CoQ-10 200 mg plus Black Pepper Extract by Nature's Truth

INSUFFICIENT RELIABLE EVIDENCE to RATE

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

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LIKELY EFFECTIVE

• Coenzyme Q10 deficiency. Taking coenzyme Q10 orally improves symptomatic deficiency. Details: Rare cases of acquired coenzyme Q10 deficiency with symptoms of weakness, fatigue, and seizures have been reported (8160,8161). In adults, deficiency can be treated with coenzyme Q10 orally, 150-2400 mg daily in up to three divided doses. In children, 30 mg/kg, or 60-250 mg daily in up to three divided doses has been used (8160,8161,89417). Data from several multinational disease registries has also evaluated the use of coenzyme Q10 in patients with primary coenzyme Q10 deficiency, a rare genetic disorder. This data indicates that patients who take coenzyme Q10 supplements have a mean reduction of 88% in proteinuria at 12 months when compared with patients who do not take coenzyme Q10. In patients under 18 years of age with primary deficiency and chronic kidney disease at baseline, taking coenzyme Q10 supplements is associated with a 5-year survival without kidney failure of 62%, compared with 19% for those not taking coenzyme Q10 (108956).
• Mitochondrial myopathies. Taking coenzyme Q10 orally seems to reduce symptoms in some patients with genetic and acquired mitochondrial dysfunction. Details: A specific coenzyme Q10 formulation (UbiQGel, Tishcon Corporation) has been evaluated for mitochondrial myopathies, including MELAS (mitochondrial encephalopathy with lactic acidosis and stroke-like episodes) syndrome, Kearns-Sayre syndrome, and MERRF (myoclonus epilepsy with ragged red fibers). Typical doses are 150-160 mg, or 2 mg/kg, daily, gradually increasing to 3000 mg daily in some cases. The onset of action is slow, with maximal effects around 6 months (8159,8162,8163,8912,11050,44240,97905).

POSSIBLY EFFECTIVE

• Congestive heart failure (CHF). Oral coenzyme Q10 may provide benefit to patients with CHF by improving some, but not all, measures of disease severity when given in combination with conventional therapy. Details: Population research has found that CHF is associated with low coenzyme Q10 levels that correlate with severity of disease, and may be a predictor of mortality risk (44059,44220). A 2017 meta-analysis of clinical research shows that taking coenzyme Q10 30-300 mg, or 2 mg/kg, orally daily in two or three divided doses for up to 2 years, in addition to conventional therapy, improves exercise capacity, reduces hospitalizations, and reduces mortality by about 30% when compared with placebo. Other clinical research shows that adding oral coenzyme Q10 seems to improve quality of life and decrease symptoms of CHF such as dyspnea, peripheral edema, enlarged liver, and insomnia in patients with mild to severe (New York Heart Association (NYHA) class II-IV) CHF (6037,6038,6407,6408,6409,8909,12170,43967,43971,44042)(44277,44288,44289,44304,44334,44352,95610,96542). Additional clinical research shows that taking coenzyme Q10 30 mg daily for 1 year in addition to standard care reduces the incidence of atrial fibrillation by about 73% when compared with standard care alone in patients with NYHA class II-IV CHF (95609). However, not all evidence is positive. Some research suggests that coenzyme Q10 does not improve objective measures of CHF, including left ventricular ejection fraction (LVEF), cardiac output, or NYHA classification (5090,5248,6037,6038,43904,43932,96542,43932,97902). It is possible that the benefit of coenzyme Q10 depends on the dose and duration, the severity of CHF, and the specific conventional therapies taken concurrently (43973). A meta-analysis of 11 small, low-quality studies concludes that coenzyme Q10 probably reduces risk of all-cause and cardiovascular mortality, and of hospital admission for CHF, but data on improvement in LVEF or exercise capacity and the risk for myocardial infarction and stroke are inconclusive. However, the included studies used a range of coenzyme Q10 doses, varying concurrent therapy, short follow-up periods, and variable measures of treatment effect (108954). In patients with CHF with preserved ejection fraction (HFpEF) and a LVEF of 50% or greater, taking coenzyme Q10 600 mg daily for 12 weeks reduces B-type natriuretic peptide levels and improves Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, level of vigor, and LVEF when compared with placebo (108959).
• Diabetic neuropathy. When taken alone or as add-on treatment with pregabalin, most research suggests that oral coenzyme Q10 reduces symptoms in patients with diabetes and neuropathy. Details: Clinical research shows that taking coenzyme Q10 400 mg orally daily for 12 weeks significantly improves nerve conduction and symptoms of neuropathic pain when compared with placebo in diabetic patients with polyneuropathy (44217). The beneficial effects of coenzyme Q10 have also been investigated as an add-on treatment in patients taking pregabalin 150 mg daily. Clinical research shows that taking coenzyme Q10 100 mg three times daily for 8 weeks reduces pain severity and sleep interference due to pain when compared with placebo. The proportion of patients taking coenzyme Q10 with a decline in pain of at least 50% was 47%, compared with 27% of those taking placebo. Despite these findings, there was no difference in patient global improvement (109391). However, some research disagrees. One clinical trial shows that taking coenzyme Q10 (Health Burst) 200 mg daily for 12 weeks does not affect neuropathic symptoms, including pain, sensations, and strength, when compared with placebo (109386).
• Fibromyalgia. Oral coenzyme Q10 seems to improve both physical and psychological symptoms of this condition. Details: Clinical research in women with fibromyalgia shows that taking coenzyme Q10 300-400 mg orally daily for 40 days to 3 months improves pain by 24% to 56%, fatigue by 22% to 47%, sleep disturbances by 33%, morning tiredness by 56%, and tender points by 44% when compared with placebo. Patients also experience an improvement in psychological symptoms, including depression and anxiety (89416,97912,97913).
• Ischemia-reperfusion injury. Oral or intravenous coenzyme Q10 may help reduce hypoxic damage during cardiac bypass or vascular surgery. Details: Clinical research shows that taking coenzyme Q10, 150-300 mg orally daily in up to 3 divided doses for 1-2 weeks before cardiac bypass or vascular surgery, or 5 mg/kg IV two hours prior to surgery, reduces hypoxic damage during the surgery (11902,11903,44031,44294). However, coenzyme Q10 has no effect on cardiac function or troponin levels (11904,44292).
• Migraine headache. The American Academy of Neurology considers oral coenzyme Q10 to be possibly effective for migraine prevention in adults. Its benefit in children is unclear. Details: Two small open-label, non-randomized clinical trials in adults show that taking coenzyme Q10 100-150 mg daily decreases the frequency of headaches by up to 50% when compared with baseline or control, although it can take up to 3 months to see benefit (8135,95608). Higher quality research suggests a smaller benefit. A meta-analysis of small randomized controlled trials in adults shows that taking coenzyme Q10 alone or with other supplements reduces migraine attacks by 1.5 times per month and reduces duration of migraines by about 12 minutes when compared with control (105070). In children and adolescents, some clinical research shows that taking coenzyme Q10 orally, as 100 mg daily or 1-3 mg/kg daily, for 12-16 weeks does not improve headache frequency, severity, or duration when compared with placebo. However, it may reduce migraine frequency in children with low coenzyme Q10 levels (15256,44197). However, another clinical study shows that taking coenzyme Q10 daily is less effective than amitriptyline after one month, but as effective after 3 months, for improving headache frequency, severity, or duration, as well as quality of life. In this study, the dose of coenzyme Q10 was based on weight; 30 mg daily for children weighing less than 30 kg and 60 mg daily for children weighing at least 30 kg (109388).
• Multiple sclerosis (MS). Oral coenzyme Q10 seems to reduce fatigue and depression associated with MS. Details: Clinical research shows that taking coenzyme Q10 500 mg orally daily for 3 months reduces fatigue and depression in patients with MS when compared with placebo (96539).
• Muscular dystrophy. Oral coenzyme Q10 seems to improve physical performance in patients with muscular dystrophy of various forms. Details: Two small clinical studies show that taking coenzyme Q10 orally 100 mg daily for 3 months seems to improve physical performance when compared with placebo in some patients with various muscular dystrophies (2127).
• Myocardial infarction (MI). Oral coenzyme Q10 seems to reduce cardiac events and improve survival in patients who have had an MI. It is unclear if coenzyme Q10 improves survival in patients after cardiac arrest. Details: One small clinical study in patients with acute MI shows that starting coenzyme Q10 60 mg twice daily within 72 hours of the MI appears to significantly reduce the risk of cardiac events, including non-fatal MI and cardiac death, by 52% when administered for 28 days and by 45% when administered for up to one year (10152,44330). Also, a small clinical study in patients with recent MI who received cardiopulmonary resuscitation, shows that administering a 250 mg loading dose of coenzyme Q10 solution followed by 150 mg three times daily through a nasogastric tube for 5 days improves the 3-month survival rate by 134% when compared with placebo (43935). However, another clinical study in a similar patient population conducted to replicate these results shows that administering coenzyme Q10 300 mg in 50 mL of Ensure every 12 hours for 7 days does not improve in-hospital mortality or neurological outcomes when compared with placebo (105068).
• Peyronie disease. Coenzyme Q10 taken orally may reduce Peyronie disease severity. Details: Clinical research shows that, in patients with early chronic Peyronie disease, taking coenzyme Q10 (Kaneka Nutrients, Osaka) 300 mg orally daily for 24 weeks reduces new plaque formation and plaque size and improves erectile function when compared with placebo. Additionally, disease progression is slowed in about 76% of patients (44180).

POSSIBLY INEFFECTIVE

• Alzheimer disease. Coenzyme Q10 appears to be ineffective for improving cognition. Details: One clinical study shows that taking coenzyme Q10 1200 mg orally daily for 16 weeks does not improve cognition scores when compared with placebo in patients with Alzheimer disease (19206).
• Amyotrophic lateral sclerosis (ALS, Lou Gehrig's disease). Oral coenzyme Q10 does not attenuate functional decline in ALS patients. Details: Clinical research shows that taking coenzyme Q10 2700 mg orally daily for 9 months does not significantly attenuate a decline in ALS functioning scores when compared with placebo (44131). Higher doses, up to 3000 mg daily, have been tolerated by patients with ALS for 5 months, although the effect on ALS functioning at this dose is not known (43955).
• Chemotherapy-related fatigue. Oral coenzyme Q10 does not seem to help with fatigue due to chemotherapy. Details: Clinical research shows that taking coenzyme Q10 100 mg orally three times daily for 24 weeks does not reduce chemotherapy-related fatigue or improve quality of life when compared with placebo in breast cancer patients undergoing chemotherapy with or without radiation (89420).
• Diabetes. Most clinical research does not show any benefit with oral coenzyme Q10 in patients with type 1 or type 2 diabetes. However, some research suggests a possible benefit on insulin resistance. Details: Although a recent meta-analysis and some individual clinical research shows that coenzyme Q10 modestly reduces fasting glucose levels and glycated hemoglobin (HbA1c) in patients with type 1 or type 2 diabetes, most clinical research shows that coenzyme Q10 has no clinically meaningful effect on these parameters (456,492,2126,9890,96544,97911,97918,99636,11877,17704,44023,103778,109389). However, a recent meta-analysis in patients with type 1 or type 2 diabetes shows that improvements in insulin resistance may be clinically meaningful when compared with placebo (109389). In people with type 2 diabetes and nephropathy requiring hemodialysis, coenzyme Q10 120 mg orally daily for 12 weeks does not improve blood glucose levels, HbA1c, or lipid levels when compared with placebo, although it is associated with a decrease in serum insulin levels and insulin resistance (99636).
• Parkinson disease. Most clinical research does not show any benefit with the use of oral coenzyme Q10 in patients with Parkinson disease. Details: While some conflicting evidence exists (8938,15255), a large clinical trial and a meta-analysis of 8 small clinical studies in patients with Parkinson disease show that taking coenzyme Q10 300-2400 mg daily for up to 2 years does not improve Parkinson disease symptoms at any stage of the disease, or slow progression of the disease, when compared with placebo (89421,95610). In addition, a clinical study in patients with mid-stage Parkinson disease shows that taking a specific nanoparticulate coenzyme Q10 supplement (Nanoquinon, MSE Pharmazeutilka) 100 mg orally three times daily does not reduce symptoms when compared with placebo (15395).
• Post-polio syndrome. Muscle function in people with post-polio syndrome is not improved by oral coenzyme Q10. Details: Clinical research shows that taking coenzyme Q10 100 mg twice daily for 12 weeks does not improve muscle strength when compared with baseline, nor does it improve muscle function or muscle endurance when compared with placebo, in patients with post-polio syndrome (44054). Other clinical research shows that taking coenzyme Q10 100 mg daily for 60 days does not improve levels of fatigue when compared with placebo in patients with post-polio syndrome (97917).

LIKELY INEFFECTIVE

• Athletic performance. There is some evidence that exercise can deplete coenzyme Q10 and that supplementation will prevent this depletion. However, there is no evidence that taking coenzyme Q10 is beneficial. Details: Clinical research shows that taking coenzyme Q10 orally does not improve aerobic or anaerobic power or perceived exertion in athletes and non-athletes (2109,2110,8911,44122,44227). While some evidence suggests coenzyme Q10 slightly improves tolerance to higher workloads, more research is needed to tell if coenzyme Q10 is effective for this purpose (8911). One clinical study shows that taking coenzyme Q10 300 mg orally daily for 8 days reduces exercise-induced fatigue when compared with placebo (44006); other research shows that doses of 100-200 mg do not have this effect (44122,44233,44299). Taking the ubiquinol form of coenzyme Q10 200 mg orally daily for one month prevents exercise-induced coenzyme Q10 depletion and decreases levels of reactive oxygen species in blood mononuclear cells in young male athletes performing an intense long-distance run. However, it does not affect physical performance or markers of muscle damage (99429).
• Huntington disease. The ubiquinol form of coenzyme Q10 does not seem to improve function in people with this condition. Details: Ubiquinol, a reduced form of coenzyme Q10, has been evaluated for use in Huntington disease (11873). However, a large, high-quality study shows that taking coenzyme Q10 2.4 grams orally daily for up to 5 years does not slow the progression or functional decline in patients with Huntington disease (96538). Other studies using doses up to 600 mg daily also show no benefit (1357,8940).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Age-related macular degeneration (AMD). Oral coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research in adults with early AMD shows that taking a specific combination product (Phototrop, Sigma-tau Health Science Ltd.) containing coenzyme Q10 10 mg, acetyl-L-carnitine 100 mg, and omega-3 fatty acids 530 mg orally daily for 12 months seems to reduce the percentage of patients who experience deterioration of vision by about 50%, and the percentage who have reduced light sensitivity by about 39%, when compared with placebo (43946). The effects of coenzyme Q10 alone are unclear.
• Aging. Although there has been interest in using oral coenzyme Q10 for aging, there is insufficient reliable information about the clinical effects of coenzyme Q10 for this purpose.
• Angina. There is some limited clinical evidence that coenzyme Q10 can improve exercise tolerance and symptoms in people with this condition. Details: Preliminary clinical research shows that taking coenzyme Q10 50 mg three times daily orally for 4 weeks improves exercise tolerance in people with angina by about 18% (2121). Also, taking 60 mg once daily for 4 weeks improves heart failure scores, angina symptoms, and heart volume when compared to baseline in patients with stable angina (44336). The validity of these findings is limited by the lack of a comparator group.
• Anthracycline cardiotoxicity. Evidence on the use of coenzyme Q10 to protect against anthracycline cardiotoxicity in adults and children is conflicting. Details: Preliminary clinical research in children aged 3-12 years shows that taking coenzyme Q10 orally 100 mg twice daily might protect against anthracycline cardiotoxicity (44279). However, evidence from larger clinical trials evaluating patients aged 16-77 years is conflicting. Results from one of these studies suggests that intravenous administration of coenzyme Q10 1 mg/kg daily the day before, the day of, and for 2 days after anthracycline treatment does not protect against cardiotoxicity (44267). Differences between the studies may be due to methodological problems, or differences in doses, route of administration, and age of participants.
• Asthma. Oral coenzyme Q10 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 coenzyme Q10 (Q-Gel, Tishcon Corporation) 120 mg, vitamin E 400 mg, and vitamin C 250 mg orally daily in addition to conventional anti-asthmatic therapy for 16 weeks might reduce the dosage of corticosteroids required by patients with mild to moderate asthma. However, it does not appear to improve lung function any more than standard therapy alone (43969).
• Attention deficit-hyperactivity disorder (ADHD). It is unclear if oral coenzyme Q10 is beneficial in children with ADHD. Details: A small clinical study in children aged 6-16 years with ADHD who are unresponsive to atomoxetine therapy shows that taking coenzyme Q10 1-3 mg/kg with atomoxetine 0.5-1.8 mg/kg daily for 6 months improves parent-rated symptoms of ADHD, particularly hyperactivity-related symptoms, when compared with placebo plus atomoxetine (107449).
• Autism spectrum disorder. It is unclear if the ubiquinol form of coenzyme Q10 taken orally is beneficial in children aged 3-6 years with this condition. Details: A small clinical study in children aged 3-6 years suggests that taking the reduced form of coenzyme Q10, ubiquinol (Li-QH, Tishcon Corporation), 50 mg orally once daily for one week followed by 50 mg twice daily for 11 weeks, improves symptoms of autism spectrum disorder, including communication with parents, ability to play with friends, verbal communication, sleeping, food rejection, aggressiveness, and self-harm, when compared with baseline, per parent assessment (89419). The validity of these findings is limited by the small study size, the use of parent assessment, and the lack of a comparator group.
• Benign prostatic hyperplasia (BPH). Oral coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical trial in patients with BPH shows that taking coenzyme Q10 100 mg plus L-carnitine daily for 8 weeks modestly decreases prostate volume and improves sexual performance when compared with placebo. There was no effect on prostate symptoms, prostate specific antigen levels, or quality of life. All patients were also taking finasteride 5 mg daily (113226). It is unclear if these effects are due to coenzyme Q10, L-carnitine, or the combination.
• Bipolar disorder. It is unclear if oral coenzyme Q10 is beneficial for bipolar disorder in older adults. Details: Preliminary clinical research in people 55 years of age or older with bipolar disorder shows that taking coenzyme Q10 800 mg orally daily for 4 weeks improves symptoms of depression when compared with baseline (95606). The validity of this finding is limited by the lack of a comparator group.
• Breast cancer. Low coenzyme Q10 levels may be associated with an increased risk of breast cancer. The benefit of coenzyme Q10 supplementation is unclear. Details: Population research in Chinese women has found that low plasma coenzyme Q10 levels are associated with an increased risk of breast cancer (44194).
• Cancer. Low coenzyme Q10 levels may increase the risk of cancer development and progression. Details: Population research has found that low coenzyme Q10 levels are associated with increased risk of metastatic melanoma (43959). Preliminary clinical research suggests that taking coenzyme Q10 150 mg twice daily along with vitamins A, C, and E, selenomethionine, beta-carotene, and folic acid extends survival time by 40% when compared with predicted survival in patients with end-stage cancer from various different primary sites (44159). It is unclear if this effect is due to coenzyme Q10, other ingredients, or the combination.
• Cardiovascular disease (CVD). It is unclear whether oral coenzyme Q10 has a role in preventing complications from CVD. Details: Preliminary clinical research shows that taking coenzyme Q10 300 mg 2 hours prior to an elective percutaneous coronary intervention does not reduce periprocedural myocardial injury or prevent major adverse cardiac events during one month of follow-up (96543). Other clinical research shows that taking a combination of coenzyme Q10 (Bio-Quinon, Pharma Nord) 100 mg twice daily plus organic selenium yeast tablets (SelenoPrecise, Pharma Nord) 200 mcg daily for 4-5 years reduces the risk of death from CVD by 7% when compared with placebo in elderly people living in Sweden (92904). This benefit appears to persist even after supplement discontinuation, with an 18% reduction at 10 years and an 11% reduction at 12 years (96546,97466,97906). In this same trial, post-hoc subgroup analyses in patients with elevated baseline D-dimer levels and/or hypertension or ischemic heart disease shows that taking this combination reduces cardiovascular mortality when compared with placebo (105874). It is unclear if these benefits are due to coenzyme Q10, selenium, or the combination.
• Cataracts. It is unclear if coenzyme Q10-containing eye drops are beneficial in patients undergoing cataract surgery. Details: Clinical research suggests that administering an ophthalmic solution containing coenzyme Q10 and vitamin E D-alpha-tocopheryl polyethylene glycol 1000 succinate twice daily for 9 months increases the speed of nerve regeneration when compared with saline solution in post-cataract surgery patients (44228).
• Cerebellar ataxia. It is unclear if coenzyme Q10 is beneficial for this condition. Details: Preliminary clinical research in patients with cerebellar ataxia shows that coenzyme Q10 30 mg/kg daily for 2 years improves ataxia scores by 48%, posture scores by 63%, and kinetic function scores by 37% when compared with baseline, but only in patients who are coenzyme Q10 deficient (44177). The validity of these findings is limited by the lack of a comparator group.
• Chronic fatigue syndrome (CFS). Oral coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: A small clinical study in patients with CFS shows that taking coenzyme Q10 200 mg plus NADH 20 mg daily for 8 weeks does not improve measures of fatigue, sleep, or quality of life when compared with placebo (107448).
• Chronic obstructive pulmonary disease (COPD). It is unclear if coenzyme Q10 is beneficial for improving exercise tolerance in people with COPD. Details: Preliminary clinical research suggests that taking coenzyme Q10 90 mg daily for 8 weeks reduces lactate production during anaerobic exercise in people with COPD, but does not improve oxygen consumption or exercise performance, when compared with baseline (44293). The validity of these findings is limited by the lack of a comparator group.
• Cocaine dependence. Oral coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in patients with cocaine dependence shows that taking a combination of coenzyme Q10 200 mg and L-carnitine 500 mg orally daily for 8 weeks does not reduce cocaine use when compared with placebo, as measured by urine benzoylecgonine levels and self-reported usage (43940).
• Coronavirus disease 2019 (COVID-19). It is unclear if oral coenzyme Q10 is beneficial for patients with persistent symptoms after COVID-19 infection. Details: Clinical research in individuals with previous confirmed COVID-19 infection and continued symptoms lasting more than 12 weeks shows that taking coenzyme Q10 (Pharma Nord) 100 mg five times daily for 6 weeks does not reduce the number or severity of symptoms when compared with placebo. The most common symptoms were concentration problems, mental and physical fatigue, headache, and/or muscle weakness (109392).
• Critical illness (trauma). It is unclear if oral coenzyme Q10 is beneficial in patients hospitalized due to acute trauma. Details: Preliminary clinical research in patients who are mechanically ventilated due to acute trauma and have low baseline coenzyme Q10 plasma levels shows that taking sublingual coenzyme Q10 (Nutri Q10, Nutri Century) 400 mg daily for 7 days reduces the duration of intensive care stay, mechanical ventilation, and hospitalization by 4 days, 2 days, and 6 days, respectively, when compared with placebo. Patients taking coenzyme Q10 also demonstrated larger improvements in organ function scores and coma scores than those taking placebo (105875).
• Cyclic vomiting syndrome (CVS). Limited evidence suggests oral coenzyme Q10 may reduce episodes of CVS. Details: Preliminary clinical research shows that taking coenzyme Q10 10 mg/kg orally twice daily is comparable to amitriptyline 0.5-1 mg/kg/day for reducing the number of CVS episodes in both children and adults (17703).
• Diabetic nephropathy. Although there has been interest in using oral coenzyme Q10 for diabetic nephropathy, there is insufficient reliable information about the clinical effects of coenzyme Q10 for this purpose.
• Dilated cardiomyopathy. Very small clinical studies suggest that children and adolescents with dilated cardiomyopathy may benefit from oral coenzyme Q10. Details: Preliminary clinical research in children with dilated cardiomyopathy suggests that taking coenzyme Q10 3-10 mg/kg daily, divided into 2-3 doses for up to 9 months, improves ejection fraction and New York Heart Association (NYHA) classification when compared to baseline (12199,13223). Also, in people under 20 years of age, taking a specific oral liquid formulation of coenzyme Q10 (QuinoMit Q10 Fluid, MSE Pharmazeutika GmbH), 10 mg/kg daily for 24 weeks produces a small increase in ejection fraction and improves NYHA class from II to I in 30% of patients (99427). The validity of these findings is limited by the lack of comparator groups.
• Dry eye. Ophthalmic coenzyme Q10 has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: Clinical research has evaluated the use of a specific eye drop (VisuXL, Visufarma) containing coenzyme Q10 and cross-linked hyaluronic acid, in a 1:1 ratio with alpha-tocopherol polyethylene glycol succinate. One study in menopausal women receiving antidepressants shows that placing 1 drop in each eye twice daily for 8 weeks reduces dry eye severity by 17% and improves tear break-up time when compared to 5 drops daily of carmellose eye drops (104553). In addition, another study in adults with mild to moderate dry eye shows that placing 1 drop in each eye four times daily for 12 weeks reduces dry eye severity by 14% and decreases some laboratory markers of dry eye when compared to hyaluronic acid alone. Both groups demonstrated similar improvement in meibomian gland function and tear break-up time (97909). The effect of coenzyme Q10 when used alone is unclear.
• Dry mouth. It is unclear if oral ubiquinol or ubiquinone improves salivary secretion. Details: Preliminary clinical research suggests that taking coenzyme Q10, as the reduced ubiquinol form or as the oxidized ubiquinone form, 100 mg orally daily for one month, improves salivary secretion by 72% to 82% when compared with baseline in patients with dry mouth (44191). The validity of these findings is limited by the lack of a comparator group.
• Erectile dysfunction (ED). It is unclear if oral coenzyme Q10 is beneficial in patients with ED. Details: A small, open-label study in patients with hypertension and complaints of ED shows that taking coenzyme Q10 200 mg daily for 3 months along with current antihypertensive therapy does not improve symptoms of ED when compared with antihypertensive therapy alone (107447).
• Fatigue. It is unclear if oral coenzyme Q10 is beneficial for reducing fatigue. Details: A meta-analysis of low- to moderate-quality clinical research in mixed populations shows that taking coenzyme Q10 modestly reduces feelings of fatigue when compared with placebo. This improvement was consistent between groups of healthy individuals and individuals with fatigue related to disease. However, a sub-group analysis shows that benefits are limited to studies in which coenzyme Q10 was studied as a single ingredient. Doses of coenzyme Q10 ranged from 60 mg to 500 mg daily for 4-12 weeks with treatment effects appearing to be both dose- and duration-dependent (109387).
• Friedreich ataxia. Oral coenzyme Q10 has been evaluated in combination with vitamin E; its effect when used alone is unclear. Details: Preliminary clinical research shows that taking coenzyme Q10 (Bio-Quinon Q10, Pharma Nord) 200 mg orally twice daily plus vitamin E (Bio-E-Vitamin, Pharma Nord) 1050 IU twice daily for 47 months improves measures of cardiovascular function by 20% when compared with baseline. However, it does not improve posture or gait, or prevent deterioration of posture, gait, speech, or eye function, when compared with baseline (43943,44064). It is unclear if these benefits are due to coenzyme Q10, vitamin E, or the combination. Also, the validity of these findings is limited by the lack of a comparator group.
• Hearing loss. There is conflicting evidence regarding the effects of oral coenzyme Q10 on hearing loss of various etiologies. Details: Some clinical research shows that taking coenzyme Q10 terclatrate (Qter), a water-soluble formulation of coenzyme Q10, 160 mg orally daily for 30 days improves hearing thresholds when compared to baseline in patients with age-related hearing loss (44171,44184). However, taking coenzyme Q10 terclatrate 200 mg daily for 7 days does not significantly improve hearing thresholds when compared with placebo in patients with noise-induced hearing loss (44143). Also, combining coenzyme Q10 with conventional steroid therapy for 2 weeks does not improve hearing when compared with steroid therapy alone in patients with sudden sensorineural hearing loss (44185).
• Hepatitis C. It is unclear if oral coenzyme Q10 is beneficial in patients with this condition. Details: Clinical research shows that taking coenzyme Q10 up to 80 mg orally daily for 28 days does not reduce serum liver enzymes when compared with placebo in patients with chronic hepatitis C who are unresponsive to conventional treatment (44172).
• Hyperlipidemia. There is conflicting evidence regarding the effects of coenzyme Q10 on cholesterol levels in adults. However, any changes are unlikely to be clinically meaningful. Details: A meta-analysis of 50 moderate-quality clinical trials shows that taking coenzyme Q10 has small beneficial effects on levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides when compared with a control, usually placebo (109394). However, whether coenzyme Q10 produces clinically meaningful changes is unclear. In a subgroup of patients with dyslipidemia, coenzyme Q10 does not seem to have significant beneficial effects on total cholesterol (109394). Also, previous individual clinical trials and meta-analyses in specific populations, including studies in which lipoprotein A was measured, as well as populations with diabetes, coronary artery disease, and others, have not shown beneficial effects on plasma lipids (17704,44187,96545,97918,109394). The effect of coenzyme Q10 on lipoprotein A has also been investigated. Individual studies and a meta-analysis show that taking coenzyme Q10 slightly reduces plasma levels of lipoprotein A when compared with placebo (17704,44187,96545). Most studies have used doses of 100-500 mg daily for 4-24 weeks (17704,44187,96545,96547,97910,109394). Coenzyme Q10 has also been studied in combination with other ingredients. A moderate-sized, open-label clinical study in adults with mild hypercholesterolemia and low cardiovascular disease risk shows that taking a combination product containing coenzyme Q10 2 mg, red yeast rice, grape seed extract, olive tree leaf extract, and B vitamins (Arichol, Epsilon Health) daily for 8 weeks reduces total cholesterol and LDL cholesterol, but not HDL cholesterol or triglycerides, when compared with placebo (111559). The validity of this effect is limited by a lack of blinding. It is unclear if this effect is due to coenzyme Q10, other ingredients, or the combination.
• Hypertension. Most research suggests that oral coenzyme Q10 may reduce systolic blood pressure (SBP), but not diastolic blood pressure (DBP). Details: Most clinical research shows that taking coenzyme Q10 100-900 mg orally daily in divided doses, either alone or with conventional medications, for up to 12 weeks significantly lowers SBP (2122,3365,9890,17702,17650,17651,44343,109393). One meta-analysis of moderate quality clinical research in patients with cardiometabolic disorders shows that supplementation with coenzyme Q10, especially 100-200 mg daily for at least 12 weeks, reduces SBP by 5 mmHg (109393). However, some studies show conflicting results. Most clinical research shows that coenzyme Q10 supplementation does not reduce DBP (8907,96541,109393). Also, a meta-analysis of two clinical studies (17651,44211) shows that taking coenzyme Q10 100-200 mg orally daily has no significant effect on blood pressure when compared with placebo (95607). Conflicting results may be due to differences in the severity of hypertension at baseline, adjustments made to conventional medications during studies, and the presence of a variety of concomitant conditions. Some data also suggest that effects may be greater in people with low baseline levels of coenzyme Q10 (2122,17650,17651).
• Hypertrophic cardiomyopathy. It is unclear if oral coenzyme Q10 is beneficial for this condition. Details: A very small clinical study of 7 patients suggests that taking coenzyme Q10 (Vitaline) 120-240 mg orally daily with the goal of raising blood levels above 2 mcg/mL, might improve symptoms of hypertrophic cardiomyopathy, including dyspnea and fatigue, and decrease cardiac wall thickness, when compared to baseline (11031). The validity of these findings is limited by the small size of the study and the lack of a comparator group.
• Infertility. It is unclear if oral coenzyme Q10 helps women undergoing assisted reproductive technology (ART) treatment. Details: A meta-analysis of 5 small clinical studies in infertile women undergoing ART treatment shows that although coenzyme Q10 increases the odds of clinical pregnancy more than 2-fold, it does not seem to affect the rate of live births or miscarriages when compared with placebo or no treatment (103780).
• Kidney failure. Oral coenzyme Q10 has been reported to improve renal function in people with kidney failure, but not in those with less severe kidney disease. Details: Preliminary clinical research in patients with kidney failure shows that taking coenzyme Q10 180 mg orally daily for 28 days improves blood urea nitrogen, serum creatinine, and creatinine clearance when compared with placebo (44347). However, other clinical research in patients with less severe kidney disease shows that taking coenzyme Q10 200 mg daily for 8 weeks does not significantly improve kidney function parameters, including urinary albumin, total protein, or glomerular filtration rate, when compared with placebo (44128).
• Lichen planus. It is unclear if topical coenzyme Q10 is beneficial for oral lichen planus. Oral coenzyme Q10 has not been studied for this condition. Details: A small clinical study in patients with oral lichen planus conducted in Egypt shows that applying topical coenzyme Q10 (ubiquinol) 120 mg as a mucoadhesive tablet 3 times daily for 4 weeks does not improve pain scores or lesion size when compared with topical corticosteroid paste (111617).
• Male Infertility. Oral coenzyme Q10 may improve some measures of sperm function in males with infertility, but there is no convincing evidence that it can increase pregnancy rates. Details: One small clinical study in males with idiopathic asthenozoospermia shows that coenzyme Q10 200 mg orally daily for 6 months improves sperm motility when compared with baseline (12169). The validity of this finding is limited by the lack of a comparator group. Coenzyme Q10 has also been studied in males with idiopathic oligoasthenoteratozoospermia, but results are conflicting. Studies have used coenzyme Q10 or its reduced form, ubiquinol, in doses of 200-300 mg orally daily for 26 weeks. Sperm density and motility are increased when compared with placebo, but pregnancy rates do not seem to improve (17413,89422). Three studies have used coenzyme Q10 200-400 mg orally daily for 12-26 weeks, with two reporting increased sperm concentration and motility when compared to baseline, but the other finding no improvements when compared with placebo (44190,102008,107444). Coenzyme Q10 has also been investigated in combination with other ingredients. In one preliminary clinical trial, taking coenzyme Q10 10 mg and vitamin E 100 mg three times daily for 3 months modestly increases levels of testosterone and improves progressive sperm motility and morphology when compared with baseline. However, taking an L-carnitine nutrient complex 15 grams twice daily was more effective for increasing testosterone and for improving sperm parameters (109390). Other small and preliminary clinical studies have investigated the effects of a specific combination product providing coenzyme Q10 20 mg twice daily for 6 months, along with acetyl-L-carnitine, L-carnitine, 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 coenzyme Q10, other ingredients, or the combination.
• Maternally inherited diabetes mellitus and deafness (MIDD). It is unclear if oral coenzyme Q10 is beneficial for MIDD. Details: One small clinical study shows that taking coenzyme Q10 150 mg orally daily for 3 years might prevent progressive insulin secretory defect, exercise intolerance, and hearing loss when compared with baseline in people with this rare form of diabetes (2125).
• Metabolic syndrome. It is unclear if oral coenzyme Q10 is beneficial in patients with metabolic syndrome. Details: A small clinical study in patients with metabolic syndrome receiving healthy dietary recommendations shows that taking coenzyme Q10 60 mg daily for 12 weeks does not have beneficial effects on blood glucose, cholesterol, waist circumference, or blood pressure when compared with placebo (109284).
• Myocarditis. It is unclear if oral coenzyme Q10 is beneficial in patients with acute viral myocarditis. Details: A small observational study in Chinese patients with acute viral myocarditis has found that taking coenzyme Q10 10 mg and trimetazidine 20 mg three times daily for 2 weeks, along with standard care, is associated with higher rates of resolution and improved quality of life when compared with coenzyme Q10 plus standard care alone (107443). While coenzyme Q10 alone appeared to improve symptoms and markers of cardiac function when compared to baseline in some patients, the validity of these findings is limited by a lack of placebo control.
• Nonalcoholic fatty liver disease (NAFLD). Coenzyme Q10 may reduce liver enzymes and the severity of NAFLD. Details: Preliminary clinical research in adults with NAFLD shows that taking coenzyme Q10 100 mg orally daily for 12 weeks reduces the clinical grade of NAFLD and decreases plasma levels of liver enzymes when compared with placebo (97907).
• Obesity. Oral coenzyme Q10 does not seem to improve weight loss in adults. Details: A meta-analysis of small, highly heterogeneous clinical trials shows that taking coenzyme Q10 100-300 mg daily for up to 24 weeks does not reduce weight or body mass index when compared with placebo. However, the included studies were not designed to assess for weight loss and involved patients with type 2 diabetes, metabolic syndrome, kidney disease, liver disease, rheumatoid arthritis, and other conditions (105067).
• Periodontitis. Data on the effects of oral or topical coenzyme Q10 are conflicting. It is unclear if coenzyme Q10 is beneficial for periodontitis. Details: Some very small, low-quality studies suggest that taking coenzyme Q10 orally, 50 mg daily for 3 weeks, might be beneficial for periodontitis (8917,8918). Preliminary research with topical coenzyme Q10 suggests it is ineffective (2107,2108). However, a meta-analysis of 11 clinical trials evaluating coenzyme Q10 topical gel shows reductions in plaque index, bleeding index, pocket index, clinical attachment level, and gingival index when compared with placebo gel or scaling and root planing alone. The greatest effects are seen when coenzyme Q10 gel is applied directly into the periodontal pocket daily for at least six weeks in combination with scaling and root planing (108958). The validity of these findings is limited by a high risk of bias and the overall low quality of the included studies. Coenzyme Q10 has also been studied in combination with other ingredients for periodontitis. A small clinical study in patients with moderate or advanced periodontitis shows that taking a supplement containing 30 mg of coenzyme Q10 in addition to alpha-lipoic acid, cranberry extract, grapeseed extract, selenium, vitamin C, vitamin E, and zinc twice daily for 8 weeks in addition to standard nonsurgical therapy does not improve periodontal indices including bleeding on probing, gingival recession, plaque index, or inflammation, among others, when compared with placebo (111708).
• Physical performance. It is unclear if oral coenzyme Q10 improves physical performance in older adults with chronic kidney disease (CKD). Details: A small clinical study in mostly older adults with CKD shows that taking coenzyme Q10 1200 mg daily for 6 weeks does not improve measures of physical exercise endurance including aerobic capacity, total work, and work efficiency when compared with placebo (111558). The validity of these effects is limited by the small sample size and short study duration.
• Polycystic ovary syndrome (PCOS). Most clinical studies suggest that oral coenzyme Q10 modestly improves symptoms in patients with PCOS. Details: A meta-analysis of clinical trials in patients with PCOS shows that taking coenzyme Q10 modestly improves measures of glycemic response, as well as plasma lipids and some sex hormones, when compared with placebo (109384). However, any changes are small and the clinical relevance is unclear. Also, although nine studies were included in the review, the number of studies included for each endpoint was much lower. Most clinical studies included in the analysis used 100-200 mg daily for 8-12 weeks (107446,109384). An additional small clinical study also shows that taking coenzyme Q10 (Nature Made) 100 mg orally daily for 12 weeks reduces fasting plasma glucose, insulin, and total cholesterol and improves insulin sensitivity when compared with placebo. This study also found that taking coenzyme Q10 reduces alopecia by about 33% and acne by 48% when compared with placebo (97914). Another small clinical study shows that taking coenzyme Q10 100 mg daily for 12 weeks reduces depression, anxiety, and hirsutism when compared with placebo (107446).
• Prader-Willi syndrome (PWS). It is unclear if oral coenzyme Q10 is beneficial in patients with PWS. Details: Preliminary clinical research in children with Prader-Willi syndrome shows that taking coenzyme Q10 2.5 mg/kg orally daily for one year improves psychomotor development similarly to growth hormone therapy, although this might reflect natural changes in the condition occurring over time (44005).
• Pre-eclampsia. Taking coenzyme Q10 orally seems to reduce the rate of pre-eclampsia in women at risk for the condition. Details: Clinical research shows that taking coenzyme Q10 (Q-absorb, Jarrow Formulas) 100 mg orally twice daily during pregnancy, starting at 20 weeks gestation and continuing until term, reduces the rate of pre-eclampsia by about 44% when compared with placebo in women at risk for developing this condition (17201).
• Schizophrenia. It is unclear if oral coenzyme Q10 improves symptoms in patients with schizophrenia or schizoaffective disorder. Details: A small clinical study in patients with schizophrenia or schizoaffective disorder shows that taking coenzyme Q10 300 mg daily for 6 months does not improve attention, working memory, negative symptoms, mood disorders, or quality of life when compared with placebo (105069). This finding is limited by insufficient power and poor protocol adherence, with only 61% of the participants taking at least 90% of the study treatment.
• Sepsis. There is no strong evidence that coenzyme Q10 is helpful in the management of sepsis or septic shock. Details: Patients with septic shock have been shown to have low levels of coenzyme Q10, but the effects of supplementation are unclear. Some preliminary clinical research shows that taking coenzyme Q10 100 mg orally twice daily for 7 days reduces the risk of in-hospital mortality by 69% and improves markers of inflammation, but does not reduce length of ICU stay, when compared with conventional treatment alone (102548). However, other preliminary research shows that taking coenzyme Q10 as ubiquinol 200 mg twice daily for 7 days has no effect on inflammatory or vascular endothelial biomarkers, mortality, or length of stay when compared with placebo (96540). Both studies were small and likely underpowered to detect a meaningful change in clinical outcomes.
• Statin-induced myalgia. There is conflicting evidence regarding the effects of oral coenzyme Q10 on statin-associated muscular adverse effects, such as myalgia. Details: Some clinical research shows that taking coenzyme Q10 (Q-Sorb softgel, Nature's Bounty) 100 mg orally daily for 30 days reduces pain intensity when compared with baseline or vitamin E control in patients with statin-induced myalgia (16008,44345). Other clinical research shows that taking coenzyme Q10 (MGC Company) 50 mg orally twice daily for 30 days reduces muscle pain and pain interference with daily activities by 30% to 40% when compared with placebo (95604). One small study in adults with statin-induced myalgia shows that taking liquid coenzyme Q10 (Q-Factor, Giellepi S.p.A) 100 mg orally daily for 3 months modestly reduces pain scores, but not plasma creatine kinase (CK) levels, when compared with placebo (102007). Other clinical research shows that taking coenzyme Q10 (Bio-Quinon, Pharma Nord) 100 mg twice daily, with or without selenium, for 3 months, reduces muscle pain and weakness, cramps, and tiredness when compared with placebo (92909). However, not all studies have shown benefit. Meta-analyses of several small randomized controlled trials show that taking coenzyme Q10 100-600 mg daily for 1-3 months does not improve muscle pain, statin tolerability, or plasma CK activity in patients with statin-induced myalgia when compared with placebo (95602,103781,106050). However, the validity of these results is limited by small population size and high heterogeneity. Other clinical research shows that taking coenzyme Q10 60 mg twice daily for 3 months does not improve muscle pain when compared with placebo (44218). Also, taking coenzyme Q10 (Q-Gel, Tishcon Corporation) 200 mg daily for 12 weeks does not affect myalgia scores when compared with placebo in patients taking simvastatin (44346). Additionally, taking high doses of coenzyme Q10 600 mg daily for 8 weeks does not affect the incidence, severity, or time to onset of statin-induced myalgia when compared with placebo in patients taking simvastatin (95603). Reasons for these conflicting findings are not entirely clear. The inconsistent results do not appear to be related to the dose of coenzyme Q10 or plasma CK levels. About 50% of patients who experience statin-induced myalgia will tolerate a statin re-challenge with a lower or equivalent dose of the same or alternative statin after a statin-free interval, which is a higher response rate than seen in currently available studies with the use of coenzyme Q10. Taking coenzyme Q10 for 30 days may be a reasonable option if other attempts to improve tolerance have failed. If a significant improvement in pain related to statin use is not seen after 30 days of taking coenzyme Q10, it is unlikely to be beneficial (96548).
• Statin-induced myopathy. There is conflicting evidence regarding the effects of coenzyme Q10 on statin-associated muscular adverse effects, including myopathy. Details: Clinical research shows that taking coenzyme Q10 (Bio-Quinon, Pharma Nord) 100 mg orally twice daily, with or without selenium, for 3 months, reduces muscle weakness and pain, cramps, and tiredness when compared with placebo in patients with statin-induced myopathy due to atorvastatin, fluvastatin, rosuvastatin, or simvastatin (92909). Preliminary clinical research also shows that taking coenzyme Q10 60 mg orally four times daily decreases the rate of dose-limiting statin-induced myopathy in patients taking high-dose lovastatin as an investigational treatment for cancer (11899,11900). However, when coenzyme Q10 (Myoquinon, Pharma Nord,) 400 mg orally daily is used in combination with selenium for 12 weeks, it does not affect atorvastatin-induced myopathy when compared with placebo (92908).
• Toxin-induced liver damage. Oral coenzyme Q10 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 coenzyme Q10 200 mg, acetyl-L-carnitine 250 mg, and alpha-lipoic acid 250 mg 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 coenzyme Q10, other ingredients, or the combination.
• Ulcerative colitis. It is unclear if oral coenzyme Q10 is beneficial in patients with ulcerative colitis. Details: Preliminary clinical research in adults with ulcerative colitis shows that taking oral coenzyme Q10 (Nutri Q10, Nutri Century Company) 100 mg twice daily for 8 weeks modestly improves ulcerative colitis disease activity and quality of life scores when compared with placebo. Taking coenzyme Q10 also reduces systolic and diastolic blood pressure by 4 mmHg and 2 mmHg, respectively, when compared with placebo (106049). The clinical relevance of these changes is unclear.
• Wrinkled skin. It is unclear if topical application of coenzyme Q10 cream can reduce wrinkles. Details: A small clinical study shows that applying a coenzyme Q10 1% cream to the skin twice daily for 5 months reduces objective wrinkle scores when compared to baseline (44082). The validity of this finding is limited by the lack of a comparator group. More evidence is needed to rate coenzyme Q10 for these uses.

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

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

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

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

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

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

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

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LIKELY SAFE ...when used orally and appropriately. Coenzyme Q10 has been used safely in studies lasting up to 5 years (2134,6037,6038,6407,8163,8938,8939,8940,15395,17413,17716,96538)(109391). ...when used topically on the gums (2107,2108,8916,8917,8918).

CHILDREN: POSSIBLY SAFE
when used orally and appropriately. Coenzyme Q10 in doses of 1-10 mg/kg/day has been used safely for up to 9 months under medical supervision (12199,13223,15256,44005,107449).

PREGNANCY: POSSIBLY SAFE
when used orally and appropriately. Coenzyme Q10 100 mg twice daily has been used with apparent safety during pregnancy, starting at 20 weeks gestation until term (17201).

LACTATION:
Insufficient reliable information available; avoid using.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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ALKYLATING AGENTS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Coenzyme Q10 has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals.  Details Theoretically, antioxidants such as coenzyme Q10 might protect tumor cells from chemotherapeutic agents that work by inducing oxidative stress, such as alkylating agents (e.g., cyclophosphamide) and radiation therapy (5158,5159). The clinical importance of this interaction is unknown.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = B Theoretically, coenzyme Q10 might have additive effects with antihypertensive drugs.  Details Some clinical research shows that coenzyme Q10 can significantly lower blood pressure (2122,3365,8907,9890,17702,17650,17651,44343,96541), although other studies have shown conflicting results (17651,44211,95607).

WARFARIN (Coumadin) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Coenzyme Q10 is chemically similar to menaquinone and might have vitamin K-like procoagulant effects, which could decrease the effects of warfarin.  Details Concomitant use of coenzyme Q10 and warfarin might reduce the anticoagulant effects of warfarin (2128,6048,6199). Four cases of decreased warfarin efficacy thought to be due to coenzyme Q10 have been reported (2128,6048,11048). However, there is some preliminary clinical research that suggests coenzyme Q10 might not significantly decrease the effects of warfarin in patients who have a stable INR (11905).

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

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

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

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

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

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General ...Orally, coenzyme Q10 is generally well tolerated. In clinical studies, no serious adverse effects have been reported.
Most Common Adverse Effects:
Orally: Gastrointestinal side effects such as appetite suppression, diarrhea, epigastric discomfort, heartburn, nausea, and vomiting. These generally occur in less than 1% of patients. Some of these adverse effects can be minimized if daily doses above 100 mg are divided.

Cardiovascular ...Palpitations have been reported as being possibly associated with coenzyme Q10 treatment (89421). Death due to myocardial infarction occurred in one Parkinson disease patient taking coenzyme Q10; causality is unclear (15395).

Dermatologic ...Two of 143 participants in a case series reported skin itching after starting treatment with oral coenzyme Q10 (6047). Allergic rash has also been reported (6409,11872). An itching exanthema was seen in two heart failure patients treated with intravenous coenzyme Q10 (44284).

Gastrointestinal ...Gastrointestinal side effects of coenzyme Q10 have included nausea (3365,6409,8907,10152,43982,44172,44179,44330,89421,109392), vomiting (3365,10152,44330,89421), epigastric discomfort (3365,44179,44330,89421), constipation (109392), diarrhea (44179,92904,89421,109392), stomach upset (8940,12170,109387,109388,109392), loss of appetite (2121), heartburn (2121,44179,109392), and flatulence (43982), although this occurs in less than 1% of patients. In one clinical study, gastrointestinal bleeding in association with angiodysplasia has been reported to be possibly related to coenzyme Q10 treatment (89421).

Genitourinary ...An uncomplicated urinary infection was reported in a patient taking oral coenzyme Q10 (nanoQuinon, MSE Pharmazeutika) (44020).

Hematologic ...Thrombocytopenia was noted in one patient treated with oral coenzyme Q10 (44296); however, other factors (viral infection, other medications) may have been responsible for this adverse effect.

Musculoskeletal ...Increased plasma creatine kinase with high-intensity exercise has been reported in patients taking coenzyme Q10 (44303). Muscle pain has been reported rarely in one clinical trial (109392).

Neurologic/CNS ...Headache and dizziness have been reported in human research (3365,11872,43982,44330,109392). Insomnia has been reported as being possibly associated with coenzyme Q10 treatment (89421). Cognitive decline, depression, and sudden falls were reported rarely in a clinical trial of patients with Huntington disease (8940). Increased lethargy was reported for one patient treated with oral coenzyme Q10 (44042). Feeling of internal trembling has been reported in a clinical trial for one patient treated with coenzyme Q10 (44020).

Ocular/Otic ...Visual sensitivity to light has been reported for a patient treated with coenzyme Q10. However, the association of this effect with coenzyme Q10 treatment was not clear (6409).
A burning sensation has been reported for 10% of patients treated with a topical eye solution containing coenzyme Q10 and alpha-tocopheryl polyethylene glycol 1000 succinate following cataract surgery (44228).

Psychiatric ...Worsening depression has been reported as being possibly associated with oral coenzyme Q10 treatment (89421).

Pulmonary/Respiratory ...Drug-induced pneumonitis was diagnosed in a 61 year-old woman who had been taking coenzyme Q10 and perilla leaf extract for two months (43978). Symptoms improved after she stopped taking the supplements and began taking oral prednisone. Causation from coenzyme Q10 was unclear.

Other ...In a case report, a naval aviator using a supplement containing coenzyme Q10 and niacin had reduced G tolerance (44186). G tolerance was regained with cessation of the supplement.

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