LE Magazine January 2003
CoQ10
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
Skin aging
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
Continued on Page 2 of
2
Back to
the Magazine Forum
|