-related cognitive decline. Details: One small clinical study shows that taking resveratrol 75 mg twice daily for 14 weeks modestly improves cognitive performance and memory after menopause, but not executive function or learning, when compared with placebo (95827). Another small clinical study in healthy, older adults shows that taking resveratrol 200 mg daily for 26 weeks improves memory retention, but not delayed recall or word recognition, when compared with placebo. In this study, resveratrol capsules were formulated to also contain 320 mg of quercetin to enhance the absorption of resveratrol (102511). It is unclear if resveratrol alone would result in similar effects. Despite these positive results, conflicting research exists. A small clinical study in sedentary, overweight, elderly adults shows that taking resveratrol 300 mg daily for 90 days does not improve measures of cognitive function such as psychomotor speed, attention, executive function, learning, or memory when compared with placebo. Taking a higher dose of 1000 mg daily for 90 days modestly improves psychomotor speed, but no other cognitive measures, in these patients (98907). Another small clinical study in healthy elderly adults shows that taking resveratrol 200 mg daily for 26 weeks does not improve verbal memory when compared with placebo (98909).
Aging skin. Although there has been interest in using oral resveratrol for aging skin, there is insufficient reliable information about the clinical effects of resveratrol for this purpose.
Beta-thalassemia. It is unclear if oral resveratrol is beneficial for beta-thalassemia. Details: A small clinical study in patients with beta-thalassemia intermedia shows that taking micronized trans-resveratrol (Xian Tianxingjian Natural Bio-Products CO., LTD) 2000 mg with piperine (Bioprex Co.) 40 mg, with or without hydroxyurea 8-15 mg/kg, daily for 6 months does not improve hemoglobin levels or affect the need for blood transfusion when compared with taking placebo with or without hydroxyurea (98908).
Cancer. It is unclear if dietary resveratrol is beneficial for cancer prevention. Details: Population research has found that a higher dietary intake of resveratrol is not associated with a reduced risk of cancer when compared to lower dietary intake (91334).
Chronic obstructive pulmonary disease (COPD). Oral resveratrol 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 resveratrol 10 mg, vitamin C 180 mg, zinc 15 mg, and flavonoids 160 mg daily for 20 days followed by 10 days without supplementation, repeated for three cycles, modestly reduces symptoms of cough and sputum production in patients with mild-to-moderate COPD when compared with control (71130). It is not clear if these effects are due to resveratrol, the other ingredients, or the combination.
Cognitive function. Oral resveratrol has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in healthy young adults shows that taking a specific supplement (Transmax by BiotiviaTM) containing trans-resveratrol 500 mg and piperine 10 mg daily for 28 days does not improve most measures of cognitive performance when compared with placebo (95834).
Cognitive impairment. Oral resveratrol has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in a small number of patients with mild cognitive impairment shows that taking resveratrol 200 mg and quercetin 350 mg daily for 26 weeks does not improve learning and memory performance when compared with placebo (102512). However, given the small sample size, it is possible this study was inadequately powered to detect significant changes in these cognitive measures.
Coronavirus disease 2019 (COVID-19). It is unclear if oral resveratrol is beneficial for COVID-19. Details: A small clinical trial in outpatients with COVID-19 shows that taking resveratrol (Vita-Age) 1 gram four times daily, for 7-15 days based on symptom duration, does not reduce the rate of hospitalization, emergency room visits, or pneumonia when compared with placebo. All patients also received a single dose of Vitamin D3 (109164). This study may have been inadequately powered to detect differences between groups.
Diabetes. Some research shows that oral resveratrol is beneficial for improving glycemic indices in patients with type 2 diabetes. However, more research is needed to determine the most effective dose or the patient population most likely to benefit. Details: Although results from individual clinical studies have been mixed (91329,95825,95832,100695,109165,109167,109170), meta-analyses of clinical research show that resveratrol modestly reduces blood glucose and glycated hemoglobin (HbA1c) levels in patients with diabetes. Studies lasted 4-24 weeks and many included patients treated with antidiabetes medications, including metformin. However, these meta-analyses have yielded differing findings regarding effective doses (91329,109165,109167,109170). One meta-analysis of clinical research in individuals aged 45 years and older shows that doses of 250-1000 mg daily modestly reduce levels of fasting blood glucose, insulin, and HbA1c, as well as insulin resistance, when compared with placebo. Doses of up to 250 mg daily are generally ineffective, and only one study used doses greater than 1000 mg daily. Although sub-analyses suggest that these benefits may be limited to individuals aged 45-59 years, the number of studies in older individuals is small and findings are unclear (109165). A second meta-analysis in adults with type 2 diabetes suggests that resveratrol doses of at least 500 mg daily were necessary for reducing levels of fasting blood glucose and insulin, as well as insulin resistance (109167). A third meta-analysis, which also included Chinese language publications, shows that doses of resveratrol of at least 1000 mg daily are needed for improved glycemic control (109170). Some studies have used a specific resveratrol product (Biotivia Bioceuticals, International SrL) (95825). Although the reasons for discrepancies between individual clinical trials are not clear, it is possible that conflicting results are related to baseline blood glucose control. Resveratrol has shown benefit in patients with diabetes that is not well-controlled at baseline (HbA1c of 8% or higher) (91329), while results are mixed in patients with diabetes that is at least moderately well-controlled prior to supplementation (HbA1c of 7% or lower) (95825,100695). It is also possible that the differences may relate to the technique used to measure outcomes. For instance, resveratrol appears to improve insulin resistance when measured by the Stumvoll insulin sensitivity index, but not by the gold-standard hyperinsulinemic-euglycemic clamp technique (95832). Resveratrol has also been evaluated for improving blood pressure, blood lipid, and liver transaminase levels in patients with type 2 diabetes. Meta-analyses of clinical trials show that resveratrol has a small, but likely clinically insignificant, effect on systolic blood pressure when compared with placebo. Two meta-analyses show similar findings for diastolic blood pressure; however, some research suggests that any benefits are limited to doses of at least 500 mg daily (102513,109167,109170). Most meta-analyses of clinical research show that resveratrol does not improve blood lipid levels (105181,109167,109170) or liver transaminase levels (105181) when compared with placebo. Other clinical research in patients with overweight and type 2 diabetes shows that taking resveratrol 1000 mg daily for 8 weeks does not affect hepatic steatosis or cardiovascular risk indices when compared with placebo (109169).
Diabetic nephropathy. It is unclear if oral resveratrol is beneficial for diabetic nephropathy. Details: Preliminary clinical research in patients with diabetic nephropathy shows that taking resveratrol 500 mg plus losartan 12.5 mg daily for 90 days can reduce urinary albumin-to-creatinine ratios, but not serum creatinine levels or glomerular filtration rates, when compared with taking placebo and losartan. When compared to baseline, the urinary albumin-to-creatinine ratio decreased by 46 mg/gram with resveratrol and increased by 25 mg/gram with placebo (100695).
Hypertension. It is unclear if oral resveratrol is beneficial for lowering blood pressure. Details: A meta-analysis of clinical research shows that resveratrol is unlikely to be beneficial for improving systolic or diastolic blood pressure when compared with placebo in patients with hypertension. In the meta-analysis, studied populations included people who are overweight or obese, as well as patients with hypertension, type 2 diabetes, metabolic syndrome, nonalcoholic fatty liver disease (NAFLD), stroke, and dyslipidemia (102513). More research is needed in patients with hypertension.
Migraine headache. It is unclear if oral resveratrol is beneficial for treating migraine headache. Details: A small clinical crossover study in patients with hormonal migraine headaches shows that taking resveratrol (Veri-te Resveratrol, Evolva SA) 75 mg twice daily for 3 months does not affect headache frequency, severity, or disability when compared with placebo (109166). However, this study did not include a wash-out period between treatments, introducing the potential for carry-over effects.
Mitochondrial myopathies. It is unclear if oral resveratrol is beneficial for increasing exercise tolerance in patients with mitochondrial myopathies. Details: A very small clinical trial in adults with mitochondrial myopathies shows that taking resveratrol (Veri-te resveratrol) 500 mg twice daily for 8 weeks does not improve exercise capacity when compared with placebo (109162). This study may have been inadequately powered to detect differences between groups.
Osteoarthritis. It is unclear if oral resveratrol is beneficial for osteoarthritis. Details: A small clinical study in patients with mild or moderate knee osteoarthritis receiving physical therapy and meloxicam 15 mg daily shows that adding resveratrol 500 mg daily for 90 days improves pain, function, and stiffness when compared with adding placebo (98910).
Osteopenia. It is unclear if oral resveratrol is beneficial for improving bone mineral density (BMD). Details: A meta-analysis of clinical research shows that taking resveratrol at doses of up to 1500 mg daily for 1-12 months does not increase BMD or alter bone biomarkers when compared with placebo (109163). The studies in this meta-analysis included various populations, such as postmenopausal or overweight individuals, or patients with type 2 diabetes or metabolic syndrome. However, a clinical study in healthy, postmenopausal females shows that taking fermented soy 200 mg, containing resveratrol 25 mg and equol 10mg, orally daily for 12 months increases whole-body BMD when compared with placebo. Levels of markers of bone formation, including osteocalcin and bone-specific alkaline phosphatase, are increased, and the level of deoxypyridinoline, a marker of bone resorption, is decreased (112942).
Periodontitis. It is unclear if oral resveratrol is beneficial for periodontitis. Details: A small clinical study in individuals with chronic moderate-to-severe periodontitis who recently received non-surgical treatment for periodontitis shows that taking resveratrol 480 mg daily for 4 weeks improves plaque index when compared with placebo, but resveratrol does not seem to improve other markers of periodontitis, including pocket depth, bleeding index, clinical attachment loss, or salivary markers of inflammation (112135). The study may have been inadequately powered and too short in duration to detect a difference between the groups.
Peritoneal dialysis. It is unclear if oral resveratrol can improve outcomes with peritoneal dialysis. Details: One clinical study shows that taking trans-resveratrol 150 mg or 450 mg daily for 12 weeks increases ultrafiltration rate and volume when compared with placebo in patients on peritoneal dialysis. The effect appears to be dose-dependent (95830).
Polycystic ovary syndrome (PCOS). It is unclear if oral resveratrol is beneficial for PCOS. Details: Clinical research in patients with PCOS shows that taking resveratrol 1000 mg daily for 3 months results in a regular menstruation cycle length in 77% of individuals, compared with 52% of those taking placebo. The occurrence of hair loss was reduced by about 50%; however, there was no effect on hormone, metabolic, or lipid profiles. There was also a small increase in fat mass and decrease in fat-free mass, although the clinical relevance of these changes is unclear (109131). A small clinical trial in adults with PCOS shows that taking micronized trans-resveratrol (RevGenetics) 1500 mg daily for 3 months decreases levels of testosterone, but does not improve weight, lipid levels, insulin sensitivity, acne, or hirsutism, when compared with placebo (95823). A meta-analysis of 4 controlled trials of resveratrol, taken orally in doses of 800-1500 mg daily for 40 days to 3 months, shows reductions in levels of testosterone, luteinizing hormone, and dehydroepiandrosterone sulfate when compared with placebo, but no effect on follicle stimulating hormone, prolactin, thyroid stimulating hormone, C-reactive protein, insulin, sex hormone binding globulin, lipids, acne, or pregnancy rates (112943).
Rheumatoid arthritis (RA). It is unclear if oral resveratrol is beneficial for RA. Details: A small clinical study shows that adding resveratrol 1 gram orally once daily as adjunct therapy to antirheumatic drugs for 2 months reduces the number of tender and swollen joints, as well as biomarkers of inflammation. It is not known whether resveratrol reduces joint damage when assessed using conventional radiography. Also, the most effective combination of resveratrol and antirheumatic drug is not known, since the patients in this study were taking different antirheumatic drugs at variable doses (95706).
Sciatica. Oral resveratrol has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in patients with sciatica secondary to a herniated disk shows that taking a combination of resveratrol 50 mg with alpha-lipoic acid, acetyl-L-carnitine, and cholecalciferol orally once daily for 30 days, concurrently with a physiotherapy protocol, reduces pain and disability, and improves quality of life when compared with the physiotherapy protocol alone (112933). It is unclear if the effects are due to resveratrol, other ingredients, or the combination.
Ulcerative colitis. It is unclear if oral resveratrol is beneficial for ulcerative colitis. Details: Preliminary clinical research shows that taking trans-resveratrol (Sumabe Company) 500 mg daily for 6 weeks reduces subjective measures of disease activity and improves quality of life measures when compared with placebo in patients with mild to moderate active ulcerative colitis (95831). More evidence is needed to rate resveratrol for these uses.

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Safety view details

Below is general information about the safety of the known ingredients contained in the product NO3 Drive Capsules. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

AGMATINE (Agmatine Sulfate)

POSSIBLY SAFE ...when used orally and appropriately in medicinal amounts, short-term. Agmatine sulfate has been used with apparent safety at doses up to 2.67 grams daily for up to 2 months and 3.56 grams daily for up to 3 weeks (94736,111144).

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

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ASTRAGALUS

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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JIAOGULAN (Gynostemma pentaphyllum)

POSSIBLY SAFE ...when used orally and appropriately, short-term. Tea containing jiaogulan 3 grams has been taken twice daily with apparent safety for up to 3 months (94054,95519,95520). Jiaogulan extract has been used with apparent safety at a dose of up to 450 mg daily for up to 4 months (7069,7070,57056,94058,100961,106651). An in vitro study suggests that low, medium, and high doses of jiaogulan polysaccharides are safe in a model of the human intestinal epithelial barrier (110700).

PREGNANCY: POSSIBLY UNSAFE
when used orally. Ginsenoside Rb1, which is identical to the jiaogulan constituent gypenoside 3, has teratogenic effects in animal models; avoid using (10447).

LACTATION:
Insufficient reliable information available; avoid using.

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L-CITRULLINE

POSSIBLY SAFE ...when used orally and appropriately. In clinical trials, L-citrulline has been used with apparent safety for up to 2 months at doses of 1.5-6 grams daily (94954,94956,94961,94962,100974). Doses of up to 15 grams have also been used as single doses or within a 24 hour period (16470,16473).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately. L-citrulline has been used with apparent safety in infants at a dose of 0.17 grams/kg daily (16472). It has also been used in children 6.5-10 years of age at a dose of 7.5 grams daily for 26 weeks (100976). ...when used intravenously and appropriately. An intravenous bolus dose of L-citrulline 150 mg/kg followed by 9 mg/kg/hour for 48 hours has been used safely in children under 6 years of age (16469).

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

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PANAX NOTOGINSENG

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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PROPIONYL-L-CARNITINE (Propionyl L-Carnitine, Glycine Propionyl L-Carnitine HCl)

LIKELY SAFE ...when used orally and appropriately at doses up to 3 grams daily for up to 6 months (1434,1435,1436,1437,94439,94446,94447,94448). ...when single intravenous doses of 15 to 30 mg/kg are used under appropriate medical supervision (1571,1572,1573,1575).

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

RESVERATROL

LIKELY SAFE ...when used in amounts found in foods (2030).

POSSIBLY SAFE ...when taken orally in doses of up to 1500 mg daily for up to 3 months (71066,71097,91328,91331,95825,95833,98910,100695,105183,109163,109167). Higher doses of 2000-3000 mg daily have been well tolerated when taken for 2-6 months, but are more likely to cause gastrointestinal side effects (91327,98908). ...when used topically for up to 30 days (71064). ...when used as an intranasal spray for up to 4 weeks (97339).

CHILDREN: LIKELY SAFE
when used in amounts found in foods.

CHILDREN: POSSIBLY SAFE
when used as an intranasal spray for up to 2 months in children 4 years of age and older (91332). There is insufficient reliable information available about the safety of resveratrol when used by mouth in larger amounts as medicine.

PREGNANCY AND LACTATION: LIKELY SAFE
when used in amounts found in foods (2030). Resveratrol is found in grape skins, grape juice, wine, and other food sources. However, wine should not be used as a source of resveratrol during pregnancy and lactation.

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Interactions with Drugs view details

Below is general information about the interactions of the known ingredients contained in the product NO3 Drive Capsules. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

AGMATINE (Agmatine Sulfate)

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, agmatine might increase the risk of hypoglycemia when taken with antidiabetes drugs.

Details

Animal and in vitro research suggest that agmatine has mild hypoglycemic effects (94734).

ANTIHYPERTENSIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, agmatine might increase the risk of hypotension when taken with antihypertensive drugs.

Details

Animal research suggests that agmatine can modestly decrease heart rate and blood pressure (94734).

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ASTRAGALUS

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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JIAOGULAN (Gynostemma pentaphyllum)

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, jiaogulan might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.

Details

In vitro research suggests that jiaogulan has antiplatelet effects (7071).

ANTIDIABETES DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, jiaogulan might increase the risk of hypoglycemia when taken with antidiabetes drugs.

Details

Clinical research shows that jiaogulan can lower blood glucose levels (94054,95519,95520).

IMMUNOSUPPRESSANTS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, jiaogulan might decrease the effectiveness of immunosuppressive therapy.

Details

Clinical and animal studies suggest that jiaogulan can stimulate the immune system (6,94056).

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L-CITRULLINE

ANTIHYPERTENSIVE DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, concomitant use of L-citrulline with antihypertensive drugs might have additive effects and increase the chance of hypotension.

Details

L-citrulline is converted to L-arginine, which can increase nitric oxide and cause vasodilation (7822,16460,16461). However, a meta-analysis of 5 small clinical studies suggests that taking L-citrulline 3-6 grams daily for 1-8 weeks does not lower blood pressure when compared with control (100974).

PHOSPHODIESTERASE-5 INHIBITORS

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, concurrent use of phosphodiesterase-5 (PDE-5) inhibitors and L-citrulline might result in additive vasodilation.

Details

L-citrulline is converted to L-arginine, which can increase nitric oxide and cause vasodilation (7822,16460,16461). Theoretically, taking L-arginine with PDE-5 inhibitors might have additive vasodilatory and hypotensive effects. However, in studies evaluating the combined use of L-arginine and sildenafil for erectile dysfunction, hypotension was not reported (105065).

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PANAX NOTOGINSENG

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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PROPIONYL-L-CARNITINE (Propionyl L-Carnitine, Glycine Propionyl L-Carnitine HCl)

ACENOCOUMAROL (Sintrom)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, propionyl-L-carnitine might increase the anticoagulant effects of acenocoumarol.

Details

L-carnitine, the parent compound of propionyl-L-carnitine, might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant similar to warfarin, but shorter-acting (9878,12165). There are at least two case reports of INR elevation when L-carnitine was taken with acenocoumarol. In one case, a 33-year-old male with a previously stable INR had an elevated INR of 4.65 after L-carnitine was started and continued for 10 weeks. INR normalized after discontinuation of the L-carnitine-containing product (12165). It is unclear if such an interaction would also occur with propionyl-L-carnitine.

THYROID HORMONE

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, acetyl-L-carnitine might decrease the effectiveness of thyroid hormone replacement.

Details

L-carnitine appears to act as a peripheral thyroid hormone antagonist by inhibiting entry of thyroid hormone into the nucleus of cells (12761). Taking L-carnitine also seems to diminish some of the symptoms of hyperthyroidism (8047). It is unclear if such an interaction would occur with propionyl-L-carnitine.

WARFARIN (Coumadin)

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, propionyl-L-carnitine might increase the anticoagulant effects of warfarin.

Details

L-carnitine, the parent compound of propionyl-L-carnitine, might increase the anticoagulant effects of acenocoumarol, a shorter-acting oral anticoagulant similar to warfarin (9878,12165). There is not enough information to know whether this interaction occurs with propionyl-L-carnitine and warfarin.

RESVERATROL

ANTICOAGULANT/ANTIPLATELET DRUGS

Interaction Rating = Moderate Be cautious with this combination.

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

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

Details

Resveratrol seems to have antiplatelet effects (2949,2950,2951,2952,2961,70813,70828,70831,70892,70968,71106).

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, resveratrol might increase levels of drugs metabolized by CYP1A1.

Details

In vitro research shows that resveratrol can inhibit CYP1A1 enzymes (70811,70862). However, this interaction has not been reported in humans.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

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

Details

In vitro research shows that resveratrol can inhibit CYP1A2 enzymes (21733). However, this interaction has not been reported in humans.

CYTOCHROME P450 1B1 (CYP1B1) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, resveratrol might increase levels of drugs metabolized by CYP1B1.

Details

In vitro research shows that resveratrol can inhibit CYP1B1 enzymes (70834). However, this interaction has not been reported in humans.

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

Theoretically, resveratrol might increase levels of drugs metabolized by CYP2C19.

Details

In vitro research shows that resveratrol can inhibit CYP2C19 enzymes (70896). However, this interaction has not been reported in humans.

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

Resveratrol might increase levels of drugs metabolized by CYP2E1.

Details

In vitro research suggests that resveratrol inhibits CYP2E1 isoenzyme (7864,70896). Also, a pharmacokinetic study shows that taking resveratrol 500 mg daily for 10 days prior to taking a single dose of chlorzoxazone 250 mg increases the maximum concentration of chlorzoxazone by about 54%, the area under the curve of chlorzoxazone by about 72%, and the half-life of chlorzoxazone by about 35% (95824). Chlorzoxazone is used as a probe drug for CYP2E1.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES

Interaction Rating = Moderate Be cautious with this combination.

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

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

Details

In vitro research shows that resveratrol can inhibit the CYP3A4 enzyme (7864,70896). However, clinical research shows that taking resveratrol 3000 mg daily for 8 weeks does not necessitate dose adjustments to medications metabolized by CYP3A4 (91327).

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Adverse Effects view details

Report an Adverse Reaction to NO3 Drive Capsules

Below is general information about the adverse effects of the known ingredients contained in the product NO3 Drive Capsules. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.

AGMATINE (Agmatine Sulfate)

General ...Orally, agmatine seems to be well tolerated when used in medicinal amounts, short-term.
Most Common Adverse Effects:
Orally: Diarrhea, dyspepsia, nausea.

Gastrointestinal ...Orally, agmatine has been reported to cause diarrhea, dyspepsia, and nausea in two small clinical studies (94736,94742). Mild-to-moderate diarrhea and nausea were reported in 3 out of 24 patients taking agmatine sulfate 3.56 grams daily. These adverse effects appeared within 2-3 days of therapy and resolved upon treatment discontinuation (94736).

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ASTRAGALUS

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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JIAOGULAN (Gynostemma pentaphyllum)

General ...Orally, jiaogulan seems to be well tolerated when used for up to 4 months.
Most Common Adverse Effects:
Orally: Diarrhea and nausea.

Gastrointestinal ...Orally, jiaogulan may cause diarrhea and nausea (6,106651). Dry mouth has also been reported with oral jiaogulan use (106651).

Neurologic/CNS ...Orally, jiaogulan may cause dizziness and insomnia (106651).

(Read more about JIAOGULAN)

L-CITRULLINE

General ...Orally, L-citrulline seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Gastrointestinal discomfort, heartburn.

Gastrointestinal ...Orally, gastrointestinal intolerance, stomach discomfort, and heartburn have been reported with L-citrulline use (94955,94963,94966).

Genitourinary ...Orally, 2 of 25 patients with pulmonary hypertension reported increased urinary frequency and edema while taking 1 gram of powdered L-citrulline in water daily (94963).

Pulmonary/Respiratory ...Orally, 2 of 25 patients with pulmonary hypertension reported cough while taking 1 gram of powdered L-citrulline in water daily (94963).

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PANAX NOTOGINSENG

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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PROPIONYL-L-CARNITINE (Propionyl L-Carnitine, Glycine Propionyl L-Carnitine HCl)

General ...Orally, propionyl-L-carnitine is well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, gastric pain, nausea, and vomiting. A metabolite of propionyl-L-carnitine has been reported to cause a fishy odor of the urine, breath, and sweat.

Gastrointestinal ...Orally, nausea, vomiting, diarrhea, and gastric pain have been reported with propionyl-L-carnitine use (1579,1580,1582,12682,94439,94443).

Musculoskeletal ...Orally, back pain was reported more frequently with propionyl-L-carnitine when compared with placebo in one clinical trial (94443).

Neurologic/CNS ...Orally, asthenia has been reported with propionyl-L-carnitine use (1579,1580,1582).

Pulmonary/Respiratory ...Orally, bronchitis was reported more frequently with propionyl-L-carnitine when compared with placebo in one clinical trial (94443).

Other ...Orally, one of the metabolites of propionyl-L-carnitine can cause the urine, breath, and sweat to have a fishy odor (12756).

RESVERATROL

General ...In foods, resveratrol is well tolerated. When used orally in higher doses, as well as topically or intranasally, resveratrol seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, gastrointestinal discomfort, and loose stools.

Dermatologic ...Orally, there is one case of a pruritic skin rash that occurred in a clinical trial. The rash resolved two weeks after stopping resveratrol (109163).
Topically, a case of allergic contact dermatitis has been reported after applying a facial cream (Resveratrol BE, Skinceuticals) containing aqueous resveratrol 1% in combination with Baikal skullcap root extract 0.5%. Patch testing identified a positive reaction to both ingredients (110024).

Gastrointestinal ...Orally, mild gastrointestinal discomfort with increased diarrhea or loose stools has been reported, especially when resveratrol is taken in doses of 2. 5-5 grams daily (71042,71052,91327,95830,109163,109164,109167).

Hematologic ...In one clinical study, a patient developed severe febrile leukopenia and thrombocytopenia after taking oral resveratrol 500 mg three times daily for 10 days. Upon re-exposure to resveratrol, febrile leukopenia recurred (109163).

Musculoskeletal ...Orally, resveratrol has been associated with muscle cramps in patients on peritoneal dialysis. The causality of this adverse effect has not been established (95830).

Neurologic/CNS ...Orally, resveratrol has been associated with headache, fatigue, and memory loss in patients on peritoneal dialysis. The causality of these adverse effects has not been established (95830).

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