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POSSIBLY EFFECTIVE

• Age-related cognitive decline. Oral acetyl-L-carnitine may improve age-related cognitive decline. Details: Clinical research shows that taking acetyl-L-carnitine 1500-2000 mg daily for 3 months seems to improve some measures of cognitive function and memory in elderly people with age-related cognitive decline (42,3600,3601).
• Age-related fatigue. Oral acetyl-L-carnitine may improve age-related physical and mental fatigue. Details: One clinical trial shows that taking acetyl-L-carnitine 2 grams twice daily for 180 days reduces physical fatigue by 52% and mental fatigue by 43%, compared with only 4% and 8%, respectively, for elderly patients taking placebo. Fatigue after exercise is also reduced by 51% in those taking acetyl-L-carnitine, compared with only 4% in those taking placebo (58375).
• Alcohol use disorder. Intravenous acetyl-L-carnitine may reduce cravings and other symptoms of withdrawal during alcohol detoxification. It is unclear if oral acetyl-L-carnitine is beneficial for managing withdrawal or complications of alcohol use disorder. Details: Clinical research in adults with alcohol use disorder who are in withdrawal shows that acetyl-L-carnitine 1-3 grams daily, administered as a slow intravenous infusion over 3-4 hours for 10 days, followed by 3 grams daily orally for an additional 80 days, improves cravings, the inability to feel pleasure (anhedonia), and melancholic symptoms and increases the time to the first drink when compared with placebo. However, most symptom improvement appears to occur during the first week, so it is unclear if taking acetyl-L-carnitine 3 grams daily orally for an additional 80 days is beneficial (90766,90767). One small clinical trial in adults with chronic alcohol use disorder and cognitive impairment shows that taking acetyl-L-carnitine 2 grams daily for 90 days seems to improve memory and visuospatial capacity when compared with placebo (1589).
• Alzheimer disease. Oral acetyl-L-carnitine may slow the progression of Alzheimer disease and improve some measures of cognitive function. Details: Clinical research shows that taking acetyl-L-carnitine 1.5-3 grams daily for 3-12 months might slow the rate of Alzheimer disease progression and improve memory, some measures of cognitive function, and behavioral performance. It is more likely to show some effect in those with early-onset Alzheimer disease who are less than 66 years of age and have a faster rate of disease progression and mental decline (1594,1595,1596,1597,1598,1599,9105,10391). It is unclear how acetyl-L-carnitine compares with prescription medications.
• Depression. Oral acetyl-L-carnitine may reduce symptoms of depression, with comparable effects to conventional antidepressants, in patients with dysthymia and depression. It may be most effective in elderly patients and at higher doses. Details: Several clinical trials addressing the use of acetyl-L-carnitine in elderly patients with dysthymia and depression have been conducted (3602,3603,3604). A meta-analysis of these and other studies, all conducted in Europe, shows that taking acetyl-L-carnitine 1-4 grams daily for 3-24 weeks moderately reduces depressive symptoms when compared with placebo, and appears to have similar effects as conventional antidepressants. Acetyl-L-carnitine seems to be most effective when used at higher dosages. Duration of follow-up and baseline symptoms do not appear to influence results (95065).
• Diabetic neuropathy. Oral acetyl-L-carnitine may reduce pain in patients with diabetic neuropathy when taken at doses of at least 2-3 grams daily. It is unclear if oral acetyl-L-carnitine can improve nerve conduction velocity in these patients. Details: Although most clinical research evaluating acetyl-L-carnitine for use in diabetic neuropathy has shown benefit, this evidence is of overall low quality. A meta-analysis shows that taking acetyl-L-carnitine 2-3 grams daily for up to 12 months modestly reduces pain scores by about 15 points on a 100-point visual analog scale, while lower doses of 1.5 grams daily improve pain scores to a similar extent as placebo. Some research included in this analysis shows that acetyl-L-carnitine seems to increase nerve fibers, regenerate nerve fiber clusters, and improve vibratory sensations. In two studies, vibration sensation improved after 12 months when compared with placebo, but numerical data are lacking (102126). Other clinical research shows that taking acetyl-L-carnitine 1000 mg 2-3 times daily decreases pain within 6 months. Acetyl-L-carnitine seems to be most effective for reducing pain in patients with a shorter duration of diabetes and in patients with poorly controlled type 2 diabetes. Some research shows that taking acetyl-L-carnitine 500 mg (Liaoning Haisike Pharmaceutical Co. Ltd.) three times daily for 24 weeks is as effective as methylcobalamin 0.5 mg three times daily for improving electrophysiological parameters and symptoms as measured by the Neuropathy Disability Score (95067,102126). However, research on the use of acetyl-L-carnitine to improve nerve conduction velocity in patients with diabetic neuropathy is conflicting (1593,12743,12753,13007,95067).
• Male infertility. Oral acetyl-L-carnitine, taken in combination with L-carnitine, may increase sperm motility in males with infertility. It is unclear if oral acetyl-L-carnitine alone can improve sperm function or pregnancy outcomes. Details: Although some research disagrees (111861), taking acetyl-L-carnitine in combination with L-carnitine, usually in doses of 1 gram and 2 grams, respectively, daily for 3-6 months seems to increase sperm motility in males with infertility of various etiologies. The evidence related to the effect of this combination on sperm count and morphology is mixed (12352,58182,58194,58469,101560,107394,111459,111890). However, it is unclear if taking L-carnitine increases the odds of pregnancy. One meta-analysis of randomized controlled trials shows that taking these carnitines in combination increases the odds of pregnancy by 3.7-fold over placebo. However most clinical research investigating the effect of L-carnitine alone or with acetyl L-carnitine on pregnancy rates disagrees (12352,58182,101560,111861,111459). Taking acetyl-L-carnitine 500 mg and L-carnitine 1 gram twice daily after taking nonsteroidal anti-inflammatory drugs for 2 months seems to increase sperm count and motility in those with abacterial prostatovesiculoepididymitis, an inflammation of the prostate gland, seminal vesicles, and epididymis (9791). Acetyl-L-carnitine has also been evaluated in combination with other ingredients. One study shows that taking acetyl-L-carnitine 50 mg in combination with L-carnitine 150 mg, L-arginine 1660 mg, and Panax ginseng 200 mg daily for 3 months increases sperm motility and sexual satisfaction in those with asthenospermia when compared with no treatment (32189). Another small clinical trial shows that taking this combination along with prulifloxacin 600 mg daily for 6 months improves sperm concentration and motility when compared with treatment with prulifloxacin alone in patients with chronic prostatitis due to Chlamydia trachomatis infection (59006). Other small and preliminary Iclinical studies have investigated the effects of a specific combination product providing acetyl-L-carnitine 500 mg twice daily for 6 months, along with L-carnitine, coenzyme Q10, selenium, zinc, vitamin C, folic acid, vitamin B12, and citric acid (Proxeed Plus). Taking this combination product has been shown to improve measures of sperm quality such as sperm count, sperm concentration, total motility, and progressive motility when compared to baseline. The effect on sperm volume and morphology is unclear. Most research has been conducted in patients with oligoasthenozoospermia, although some benefit has also been shown in patients with varicocele-related infertility, especially those with more severe varicocele (102017,107395,111296). The validity of these findings is limited by the lack of comparator group. Also, it is unclear if these effects are due to L-carnitine, other ingredients, or the combination.

POSSIBLY INEFFECTIVE

• Chemotherapy-induced peripheral neuropathy. The evidence related to the effect of oral acetyl-L-carnitine on symptoms of chemotherapy-induced peripheral neuropathy is mixed. Some research shows that it may actually worsen symptoms. Details: High quality clinical research in females treated with taxane-based therapy for early-stage breast cancer shows that taking acetyl-L-carnitine 1000 mg three times daily for 24 weeks does not improve symptoms of neuropathy when compared with placebo. In fact, acetyl-L-carnitine treatment may actually make symptoms worse in some patients, with worsened symptoms persisting for up to at least 2 years (90758,96938,111882). Also, a small clinical trial in patients with multiple myeloma receiving bortezomib, doxorubicin, and dexamethasone shows that taking acetyl-L-carnitine 1.5 grams daily does not reduce symptoms of peripheral neuropathy when compared with not taking acetyl-L-carnitine (90756). A small clinical trial in patients with ovarian cancer or castration-resistant prostate cancer receiving sagopilone shows that taking acetyl-L-carnitine 1000 mg every three days appears to reduce the more severe symptoms of peripheral neuropathy; however, the overall incidence or duration of peripheral neuropathy is not reduced when compared with placebo (90757). Some research disagrees. One clinical trial in patients with taxoid-related neuropathy shows that taking acetyl-L-carnitine3 grams daily for 8 weeks modestly improves the severity of neuropathy by at last one grade in 51% of patients compared with 24% of those taking placebo. Functional improvement was also modestly improved (111862). Based on the available research, the American Society of Clinical Oncology strongly discourages the use of acetyl-L-carnitine for the prevention of chemotherapy-induced peripheral neuropathy, noting that the harms outweigh the potential benefits (104168).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related testosterone deficiency. Oral acetyl-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 acetyl-L-carnitine 2 grams, in combination with propionyl-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 acetyl-L-carnitine, propionyl-L-carnitine, or the combination.
• Aging skin. Although there has been interest in using oral acetyl-L-carnitine for aging skin, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Amenorrhea. Although there has been interest in using oral acetyl-L-carnitine for amenorrhea, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). It is unclear if oral acetyl-L-carnitine is beneficial in patients with ALS. Details: One small clinical trial in patients with ALS shows that taking acetyl-L-carnitine 1000 mg three times daily for 48 weeks, along with riluzole 50 mg twice daily, reduces the number of patients who lose self-sufficiency by about 17%, increases patient survival by a median of 23 months, and improves some measures of physical function when compared with riluzole alone (90755).
• Antiretroviral toxic neuropathy. Small clinical studies suggest that oral acetyl-L-carnitine may modestly improve symptoms in patients with antiretroviral toxic neuropathy. It is unclear if intramuscular or intravenous acetyl-L-carnitine is beneficial in patients with this condition. Details: Small clinical trials show that taking acetyl-L-carnitine 1000-1500 mg twice daily for up to 33 months might relieve symptoms of distal symmetrical polyneuropathy caused by antiretroviral treatment in HIV-positive patients (12745,58342). Also, a small, uncontrolled clinical study shows that intramuscular or intravenous administration of acetyl-L-carnitine 500-1000 mg daily for 3 weeks reduces pain intensity when compared to baseline in some HIV-positive patients receiving antiretroviral therapy (12747). However, another clinical study shows that intramuscular acetyl-L-carnitine 500 mg twice daily for 14 days does not reduce pain when compared with placebo (58342).
• Athletic performance. Although there has been interest in using oral acetyl-L-carnitine for athletic performance, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Attention deficit-hyperactivity disorder (ADHD). Small clinical trials suggest that oral acetyl-L-carnitine is not beneficial in children with ADHD. Details: One small clinical trial in children and adolescents with ADHD shows that taking acetyl-L-carnitine 1-3 grams daily, based on body weight, in two divided doses along with methylphenidate 20-30 mg daily for 3 weeks does not reduce symptoms of ADHD when compared with methylphenidate alone (90754). Based on this and another small trial, Guidelines from The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety Treatments (CANMAT) Taskforce state that acetyl-L-carnitine in doses of 1-3 grams daily is not recommended for adjunctive or monotherapy use for ADHD in children (110318).
• Bell palsy. Although there has been interest in using oral acetyl-L-carnitine for Bell palsy, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Bipolar disorder. Oral acetyl-L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical trial in patients with type I or type II bipolar disorder shows that taking acetyl-L-carnitine 1000 mg plus alpha-lipoic acid 600 mg up to three times daily for 12 weeks does not improve depression when compared with placebo (90441).
• Cancer-related fatigue. Although there has been interest in using oral acetyl-L-carnitine for cancer-related fatigue, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Carpal tunnel syndrome. It is unclear if oral acetyl-L-carnitine is beneficial in patients undergoing surgery for carpal tunnel syndrome. Details: A small clinical study in adults undergoing carpal tunnel release surgery shows that taking acetyl-L-carnitine 3000 mg daily for 2 months postoperatively does not improve nerve regeneration or functional recovery when compared with placebo (100349). However, this study may have been inadequately powered to detect a difference between groups. Acetyl-L-carnitine has also been investigated in combination with other ingredients. In patients with mild to moderate symptoms awaiting carpal tunnel release, preliminary clinical research shows that taking acetyl-L-carnitine as part of a multi-ingredient formulation for 60 days reduces pain by 31%, but does not improve function, when compared with no treatment. The formulation provided a total of 600 mg twice daily of acetyl-L-carnitine with alpha-lipoic acid, phosphatidylserine, curcumin, thiamine, riboflavin, and vitamins C, E, B6, and B12 (111702).
• Cataracts. Although there has been interest in using oral acetyl-L-carnitine for cataracts, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Chronic fatigue syndrome (CFS). It is unclear if oral acetyl-L-carnitine is beneficial in patients with CFS. Details: Preliminary clinical research in patients with CFS shows that taking acetyl-L-carnitine 2 grams daily for 6 months improves general fatigue in up to 59% of patients when compared with baseline. The combination of acetyl-L-carnitine and propionyl-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).
• Diabetes. It is unclear if oral acetyl-L-carnitine improves glycemic control in people with type 2 diabetes. Details: Clinical research in patients with type 2 diabetes, hypertension, and dyslipidemia shows that taking acetyl-L-carnitine 1 gram twice daily for 6 months does not improve blood glucose levels, glycated hemoglobin, fasting insulin levels, insulin resistance, or glucose disposal rate when compared with placebo. Most patients were already taking one or more antidiabetes drug, as well as medication for hypertension and dyslipidemia (96937). It is unclear if acetyl-L-carnitine improves glycemic profile in patients with uncontrolled diabetes.
• Down syndrome. Although there has been interest in using oral acetyl-L-carnitine for Down syndrome, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Dyslipidemia. It is unclear if oral acetyl-L-carnitine reduces lipid levels in adults with dyslipidemia. Details: Clinical research in patients with dyslipidemia, type 2 diabetes, and hypertension shows that taking acetyl-L-carnitine 1 gram twice daily for 6 months does not improve cholesterol, triglycerides, or lipoprotein(a) levels when compared with placebo. All patients were taking statins prior to treatment with acetyl-L-carnitine, and most were receiving medication for hypertension and diabetes (96937). It is unclear if acetyl-L-carnitine is beneficial in patients not taking statins.
• Fibromyalgia. It is unclear if oral and/or intramuscular acetyl-L-carnitine can improve symptoms of fibromyalgia. Details: One clinical study in patients with fibromyalgia shows that taking acetyl-L-carnitine 1000 mg daily orally plus acetyl-L-carnitine 500 mg daily intramuscularly for 2 weeks, followed by acetyl-L-carnitine 1500 mg daily orally for 8 weeks, reduces muscle pain and improves mood, general health, and quality of life when compared with placebo (90768). A smaller clinical study in patients with fibromyalgia shows that taking acetyl-L-carnitine 500 mg three times daily for 12 weeks improves quality of life (physical) scores and symptoms of depression, but not pain, anxiety, or quality of life (mental) scores when compared with baseline (90761). The validity of these findings is limited by the lack of a comparator group. Acetyl-L-carnitine has also been investigated in combination with other ingredients. Clinical research shows that taking acetyl-L-carnitine 500 mg and palmitoylethanolamide (PEA) 600 mg twice daily for 12 weeks increases the proportion of patients with at least a 30% reduction in pain by 86% when compared with not taking this combination. There was also a modest improvement in the overall assessment of status. All patients were on stable treatment with duloxetine and pregabalin for 3 months prior to the initiation of acetyl-L-carnitine and PEA, and this treatment continued throughout the study (111901).
• Fragile X syndrome. Small clinical studies suggest that oral acetyl-L-carnitine is not beneficial in children with fragile X syndrome. Details: Two small clinical studies in children with fragile X syndrome shows that acetyl-L-carnitine 20-50 mg/kg daily for one year does not improve intellectual function when compared with placebo. Also, while it may reduce hyperactive behavior in these patients based on parent assessment, it does not appear to reduce hyperactive behavior based on teacher assessment (9956,93063).
• Frailty. It is unclear if oral acetyl-L-carnitine prevents frailty. Details: Clinical research in pre-frail older adults shows that taking acetyl-L-carnitine 1.5 grams twice daily for 3 months modestly improves cognition and the distance walked in 6 minutes when compared with taking placebo (111889). It is unclear whether taking acetyl-L-carnitine is beneficial for frailty treatment or prevention.
• Hepatic encephalopathy. Small clinical studies suggest that oral acetyl-L-carnitine may not improve quality of life or fatigue in patients with hepatic encephalopathy due to cirrhosis. Details: The benefits of acetyl-L-carnitine in the management of hepatic encephalopathy due to cirrhosis are unclear (58922,58949,59002,90759). A meta-analysis of the available clinical research shows that taking acetyl-L-carnitine 2 grams twice daily for 90 days does not improve quality of life or fatigue in this population when compared with placebo. However, major clinical outcomes, such as all-cause mortality, days of hospitalization, and serious adverse events, have not been evaluated. Additionally, the validity of these findings is limited by the small size, high risk for bias, and heterogeneity of the included studies (100350).
• Hypertension. It is unclear if oral acetyl-L-carnitine lowers blood pressure in adults with hypertension. Details: Clinical research in patients with hypertension, type 2 diabetes, and dyslipidemia shows that taking acetyl-L-carnitine 1 gram twice daily for 6 months does not improve systolic or diastolic blood pressure when compared with placebo. Most patients were already being treated with antihypertensive drugs prior to treatment with acetyl-L-carnitine, in addition to medications for dyslipidemia and diabetes (96937). It is unclear if acetyl-L-carnitine reduces blood pressure in patients with uncontrolled hypertension.
• Infertility. Although there has been interest in using oral acetyl-L-carnitine for infertility in females, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Lyme disease. Although there has been interest in using oral acetyl-L-carnitine for Lyme disease, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Multiple sclerosis-related fatigue. It is unclear if oral acetyl-L-carnitine is beneficial in patients with multiple sclerosis-related fatigue. Details: One small clinical study in patients with multiple sclerosis shows that taking acetyl-L-carnitine 1 gram twice daily for one month reduces fatigue by approximately 25% when compared with placebo (90760).
• Obesity. Although there has been interest in using oral acetyl-L-carnitine for obesity, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Peripheral neuropathy. Although there has been interest in using oral acetyl-L-carnitine for peripheral neuropathy, there is insufficient reliable information about the clinical effects of acetyl-L-carnitine for this purpose.
• Peyronie disease. A small clinical study suggests that oral acetyl-L-carnitine may modestly improve symptoms of Peyronie disease. Details: One small clinical trial in patients with acute and early chronic Peyronie disease shows that taking acetyl-L-carnitine 1 gram twice daily for 3 months reduces pain and slows disease progression when compared with tamoxifen 20 mg twice daily (10076).
• Polycystic ovary syndrome (PCOS). It is unclear if acetyl-L-carnitine is beneficial in patients with PCOS. Details: A clinical study in patients with PCOS shows that taking acetyl-L-carnitine 1.5 grams, in combination with metformin and pioglitazone, twice daily for 12 weeks improves menstrual irregularity and insulin resistance when compared with baseline. The lack of statistical comparison to placebo, as well as the combined use with metformin and pioglitazone, limits the validity of these findings (107396).
• Schizophrenia. It is unclear if oral acetyl-L-carnitine is beneficial in patients with schizophrenia. Details: A very small, open-label clinical study in patients with schizophrenia who partially responded to clozapine therapy shows that taking acetyl-L-carnitine 1 gram daily, in combination with clozapine 300-600 mg daily, for 12 weeks reduces positive symptoms of schizophrenia, but not cognitive function or other clinical symptoms, when compared with baseline (95063). The validity of these findings is limited by the lack of a comparator group.
• Sciatica. It is unclear if oral acetyl-L-carnitine is beneficial in patients with sciatica. Details: One small clinical trial in patients with sciatica secondary to a herniated disc shows that taking acetyl-L-carnitine (Nicetile, SigmaTau Ind. Farm. Riunite SpA,) 1180 mg daily for 60 days decreases the use of analgesics when compared with baseline. However, acetyl-L-carnitine appears to be less effective than alpha-lipoic acid (Byodiniral 300 QR, MDM SpA,) 600 mg daily for reducing lower limb pain and the use of analgesics (21671).
• Stroke. It is unclear if oral acetyl-L-carnitine is beneficial following a stroke. Details: Clinical research in patients with an acute ischemic stroke given routine care shows that oral or nasogastric acetyl-L-carnitine 1 gram three times daily for 3 days modestly improves stroke impairment and overall function 3 months after the stroke when compared with taking placebo. The proportion of patients taking acetyl-L-carnitine with no symptoms or obvious disability at 3 months was 53%, compared with 29% of patients taking placebo. The patients in this study were not candidates of reperfusion therapy and initiated acetyl-L-carnitine within 24 hours of the stroke (111894).
• Toxin-induced liver damage. Oral acetyl-L-carnitine has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients being treated with anti-tuberculosis drugs shows that taking acetyl-L-carnitine 250 mg, along with coenzyme Q10 and alpha-lipoic acid, twice daily for 2 weeks reduces the risk of drug-induced liver injury by 73% when compared with placebo (107445). It is unclear if these findings are due to acetyl-L-carnitine, other ingredients, or the combination. More evidence is needed to rate acetyl-L-carnitine for these uses.

(Read more about ACETYL-L-CARNITINE)

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Acne. Although there is interest in using oral danshen for acne, there is insufficient reliable information about the clinical effects of danshen for this condition.
• Angina. Preliminary clinical research suggests that compound danshen dripping pill, containing danshen extract, Panax notoginseng, and borneol, reduces symptoms and improves electrocardiogram (ECG) parameters in adults with angina. The effect of danshen alone is unclear. Details: Analyses of preliminary clinical research, as well as individual lower-quality clinical studies, have shown that danshen dripping pill is effective in reducing symptoms of angina, although the extent of this effect and place in therapy is unclear (47021,47025,96442,96443,96445). Analyses of the available clinical research, involving up to 109 studies with 11,973 patients, show that compound danshen dripping pill, 216-270 mg, taken as 8-10 pills, three times daily for 1-6 months, is more effective than isosorbide dinitrate taken as 5-20 mg three times daily in improving the symptoms and ECG parameters associated with angina (96442,96445). Another analysis involving 17 studies with 1,433 patients found that danshen injection as an adjunct to standard treatment options was more effective in improving symptoms of angina and ECG parameters when compared with standard treatment alone. However, details on the dose of danshen injection and the standard treatments used in the reviewed studies were not provided (96443). The low quality and high heterogeneity of the reviewed studies limit the validity of these findings. Also, the optimal dose and optimal form of danshen for treating angina has not been identified. Additionally, the effects of danshen alone are unclear. Salvianolate, a component of danshen, has been evaluated for the treatment of angina. A review of the available research shows that giving salvianolate as an intravenous infusion 250 mg in 250 mL dextrose daily for 10-14 days reduces angina severity and nitroglycerin tablet use in about 28% of people with stable angina. The patients most likely to respond are overweight, hypertensive, or experience at least 3 angina episodes per week (99069).
• Atopic dermatitis (eczema). Although there is interest in using oral danshen for eczema, there is insufficient reliable information about the clinical effects of danshen for this condition.
• Cancer. It is unclear if oral danshen is beneficial for cancer treatment. Details: A meta-analysis of 13 small, heterogenous clinical trials shows that taking various formulas containing danshen in combination with chemotherapy increases the odds of response and survival over 1-5 years when compared with chemotherapy alone. In patients with various types of cancer, including leukemia, and lung, liver, breast, colon, and gastric cancer, the odds of survival were increased by at least 1.7-fold (101976). It is unclear what other treatments these patients were receiving.
• Cirrhosis. It is unclear if oral or intravenous danshen are beneficial for cirrhosis. Details: A meta-analysis of results from low-quality clinical research, including 11 studies involving 1,086 patients, suggests that compound danshen injection or danshen injection 16-30 mL in conjunction with astragalus injection 10-30 mL daily for up to 90 days is superior to control in reducing liver function enzyme levels, increasing albumin levels, and reducing markers of fibrosis in adults with cirrhosis. However, the variability of treatments used as control, the wide range of outcomes assessed, and the significant heterogeneity between trials limits the validity of these findings (90622). Additionally, the effect of danshen injection alone is unclear.
• Coronary heart disease (CHD). Preliminary clinical research suggests that taking compound danshen dripping pills containing danshen extract, Panax notoginseng, and borneol may improve some cardiac symptoms, surrogate markers of cardiac function, and metabolic indices in patients with CHD. The effect of danshen alone is unclear. Details: A meta-analysis of the results of low-quality clinical research, including 10 studies involving 1,367 patients, shows that taking compound danshen dripping pills 240-270 mg as 10 tablets three times daily in combination with aspirin 25-100 mg daily for 4 weeks to 2 years reduces symptoms of CHD and pain when compared with aspirin alone in adults with CHD (96439). Also, meta-analyses of low-quality clinical research, including up to 19 studies, show that taking compound danshen dripping pills in combination with aspirin reduces total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride levels, as well as plasma viscosity and platelet aggregation, and increases high-density lipoprotein (HDL) cholesterol levels, when compared with aspirin alone in adults with CHD (96439,109369). The low quality and high heterogeneity of the reviewed studies limit the validity of these findings. A meta-analysis of randomized clinical trials in adults with CHD that require percutaneous coronary intervention (PCI) shows that taking compound danshen dripping pills three times daily for 1-6 months reduces the risk of recurrent angina by 80%, coronary restenosis by 71%, heart failure by 55%, and malignant arrhythmia by 47% when compared with usual treatment, although there was no reduction in the risk for acute myocardial infarction or sudden cardiac death. Taking compound danshen dripping pills also improved LDL cholesterol levels, but not HDL cholesterol or triglyceride levels (105516). The validity of this study is limited by an unreported dose of compound danshen dripping pills, unclear use of antiplatelet and other adjunctive therapies in the control group, and possible publication bias. A more recent large clinical trial in adults with CHD complicated with anxiety and depression who recently underwent PCI shows that taking compound danshen dripping pills 400 mg three times daily for three months improves quality of life, anxiety, angina symptoms, and surrogate biomarkers such as endothelin and high-sensitivity C-reactive protein compared with placebo (112398).
• Diabetes. Although there is interest in using oral danshen for diabetes, there is insufficient reliable information about the clinical effects of danshen for this condition.
• Diabetic foot ulcers. Although there is interest in using oral danshen for diabetic foot ulcers, there is insufficient reliable information about the clinical effects of danshen for this condition.
• Diabetic nephropathy. It is unclear if oral or intravenous danshen are beneficial for diabetic nephropathy. Details: A meta-analysis of up to 13 preliminary clinical trials in patients with early diabetic kidney disease shows that intravenous administration of danshen and Ligusticum striatum extract for 2-4 weeks, in combination with conventional medications such as angiotensin receptor blockers, alprostadil, benazepril, and others, modestly reduces urinary albumin and serum creatinine levels when compared with conventional medications alone (109380). The effects of oral danshen or intravenous danshen alone in patients with diabetic nephropathy are unclear.
• Diabetic retinopathy. Preliminary clinical research suggests that taking compound danshen dripping pills, containing danshen extract, Panax notoginseng, and borneol, may improve visual acuity and the severity of diabetic retinopathy. The effect of danshen alone is unclear. Details: Meta-analyses of available preliminary clinical research in adults with diabetic retinopathy, including up to 13 studies, show that taking compound danshen dripping pill at doses of 270-540 mg or ten pills three times daily improves retinal and choroid circulation, visual field, and visual acuity, and reduces the occurrence of microaneurysm and retinal hemorrhage when compared with placebo, control, or conventional treatment alone. However, the low quality and high heterogeneity of the reviewed studies limit the validity of these findings (96437,109376). Some clinical research shows that taking compound danshen dripping pill 5 mg three times daily for 6 months may be more effective than taking captopril 12.5 mg two or three times daily for reducing macular edema and the severity of retinopathy and improving vision (109372). Additional clinical research shows that higher doses of compound danshen dripping pill of 540-810 mg three times daily may be most effective in improving symptoms of diabetic retinopathy when compared with placebo (96444).
• Endometriosis. Preliminary clinical research suggests that taking danshen-containing herbal products with gonadotropin-releasing hormone agonist (GnRH-a) may improve postoperative management of endometriosis. The effect of danshen alone is unclear. Details: A meta-analysis of eight preliminary clinical trials shows that taking danshen-containing herbal products along with GnRH-a following surgery for endometriosis reduces the recurrence of endometriosis by 74% when compared with GnRH-a alone. Some research also suggests that danshen-containing products reduce symptoms such as abnormal vaginal bleeding and hot flashes and increase the pregnancy rate (109381).
• Heart failure. Oral danshen has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A meta-analysis of small clinical trials in adults with heart failure shows taking a danshen decoction 400 to 1600 mL daily for 2 to 8 weeks in combination with conventional therapy improves some markers of cardiac function such as left ventricular ejection fraction, left ventricular end-diastolic dimension, left ventricular end-systolic diameter, and serological indicators such as brain natriuretic peptide, N-terminal pro-B type natriuretic peptide, and C-reactive protein when compared with conventional therapy alone (112397). Danshen comprised 75% of the herbs in the decoction and Tanxiang and Sha ren equally comprised the other 25%. It is unclear if these findings are due to danshen, other ingredients, or the combination. The moderate to low quality of the evidence limits the validity of these findings. All studies in this analysis were conducted in China which may limit generalizability to other geographic regions.
• Hepatitis. Although there is interest in using oral danshen for chronic hepatitis, there is insufficient reliable information about the clinical effects of danshen for this condition.
• Hyperlipidemia. It is unclear if oral or intravenous danshen are beneficial for hyperlipidemia. Details: Preliminary clinical research in adults with hyperlipidemia shows that taking lipid-lowering medication and injecting 1 mL of danshen into two of four possible acupuncture points daily for 30 days decreases total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides, and increases high-density lipoprotein (HDL) cholesterol. Improvements appear to occur in 90% of patients using danshen plus lipid-lowering medication, compared with only 44% of patients using lipid-lowering medication alone (47072). However, other preliminary clinical research shows that taking danshen extract 3 grams three times daily for 28 days leads to increases in total cholesterol and LDL cholesterol levels, with no change in HDL cholesterol levels, when compared with placebo in adults with hyperlipidemia and hypertension (96441).
• Hypertension. It is unclear if oral danshen is beneficial for hypertension. Details: Clinical research in adults with uncontrolled hypertension shows that taking a mixture of extracts of danshen 450 mg, rhodiola 40 mg, chrysanthemum 200 mg, and kudzu 200 mg twice daily for 12 weeks along with antihypertensive drugs does not increase response to treatment, defined as a sitting systolic blood pressure (SBP) less than 140 mmHg and/or sitting diastolic blood pressure (DBP) less than 90 mmHg OR achieving a reduction of more than 10 mmHg in SBP or more than 5 mmHg in DBP. However, taking this combination along with antihypertensive drugs increases the percentage of patients with a sitting SBP less than 140 mmHg and/or sitting DBP less than 90 mmHg by about 3.5-fold when compared with antihypertensive drugs alone (94396). However, other preliminary clinical research shows that taking danshen extract 3 grams three times daily for 28 days does not lower SBP or DBP when compared with placebo in adults with hyperlipidemia and hypertension (96441).
• Hypoparathyroidism. Intravenous danshen has only been evaluated in combination with other ingredients; its effect when used alone is unclear. The effect of oral danshen is unclear. Details: Preliminary clinical research in patients with postoperative hypoparathyroidism after a total thyroidectomy shows that intravenous danshen and the rhizome of Ligusticum chuanxiong 10 mL daily for one week reduces the time to recovery of parathyroid function by about 2 weeks, and results in increased serum parathyroid hormone and calcium levels over 6 months, when compared with conventional treatment including calcitriol and calcium gluconate. Also, there was a reduction in the number of patients with permanent hypoparathyroidism (109379).
• Intrauterine Adhesions. Intrauterine danshen has only been evaluated in combination with various oral ingredients; its effect when used alone is unclear. The effect of oral danshen is unclear. Details: Preliminary clinical research in patients with moderate to severe intrauterine adhesions shows that use of intrauterine danshen (Harbin Pharm Group Sanjing Pharmaceutical Co, Ltd.) 5 mL, along with oral Chinese medications for 6 months after adhesion resection and balloon uterine stent placement, may improve clinical efficacy when compared with a control group receiving hyaluronic acid and an intrauterine device (IUD). Clinical efficacy, defined as normal menstruation with at least a near normal intrauterine lining and normal or slightly reduced blood volume, was 89% after treatment with danshen, compared with 69% in the control group. Uterine re-adhesion after 3 months was also reduced. However, there was no difference in the 6-month follow-up pregnancy rate (109374).
• Kidney transplant. It is unclear if oral or intravenous danshen are beneficial following kidney transplantation. Details: Preliminary clinical research shows that injection with danshen 60 mL daily for 10 days in addition to conventional treatment improves urinary volume and creatinine clearance and reduces the incidence of renal function recovery after kidney transplantation when compared with conventional treatment alone. However, the risk of acute rejection does not seem to be affected (47019).
• Obesity. Although there is interest in using oral danshen for obesity, there is insufficient reliable information about the clinical effects of danshen for this condition.
• Oral submucous fibrosis. It is unclear if oral or intravenous danshen are beneficial for oral submucous fibroids. Details: A meta-analysis of 13 generally low-quality randomized controlled trials shows that danshen injection with corticosteroids, usually triamcinolone acetonide, improves symptoms of oral submucous fibrosis better than conventional corticosteroid treatment alone. Danshen modestly improved maximal mouth opening and moderately improved the oral mucosal lesion area and sensation of burning (101975). The effect of oral danshen is unclear.
• Pancreatitis. Although there is interest in using oral danshen for pancreatitis, there is insufficient reliable information about the clinical effects of danshen for this condition.
• Polycystic ovary syndrome (PCOS). It is unclear if oral danshen is beneficial for PCOS. Details: A meta-analysis of two preliminary clinical trials in patients with PCOS shows that taking danshen along with medication does not increase the pregnancy rate when compared with medication alone. However, these studies differed in their findings, with a 2.6-fold increase in pregnancy rate when compared with letrozole alone in one study and no increase when compared with cyproterone acetate in the other. Taking danshen may decrease fasting levels of glucose and insulin and improve levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and reproductive hormones when compared with placebo or medications alone (109378). However, the number of clinical trials in each meta-analysis was small.
• Pre-eclampsia. It is unclear if intravenous or oral danshen is beneficial for pre-eclampsia. Details: Preliminary clinical research in patients with severe pre-eclampsia on bed rest shows that intravenous danshen 16 mL in combination with magnesium sulfate up to 30 grams daily for 7 days results in clinical improvements when compared with magnesium sulfate alone. Blood pressure reductions to below 150/100 mmHg and improvement in clinical symptoms occurred in 93% of patients, compared with 77% of those in the control group. There were also modest improvements in liver and kidney function indices (109382). The effect of oral danshen is unclear.
• Pregnancy-induced hypertension. It is unclear if intravenous or oral danshen is beneficial for pregnancy-induced hypertension. Details: Preliminary clinical research in patients with pregnancy-induced hypertension shows that intravenous danshen 10-20 mL in combination with magnesium sulfate 4-10 mL once daily for 10 days modestly reduces systolic and diastolic blood pressure, as well as 24-hour urinary protein levels, when compared with magnesium sulfate alone. Also, the number of patients with a reduction or elimination of clinical symptoms was increased (109373).
• Psoriasis. Although there is interest in using oral danshen for psoriasis, there is insufficient reliable information about the clinical effects of danshen for this condition.
• Stroke. Preliminary clinical research suggests that oral or intravenous danshen may be beneficial for reducing symptoms following a stroke. Details: Preliminary clinical research shows that taking danshen orally or intravenously, usually as composite products, or administering the constituent salvianolic acid intravenously, might produce some improvement in neurological deficits, sleep quality, and blood flow indices after acute ischemic stroke (15538,47002,47017,101978,109371,109377). In one study, compound danshen dripping pills prepared with Panax notoginseng, borneol, and extracts of danshen, 270 mg (10 pills) three times daily for 28 days was used (15538). Compound danshen 16 mL or 20 mL and danshen 30 mL injection have been used for up to 28 days, occasionally in combination with snake venom (15538,96436). Other research shows that danshen injection is not as effective as danhong injection, an extract of danshen and safflower, in improving neurological deficits after acute ischemic stroke; however, the clinical relevance of this finding in the context of standard treatments is unclear (96436).
• Unstable angina. Oral danshen has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with unstable angina shows that taking danshen dripping pill 0.4 grams three times daily, alone or in combination with andrographis 0.2 grams three times daily, for 4 weeks modestly improves symptoms, although the combination of andrographis with danshen dripping pill was more effective than danshen dripping pill alone (109370).
• Venous Thromboembolism (VTE). Oral danshen has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Preliminary clinical research in patients with multiple myeloma receiving treatment with thalidomide shows that taking compound danshen dripping pill, containing danshen extract, Panax notoginseng, and borneol, 108 mg (4 tablets) three times daily for 8 months is as effective as warfarin for preventing VTE. Compound danshen dripping pills and warfarin demonstrate equal efficacy in preventing thalidomide-induced elevations in D-dimer and fibrinogen levels after 3 months of prophylaxis (96440). The effects of danshen alone are unclear.
• Wound healing. Although there is interest in using oral danshen for wound healing, there is insufficient reliable information about the clinical effects of danshen for this purpose. More evidence is needed to rate danshen for these uses.

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LIKELY EFFECTIVE

• Constipation. Rectal glycerol is beneficial in children and adults with constipation. Details: Glycerol rectal suppositories and enemas are approved by the US Food and Drug Administration (FDA) for over-the-counter use to treat occasional constipation in adults and children at least 2 years of age (15).

POSSIBLY EFFECTIVE

• Athletic performance. Oral glycerol may improve hydration during exercise, but clinical studies evaluating glycerol for improving measures of athletic performance are limited and conflicting. Details: Several clinical studies show that glycerol increases serum osmolality and improves hydration status during exercise (2475,2476,93757,93760,93761,93765). One meta-analysis, including 14 studies and 99 patients, shows that glycerol-induced hyperhydration increases body water by approximately 2.5-fold when compared with water-induced hyperhydration (93757). Also, taking glycerol along with table salt 7.5 grams per liter fluid seems to improve hydration status when compared withg glycerol alone (99162). Research regarding the effects of glycerol on thirst, comfort, temperature regulation, sweating, and heart rate is conflicting (2475,2476,93760,99162). While glycerol may improve hydration status during exercise, it is unclear whether it can improve measures of athletic performance. An early meta-analysis including a total of 36 athletes shows that taking glycerol increases endurance performance by 2.6%. Although this is a small difference, it might be considered meaningful to athletes (93757). Some small clinical studies in athletes suggest that glycerol increases endurance and time to exhaustion, with no effect on heat regulation (2475,2479,93764). However, other small studies suggest that glycerol does not reduce perceived exhaustion or improve exercise performance (2476,93760). Also, glycerol has not been shown to increase time to exhaustion in triathletes (2492). When used to improve athletic performance, glycerol is most often taken at doses of 1-1.5 gram/kg in conjunction with approximately 1.5 L of fluid, 60-120 minutes before competition, and in some cases continued during the competition (2475,93757,93760,93764).
• Ichthyosis. Topical application of a specific product containing glycerol and paraffin may improve symptoms of ichthyosis in children. The benefits of topical glycerol alone in these patients is unknown. Details: A large clinical trial in children aged 1 month to 18 years shows that applying a specific product (Dexeryl, Pierre Fabre Laboratoires) containing glycerol 15% and paraffin 10% for 4 weeks reduces symptoms of non-bullous ichthyosis by at least 50% in an additional 17% of children when compared with a placebo cream. Applying this specific product also improves pruritus by an additional 45% when compared with placebo (93756). It is unclear if these findings are due to glycerol, paraffin, or the combination.

POSSIBLY INEFFECTIVE

• Meningitis. Some clinical research suggests that oral glycerol does not reduce the risk of mortality or seizures in adults and children with bacterial meningitis, although it may reduce certain sequelae. Details: A meta-analysis of five low-quality clinical trials including 1,270 patients shows that adjunctive treatment with glycerol as an oral osmotic agent does not reduce the risk of mortality, seizures, or gastrointestinal symptoms in adults and children with acute bacterial meningitis, although it may modestly reduce the risk of deafness and residual neurological deficit in surviving children (99160). Clinical research included in the meta-analysis has used glycerol 1.5 grams/kg every 6 hours in children aged 2 months to 16 years (93762,93763).
• Prematurity. Rectal glycerol does not appear to reduce the time to enteral feeding in premature infants. Details: Glycerol is used as an enema or given by suppository to facilitate the evacuation of meconium in premature infants in order to reduce the time to enteral feeding. However, two meta-analyses of small studies in preterm infants, that include some of the same studies, show that administering glycerol suppositories does not reduce the number of days to full enteral feeds when compared with placebo or no treatment (99166,112003). However, the interpretation of these findings is limited by the heterogeneity of dosages used in the included studies.

LIKELY INEFFECTIVE

• Stroke. Intravenous glycerol may not improve mortality or symptoms in patients with acute ischemic stroke. Details: Several clinical studies show that intravenous administration of glycerol does not improve symptoms of acute stroke (2480,2481,2482,2484,2486). Additionally, one clinical study in elderly patients with acute ischemic stroke shows that while glycerol can improve initial survival, it does not reduce the risk of overall mortality when compared with placebo (2483).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Dandruff. Topical glycerol has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical trial in adults with dandruff shows that applying a leave-in hair lotion containing glycerol 10%, stearic acid 2.5%, and sunflower seed oil 0.6%, 3 times weekly for 8 weeks, modestly reduces dandruff severity throughout use and for up to one week after the last application when compared with a placebo lotion. The glycerol lotion also reduced total water loss from the scalp by 8% and increased moisturization by 23% (93758). It is unclear if these findings are due to glycerol, other ingredients, or the combination.
• Dry skin. Topical glycerol has only been evaluated in combination with other ingredients for the management of dry skin associated with kidney failure; its effect when used alone is unclear. Details: One small, open-label clinical study in adults with kidney failure and moderate to severe uremic xerosis shows that applying an emulsion containing glycerol 15% and paraffin 10% twice daily for 7 days reduces the severity of xerosis when compared with a placebo emulsion. The glycerol-containing emulsion produces a treatment response in an additional 29% of patients, improves quality of life, and reduces scale density and thickness when compared with placebo (93754). It is unclear if these findings are due to glycerol, paraffin, or the combination.
• Glaucoma. Although there has been interest in using oral glycerol for glaucoma, there is insufficient reliable information about the clinical effects of glycerol for this purpose.
• Intracranial hypertension. Although there has been interest in using intravenous glycerol to reduce intracranial pressure in patients with brain tumors, central nervous system (CNS) trauma, encephalitis, idiopathic intracranial hypertension, meningitis, and Reye syndrome, there is insufficient reliable information about the clinical effects of glycerol for this purpose.
• Meniere disease. It is unclear if intravenous glycerol is beneficial in patients with Meniere disease. Details: A small, uncontrolled clinical study in adults with unilateral, intractable Meniere disease shows that intravenous administration of glycerol 10% at a dose of 0.5 grams/kg once daily for 2 consecutive days, twice monthly for 6 months, reduces the frequency of vertigo attacks and improves quality of life when compared to baseline. Patients reported an average of 3.2 vertigo attacks per month at baseline and 1.2 vertigo attacks per month after 6 months of treatment (106649). The lack of a control group limits the validity of these findings.
• Neonatal jaundice. It is unclear if rectal glycerol improves jaundice-related outcomes in premature infants. Details: A small clinical study in neonates receiving phototherapy for jaundice shows that administering glycerol suppositories has no effect on the duration of phototherapy needed for jaundice treatment, or on bilirubin levels or the rate of bilirubin decline when compared with no glycerol suppositories (99165).
• Obesity. It is unclear if oral glycerol is beneficial in patients who are overweight or obese. Details: One small clinical study in adults on a low-calorie diet shows that taking glycerol 7.5 grams before meals for 6 weeks does not increase weight loss when compared with placebo (2485).
• Otitis externa. Topical glycerol has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One small clinical study in adults with otitis externa shows that inserting ribbon gauze soaked in glycerol and ichthammol into the ear canal reduces pain and swelling as effectively as the application of antibiotic and steroid drops three times daily (93759). It is unclear if these findings are due to glycerol, ichthammol, or the combination. More evidence is needed to rate glycerol for these uses.

(Read more about GLYCEROL)

There is insufficient reliable information available about the effectiveness of quebracho blanco.

(Read more about QUEBRACHO BLANCO)

LIKELY SAFE ...when used orally and appropriately. Acetyl-L-carnitine has been used safely in doses up to 3 grams daily in clinical trials lasting up to 33 months (42,1589,1594,1595,1596,1597,1598,1599,3600,3601) (9105,9791,10076,12743,12745,58375,90755,90756,90759,90761)(90766,90767,90768,95063,95067,111862).

POSSIBLY SAFE ...when used parenterally and appropriately under medical supervision (1591,1592,12743).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term. Acetyl-L-carnitine has been safely used orally in children for up to 6 weeks (90754).

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

(Read more about ACETYL-L-CARNITINE)

POSSIBLY SAFE ...when used orally and appropriately (12,94396,96441,96444). There is insufficient reliable information available about the safety of danshen when used by intravenous injection.

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

(Read more about DANSHEN)

LIKELY SAFE ...when used rectally and appropriately. Glycerol rectal suppositories and enemas are approved by the US Food and Drug Administration (FDA) for over-the-counter use to treat occasional constipation (15,272). ...when used topically and appropriately as a lotion, emulsion, or humectant (15,272,93754,93758,93759,99164).

POSSIBLY SAFE ...when used orally, short-term. Glycerol has been used with apparent safety in clinical trials at doses of up to 1.5 grams/kg (2474,2475,99162).

POSSIBLY UNSAFE ...when used intravenously. While some research suggests that intravenous glycerol can be safely administered for two consecutive days twice monthly for up to 6 months (106649), in another study, hemolysis was reported in 98% of patients treated with intravenous glycerol for acute ischemic stroke (2482).

CHILDREN: LIKELY SAFE
when used rectally and appropriately. Glycerol rectal suppositories and enemas are approved by the US FDA for over-the-counter use to treat occasional constipation in children 2 years of age and older (15,272). ...when used topically and appropriately as an emulsion or humectant in children 1 month of age and older (15,272,93756).

CHILDREN: POSSIBLY SAFE
when used orally, short-term. Glycerol has been used with apparent safety in clinical trials in children 2 months to 16 years of age at doses of 1.5 gram/kg, up to a maximum dose of 25 grams, taken every 6 hours (93762,93763).

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

(Read more about GLYCEROL)

LIKELY SAFE ...when used in amounts commonly found in foods. Quebracho blanco bark has Generally Recognized As Safe (GRAS) status for use in foods in the US (4912). There is insufficient reliable information available about the safety of using quebracho blanco bark in medicinal amounts.

PREGNANCY AND LACTATION:
There is insufficient reliable information available about the safety of using medicinal amounts of quebracho blanco during pregnancy and breast-feeding; avoid using.

(Read more about QUEBRACHO BLANCO)

ACENOCOUMAROL (Sintrom) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of acenocoumarol.  Details L-carnitine, the parent compound of acetyl-L-carnitine, might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant that is 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 acetyl-L-carnitine.

SEROTONERGIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, acetyl-L-carnitine might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders, when taken with serotonergic drugs.  Details Animal research shows that acetyl-L-carnitine can increase levels of serotonin in the brain (95065).

THYROID HORMONE Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  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 acetyl-L-carnitine.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of warfarin.  Details L-carnitine, the parent compound of acetyl-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 acetyl-L-carnitine and warfarin.

(Read more about ACETYL-L-CARNITINE)

AMLODIPINE (Norvasc) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking danshen in combination with amlodipine may decrease the clinical effects of amlodipine.  Details In animal research, taking danshen orally in combination with amlodipine reduced blood levels of amlodipine by about 52%. This may have been due to induction of cytochrome P450 3A4 (CYP3A4) by danshen, which has been demonstrated in vitro (101977). So far, this interaction has not been reported in humans.

ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, danshen may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.  Details Danshen has been reported to have antithrombotic effects (6048,96440). Animal research also suggests that taking a danshen combination formula with clopidogrel exhibits a synergistic increase in antiplatelet aggregation and prolongation of coagulation time when compared with either taken alone (112399).

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, taking danshen with antihypertensive drugs might increase the risk of hypotension.  Details Animal research suggests that danshen can produce dose-dependent hypotensive effects. Furthermore, concomitant use with captopril appears to potentiate this effect (47071).

ASPIRIN Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, danshen may increase the levels of aspirin and the risk of bleeding.  Details Research in healthy adult males shows that taking a combination of danshen and kudzu with aspirin increases plasma aspirin area under the curve by approximately 3.4-fold (105517). Animal research also shows that taking a combination of danshen and kudzu (danshen-gegen formula) with aspirin increases maximal blood levels of aspirin and salicylic acid by approximately 4-fold and 3.7-fold, respectively, without impacting blood loss (94399). Taking danshen increases the antiplatelet activity of aspirin and might increase the side effects of aspirin (105517).

CLOPIDOGREL (Plavix) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, danshen may increase the risk of bleeding if taken with clopidogrel.  Details Clopidogrel is an antiplatelet prodrug that is metabolized by carboxyl esterase 1 (CES1) to an inactive metabolite. Animal research shows that a danshen combination formula decreases the activity of CES1, decreasing levels of the inactive metabolite in the blood and possibly increasing levels of the active metabolite (94389). Animal research also suggests that taking a danshen combination formula with clopidogrel exhibits a synergistic increase in antiplatelet aggregation and prolongation of coagulation time when compared with either taken alone (112399).

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, danshen may increase the levels and clinical effects of drugs metabolized by CYP1A2.  Details In vitro research shows that danshen tincture and various constituents of danshen inhibit the activity of CYP1A2 (94393,94394). However, this activity has not been shown in humans when theophylline, a CYP1A2 substrate, was used as a target drug (94398).

CYTOCHROME P450 2C9 (CYP2C9) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, danshen may increase the levels and clinical effects of drugs metabolized by CYP2C9.  Details In vitro research shows that various constituents of danshen inhibit the activity of CYP2C9 (94393). So far, this interaction has not been reported in humans.

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, danshen may increase the levels and clinical effects of drugs metabolized by CYP2E1.  Details In vitro research shows that various constituents of danshen inhibit the activity of CYP2E1 (94393). So far, this interaction has not been reported in humans.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Danshen might alter the levels and clinical effects of drugs metabolized by CYP3A4.  Details Preliminary clinical research in healthy males shows that the administration of danshen for 10-14 days induces intestinal CYP3A4 and increases the clearance of midazolam, a CYP3A4 substrate. The maximum concentration of midazolam was decreased by 31% to 67%, and drug levels were decreased by 27% to 80% (17404,94390). However, a single dose of danshen has the opposite effect, increasing maximum concentrations of midazolam by 87% (94390).

DIGOXIN (Lanoxin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Theoretically, using danshen with digoxin might increase the risk of adverse effects.  Details Danshen has structural and pharmacological similarities to cardiac glycosides (5884,6048,7311).

FEXOFENADINE (Allegra) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Danshen might increase the levels and clinical effects of fexofenadine.  Details Pharmacokinetic research in healthy volunteers shows that taking danshen extract 1 gram three times daily for 10 days prior to receiving fexofenadine 60 mg increases peak levels of fexofenadine, a p-glycoprotein substrate, by 27.4% and area under the curve (AUC) by 37.2% (94391).

GLUCURONIDATED DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, danshen might affect the levels and clinical effects of drugs requiring glucuronidation.  Details In vitro research shows that danshen induces the expression of glucuronosyltransferases. However, it also inhibits the activity of glucuronosyltransferases, including various members of the 1A and 2B families. The extent of inhibition of a specific glucuronosyltransferase seems to be dependent on whether or not the danshen is processed via 'sweating'. This type of processing may affect the levels of constituents in danshen that alter glucuronosyltransferase activity (109375). So far, this interaction has not been reported in humans.

MIDAZOLAM (Versed) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Danshen might alter the levels and clinical effects of midazolam.  Details Preliminary clinical research in healthy males shows that the administration of danshen for 10-14 days induces intestinal CYP3A4 and increases midazolam clearance. The maximum concentration was decreased by 31% to 67%, and drug levels were decreased by 27% to 80% (17404,94390). However, a single dose of danshen has the opposite effect, increasing maximum concentrations of midazolam by 87% (94390).

P-GLYCOPROTEIN SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Danshen might alter the levels of drugs cleared by p-glycoprotein.  Details Pharmacokinetic research in healthy volunteers suggests that danshen might affect p-glycoprotein activity. Taking danshen extract 1 gram three times daily for 10 days prior to receiving fexofenadine 60 mg increases peak levels of fexofenadine, a p-glycoprotein substrate, by 27.4% and area under the curve (AUC) by 37.2% (94391).

ROSUVASTATIN (Crestor) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, danshen might increase the levels and clinical effects of rosuvastatin.  Details Animal research shows that a single dose of danshen increases levels of rosuvastatin at least 2-fold, possibly by increasing absorption and/or decreasing elimination (94395). So far, this interaction has not been reported in humans.

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Theoretically, danshen may increase the risk of bleeding if used with warfarin.  Details There have been several case reports of increased international normalized ratio (INR) after concomitant use of danshen and warfarin. Elevations in INR have occurred as early as 3-5 days after start of danshen (611,612,2237,5883,5884). However, a clinical trial in adults taking warfarin with stable INR found that the addition of compound danshen dripping pills, containing danshen extract, Panax notoginseng, and borneol, 270 mg three times daily for 4 weeks did not alter INR levels or the average required warfarin dose when compared to baseline (96438). These findings are consistent with animal research, which found no change in warfarin pharmacokinetics with the use of danshen (94388,94397,94399). Other research in healthy adult males also shows that taking a combination of danshen and kudzu with warfarin does not increases plasma warfarin area under the curve, but may reduce plasma soluble thrombomodulin levels (105517). However, other research shows that danshen might increase the rate of absorption and decrease the elimination rate of warfarin (5884,6048,94398). Also, research in healthy adult males shows that taking a combination of danshen and kudzu with warfarin increases plasma area under the curve of danshensu, a constituent of danshen, by approximately 29.5-fold (105517). Danshen should be used cautiously in patients taking warfarin.

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General ...Orally, acetyl-L-carnitine is generally well tolerated.
Most Common Adverse Effects:
Orally: Agitation, dry mouth, headache, insomnia, and reduced appetite. A metabolite of acetyl-L-carnitine has been reported to cause a fishy odor of the urine, breath, and sweat.

Cardiovascular ...Orally, one patient in a pharmacokinetic study reported high blood pressure 8 hoursafter taking acetyl-L-carnitine 500 mg; however, it is unclear if this was due to acetyl-L-carnitine or another factor (95061).

Dermatologic ...Orally, a combination of acetyl-L-carnitine and alpha-lipoic acid may cause rash (90441).

Gastrointestinal ...Orally, acetyl-L-carnitine may cause nausea, vomiting, diarrhea, constipation, hiccups, abdominal distension and gastrointestinal upset or pain. However, gastrointestinal symptoms do not usually occur more often in patients receiving acetyl-L-carnitine than in patients receiving placebo (1596,1599,12743,13007,58922,90755,95063,95067,111889,111894). Acetyl-L-carnitine may also cause dry mouth and anorexia (58342). When taken orally, a combination of acetyl-L-carnitine and alpha-lipoic acid may cause diarrhea, constipation, and dyspepsia (90441).

Neurologic/CNS ...Orally, acetyl-L-carnitine may cause headache and insomnia (90760,90767,95063). In one clinical trial, two patients with antiretroviral toxic neuropathy reported paresthesia, pain, and neuropathy after taking acetyl-L-carnitine 1000 mg daily (58342). A case of mania has been reported for a patient with bipolar I disorder currently in remission. The patient presented with symptoms after taking multiple supplements for the past 4 weeks including acetyl-L-carnitine 1000 mg twice daily. The symptoms appeared 3 days after beginning to take acetyl-L-carnitine and worsened over the next week. The patient had increased speech rate and volume and reported increased energy levels and racing thoughts. The patient's parent reported irritability and an increase in loud behaviors at home, similar to a previous episode of mania. The patient was advised to discontinue acetyl-L-carnitine, and the manic symptoms disappeared 3 days later (95062).

Psychiatric ...Orally, acetyl-L-carnitine may cause agitation (restlessness and motor overactivity) (1596,1599,12743,13007). Side effects reported in people with Alzheimer disease include psychiatric disturbances such as depression, mania, confusion and aggression, but it is not clear whether these are due to acetyl-L-carnitine or the condition itself (1594,1595,1596,1597,1598,1599,9105,10391).

Other ...One of the metabolites of acetyl-L-carnitine can cause the urine, breath, and sweat to have a fishy odor (12756). Also, foul smelling urine has been reported following oral use of a combination of acetyl-L-carnitine and alpha-lipoic acid (90441).

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General ...Orally, danshen seems to be well tolerated. There is limited reliable information available about the adverse effects of danshen when used intravenously.
Most Common Adverse Effects:
Orally or intravenously: Upset stomach, pruritus, and reduced appetite.

Cardiovascular ...Orally, in clinical trials, side effects of danshen preparations include palpitations; however, it is not known if these effects were due to danshen or other drugs (109370).

Dermatologic ...Orally or intravenously, danshen can cause pruritus (12,96440).

Gastrointestinal ...Orally or intravenously, danshen can cause upset stomach and reduced appetite (12). In clinical trials, side effects of danshen preparations include loose stools; however, it is not known if these effects were due to danshen or other drugs (109370).

Hematologic ...Orally or intravenously, side effects of danshen preparations reported in clinical trials include thrombocytopenia; however, it is not known if this effect was due to danshen or other drugs (15538).

Neurologic/CNS ...Orally or intravenously, in clinical trials, side effects of danshen preparations include drowsiness, dizziness, or headache; however, it is not known if these effects were due to danshen or other drugs (15538,109370).

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General ...Orally, rectally, and topically, glycerol seems to be well tolerated. Intravenously, glycerol may be unsafe.
Most Common Adverse Effects:
Orally: Bloating, diarrhea, nausea, vomiting, dizziness, and headache.
Topically: Burning, irritation, and pruritus.
Intravenously: Hemolysis in patients with acute ischemic stroke.

Dermatologic ...Topically, glycerol has been reported to cause burning, irritation, and pruritus (93754,93756). Rectally, the regular administration of glycerol 50% enemas has been reported to cause generalized urticaria in at least two patients; in both patients, symptoms resolved after discontinuation (110019,110025).

Gastrointestinal ...Orally, glycerol can cause bloating, nausea, vomiting, thirst, and diarrhea (15,2475).

Hematologic ...Intravenously, glycerol has been reported to caused hemolysis in people treated for acute ischemic stroke (2480,2482).

Neurologic/CNS ...Orally, glycerol can cause mild headache and dizziness (15,2475).

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General ...Orally, quebracho blanco seems to be well tolerated. However, a thorough evaluation of safety outcomes has not been conducted. Some people who take quebracho blanco bark may experience salivation, headache, outbreaks of sweating, vertigo, stupor, and drowsiness. In large doses, it can cause nausea and vomiting (18).

Dermatologic ...Orally, quebracho blanco bark may cause sweating (18).

Gastrointestinal ...Orally, quebracho blanco bark may cause salivation. In large doses, it can cause nausea and vomiting (18).

Neurologic/CNS ...Orally, quebracho blanco bark may cause headache, vertigo, stupor, and drowsiness (18).

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