A Clinical Study of the Effect of Coenzyme Q on Congestive Heart Failure Taro
ISHIYAMA,
TOYAMA,
M.D.,
M.D.,*
TSUKAMOTO,
Yoshiharu Toru
M.D.,**
Masaaki Yuichi
MORITA,
YAMAGAMI, Noboru
OHKUBO,
WADA,
M.D.,***
YAMAMURA,
M.D.,
M.D.,*
Seiichi
Nozomu M.D.,***
and
M.D.
SUMMARY Expecting activation of myocardial energy liberation, coenzyme Q was applied as a treatment to 55 patients suffering from congestive heart failure. Daily doses of 50 to 100mg of coenzyme Q7 were injected intravenously in 21 cases for 3 to 35 days. Daily doses of 60mg of coenzyme Q7 were administered perorally in 17 cases for 14 to 196 days. Daily doses of 30mg of coenzyme Q10 were administered perorally in 17 cases for 7 to 182 days. Clinical effects were evaluated within 4 weeks by the criteria using a scoring method of severity of congestive heart failure which was devised by the authors. In summary a certain effect was found in 20 cases and a mild effect was observed in 29 cases. No significant changes were observed in heart rate and blood pressure. Exanthema appeared in 2 patients of the group of coenzyme Q7 intravenous injection. In conclusion the therapeutic effect of coenzyme Q was thought to be mild but stable in supplement to digitalis therapy in cases of congestive heart failure. Additional Indexing Words: Activation of myocardial energy liberation Coenzyme Q7 and Q10 Intravenous injection Peroral administration A scoring method to evaluate severity of congestive heart failure
ECENTLY clinical application of substances affecting to myocardial energy metabolism such as vitamin B complexes, adenosine triphosphate or its precursors, cytochrome C, and some metabolites has revealed a certain effect in therapeutics of cardiac diseases. Coenzyme Q was isolated by Crane and his coworkers and it was evidenced to localize mainly in mitochondria of subcellular fraction and to play an important role in oxidative Fromthe Third Department of InternalMedicine,OsakaUniversity MedicalSchool,Osaka. *The CenterforAdultDiseases , Osaka **Departmentof InternalMedicine, Nishinomiya CityCentralHospital , Nishinomiya ***KobeShoseiHospital , Kobe ReceivedforpublicationApril19,1975. 32
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ISHIYAMA, ET AL.
33
phosphorylation in the electron transfer system.1) Therefore it was expected to reveal a same kind of effect in biomedical or clinical field. Although actions of these substances administered exogenously are difficult to prove directly in clinical cases, the effect of these substances on cardiac dysfunctions is able to be evaluated clinically. In congestive heart failure myocardial energy liberation is considered to be impaired secondarily because of continuous relative reduction of coronary blood supply as well as relative increase of oxygen demand. It is expected that exogenous coenzyme Q acts a role of trigger to activate deteriorated mitochondrial energy liberation. This expected action is thought to reveal a different kind of effect when compared with that of digitalis or diuretics. According to the above-mentioned concept, a clinical trial was attempted to apply coenzyme Q to cases of congestive heart failure. SUBJECTS ANDMETHODS Subjects were 21 inpatients and 34 outpatients suffering from congestiveheart failure. Underlying diseaseswere valvular diseases,congenital heart diseases,hypertension, arteriosclerosis,pulmonary diseases, and primary myocardial diseases. Classificationsof cardiac function before the treatment were the second grade of NYHA in almost all cases and the third grade in a few cases. Preceding the start of the treatment, all patients were observedat least 1 week either without medication or continuing the same medication hitherto. Table
I.
A
Proposed
Scoring
Method
of
Severity
of
Congestive
Heart
Failure
34
EFFECT OF COENZYME Q ON CONGESTIVE HEART FAILURE
Jap. Heart J. January, 1976
Subjects were divided into the following 3 groups according to the difference of the treatment: IntravenouscoenzymeQ7 group: included 21 inpatients. The grade of congestive heart failure was more severe in average in this group than the other 2 groups. Daily doses of 50 to 100mg of coenzyme Q7 was injected intravenously for 3 to 35 days. Table
*Prescription sufficiency,
was not changed MI:
mitral
from
insufficiency,
at least AI:
one week
aortic
before
insufficiency.
II.
Results
of Treatment:
the start of the treatment
until
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ISHIYAMA, ET AL.
35
Peroral coenzymeQ7 group: included 17 outpatients. Coenzyme Q7 was administered perorally 50 to 100mg daily to all cases except 1 case for 14 to 196 days. Peroral coenzymeQ10 group: included 17 outpatients. Coenzyme Q10 was administered perorally 30mg daily to all cases for 7 to 182 days. Subjects were classified randomly into the 2 peroral groups. Although combined use of other drugs was not restricted, alternation of prescripIntravenous Coenzyme Q7 Group
the judgment of effects, **fb: finger breadth,
MS: mitral
stenosis ,
MSI: mitral stenoin-
36 tion
was
date
of
start
of
reveal
prohibited
strictly
evaluation the
of
A
as
the was
substances
slowly
were
devised and
shown
of
ment
effect
than
start
as
other
of
judged
the
treatment
within
coenzyme
4
Q
prevalent
drugs
weeks
were
until
the
after
the
considered
which
had
to
a certain
action.
in
expressed
ferences
before
The such
more
method
Symptoms
scores
1 week
effect.
because
action
scoring
effect.
since
the
treatment,
metabolic
pharmacological
was
Jap. Heart J. January, 1976
EFFECT OF COENZYME Q ON CONGESTIVE HEART FAILURE
by
signs
Table
of
I.
Severity
quantitatively the
total
evaluated
(TOTAL
by
scores as
the
authors
congestive
the
before
the
of total
was
adopted
heart congestive of
each
and
the
order
were
heart
scores
treatment
in
failure
failure
in
symptoms total
to
graded
evaluate and
individual and
scores
after
the
assigned cases
signs.
Dif-
the
treat-
follows:
SCOREbefore
treatment)-(TOTAL
SCOREafter
treatment)•†4
as
"ef-
fective", "mildly
3•†(TOTAL effective"
SCOREbefore
treatment)-(TOTAL
SCOREafter
treatment)•†1
as
, and (TOTAL
SCOREbefore
treatment)-(TOTAL
SCOREafter
treatment)•…0
as
"in-
effective". Heart ment.
Daily
rate
and amount
blood of
pressure urine
was
were
also
recorded
checked on
the
before all
and
after
the
treat-
inpatients.
RESULTS 1. Intravenous Coenzyme Q7 Group Results were summarized in Table II.
Fig.1.
Changes
of heart
rate
before
"Effectives"
and
after
the
treatment.
were found in 10
Vol.17 No.1
ISHIYAMA, ET AL.
cases.
"Mildly
effectives"
were
cases.
As shown
in Fig.1,
changes
ency
after
the
treatment.
in
7 cases,
and"
of heart
Changes
37
rate
of blood
ineffectives"
showed
pressure
no were
were
consistent not
remarkable.
Fig.2. Changes of daily amount of urine before and after the treatment in cases of the inpatients (intravenous coenzyme Q7 group).
Fig.3. before mean
and total
Changes after scores
the
of
total
scores
treatment.
before
and
The after
of severity thick
treatments.
lines
of
congestive represent
heart changes
failure of
in tend-
the
4
38
EFFECT OF COENZYME Q ON CONGESTIVE HEART FAILURE
Jap. Heart J. January, 1976
Vol.17 No.1
ISHIYAMA, ET AL.
39
40
EFFECT OF COENZYME Q ON CONGESTIVE HEART FAILURE
Fig.2
shows
ment.
changes
More
Changes
of
the of
observed
easily
by
Results cases, As
shown
in
the
1.7)
were
as
a whole
lower
dominant
signs.
was
"mildly
but
were
not
all
dominant of
than
those
side
severe.
treat-
of
urine. Fig.3.
exanthema
It
disappeared
heart
rate
subjects
the
in
the
all
7
2 cases. treatof
the
outpatients
deviation=3.6•} coenzyme
Q7
improvement
of
disappearance
peroral from
after
were
intravenous
showed
that
in
Changes
(mean•}standard of
found
were
remarkable.
(p