Benefits of CoenzymeQ10 in Treatment of
Mitochondrial and Neuromuscular Diseases:
Since the discovery of
the first genetic disease of the mitochondria in 1988, the number of
recognized mitochondrial diseases has ballooned. These diseases present
extraordinarily complicated genetic and clinical pictures that cut
across established diagnostic categories. They primarily affect the
brain, nerve, muscle, heart, kidney and endocrine system, whose high
energy requirements can no longer be fully met. In addition, a wide
range of degenerative diseases have been found to involve one or more of
hundreds of known mitochondrial mutations.
Patients with genetic
Coenzyme Q10 deficiency may suffer dysfunctions in brain, nerve and
muscle, often including exertional fatigue and seizures. Such patients
appear to respond to Coenzyme Q10 supplementation, but observations are
limited since diagnosis of this disorder is in its infancy. Coenzyme Q10
deficiency is one of the mitochondrial diseases caused by mutations in
non-mitochondrial DNA, that is DNA in the cell nucleus.
Case reports and pilot
studies have found that some patients with mitochondrial diseases
respond to long-term Coenzyme Q10 therapy. For example, promising
results have been reported in MELAS, Kearns-Sayre syndrome and
maternally inherited diabetes with deafness. An Italian study
demonstrated the impact of Coenzyme Q10 therapy on the living tissue of
six patients with mitochondrial cytopathies. They measured the
bioenergetic activity in the brain and skeletal muscle of the patients
using high-technology diagnostic equipment (phosphorus magnetic
resonance spectroscopy). After six months of Coenzyme Q10 therapy at 150
mg per day, brain bioenergetics returned to normal in all patients, and
skeletal muscle energetics improved significantly. A new study applies
this diagnostic technology to Friedrich’s Ataxia, which is characterized
by a deficiency of a mitochondrial protein called frataxin recently
discovered to activate cellular respiration. The study found that
supplementation with Coenzyme Q10 plus vitamin E brought a “dramatic
improvement of cardiac and skeletal muscle bioenergetics. . . after only
three months of therapy” (Lodi R et al., 2001)1.
A just-published study of familial ataxias with no known genetic cause
reports that Coenzyme Q10 supplementation improved patients’ scores by
25% on a scale measuring balance, speech and movement. The five patients
who could not walk at the beginning of the trial were able to walk with
some assistance after supplementation (dose levels varied).
Since all cells (except
red blood cells) contain mitochondria, mitochondrial diseases tend to
affect multiple body systems. Of course some organs and tissues depend
more than others upon the energy the mitochondria produce.
At the genetic level,
the picture is more complex. The level of inherited mitochondrial DNA
defects may establish an individual’s “bioenergetic baseline.” As
additional mitochondrial DNA defects develop over the course of a
lifetime, bioenergetic capacity may decline until thresholds are crossed
where organs malfunction or become susceptible to degeneration.
Another genetic
complication is that each mitochondrion contains many copies of
mitochondrial DNA, and each cell and tissue contains many mitochondria.
At both these levels, there may be many different defects in different
copies of the mitochondrial genome. This is especially true of the
defects that cause clinical pathologies.
For a particular tissue
or organ to become dysfunctional, a critical number of its mitochondrial
DNA’s must be mutated. This is called the “threshold effect.” Each organ
or tissue is more susceptible to some mutations than others and has its
own particular mutational threshold, energy requirement and sensitivity
to oxidative stress. All these factors combine to determine how it will
respond to genetic damage. The picture is further complicated by
interactions between DNA in mitochondria and in the cell nucleus. The
result is that the same mitochondrial DNA mutations can produce
remarkably different symptoms in members of the same family, while
different mutations can produce the same symptoms.
Some of the specific
mitochondrial mutations found in mitochondrial diseases develop
spontaneously in the aged. More generally, the picture we have sketched
of mitochondrial disease illuminates the consequences of Linnane’s
theory: it helps explain how mitochondrial mutation-driven bioenergetic
decline can have such varied and complex effects over the course of
aging.
There is a
heterogeneous group of neuromuscular disorders whose exact cause and
effective treatment remain largely unknown. These include muscular
dystrophy, some encephalomyopathies and various neurogenic atrophies.
Several small trials and case reports suggest that some patients with
these diseases respond to Coenzyme Q10 therapy.
Coenzyme Q10 pioneer
Karl Folkers observed that cardiovascular disorders are associated with
these conditions, as might be expected if cellular energy production
were impaired. He therefore conducted a double-blind trial to assess the
effect of Coenzyme Q10 on cardiac performance in patients with muscular
dystrophies and neurogenic atrophies. After three months of treatment
with 100 mg of Coenzyme Q10 per day, cardiac function was significantly
improved in all patients and half the patients showed distinct
improvement in movement and exercise capacity. Folkers hypothesized that
these conditions have in common a deficiency of Coenzyme Q10.
By the same token,
mitochondrial defects may contribute to heart disease in some patients.
A recent study of dilated cardiomyopathy found that about one in four
patients had pathological mutations in the mitochondrial DNA of heart
tissue.
See References
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