ken
Well-known member
http://wwwcsi.unian.it/coenzymeQ/overview.html
Controlled Trials in Cardiovascular Surgery
The first controlled study evaluating the effectiveness of CoQ10, administered preoperatively, was published by Tanaka et al. in 1982 [77]. Fifty patients undergoing heart valve replacement were randomized to receive either placebo or CoQ10 at a dose of 30-60 mg per day for six days before surgery. The treatment group showed a significantly lower incidence of low cardiac output state during the postoperative recovery period. In 1991, Sunamori et al. studied 78 patients undergoing coronary artery bypass graft surgery [74]. Sixty of these patients were given 5 mg per/kg of CoQ10 intravenously two hours prior to cardiopulmonary bypass. Postoperatively, there was a significant benefit to left ventricular stroke work index in the CoQ10 treated group as compared to controls and a significant decrease in postoperative CPK MB measurements in the treated group. In 1993, Judy et al. studied 20 patients undergoing either coronary artery bypass surgery (16 patients) or combined bypass surgery with valve replacement (4 patients) [27]. Patients were randomized to receive either placebo or administration of oral 100 mg per day of CoQ10 for 14 days prior to surgery and continued for 30 days postoperatively. The treatment group showed significant elevations not only in blood CoQ10 level but also in myocardial tissue CoQ10 content as measured in atrial appendage. Significant improvement in postoperative cardiac index and left ventricular ejection fraction were noted in the treatment group, and a significant shortening of the postoperative recovery time was observed. In 1994, Chello et al. randomized 40 patients to receive either placebo or 150 mg per day of oral CoQ10 one week prior to coronary artery bypass graft surgery [6]. A significant decrease in postoperative markers of oxidative damage was observed in the treatment group with lower concentrations of coronary sinus thiobarbituric acid reactive substances, conjugated dienes and cardiac isoenzymes of creatine kinase. The treatment group also showed a significantly lower incidence of ventricular arrhythmias in the recovery period and the mean dose of dopamine required to maintain stable hemodynamics was significantly lower in the CoQ10 treated group. In 1994, Chen et al. randomized 22 patients to receive either CoQ10 or placebo prior to coronary artery bypass surgery and observed improvement in left atrial pressure and an improvement in the incidence of low cardiac output state in the postoperative period [8]. Right and left ventricular myocardial ultrastructure was better preserved in the CoQ10 treated group as compared to placebo. In 1996, Chello randomized 30 patients to receive either placebo or 150 mg oral CoQ10 for 7 days before abdominal aortic surgery and documented a significant decrease in markers of peroxidative damage in the CoQ10 treated patients [7]. In 1996 Taggart et al. randomized 20 patients undergoing coronary revascularization surgery to receive either placebo or 600 mg of oral CoQ10 12 hours prior to operation with no significant effects observed, confirming the lack of acute pharmacologic or clinical changes with CoQ10 [76]. Typically, oral CoQ10 supplementation rarely causes measurable effect before one week and is not maximal for several months.
Conclusions
In summary, coenzyme Q10 is a deceptively simple molecule which lies at the center of mitochondrial ATP production and appears to have clinically relevant antioxidant properties manifested by tissue protection in settings of ischemia and reperfusion. Congestive heart failure has served as a model for measurable deficiency of CoQ10 in blood and tissue, which when corrected, results in improved myocardial function. Ischemic heart disease, anginal syndromes, and most recently the ischemia reperfusion injury of coronary revascularization has provided clear evidence of clinically relevant antioxidant cell protective effects of CoQ10. Newer P31 NMR spectroscopy studies such as those conducted by Whitman's group in Philadelphia have documented enhanced cellular high energy phosphate concentrations with CoQ10 supplementation in models of ischemia and reperfusion [13]. Sophisticated biochemical markers of oxidative injury are now demonstrating in-vivo the antioxidant cell protective effects of CoQ10. Upon review of the 30 years of clinical publications on CoQ10 and the author's own clinical experience, it is clear that there are several consistent and unique characteristics of the clinical effects of CoQ10 supplementation which are worthy of discussion and may for simplicity be termed the "Q effect". The benefits of CoQ10 supplementation are likely not due solely to a correction of deficiency in so far as clinical improvements are frequently seen in patients with "normal" pre-treatment CoQ10 blood levels and optimum clinical benefit requires above normal CoQ10 blood levels (2 to 4 times higher). High blood levels may be required to attain an elevation of tissue CoQ10 levels or to rescue defective mitochondrial function perhaps by driving cytosolic glycolysis or the plasma membrane oxidoreductase or by directly enhancing the function of defective mitochondria. There is almost always a delay in the onset of clinical change of one to four weeks and a further delay in maximal clinical benefit of several months. Possible reasons for this delay include time to attain adequate tissue levels of CoQ10 or time to synthesize CoQ10-dependent apoenzymes. Supplemental CoQ10 appears to affect much more than just cardiac myocytes and many aspects of patients' health tend to improve which cannot be explained by the observed improvement in heart function. CoQ10 does not lend itself to traditional organ-specific or disease-specific strategy and requires a reassessment and a rethinking of medical theory and practice. The combination of the ready availability of pure crystalline CoQ10 in quantity from the Japanese pharmaceutical industry and increasingly sophisticated and standardized methodology to directly measure CoQ10 in both blood and tissue, brings us to a point where we can more readily and accurately expand upon the preceding 30 years of pioneering clinical work on this extraordinary molecule.
Controlled Trials in Cardiovascular Surgery
The first controlled study evaluating the effectiveness of CoQ10, administered preoperatively, was published by Tanaka et al. in 1982 [77]. Fifty patients undergoing heart valve replacement were randomized to receive either placebo or CoQ10 at a dose of 30-60 mg per day for six days before surgery. The treatment group showed a significantly lower incidence of low cardiac output state during the postoperative recovery period. In 1991, Sunamori et al. studied 78 patients undergoing coronary artery bypass graft surgery [74]. Sixty of these patients were given 5 mg per/kg of CoQ10 intravenously two hours prior to cardiopulmonary bypass. Postoperatively, there was a significant benefit to left ventricular stroke work index in the CoQ10 treated group as compared to controls and a significant decrease in postoperative CPK MB measurements in the treated group. In 1993, Judy et al. studied 20 patients undergoing either coronary artery bypass surgery (16 patients) or combined bypass surgery with valve replacement (4 patients) [27]. Patients were randomized to receive either placebo or administration of oral 100 mg per day of CoQ10 for 14 days prior to surgery and continued for 30 days postoperatively. The treatment group showed significant elevations not only in blood CoQ10 level but also in myocardial tissue CoQ10 content as measured in atrial appendage. Significant improvement in postoperative cardiac index and left ventricular ejection fraction were noted in the treatment group, and a significant shortening of the postoperative recovery time was observed. In 1994, Chello et al. randomized 40 patients to receive either placebo or 150 mg per day of oral CoQ10 one week prior to coronary artery bypass graft surgery [6]. A significant decrease in postoperative markers of oxidative damage was observed in the treatment group with lower concentrations of coronary sinus thiobarbituric acid reactive substances, conjugated dienes and cardiac isoenzymes of creatine kinase. The treatment group also showed a significantly lower incidence of ventricular arrhythmias in the recovery period and the mean dose of dopamine required to maintain stable hemodynamics was significantly lower in the CoQ10 treated group. In 1994, Chen et al. randomized 22 patients to receive either CoQ10 or placebo prior to coronary artery bypass surgery and observed improvement in left atrial pressure and an improvement in the incidence of low cardiac output state in the postoperative period [8]. Right and left ventricular myocardial ultrastructure was better preserved in the CoQ10 treated group as compared to placebo. In 1996, Chello randomized 30 patients to receive either placebo or 150 mg oral CoQ10 for 7 days before abdominal aortic surgery and documented a significant decrease in markers of peroxidative damage in the CoQ10 treated patients [7]. In 1996 Taggart et al. randomized 20 patients undergoing coronary revascularization surgery to receive either placebo or 600 mg of oral CoQ10 12 hours prior to operation with no significant effects observed, confirming the lack of acute pharmacologic or clinical changes with CoQ10 [76]. Typically, oral CoQ10 supplementation rarely causes measurable effect before one week and is not maximal for several months.
Conclusions
In summary, coenzyme Q10 is a deceptively simple molecule which lies at the center of mitochondrial ATP production and appears to have clinically relevant antioxidant properties manifested by tissue protection in settings of ischemia and reperfusion. Congestive heart failure has served as a model for measurable deficiency of CoQ10 in blood and tissue, which when corrected, results in improved myocardial function. Ischemic heart disease, anginal syndromes, and most recently the ischemia reperfusion injury of coronary revascularization has provided clear evidence of clinically relevant antioxidant cell protective effects of CoQ10. Newer P31 NMR spectroscopy studies such as those conducted by Whitman's group in Philadelphia have documented enhanced cellular high energy phosphate concentrations with CoQ10 supplementation in models of ischemia and reperfusion [13]. Sophisticated biochemical markers of oxidative injury are now demonstrating in-vivo the antioxidant cell protective effects of CoQ10. Upon review of the 30 years of clinical publications on CoQ10 and the author's own clinical experience, it is clear that there are several consistent and unique characteristics of the clinical effects of CoQ10 supplementation which are worthy of discussion and may for simplicity be termed the "Q effect". The benefits of CoQ10 supplementation are likely not due solely to a correction of deficiency in so far as clinical improvements are frequently seen in patients with "normal" pre-treatment CoQ10 blood levels and optimum clinical benefit requires above normal CoQ10 blood levels (2 to 4 times higher). High blood levels may be required to attain an elevation of tissue CoQ10 levels or to rescue defective mitochondrial function perhaps by driving cytosolic glycolysis or the plasma membrane oxidoreductase or by directly enhancing the function of defective mitochondria. There is almost always a delay in the onset of clinical change of one to four weeks and a further delay in maximal clinical benefit of several months. Possible reasons for this delay include time to attain adequate tissue levels of CoQ10 or time to synthesize CoQ10-dependent apoenzymes. Supplemental CoQ10 appears to affect much more than just cardiac myocytes and many aspects of patients' health tend to improve which cannot be explained by the observed improvement in heart function. CoQ10 does not lend itself to traditional organ-specific or disease-specific strategy and requires a reassessment and a rethinking of medical theory and practice. The combination of the ready availability of pure crystalline CoQ10 in quantity from the Japanese pharmaceutical industry and increasingly sophisticated and standardized methodology to directly measure CoQ10 in both blood and tissue, brings us to a point where we can more readily and accurately expand upon the preceding 30 years of pioneering clinical work on this extraordinary molecule.
