Idebenone
Coenzyme Q10/Drug Interactions:
GeneralGeneral: Scott et al. wrote a review on natural product-drug interactions, including coenzyme Q10 (CoQ10) (397). Further details are lacking. Acetylsalicylic acidAcetylsalicylic acid: In human research, effects of acetylsalicylic acid on CoQ10 were lacking in healthy volunteers (398). Alzheimer's agentsAlzheimer's agents: In clinical research, idebenone, a synthetic analog of CoQ10, showed dose-dependent improvements in the Alzheimer's Disease Assessment Scale (ADAS-Total) vs. placebo, as well as improvements in Efficacy Index Scores (EIS) vs. tacrine (210; 239; 240; 241; 242). In human research, use of antioxidants, including CoQ10, improved oxidative stress in patients treated with a cholinesterase inhibitor (399). AmiodaroneAmiodarone: In vitro, CoQ10 prevented cardiotoxicity associated with amiodarone (400). AmitriptylineAmitriptyline: In human research, CoQ10 prevented vomiting associated with amitriptyline (43). In vitro, CoQ10 protected against amitriptyline toxicity (401). Reactive oxygen species production, lipid peroxidation, mitochondrial dysfunction, and cell death were all reduced. Anabolic androgenic steroidsAnabolic androgenic steroids: In human research, use of anabolic androgenic steroids increased serum ubiquinone (402). Angiotensin-converting enzyme inhibitorsAngiotensin-converting enzyme inhibitors: In human research, CoQ10 improved ejection fraction, with a greater effect in those not taking angiotensin-converting enzyme inhibitors (303). AntiarrhythmicsAntiarrhythmics: In human research, coenzyme Q10 has been shown to assist in the preservation of myocardial sodium-potassium ATP-ase activity and stabilize myocardial calcium-dependent ion channels; however, evidence is conflicting (224; 225; 182; 226; 206). In vitro, CoQ10 prevented cardiotoxicity associated with amiodarone (400). AntiasthmaticsAntiasthmatics: In patients with bronchial asthma, CoQ10 reduced the corticosteroids needed to control asthma symptoms (403). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: According to case reports, CoQ10 may reduce the effectiveness of warfarin (201; 202). In human research, effects of acetylsalicylic acid on CoQ10 were lacking in healthy volunteers (398). In human research, CoQ10 lacked an effect on the international normalized ratio (INR) in patients treated with warfarin (404). This study was also discussed in a letter to the editor (405). Thrombocytopenia was reported in one patient in a case series (211); however, other factors (e.g., viral infection, other medications) may have been responsible. Antidepressant agentsAntidepressant agents: Kishi et al. discussed the inhibition of myocardial respiration by psychotherapeutic drugs and the prevention by CoQ (406). According to secondary sources, antidepressants may reduce the natural production of CoQ10; therefore, use of both agents may result in diminished effects of CoQ10. Specific medications noted in anecdotal reports include amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, nortriptyline, and perphenazine. In human research, CoQ10 prevented vomiting associated with amitriptyline (43). In vitro, CoQ10 protected against amitriptyline toxicity (401). Reactive oxygen species production, lipid peroxidation, mitochondrial dysfunction, and cell death were all reduced. Antidiabetic agentsAntidiabetic agents: According to secondary sources, some oral diabetic medications, such as chlorpropamide, glimepiride, glipizide, glyburide, tolazamide, tolbutamide, acetohexamide, and biguanides, may reduce CoQ10 concentrations. Evidence is conflicting regarding the actions of CoQ10 on blood glucose (213; 216; 215). Antifungal agentsAntifungal agents: In vitro, atovaquone had antifungal effects against Candida albicans (407). AntihypertensivesAntihypertensives: In human research, CoQ10 lowered systolic and diastolic blood pressure (217; 267; 219; 220; 221; 222; 223). However, in healthy people, these effects were transient and mild (408). In human research, the use of CoQ10 resulted in a decreased need for antihypertensives (218), and in combination with enalapril, CoQ10 resulted in normalization of vascular endothelial function and an improvement in the correction of the 24-hour blood pressure profile (409). According to secondary sources, clonidine and hydralazine may each reduce CoQ10 concentrations. In vitro, diazoxide was found to inhibit CoQ10-succinoxidase, propranolol was found to inhibit CoQ10-NADH-oxidase, and hydrochlorothiazide, hydralazine, and clonidine were found to inhibit CoQ10-NADH-oxidase in heart tissue (410). Anti-inflammatory agentsAnti-inflammatory agents: In vitro, CoQ10 partially attenuated the effect of tumor necrosis factor-alpha on peroxisome proliferator-activated receptor-gamma (but not alpha) (33). In human research, effects of acetylsalicylic acid on CoQ10 were lacking in healthy volunteers (398). In vitro, MitoQ suppressed the release of proinflammatory cytokines and increased production of IL-10 (37). Antilipemic agentsAntilipemic agents: In human research, the use of HMG-CoA reductase inhibitors (lovastatin, pravastatin, rosuvastatin, and simvastatin) (411; 412; 413; 414; 415; 416; 417; 418; 419; 420; 421; 422; 423; 424; 425; 426; 427; 428; 429) and gemfibrozil (430; 431) led to a decreased concentration of CoQ10. Changes in blood levels of CoQ10 in plasma or muscle, or myotubes in vitro, were lacking with coadministration of rosuvastatin, ezetimibe, and colestimide, or rosuvastatin or other statins alone in some studies (432; 433; 434; 435; 436; 437; 426; 438). The effect of statins on CoQ10 levels was the topic of a review (439). According to case reports, CoQ10 has been administered to ameliorate the toxic effects of lovastatin (440; 441), and in human research, CoQ10 supplementation prevented a decrease in plasma and platelet CoQ10 (442; 443) and increased CoQ10 in lipoproteins (444). In human research, CoQ10 has been shown to decrease triglycerides and total cholesterol and increase high-density lipoprotein (HDL) (319; 213); however, decreased HDL cholesterol has also been shown (353). In a clinical trial, adverse effects to idebenone included increased blood cholesterol (N=1) (370), and, according to a systematic review and meta-analysis, adverse effects experienced by participants receiving CoQ10 included hypercholesterolemia (349). In human research, fenofibrate increased plasma CoQ10 concentrations (12). Antineoplastic agentsAntineoplastic agents: In clinical trials, there was promising evidence to support the use of CoQ10, in addition to other medications and supplements, in the treatment of breast cancer (445; 193; 446). In human research and according to other publications, CoQ10 had cardioprotective effects when used with anthracycline and other antineoplastic therapy (447; 448; 270; 357; 449), and CoQ10 may prevent the inhibition of Adriamycin-inhibited enzymes (450; 451). In animal research, injection of CoQ10 prevented cardiotoxicity associated with anthracycline derivatives (452), and reduction of chemotoxicity due to CoQ10 has been shown in other studies (details are lacking) (453). In human research, CoQ10 reduced angiogenesis markers and lipid levels, and increased antioxidant status, during tamoxifen use (454; 455; 456; 457). In human research, doxorubicin increased plasma CoQ10 (458). In vitro, cell survival from chemotherapy depended on the NF-kappaB transcriptional upregulation of the biosynthesis of CoQ (459). In animal research, CoQ10 affected the tissue concentration of doxorubicin and its major metabolite, aglycone-1 (460). Limited clinical research suggests that doxorubicin of up to 900mg/m2 may be administered safely during chemotherapy as long as CoQ10 is administered concurrently (461). Antipsychotic agentsAntipsychotic agents: Kishi et al. discussed the inhibition of myocardial respiration by psychotherapeutic drugs and the prevention by CoQ (406). Further details are limited. According to secondary sources, antipsychotics may reduce the natural production of CoQ10. Specific antipsychotics mentioned in anecdotal reports include chlorpromazine, fluphenazine, haloperidol, mesoridazine, prochlorperazine, promethazine, thioridazine, trifluoperazine, and trimipramine. Supplementation of CoQ10 may also reduce the cardiac side effects from the use of phenothiazine and tricyclic antidepressants.Antiretroviral agentsAntiretroviral agents: According to the results of a case report, supplementation with CoQ10 may reduce symptoms of "ragged-red" fiber myopathy associated with zidovudine (462). Beta-blockersBeta-blockers: In human research, CoQ10 reduced timolol-induced changes in heart rate (463). According to secondary sources, beta-blockers may reduce serum concentrations of CoQ10. Cardiovascular agentsCardiovascular agents: In human research, CoQ10 was found to show benefit in the majority of clinical trials (254; 255; 207; 184; 226; 256; 219; 257; 258; 185; 259; 260; 261; 262; 266; 267; 268; 306; 196). In human research, CoQ10 improved measures of cardiovascular functions, such as cardiac output (CO), cardiac index (CI), stroke volume (SV), ejection fraction (EF), end-diastolic volumes (EDV), stroke index, and EKG combined in most studies (294; 303; 302; 219; 183; 297; 295; 265; 300; 464; 305; 465); significant changes were lacking in most or all endpoints in some (264; 263; 221; 301; 208). CoQ10 reduced cardiovascular mortality and all-cause mortality in heart failure patients in one study (196). In patients with well-preserved left ventricular function (ejection fraction >0.50) undergoing elective coronary revascularization, atrial fibrillation requiring digitalis occurred in two in the control group and three in the CoQ10 group; however, this was not considered an adverse event (311). In human research, CoQ10 resulted in a decreased need for dopamine and epinephrine, as well as mediastinal drainage, blood product requirement, and hospital stays (215; 196). In human research, CoQ10 enhanced systolic function in chronic heart failure, but its effectiveness may be reduced with concomitant use of standard therapies (303). According to a review examining the results of various clinical studies, CoQ10 may be a cardioprotective agent (466). In human research, CoQ10 improved recovery following ischemia of isolated atrial tissue (467). In animal research, CoQ10 improved recovery of work after rapid pacing in senescent rat hearts (467). In vitro, CoQ10 prevented cardiotoxicity associated with amiodarone (400). In human research, CoQ10 resulted in a decreased need for nitroglycerin (225). ClonidineClonidine: According to secondary sources, clonidine may reduce CoQ10 concentrations.CorticosteroidsCorticosteroids: In patients with bronchial asthma, CoQ10 reduced the corticosteroids needed to control asthma symptoms (403). Cyclosporin ACyclosporin A: The preparation, characterization, and in silico modeling of biodegradable nanoparticles containing cyclosporin A and CoQ10 have been described (468). The authors indicated that CoQ10 reduces the release of cyclosporine. Dermatological agentsDermatological agents: Pardeike et al. conducted a nonrandomized study and determined that after seven applications of Cutanova Nanorepair Q10 cream, there was an increase in skin hydration (237). In vitro in keratinocytes and fibroblasts, CoQ10 inhibited UVB-induced production of reactive oxygen species, DNA damage, matrix metalloproteinases, and IL-6 production (355). In dermal and epidermal cells in vitro, CoQ10 protected against oxidative stress-induced cell death and enhanced the synthesis of basement membrane components (laminin 332, type IV and VII collagens) (469). DiureticsDiuretics: According to secondary sources, diuretics may reduce CoQ10 concentrations. Specific diuretics mentioned in anecdotal reports include benzthiazide, chlorothiazide, hydrochlorothiazide, indapamide, methyclothiazide, metolazone, and polythiazide.Dopamine agonistsDopamine agonists: In vitro and in animal models (nigrostriatal tract), CoQ10 levels increased following treatment with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridinium (MPP(+)) (470). Dopamine antagonistsDopamine antagonists: In vitro and in animal models (nigrostriatal tract), CoQ10 levels increased following treatment with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridinium (MPP(+)) (470). DoxorubicinDoxorubicin: In animal research, CoQ10 affected the tissue concentration of doxorubicin and its major metabolite, aglycone-1 (460). Limited clinical research suggests that doxorubicin of up to 900mg/m2 may be administered safely during chemotherapy, as long as CoQ10 is administered concurrently (461). Exercise performance enhancement agentsExercise performance enhancement agents: In human research, CoQ10 was found to increase autonomic nervous activity and energy metabolism during exercise (471). CoQ10 was also found to induce further lipid oxidation. In human research, muscle CoQ10 (ubiquinone) was positively related to exercise capacity (472). EzetimibeEzetimibe: In human research, the combination simvastatin and ezetimibe significantly decreased plasma CoQ10 levels, although ezetimibe monotherapy did not (432). FenofibrateFenofibrate: In human research, fenofibrate increased plasma CoQ10 concentrations (12). In human research, a combination of fenofibrate and CoQ10 reduced 24-hour systolic blood pressure and nocturnal blood pressure (221). Fertility agentsFertility agents: In patients with oligospermia or asthenozoospermia, CoQ10 levels were higher in the sperm; increased levels were lacking in varicocele patients (473). In seminal fluid and plasma, CoQ10 levels showed a significant correlation with sperm count and with sperm motility in nonvaricocele patients (474; 475; 476). In human research, CoQ10, alone or in combination with other agents, resulted in improvements in sperm density, sperm motility, and sperm morphology (323; 477). In human research, there were improvements in sperm motility, curvilinear velocity, straight progressive velocity, and forward motility (324). In patients with Peyronie's disease, CoQ10 improved erectile function (350). In vitro, CoQ10 increased motility in sperm from asthenospermic men (p<0.05 from a mean of 19.1% to 35.7%) (325). Heart-regulating agentsHeart-regulating agents: In human research, coenzyme Q10 has been shown to assist in the preservation of myocardial sodium-potassium ATP-ase activity and stabilize myocardial calcium-dependent ion channels; however, evidence is conflicting (224; 225; 182; 226; 206). In vitro, CoQ10 prevented cardiotoxicity associated with amiodarone (400). In human research, CoQ10 decreased heart rate (220). Hormonal agentsHormonal agents: In males with secondary hypogonadism, testosterone increased levels of CoQ10 (478). In human research, use of anabolic androgenic steroids increased serum ubiquinone (402). HydralazineHydralazine: According to secondary sources, hydralazine may reduce CoQ10 concentrations.ImmunoglobulinsImmunoglobulins: In human research, CoQ10 increased serum levels of IgG (479). ImmunosuppressantsImmunosuppressants: In theory, CoQ10 may have positive effects on immune response, based on its antioxidant effects (480; 481; 482; 483; 484). The preparation, characterization, and in silico modeling of biodegradable nanoparticles containing cyclosporin A and CoQ10 have been described (468). The authors indicated that CoQ10 reduces the release of cyclosporine. In human peripheral blood mononuclear cells in vitro, CoQ10 decreased secretion of tumor necrosis factor (TNF)-alpha and interleukin (IL)-2 (485). IridiumIridium: Hematic CoQ10 levels were investigated after treatment with 131-iridium in patients affected by thyroid cancer (486). Further details are lacking.MercuryMercury: In fisherman, seasonal mercury exposure increased total CoQ10 and ubiquinone levels (487). MethyldopaMethyldopa: According to secondary sources, methyldopa may reduce CoQ10 concentrations.Neurologic agentsNeurologic agents: In vitro, CoQ10 attenuated changes in Parkinson's disease cybrid peroxide, protein carbonyl, and protein sulfhydryl levels (488). In animal research, CoQ10 reduced beta-amyloid plaque in an APP/PS1 transgenic mouse model of Alzheimer's disease (489). In animal research, CoQ10 attenuated the pathology of beta-amyloid (production and deposit) (490). In human research, combination topical treatment with CoQ10 and alpha-tocopheryl polyethylene glycol 1000 succinate following cataract surgery resulted in faster nerve regeneration and better stability of ocular surface than saline (385). NicotineNicotine: In human research, smoking was not associated with differences in plasma CoQ10 levels (491). NitroglycerinNitroglycerin: In human research, CoQ10 resulted in a decreased need for nitroglycerin (225). Ophthalmic agentsOphthalmic agents: In vitro, CoQ10 prevented apoptotic cell death in human lens epithelial cells; a reduction in oxidative stress and the stabilization of the BAX:Bcl-2 ratio played a role (492). In human research, combination topical treatment with CoQ10 and alpha-tocopheryl polyethylene glycol 1000 succinate following cataract surgery resulted in faster nerve regeneration and better stability of ocular surface than saline (385). OrlistatOrlistat: In a case report, myopathy associated with chronic orlistat consumption was described (493). The role of CoQ10 is not clear. P-glycoprotein-regulated agentsP-glycoprotein-regulated agents: Itagaki et al. published a report on the interaction of CoQ10 with the intestinal drug transporter glycoprotein (494). The authors indicated that CoQ10 affected the transport activity of p-glycoprotein. Respiratory agentsRespiratory agents: In patients with bronchial asthma, CoQ10 reduced the corticosteroids needed to control asthma symptoms (403). In patients with sleep apnea, an antioxidant cocktail containing CoQ10 reduced progressive augmentation and ventilatory long-term facilitation, which are normally enhanced in these patients (495). SalicylatesSalicylates: In human research, effects of acetylsalicylic acid on CoQ10 were lacking in healthy volunteers (398). SimvastatinSimvastatin: In human research, simvastatin and the combination simvastatin and ezetimibe decreased plasma CoQ10 levels (432). StatinsStatins: In human research in hypercholesterolemic patients, statins reduced serum CoQ10 levels (496; 411; 412; 413; 432; 414; 497). CoQ10 has been shown to improve diastolic function in patients taking statins (321). SteroidsSteroids: In human research, use of anabolic androgenic steroids increased serum ubiquinone (402). In patients with bronchial asthma, CoQ10 reduced the corticosteroids needed to control asthma symptoms (403). Thyroid hormonesThyroid hormones: In theory, CoQ10 may affect thyroid hormone levels and alter the effects of thyroid drugs such as levothyroxine (Synthroid?), although this has not been proven in humans.TimololTimolol: In human research, CoQ10 reduced the timolol-induced change in heart rate (463). Weight loss agentsWeight loss agents: In a case report, myopathy associated with chronic orlistat consumption was described (493). The role of CoQ10 is not clear. Coenzyme Q10/Herb/Supplement Interactions:
Alpha-lipoic acidAlpha-lipoic acid: According to a review the coadministration of alpha-lipoic acid with CoQ10 improved cognitive dysfunction and reduced mitochondrial dysfunction vs. alpha-lipoic acid alone (498). Alzheimer's agents Alzheimer's agents : In human research, idebenone, a synthetic analog of CoQ10, has shown dose-dependent improvements in the Alzheimer's Disease Assessment Scale (ADAS-Total) vs. placebo, as well as improvements in Efficacy Index Scores (EIS) vs. tacrine (210; 239; 240; 241; 242). AntiarrhythmicsAntiarrhythmics: In human research, CoQ10 has been shown to assist in the preservation of myocardial sodium-potassium ATP-ase activity and stabilize myocardial calcium-dependent ion channels; however, evidence is conflicting (224; 225; 182). For instance, a study examining treatment with CoQ10 (33.3mg three times daily) did not report an effect on the incidence of ventricular arrhythmias (226), but a randomized controlled trial using 120mg of CoQ10 daily showed significant reductions in total arrhythmias (206). AntiasthmaticsAntiasthmatics: In patients with bronchial asthma, CoQ10 reduced the corticosteroids needed to control asthma symptoms (403). Anticoagulants and antiplateletsAnticoagulants and antiplatelets: According to case reports, CoQ10 may reduce the effectiveness of warfarin (201; 202). In human research, effects of acetylsalicylic acid on CoQ10 were lacking in healthy volunteers (398). In human research, CoQ10 lacked an effect on the international normalized ratio (INR) in patients treated with warfarin (404). This study was also discussed in a letter to the editor (405). Thrombocytopenia was reported in one patient in a case series (211); however, other factors (e.g., viral infection, other medications) may have been responsible. Antidepressant herbs and supplementsAntidepressant herbs and supplements: Kishi et al. discussed the inhibition of myocardial respiration by psychotherapeutic drugs and the prevention by CoQ (406). According to secondary sources, antidepressants may reduce the natural production of CoQ10; therefore, use of both agents may result in diminished effects of CoQ10.Antifungal agentsAntifungal agents: In vitro, atovaquone had antifungal effects against Candida albicans (407). Anti-inflammatory agentsAnti-inflammatory agents: In vitro, CoQ10 partially attenuated the effect of tumor necrosis factor-alpha on peroxisome proliferator-activated receptor-gamma (but not alpha) (33). In vitro, MitoQ suppressed the release of proinflammatory cytokines and increased production of IL-10 (37). AntilipemicsAntilipemics: In human research, CoQ10 has been shown to decrease triglycerides and total cholesterol and increase HDL cholesterol (319; 213); however, decreased HDL cholesterol has also been shown (353). In a clinical trial, adverse effects to idebenone included increased blood cholesterol (N=1) (370), and, according to a systematic review and meta-analysis, adverse effects experienced by participants receiving CoQ10 included hypercholesterolemia (349). AntineoplasticsAntineoplastics: There is promising evidence to support the use of CoQ10, along with other medications and supplements, in the treatment of breast cancer (445; 193; 446). AntioxidantsAntioxidants: In human research, many of the therapeutic benefits of CoQ10 were attributed to its role in the generation of adenosine triphosphate (ATP) and its antioxidant effects (483). Antioxidant effects have been shown in vitro and in vivo (28; 250; 499; 500; 501; 250; 246; 250); however, antioxidant effects of CoQ10 were generally lacking in well-designed or lesser-quality human research (247; 248; 249; 502). AntipsychoticsAntipsychotics: Kishi et al. discussed the inhibition of myocardial respiration by psychotherapeutic drugs and the prevention by CoQ (406). Further details are limited. According to secondary sources, antipsychotics may reduce the natural production of CoQ10. Supplementation of CoQ10 may also reduce the cardiac side effects from the use of phenothiazine and tricyclic antidepressants.Antiviral agentsAntiviral agents: According to results of a case report, supplementation with CoQ10 may reduce symptoms of "ragged-red" fiber myopathy associated with zidovudine (462). Athletic performance enhancersAthletic performance enhancers: In human research, CoQ10 was found to increase the autonomic nervous activity and energy metabolism during exercise (471). CoQ10 was also found to induce further lipid oxidation. In human research, muscle CoQ10 (ubiquinone) was positively related to exercise capacity (472). Beta-caroteneBeta-carotene: In human research, CoQ10 was shown to increase plasma beta-carotene (206). Cardiovascular agentsCardiovascular agents: In human research, CoQ10 was found to show benefit in the majority of clinical trials (254; 255; 207; 184; 226; 256; 219; 257; 258; 185; 259; 260; 261; 262; 266; 267; 268; 306; 196). In human research, CoQ10 improved measures of cardiovascular functions, such as cardiac output (CO), cardiac index (CI), stroke volume (SV), ejection fraction (EF), end-diastolic volumes (EDV), stroke index, and EKG combined in most studies (294; 303; 302; 219; 183; 297; 295; 265; 300; 464; 305; 465); significant changes were lacking in most or all endpoints in some (264; 263; 221; 301; 208). CoQ10 reduced cardiovascular mortality and all-cause mortality in heart failure patients on one study (196).. In patients with well-preserved left ventricular function (ejection fraction >0.50) undergoing elective coronary revascularization, atrial fibrillation requiring digitalis occurred in two in the control group and three in the CoQ10 group; however, this was not considered an adverse event (311). In human research, CoQ10 resulted in a decreased need for dopamine and epinephrine, as well as mediastinal drainage, blood product requirement, and hospital stays (215; 196). According to a meta-analysis, CoQ10 enhanced systolic function in chronic heart failure, but its effectiveness may be reduced with concomitant use of standard therapies (303). According to a review examining the results of various clinical studies, CoQ10 may be a cardioprotective agent (466). In human research, CoQ10 improved recovery following ischemia of isolated atrial tissue (467). In animal research, CoQ10 improved recovery of work after rapid pacing in senescent rat hearts (467). Dermatological agentsDermatological agents: Pardeike et al. conducted a nonrandomized study and determined that after seven applications of Cutanova Nanorepair Q10 cream, there was an increase in skin hydration (237). In vitro in keratinocytes and fibroblasts, CoQ10 inhibited UVB-induced production of reactive oxygen species, DNA damage, matrix metalloproteinases, and IL-6 production (355). In dermal and epidermal cells in vitro, CoQ10 protected against oxidative stress-induced cell death and enhanced the synthesis of basement membrane components (laminin 332, type IV and VII collagens) (469). DiureticsDiuretics: According to secondary sources, herbs and supplements with diuretic activity may reduce CoQ10 concentrations.Dopamine agonistsDopamine agonists: In vitro and in animal models (nigrostriatal tract), CoQ10 levels increased following treatment with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridinium (MPP(+)) (470). Dopamine antagonistsDopamine antagonists: In vitro and in animal models (nigrostriatal tract), CoQ10 levels increased following treatment with the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/1-methyl-4-phenylpyridinium (MPP(+)) (470). Fertility agentsFertility agents: In patients with oligospermia or asthenozoospermia, CoQ10 levels were higher in the sperm; increased levels were lacking in varicocele patients (473). In seminal fluid and plasma, CoQ10 levels showed a significant correlation with sperm count and with sperm motility in nonvaricocele patients (474; 475; 476). In human research, CoQ10, alone or in combination with other agents, resulted in improvements in sperm density, sperm motility, and sperm morphology (323; 477). In human research, there were improvements in sperm motility, curvilinear velocity, straight progressive velocity, and forward motility (324). In patients with Peyronie's disease, CoQ10 improved erectile function (350). In vitro, CoQ10 increased motility in sperm from asthenospermic men (p<0.05 from a mean of 19.1% to 35.7%) (325). GarlicGarlic: In firefighters with occupational stress, a mixture of CoQ10 and aged garlic extract resulted in an improvement of vascular elasticity and endothelial function (503). GeranylgeraniolGeranylgeraniol: In vitro, geranylgeraniol prevented the cytotoxic effects of mevastatin on ubiquinone synthesis (504). Gum arabicGum arabic: In human and animal research, CoQ10 emulsified using gum arabic increased serum CoQ10 levels compared with an unemulsified formulation (505). Heart rate-regulating agentsHeart rate-regulating agents: In human research, coenzyme Q10 has been shown to assist in the preservation of myocardial sodium-potassium ATP-ase activity and stabilize myocardial calcium-dependent ion channels; however, evidence is conflicting (224; 225; 182; 226; 206). In human research, CoQ10 decreased heart rate (220). Hormonal agentsHormonal agents: In human research, use of anabolic androgenic steroids increased serum ubiquinone (402). In males with secondary hypogonadism, testosterone increased levels of CoQ10 (478). Hyperglycemics or hypoglycemicsHyperglycemics or hypoglycemics: In human research, evidence was conflicting about the actions of CoQ10 on blood glucose (213; 216; 215) Hypertensives or hypotensivesHypertensives or hypotensives: In human research, CoQ10 lowered systolic and diastolic blood pressure (217; 267; 219; 220; 221; 222; 223). However, in healthy people, these effects were transient and mild (408). In human research, the use of CoQ10 resulted in a decreased need for antihypertensives (218), and in combination with enalapril, CoQ10 resulted in normalization of vascular endothelial function and an improvement in the correction of the 24-hour blood pressure profile (409). In human research, CoQ10 improved ejection fraction, with a greater effect in those not taking angiotensin-converting enzyme inhibitors (303). In human research, a combination of policosanol, red yeast rice extract, berberine, folic acid, and CoQ10 only reduced blood pressure when given in addition to Orthosiphon stamineus (506). ImmunomodulatorsImmunomodulators: In theory, CoQ10 may have positive effects on immune response, based on its antioxidant effects (480; 481; 482; 483; 484). In human peripheral blood mononuclear cells in vitro, CoQ10 decreased secretion of TNF-alpha and IL-2 (485). L-carnitineL-carnitine: According to secondary sources, CoQ10 may have synergistic effects when used with L-carnitine.MyoViveTMyoViveT: In human research, MyoViveT, a nutritional supplement aimed at providing essential cardiac myocyte nutrients, increased myocardial levels of CoQ10 (507). Neurologic agentsNeurologic agents: In vitro, CoQ10 attenuated changes in Parkinson's disease cybrid peroxide, protein carbonyl, and protein sulfhydryl levels (488). In animal research, CoQ10 reduced beta-amyloid plaque in an APP/PS1 transgenic mouse model of Alzheimer's disease (489). In animal research, CoQ10 attenuated the pathology of beta-amyloid (production and deposit) (490). In human research, combination topical treatment with CoQ10 and alpha-tocopheryl polyethylene glycol 1000 succinate following cataract surgery resulted in faster nerve regeneration and better stability of ocular surface than saline (385). Nutritional mitochondrial agentsNutritional mitochondrial agents: According to a review, a mitochondrial cocktail containing creatine monohydrate, CoQ10, and alpha-lipoic acid reduced lactate and markers of oxidative stress in patients with mitochondrial cytopathies (508). Omega-3 fatty acidsOmega-3 fatty acids: In human research, omega-3 fatty acids reduced the increased CoQ10 in plasma that occurred with CoQ10 supplementation (353). Ophthalmic agentsOphthalmic agents: In vitro, CoQ10 prevented apoptotic cell death in human lens epithelial cells; a reduction in oxidative stress and the stabilization of the BAX:Bcl-2 ratio played a role (492). In human research, combination topical treatment with CoQ10 and alpha-tocopheryl polyethylene glycol 1000 succinate following cataract surgery resulted in faster nerve regeneration and better stability of ocular surface than saline (385). Orthosiphon stamineusOrthosiphon stamineus: In human research, a combination of policosanol, red yeast rice extract, berberine, folic acid, and CoQ10 only reduced blood pressure when given in addition to Orthosiphon stamineus (506). P-glycoprotein regulated agentsP-glycoprotein regulated agents: Itagaki et al. published a report on the interaction of CoQ10 with the intestinal drug transporter glycoprotein (494). The authors indicate that CoQ10 affected the transport activity of p-glycoprotein. Respiratory agentsRespiratory agents: In patients with bronchial asthma, CoQ10 reduced the corticosteroids needed to control asthma symptoms (403). In patients with sleep apnea, an antioxidant cocktail containing CoQ10 reduced progressive augmentation and ventilatory long-term facilitation, which are normally enhanced in these patients (495). Red yeast rice (Monascus purpureus)Red yeast rice (Monascus purpureus): In a case report, Chinese red rice depleted muscle CoQ10 after discontinuation of statin treatment (509). SalicylatesSalicylates: In human research, effects of acetylsalicylic acid on CoQ10 were lacking in healthy volunteers (398). Thyroid agentsThyroid agents: In theory, CoQ10 may affect thyroid hormone levels, although this has not been proven in humans.Vitamin AVitamin A: In human research, CoQ10 was shown to increase plasma vitamin A levels (206). Vitamin B6Vitamin B6: In humans, a positive correlation existed between blood levels of CoQ10 and the percent saturation of erythrocyte glutamate oxaloacetate transaminase (EGOT) with pyridoxal phosphate (a measurement of B6 status) (510). Vitamin CVitamin C: In human research, CoQ10 was shown to increase plasma vitamin C levels (206). Vitamin EVitamin E: In human research, supplementation with d-alpha-tocopherol (vitamin E) attenuated the elevation of plasma CoQ10 concentration in patients given supplemental CoQ10 (511; 511). In vitro, alpha-tocopheryl succinate induced apoptosis in cancer cells by targeting ubiquinone-binding sites in the mitochondrial respiratory complex II (512). Piccinetti et al. discussed the interactions of CoQ and alpha-tocopherol in bilayer membranes (513). Further details are limited. Weight loss agentsWeight loss agents: In a case report, myopathy associated with chronic orlistat consumption was described (493). The role of CoQ10 is not clear. Coenzyme Q10/Food Interactions:
GeneralGeneral: In human research, food increased the absorption of idebenone (379). Elimination dietElimination diet: In human research, effects on CoQ10 levels were lacking following use of an elimination diet due to food sensitivities (514). Functional foods enriched with Sideritis euboeaFunctional foods enriched with Sideritis euboea: In human research, blood levels of CoQ10 increased following consumption of a functional food enriched with Sideritis euboea (515). GarlicGarlic: In firefighters with occupational stress, a mixture of CoQ10 and aged garlic extract resulted in an improvement of vascular elasticity and endothelial function (503). MargarineMargarine: In human research, use of a margarine made with oil made with a modified processing system to prevent loss of micronutrients resulted in an increase in CoQ10 levels (516). Mediterranean dietMediterranean diet: In human research, addition of CoQ10 to a Mediterranean diet resulted in a decreased postprandial total nitrite and protein carbonyl levels (517) and altered gene expression (518) compared with consumption of the Mediterranean diet alone. Monounsaturated fat-enriched dietMonounsaturated fat-enriched diet: In human research, effects on CoQ10 of a diet high in monounsaturated fat were lacking (519). Phenylketonuria (PKU) dietPhenylketonuria (PKU) diet: In human research, serum CoQ10 levels (ubiquinone-10) were reduced in PKU patients; this was likely due to the PKU diet (520). Artuch et al. discussed ubiquinone deficiency in PKU (521). Further details are lacking. SalmonSalmon: In pregnant women, CoQ10 levels decreased following salmon consumption twice weekly (391). Total parenteral nutritionTotal parenteral nutrition: In human research, use of total parenteral nutrition resulted in decreased levels of serum CoQ10 (522). Coenzyme Q10/Lab Interactions:
Beta-caroteneBeta-carotene: In human research, CoQ10 was shown to increase plasma beta-carotene (206). Blood glucoseBlood glucose: In human research, the effects of CoQ10 on blood glucose are conflicting. Although one study showed that CoQ10 reduced fasting and two-hour postprandial blood glucose concentrations in patients with diabetes (213), another study showed that CoQ10 did not have effects on blood glucose (216). CoQ10 reduced blood glucose in other studies of nondiabetic individuals (215). Blood pressureBlood pressure: In human research, CoQ10 lowered systolic and diastolic blood pressure (217; 267; 213; 219; 220; 221; 222; 223). Blood viscosityBlood viscosity: According to a review, CoQ10 decreases blood viscosity (41). Cardiovascular functionCardiovascular function: In human research, CoQ10 improved measures of cardiovascular functions, such as cardiac output (CO), cardiac index (CI), stroke volume (SV), ejection fraction (EF), end-diastolic volumes (EDV), stroke index, and EKG combined in most studies (294; 303; 302; 219; 183; 297; 295; 265; 300; 464; 305; 465); significant changes were lacking in most or all endpoints in some (264; 263; 221; 301; 208). In human research, CoQ10 supplementation caused a slight reduction in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (196). CD4/CD8CD4/CD8: In human research, CoQ10 increased the CD4:CD8 ratio in HIV patients (313). Coagulation panelCoagulation panel: According to case reports, CoQ10 may reduce the effectiveness of warfarin (201; 202). In human research, effects of acetylsalicylic acid on CoQ10 were lacking in healthy volunteers (398). Creatine kinaseCreatine kinase: In cardiovascular patients, CoQ10 reduced creatine kinase (308). Increased plasma creatine kinase with high-intensity exercise has been reported (384). Creatinine clearanceCreatinine clearance: In human research, CoQ10 was shown to increase creatinine clearance in chronic renal failure patients (352).CytokinesCytokines: In human peripheral blood mononuclear cells in vitro, CoQ10 decreased secretion of TNF-alpha and IL-2 (485). In women with pre-eclampsia, plasma levels of IL-18 were correlated with levels of reduced CoQ10 (527). In men, effects on IL-6, adiponectin, and TNF-alpha were lacking following supplementation with CoQ10 (528); however, IL-6 levels decreased in patients with coronary artery disease (526). In vitro, MitoQ suppressed the release of proinflammatory cytokines and increased production of IL-10 (37). DNA oxidationDNA oxidation: In human research, the effect of CoQ10 on DNA oxidation was examined (20). Further details are lacking. Free fatty acidsFree fatty acids: In human research, CoQ10 reduced postexercise levels of free fatty acids (529). HbA1cHbA1c: In human research, there were small decreases in HbA1c following CoQ10 supplementation (222; 223). HDL concentrationsHDL concentrations: In human research, CoQ10 significantly increased HDL cholesterol in patients with essential hypertension (319; 213). Heart rateHeart rate: In human research, CoQ10 decreased heart rate (220). HormonesHormones: In human research, CoQ10 decreased levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and increased levels of inhibin B and testosterone (323). ImmunoglobulinsImmunoglobulins: In human research, CoQ10 increased serum levels of IgG (479). Lactate dehydrogenase (LDH)Lactate dehydrogenase (LDH): According to a review, CoQ10 at doses of 300mg daily or greater may result in elevations in LDH concentrations (200). In heart patients, CoQ10 reduced LDH (308). LactateLactate: In human research, CoQ10 normalized ore reduced the lactate:pyruvate ratio in patients with mitochondrial myopathies (530; 272) and increased lactate levels in a patient with mitochondrial myopathy, encephalopathy, lactic acidemia, and strokelike episodes (531). In patients with myotonic dystrophy, there was a borderline inverse correlation between CoQ10 and lactate levels (68). In human research, CoQ10 decreased levels of cortical lactate in patients with Huntington's disease (532). In human research, CoQ10 was shown to decrease postexercise levels of lactate in patient with maternally inherited diabetes mellitus and deafness (533). Lipid panelLipid panel: In human research, positive, significant correlations were found between the ratio of LDL cholesterol to CoQ10 and the ratio of total to HDL cholesterol (534). In patients with congestive heart failure secondary to ischemic heart disease, CoQ10 increased HDL by 3% (297). In human research, CoQ10 decreased total cholesterol levels (319). Ninety milligrams of CoQ10 daily did not increase the oxidation resistance of VLDL/LDL fraction (535). In human research, CoQ10 was shown to reduce triglycerides (213). In human research, CoQ10 significantly increased HDL cholesterol in patients with essential hypertension (319; 213); however, decreased HDL cholesterol has also been shown (353). LipoproteinsLipoproteins: In human research, CoQ10 significantly decreased serum lipoprotein (a) (536; 322). Liver enzymesLiver enzymes: In animal research, MitoQ resulted in reduced levels of biochemical markers of acute liver dysfunction (37). In a clinical trial, elevated hepatic enzymes were reported in two subjects (240); however, CoQ10 improved liver enzyme markers in a clinical trial of patients with chronic hepatitis C infection (232). MyoglobinMyoglobin: In human research, CoQ10 decreased blood levels of myoglobin (231). PeroxidesPeroxides: In human seminal plasma and seminal fluid, there was an inverse correlation between ubiquinol content and hydroperoxide levels (476). In human research, CoQ10 decreased lipid peroxide levels (231). Plasma insulin concentrationsPlasma insulin concentrations: In human research, CoQ10 was shown to reduce fasting and two-hour plasma insulin in hypertensive patients with coronary artery disease (213). Plasma uric acidPlasma uric acid: In human research, CoQ10 decreased plasma uric acid levels in patients with chronic heart failure (297). Renal markersRenal markers: In animal research, MitoQ resulted in decreased levels of acute renal dysfunction markers (37). Serum transaminaseSerum transaminase: In human research, CoQ10 was shown to increase (210) or normalize (537) serum transaminase. Serum glutamic oxaloacetic transaminase (SGOT)Serum glutamic oxaloacetic transaminase (SGOT): In human research, CoQ10 at doses of 300mg daily or greater may result in elevations in SGOT concentrations (200). Sperm parametersSperm parameters: In seminal fluid and plasma, CoQ10 levels showed a significant correlation with sperm count and with sperm motility in nonvaricocele patients (474; 475; 476). In human research, CoQ10 resulted in improvements in sperm density, sperm motility, and sperm morphology (323). In human research, there were improvements in sperm motility, curvilinear velocity, straight progressive velocity, and forward motility (324). In vitro, CoQ10 increased motility in sperm from asthenospermic men (p<0.05 from a mean of 19.1% to 35.7%) (325). In human research, a combination of L-carnitine, acetyl-L-carnitine, fructose, citric acid, selenium, zinc, ascorbic acid, folic acid, cyanocobalamin, and CoQ10 increased sperm progressive motility (477). Thiobarbituric active reagent species (TBARS)Thiobarbituric active reagent species (TBARS): In human research, CoQ10 decreased TBARS (246). Total cholesterolTotal cholesterol: In human research, CoQ10 decreased total cholesterol levels (319). Ninety milligrams of CoQ10 daily did not increase the oxidation resistance of VLDL/LDL fraction (535). TriglyceridesTriglycerides: In human research, CoQ10 was shown to reduce triglycerides (213). Vitamin AVitamin A: In human research, CoQ10 was shown to increase plasma vitamin A levels (206). Vitamin B6Vitamin B6: In humans, a positive correlation existed between blood levels of CoQ10 and the percent saturation of erythrocyte glutamate oxaloacetate transaminase (EGOT) with pyridoxal phosphate (a measurement of B6 status) (510). Vitamin CVitamin C: In human research, CoQ10 was shown to increase plasma vitamin C levels (206). Vitamin EVitamin E: In human research, CoQ10 was shown to increase plasma vitamin E levels (206). White blood cell countWhite blood cell count: In human research, although the white blood cell count decrease from baseline after 12 weeks of treatment lacked statistical significance in the coenzyme Q10 group, the change was statistically significant when compared to the placebo group (269). Coenzyme Q10/Treatment Interactions:
Therapeutic hypothermiaTherapeutic hypothermia: In human research, CoQ10 combined with mild hypothermia immediately after cardiopulmonary resuscitation after cardiac arrest improved survival and neurological outcome in survivors (293).