Perspectives on therapy of cardiovascular diseases with coenzyme Q10 (ubiquinone).
A defective myocardial energy supply-due to lack of substrates and/or essential cofactors and a poor utilization efficiency of oxygen-may be a common final pathway in the progression of myocardial diseases of various etiologies. The vitamin-like essential substance coenzyme Q10, or ubiquinone, is a natural antioxidant and has a key role in oxidative phosphorylation. A biochemical rationale for using coenzyme Q10 as a therapy in heart disease was established years ago by Folkers and associates; however, this has been further strengthened by investigations of viable myocardial tissue from the author's series of 45 patients with various cardiomyopathies. Myocardial tissue levels of coenzyme Q10 determined by high-performance lipid chromatography were found to be significantly lower in patients with more advanced heart failure compared with those in the milder stages of heart failure. Furthermore, the myocardial tissue coenzyme Q10 deficiency might be restored significantly by oral supplementation in selected cases. In the author's open clinical protocol study with coenzyme Q10 therapy (100 mg daily) nearly two-thirds of patients revealed clinical improvement, most pronounced in those with dilated cardiomyopathy. Double-blind placebo-controlled trials have definitely confirmed that coenzyme Q10 has a place as adjunctive treatment in heart failure with beneficial effects on the clinical outcome, the patients' physical activity, and their quality of life. The positive results have been above and beyond the clinical status obtained from treatment withtraditional principles-including angiotensin-converting enzyme inhibitors.
Clin Investig 1993;71(8 Suppl):S116-23
Isolated diastolic dysfunction of the myocardium and its response to CoQ10 treatment.
Symptoms of fatigue and activity impairment, atypical precordial pain and cardiac arrhythmia frequently precede by years the development of congestive heart failure. Of 115 patients with these symptoms, 60 were diagnosed as having hypertensive cardiovascular disease, 27 mitral valve prolapse syndrome, and 28 chronic fatigue syndrome. These symptoms are common with diastolic dysfunction, and diastolic function is energy dependent. All patients had blood pressure, clinical status, coenzyme Q10 (CoQ10) blood levels and echocardiographic measurement of diastolic function, systolic function and myocardial thickness recorded before and after CoQ10 replacement. At control, 63 patients were functional class III and 54 class II; all showed diastolic dysfunction; the mean CoQ10 blood level was 0.855 micrograms/ml; 65%, 15% and 7% showed significant myocardial hypertrophy, and 87%, 30% and 11% had elevated blood pressure readings in hypertensive disease, mitral valve prolapse and chronic fatigue syndrome, respectively. Except for higher blood pressure levels and more myocardial thickening in the hypertensive patients, there was little difference between the three groups. CoQ10 administration resulted in improvement in all; reduction in high blood pressure in 80%, and improvement in diastolic function in all patients with follow-up echocardiograms to date; a reduction in myocardial thickness in 53% of hypertensives and 36% of the combined prolapse and fatigue syndrome groups; and a reduced fractional shortening in those high at control and an increase in those initially low.
Clin Investig 1993;71(8 Suppl):S140-4
Pronounced increase of survival of patients with cardiomyopathy when treated with coenzyme Q10 and conventional therapy.
During 1982 to 1986, 43/137 patients with cardiomyopathy, Classes II, III and IV, had ejection fractions (EF) below 40%, and a mean EF of 25.1 +/- 10.3%. During treatment of these 43 patients with coenzyme Q10 (CoQ10), EF increased to 41.6 +/- 14.3% (p less than 0.001) over a mean period of three months (range, two to four months). At four subsequent periods up to 36 months EF ranged from 43.1 +/- 13.3 to 49.7 +/- 6.4% (each period, p less than 0.001). The mean CoQ10 control blood level was 0.85 +/- 0.26 micrograms/ml, which increased on treatment to 1.7 to 2.3 micrograms/ml for five periods up to 36 months (each period, p less than 0.001). The survival rates for all 137 patients treated with CoQ10 and for the 43 patients with EF below 40% were both about 75%/46 months. These two survival rates were comparable between 24 and 46 months, which is of extraordinary significance and importance when compared to survival of about 25%/36 months for 182 patients with EF below 46% on conventional therapy without CoQ10. The improved cardiac function and pronounced increase of survival show that therapy with CoQ10 is remarkably beneficial due to correction of CoQ10 deficiency in mechanisms of bioenergetics.
Int J Tissue React 1990;12(3):163-8
Low molecular weight antioxidants and their role in skin aging.
There is increasing evidence that reactive oxygen species play a pivotal role in the process of aging. The skin, as the outermost barrier of the body, is exposed to various exogenous sources of oxidative stress, in particular UV-irradiation. These are believed to be responsible for the extrinsic type of skin aging, termed photo-aging. It therefore seems reasonable to try to increase levels of protective low molecular weight antioxidants through a diet rich in fruits and vegetables or by direct topical application. Indeed, various in vitro and animal studies have proved that low molecular weight antioxidants, especially vitamins C and E, ascorbate and tocopherol, as well as lipoic acid, exert protective effects against oxidative stress. However, controlled long-term studies on the efficacy of low molecular weight antioxidants in the prevention or treatment of skin aging in humans are still lacking.
Clin Exp Dermatol 2001 Oct;26(7):578-82
Photoaging is associated with protein oxidation in human skin in vivo.
There is increasing evidence for the generation of reactive oxygen species in skin upon ultraviolet exposure, but little is known about their pathophysiologic relevance in human skin in vivo. We hypothesized that chronic and acute photodamage is mediated by depleted antioxidant enzyme expression and increased oxidative protein modifications. Biopsies from patients with histologically confirmed solar elastosis, from non-ultraviolet-exposed sites of age-matched controls, and from young subjects were analyzed. To evaluate the influence of acute ultraviolet exposures, buttock skin of 12 healthy subjects was irradiated repetitively on 10 d with a solar simulator and compared intra-individually to non-ultraviolet-treated contralateral sites. The antioxidant enzymes catalase, copper-zinc superoxide dismutase and manganese superoxide dismutase were investigated by immunohistochemistry. Protein carbonyls were analyzed by immunohistochemical and immunoblotting techniques in human skin and in cell models. Whereas overall expression of antioxidant enzymes was very high in the epidermis, low baseline levels were found in the dermis. In photoaged skin, a significant depletion of antioxidant enzyme expression was observed within the stratum corneum and in the epidermis. Importantly, an accumulation of oxidatively modified proteins was found specifically within the upper dermis of photoaged skin. Upon acute ultraviolet exposure of healthy subjects, depleted catalase expression and increased protein oxidation were detected. Exposures of keratinocytes and fibroblasts to ultraviolet B, ultraviolet A and H2O2 led to dose-dependent protein oxidation and thus confirmed in vivo results. In conclusion, the correlation between photodamage and protein oxidation was demonstrated for the first time, which hence may be a relevant pathophysiologic factor in photoaging.
J Invest Dermatol 2002 Apr;118(4):618-25
Double-blind, half-face study comparing topical vitamin C and vehicle for rejuvenation of photodamage.
BACKGROUND: Aging of the population, in particular the "baby boomers," has resulted in increased interest in methods of reversal of photodamage. Non-invasive treatments are in high demand, and our knowledge of mechanisms of photodamage to skin, protection of the skin and repair of photodamage are becoming more sophisticated and complex. OBJECTIVE: The objective of this study is to determine if the topical use of a vitamin C preparation can stimulate the skin to repair photodamage and result in clinically visible differences, as well as microscopically visible improvement. METHODS: Ten patients applied in a double-blind manner a newly formulated vitamin C complex having 10% ascorbic acid (water soluble) and 7% tetrahexyldecyl ascorbate (lipid soluble) in an anhydrous polysilicone gel base to one-half of the face and the inactive polysilicone gel base to the opposite side. Clincial evaluation of wrinkling, pigmentation, inflammation and hydration was performed prior to the study and at weeks 4, 8 and 12. Two mm punch biopsies of the lateral cheeks were performed at 12 weeks in four patients and stained with hematoxylin and eosin, as well as in situhybridization studies using an anti-sense probe for mRNA for type I collagen. A questionnaire was also completed by each patient. RESULTS: A statistically significant improvement of the vitamin C-treated side was seen in the decreased photoaging scores of the cheeks (P = 0.006) and the peri-oral area (P = 0.01). The peri-orbital area improved bilaterally, probably indicating improved hydration. The overall facial improvement of the vitamin C side was statistically significant (P = 0.01). Biopsies showed increased Grenz zone collagen, as well as increased staining for mRNA for type I collagen. No patients were found to have any evidence of inflammation. Hydration was improved bilaterally. Four patients felt that the vitamin C-treated side improved unilaterally. No patient felt the placebo side showed unilateral improvement. CONCLUSION: This formulation of vitamin C results in clinically visible and statistically significant improvement in wrinkling when used topically for 12 weeks. This clinical improvement correlates with biopsy evidence of new collagen formation.
Dermatol Surg 2002 Mar;28(3):231-6