INTRODUCTION TO COENZYME
Q10
By PETER H. LANGSJOEN, M.D., F.A.C.C.
Permission is granted to reproduce this material for noncommercial
use provided that the text, author's name, and copyright
statement are not changed in any way.
DEFINITION
Coenzyme Q10 (CoQ 10) or ubiquinone is essentially a vitamin
or vitamin-like substance. Disagreements on nomenclature
notwithstanding, vitamins are defined as organic compounds
essential in minute amounts for normal body function acting
as coenzymes or precursors to coenzymes. They are present
naturally in foods and sometimes are alsosynthesized in
the body. CoQ10 likewise is found in small amounts in a
wide variety of foods and is synthesized in all tissues.
The biosynthesis of CoQ10 from the amino acid tyrosine is
a multistage process requiring at least eight vitamins and
several trace elements. Coenzymes are cofactors upon which
the comparatively large and complex enzymes absolutely depend
for their function. Coenzyme Q10 is the coenzyme for at
least three mitochondrial enzymes (complexes I, II and III)
as well as enzymes in other parts of the cell. Mitochondrial
enzymes of the oxidative phosphorylation pathway are essential
for the production of the high-energy phosphate, adenosine
triphosphate (ATP), upon which all cellular functions depend.
The electron and proton transfer functions of the quinone
ring are of fundamental importance to all life forms; ubiquinone
in the mitochondria of animals, plastoquinone in the chloroplast
of plants, and menaquinone in bacteria. The term "bioenergetics"
has been used to describe the field of biochemistry looking
specifically at cellular energy production. In the related
field of free radical chemistry, CoQ10 has been studied
in its reduced form (Fig. 1) as a potent antioxidant.
The bioenergetics and free radical chemistry of CoQ10 are
reviewed in Gian Paolo Littarru's book, Energy and Defense,
published in 1994(1).
HISTORY
CoQ10 was first isolated from beef heart mitochondria by
Dr. Frederick Crane of Wisconsin, U.S.A., in 1957 (2). The
same year, Professor Morton of England defined a compound
obtained from vitamin A deficient rat liver to be the same
as CoQ10(3). Professor Morton introduced the name ubiquinone,
meaning the ubiquitous quinone. In 1958, Professor Karl
Folkers and coworkers at Merck, Inc., determined the precise
chemical structure of CoQ10: 2,3 dimethoxy-5 methyl-6 decaprenyl
benzoquinone (Fig. 1), synthesized it, and were the first
to produce it by fermentation. In the mid-1960's, Professor
Yamamura of Japan became the first in the world to use coenzyme
Q7 (a related compound) in the treatment of human disease:
congestive heart failure. In 1966, Mellors and Tappel showed
that reduced CoQ6 was an effective antioxidant (4,5). In
1972 Gian Paolo Littarru of Italy along with Professor Karl
Folkers documented a deficiency of CoQ10 in human heart
disease (6). By the mid-1970's, the Japanese perfected the
industrial technology to produce pure CoQ10 in quantities
sufficient for larger clinical trials. Peter Mitchell received
the Nobel Prize in 1978 for his contribution to the understanding
of biological energy transfer through the formulation of
the chemiosmotic theory, which includes the vital protonmotive
role of CoQ10 in energy transfer systems (7,8,9,10).
In the early 1980's, there was a considerable acceleration
in the number and size of clinical trials. These resulted
in part from the availability of pure CoQ10 in large quantities
from pharmaceutical companies in Japan and from the capacity
to directly measure CoQ10 in blood and tissue by high performance
liquid chromatography. Lars Ernster of Sweden, enlarged
upon CoQ10's importance as an antioxidant and free radical
scavenger (11). Professor Karl Folkers went on to receive
the Priestly Medal from the American Chemical Society in
1986 and the National Medal of Science from President Bush
in 1990 for his work with CoQ10 and other vitamins.
COENZYME Q10 DEFICIENCY
Normal blood and tissue levels of CoQ10 have been well
established by numerous investigators around the world.
Significantly decreased levels of CoQ10 have been noted
in a wide variety of diseases in both animal and human studies.
CoQ10 deficiency may be caused by insufficient dietary CoQ10,
impairment in CoQ10 biosynthesis, excessive utilization
of CoQ10 by the body, or any combination of the three. Decreased
dietary intake is presumed in chronic malnutrition and cachexia(12).
The relative contribution of CoQ10 biosynthesis versus
dietary CoQ10 is under investigation. Karl Folkers takes
the position that the dominant source of CoQ10 in man is
biosynthesis. This complex, 17 step process, requiring at
least seven vitamins (vitamin B2 - riboflavin, vitamin B3
- niacinamide, vitamin B6, folic acid, vitamin B12, vitamin
C, and pantothenic acid) and several trace elements, is,
by its nature, highly vulnerable. Karl Folkers argues that
suboptimal nutrient intake in man is almost universal and
that there is subsequent secondary impairment in CoQ10 biosynthesis.
This would mean that average or "normal" levels
of CoQ10 are really suboptimal and the very low levels observed
in advanced disease states represent only the tip of a deficiency
"ice berg".
HMG-CoA reductase inhibitors used to treat elevated blood
cholesterol levels by blocking cholesterol biosynthesis
also block CoQ10 biosynthesis(13). The resulting lowering
of blood CoQ10 level is due to the partially shared biosynthetic
pathway of CoQ10 and cholesterol. In patients with heart
failure this is more than a laboratory observation. It has
a significant harmful effect which can be negated by oral
CoQ10 supplementation(14).
Increased body consumption of CoQ10 is the presumed cause
of low blood CoQ10 levels seen in excessive exertion, hypermetabolism,
and acute shock states. It is likely that all three mechanisms
(insufficient dietary CoQ10, impaired CoQ10 biosynthesis,
and excessive utilization of CoQ10) are operable to varying
degrees in most cases of observed CoQ10 deficiency.
TREATMENT OF HEART DISEASE WITH COENZYME Q10
CoQ10 is known to be highly concentrated in heart muscle
cells due to the high energy requirements of this cell type.
For the past 14 years, the great bulk of clinical work with
CoQ10 has focused on heart disease. Specifically, congestive
heart failure (from a wide variety of causes) has been strongly
correlated with significantly low blood and tissue levels
of CoQ10 (15). The severity of heart failure correlates
with the severity of CoQ10 deficiency (16). This CoQ10 deficiency
may well be a primary etiologic factor in some types of
heart muscle dysfunction while in others it may be a secondary
phenomenon. Whether primary, secondary or both, this deficiency
of CoQ10 appears to be a major treatable factor in the otherwise
inexorable progression of heart failure.
Pioneering trials of CoQ10 in heart failure involved primarily
patients with dilated weak heart muscle of unknown cause
(idiopathic dilated cardiomyopathy). CoQ10 was added to
standard treatments for heart failure such as fluid pills
(diuretics), digitalis preparations (Lanoxin), and ACE inhibitors.
Several trials involved the comparison between supplemental
CoQ10 and placebo on heart function as measured by echocardiography.
CoQ10 was given orally in divided doses as a dry tablet
chewed with a fat containing food or an oil based gel cap
swallowed at mealtime. Heart function, as indicated by the
fraction of blood pumped out of the heart with each beat
(the ejection fraction), showed a gradual and sustained
improvement in tempo with a gradual and sustained improvement
in patients' symptoms of fatigue, dyspnea, chest pain, and
palpitations. The degree of improvement was occasionally
dramatic with some patients developing a normal heart size
and function on CoQ10 alone. Most of these dramatic cases
were patients who began CoQ10 shortly after the onset of
congestive heart failure. Patients with more established
disease frequently showed clear improvement but not a return
to normal heart size and function.
Internationally, there have been at least nine placebo
controlled studies on the treatment of heart disease with
CoQ10:two in Japan, two in the United States, two in Italy,
two in Germany, and one in Sweden (17,18,19,20,21,22,23,24,25).
All nine of these studies have confirmed the effectiveness
of CoQ10 as well as its remarkable safety. There have now
been eight international symposia on the biomedical and
clinical aspects of CoQ10 (from 1976 through 1993 (26,27,28,29,30,31,32,33)).
These eight symposia comprised over 300 papers presented
by approximately 200 different physicians and scientists
from 18 different countries. The majority of these scientific
papers were Japanese (34%), with American (26%), Italian
(20%) and the remaining 20% from Sweden, Denmark, Germany,
United Kingdom, Belgium, Australia, Austria, France, India,
Korea, Netherlands, Poland, Switzerland, USSR, and Finland.
The majority of the clinical studies concerned the treatment
of heart disease and were remarkably consistent in their
conclusions: that treatment with CoQ10 significantly improved
heart muscle function while producing no adverse effects
or drug interactions.
It should be mentioned that a slight decrease in the effectiveness
of the blood thinner, coumadin, was noted in a case by a
Norwegian clinician (34). This possible drug - CoQ10 interaction
has not been observed by other investigators even when using
much higher doses of CoQ10 for up to seven years and involving
25 patients treated with coumadin concomitantly with CoQ10
(this is still, as of this date, unpublished data).
The efficacy and safety of CoQ10 in the treatment of congestive
heart failure, whether related to primary cardiomyopathies
or secondary forms of heart failure, appears to be well
established (35,36,37,38,39, 40,41,42). The largest study
to date is the Italian multicenter trial, by Baggio et al.,
involving 2664 patients with heart failure (43).
The most recent work in heart failure examined the effect
of CoQ10 on diastolic dysfunction, one of the earliest identifiable
signs of myocardial failure that is often found in mitral
valve prolapse, hypertensive heart disease and certain fatigue
syndromes (44,45). Diastolic dysfunction might be considered
the common denominator and a basic cause of symptoms in
these three diagnostic groups of disease. Diastole is the
filling phase of the cardiac cycle. Diastolic function has
a larger cellular energy requirement than the systolic contraction
and, therefore, the process of diastolic relaxation is more
highly energy dependent and thus more highly dependent on
CoQ10. In simplier terms, it takes more energy to fill the
heart than to empty it. Diastolic dysfunction is a stiffening'
of the heart muscle which interferes with the heart's ability
to function as an effective pump. It is seen early in the
course of many common cardiac disorders and is demonstrable
by echocardiography. This stiffening returns towards normal
with supplemental CoQ10 in tempo with clinical improvement.
It is important to note that in all of the above clinical
trials, CoQ10 was used in addition to traditional medical
treatments, not to their exclusion. In one study by Langsjoen
et al (46), of 109 patients with essential hypertension,
51% were able to stop between one and three antihypertensive
drugs at an average of 4.4 months after starting CoQ10 treatment
while the overall New York Heart Association (NYHA) functional
class improved significantly from a mean of 2.40 to 1.36.
Hypertension is reduced when diastolic function improves.
In another study(39), there was a gradual and sustained
decrease in dosage or discontinuation of concomitant cardiovascular
drug therapy: Of 424 patients with cardiovascular disease,
43% were able to stop between one and three cardiovascular
drugs with CoQ10 therapy. The authors conclude that the
vitamin-like substance, CoQ10, "may be ushering in
the new era of cellular/biochemical treatment of disease,
complementing and extending the systems-oriented, macro
and microscopic approach that has served us well to this
point".
FREQUENTLY ASKED QUESTIONS
Over the past several years, there has been a steady increase
in public interest and awareness of nutritional supplements
and vitamins. Along with this accelerated interest has come
an understandable explosion in the number and complexity
of questions raised by patients about vitamins in general.
By and large, these questions are quite difficult to answer.
I personally am frequently asked the following questions:
1. What is CoQ10?
It is a fat-soluble vitamin-like substance present in every
cell of the body and serves as a coenzyme for several of
the key enzymatic steps in the production of energy within
the cell. It also functions as an antioxidant which is important
in its clinical effects. It is naturally present in small
amounts in a wide variety of foods but is particularly high
in organ meats such as heart, liver and kidney, as well
as beef, soy oil, sardines, mackerel, and peanuts. To put
dietary CoQ10 intake into perspective, one pound of sardines,
two pounds of beef, or two and one half pounds of peanuts,
provide 30 mg of CoQ10. CoQ10 is also synthesized in all
tissues and in healthy individuals normal levels are maintained
both by CoQ10 intake and by the body's synthesis of CoQ10.
It has no known toxicity or side effects.
2. Should I take CoQ10?
This question can be asked in two ways. First, should a
reasonably healthy person take CoQ10 to stay healthy or
to become more robust?
At present I do not believe anyone knows the answer to
this question.
Second, should a person with an illness such as congestive
heart failure take CoQ10? As with any change in nutrition,
diet, medication, or even activity, CoQ10 should be discussed
with one's physician. As improvement in heart function occurs,
a patient should have regular medical follow up with particular
attention to concomitant drug therapy. The attached references
will provide detailed information on the clinical use of
CoQ10 and can be obtained from any good medical library.
3. What is the dosage of CoQ10?
The dosage of CoQ10 used in clinical trials has evolved
over the past 20 years. Initially, doses as small as 30
to 45 mg per day were associated with measurable clinical
responses in patients with heart failure. More recent studies
have used higher doses with improved clinical response,
again in patients with heart failure. Most studies with
CoQ10 involve the measurement of the level of CoQ10 in blood.
CoQ10 shows a moderate variability in its absorption, with
some patients attaining good blood levels of CoQ10 on 100
mg per day while others require two or three times this
amount to attain the same blood level. All CoQ10 available
today in the United States is manufactured in Japan and
is distributed by a number of companies who place the CoQ10
either in pressed tablets, powder-filled capsules, or oil-based
gelcaps. CoQ10 is fat-soluble and absorption is significantly
improved when it is chewed with a fat-containing food. Published
data on the dosage of CoQ10 relates almost exclusively to
the treatment of disease states. There is no information
on the use of CoQ10 for prevention of illness. This is an
extremely important question which, to date, does not have
an answer.
4. If CoQ10 is so effective in the treatment of heart failure,
why is it not more generally used in this country?
The answer to this question is found in the fields of politics
and marketing and not in the fields of science or medicine.
The controversy surrounding CoQ10 likewise is political
and economic as the previous 30 years of research on CoQ10
have been remarkably consistent and free of major controversy.
Although it is not the first time that a fundamental and
clinically important discovery has come about without the
backing of a pharmaceutical company, it is the first such
discovery to so radically alter how we as physicians must
view disease. While the pharmaceutical industry does a good
job at physician and patient education on their new products,
the distributors of CoQ10 are not as effective at this.
This education is very costly and can only be done with
the reasonable expectation of patent protected profit. CoQ10
is not patentable. The discovery of CoQ10 was based primarily
on support from the National Heart Institute of NIH (National
Institute of Health) at the Institute for Enzyme Research,
University of Wisconsin.
THE FUTURE OF COENZYME Q10
In the past 50 years the driving force in medicine has
been the development of drugs and procedures to modify the
pathophysiology of illness. As viewed from the trenches
of medical practice, the advances in drug therapy, although
notable and clearly helpful, appear to have reached a plateau.
Most of the "new" drugs over the past several
years are primarily variants of old drugs. By comparison,
the impressive advances made by basic scientists, biochemists,
and molecular biologists, are only now beginning to be appreciated
by the medical profession, and the enormous potential of
these basic science advances has yet to be pursued.
Modern medicine seems to be based on an "attack strategy",
a philosophy of treatment formed in response to the discovery
of antibiotics and the development of surgical/anesthetic
techniques. Disease is viewed as something that can be attacked
selectively - with antibiotics, chemotherapy, or surgery
- assuming no harm to the host. Even chronic illnesses,
such as diabetes and hypertension, yield simple numbers
which can be furiously assaulted with medications. Amidst
the miracles and drama of 20th century medicine we may have
forgotten the importance of host support, as if time borrowed
with medications and surgery were restorative in and of
itself. Yet, in this age, a patient may be cured of leukemia
through multiple courses of chemotherapy and bone marrow
transplantation, only to die slowly of unrecognized thiamine
(vitamin B1) deficiency(47). Like the vitamins discovered
in the early part of this century, CoQ10 is an essential
element of food that can now be used medicinally to support
the sick host in conditions where nutritional depletion
and cellular dysfunction occur. Surely, the combination
of disease attacking strategy and host supportive treatments
would yield much better results in clinical medicine.
Since CoQ10 is essential to the optimal function of all
celltypes,it is not surprising to find a seemingly diverse
number of disease states which respond favorably to CoQ10
supplementation. All metabolically active tissues are highly
sensitive to a deficiency ofCoQ10. CoQ10's function as a
free radical scavenger only adds to the protean manifestations
of CoQ10 deficiency. Preliminary observations in a wide
variety of disease states have already been published (48,49,50,51,52,53,54,55,56,57,58).
One of the disease states which has received attention
is cancer. Low levels of CoQ10 in the blood of some cancer
patients have been noted (59), but overall, there is little
data regarding cancer. The best work to date documents a
significant reduction in the cardiac toxicity of the chemotherapy
drug, Adriamycin (52,53,54). The cardiac toxicity of Adriamycin
and related drugs may well relate to free radical generation
and this might explain the benefit of CoQ10 in its capacity
as a free radical scavenger. The studies on Adriamycin cardiotoxicity
were of short duration and did not specifically note any
favorable or detrimental effect on the clinical course of
the cancer itself. It is reasonable to assume that optimal
nutrition (which would include optimal levels of CoQ10)
is generally beneficial in any disease state, including
cancer.
Another interesting topic is the relationship between the
immune system and CoQ10. Immune function is extraordinarily
complex and undoubtedly is influenced by numerous nutritional
variables. There are some encouraging preliminary data from
the study of AIDS patients (50,51). End stage AIDS, like
other overwhelming illnesses, has been associated with a
significant deficiency in CoQ10. Regarding AIDS and cancer,
it would be foolish to make premature statements about future
utility of CoQ10, but it is even more foolish to ignore
the importance of adequate CoQ10 levels in these disease
states. Adequate CoQ10 supplementation (with close attention
to plasma CoQ10 levels) is analogous to adequate hydration,
and any treatment of critically ill patients should not
ignore this easily measured and correctable deficiency.
The antioxidant or free radical quenching properties of
CoQ10 serve to greatly reduce oxidative damage to tissues
as well as significantly inhibit the oxidation of LDL cholesterol
(much more efficiently than vitamin E) (60,61). This has
great implications in the treatment of ischemia and reperfusion
injury as well as the potential for slowing the development
of atherosclerosis. In keeping with the free radical theory
of aging, these antioxidant properties of CoQ10 have clear
implications in the slowing of aging and age related degenerative
diseases. There is epidemiologic evidence in humans that
uniformly shows a gradual decline in CoQ10 levels after
the age of twenty.
Until recently, attention has been focused on requirements
for CoQ10 in energy conversion in the mitochondrial compartment
of cells or on the antioxidant properties of CoQ10. New
evidence shows that CoQ10 is present in other cell membranes.
In the outer membrane it may contribute to the control of
cell growth, especially in lymphocytes (the implications
are far reaching (62,63,64,65)). The clinical experience
with CoQ10 in heart failure is nothing short of dramatic,
and it is reasonable to believe that the entire field of
medicine should be re-evaluated in light of this growing
knowledge. We have only scratched the surface of the biomedical
and clinical applications of CoQ10 and the associated fields
of bioenergetics and free radical chemistry.
ACKNOWLEDGEMENTS
Sincere appreciation is expressed to Hans Langsjoen of
the University of Texas Medical Branch at Galveston, Karl
Folkers and Richard Willis of the University of Texas at
Austin, Frederick Crane of Purdue University in Indiana,
Lars Ernster of the Stockholm University, Sweden, Gian Paolo
Littarru, of the University of Ancona Medical School, Italy,
and my wife Alena Langsjoen for their help in the completion
of this manuscript.
Peter H. Langsjoen, M.D., F.A.C.C.,P.A.
1120 Medical Dr.
Tyler, Tx 75701
Copyright 1994
N.B. To see the 65 REFERENCES to the above article see Refeences.
NEGLECT OF Coenzyme Q10 IN US MEDICINE.
SUMMARY OF A RECENT SEARCH AND OTHER MATERIALS
All medical scientists contacted agree: (1) the common occurrence
of Q10 "deficiency states" and their tragic consequences
in numerous disorders are not widely recognized today; altho
(2) it has long been textbook knowledge that Q10 (Coenzyme
Q10 or CoQ or ubiquinone) is a molecule that has great importance
in bioenergetics in the mitochondria of all human cells.
It is synthesized in all tissues (from tyrosine using a
complex and easily imperiled process requiring a number
of vitamins and trace elements). It is available in the
diet at very low levels (< 20 ppm). In addition, it is
reported that certain pharmaceuticals designed to lower
cholesterol (unnecessary in most cases, it has also been
reported for years, if vitamin E is adequate) block mevalonic
acid, an intermediate of both cholesterol and Q10! Even
a high metabolic rate or strenuous physical work or endurance
exercise accelerate Q10 turnover lowering levels unless
the increased demands are met. Synthesis falls significantly
with age. Thus there are a number of common ways blood and
tissue levels of Q10 can be low resulting in an unending
variety of disorders in the heart, lymphoid tissue and etc
throughout the body.
Striking results have been reported in many patients simply
by oral supplementation of the innocuous and readily available
Q10 at doses costing circa $1 per day. Karl Folkers (to
whom I talked only once prior to my design in the 1980's
of an experiment to study the effect of Q10 on thymic involution
in young and old mice) and a cardiologist named Peter Langsjoen
have been leaders in research and clinical trials on Q10.
The following abstrs I pulled from MedLine to show the flavor
of some of their work in cardiology and cancer primarily
(and the incredible potential that may be there). Unfortunately,
there appears to be no convenient economical assay available.
If one were, it is my opinion (and that of the researchers
I know) that our cardiologists, oncologists, neurologists,
psychiatrists, gerontologists, internists, allergists, immunologists,
etc, would all be able to identify rapidly (ie, 1-3 months)
patients whose symptoms abate with rising blood Q10 (on
Q10 p.o.) and modify treatment plans early (as is already
done in Japan, Italy, and other countries). This appears
possible if there is enough demand for UW Medical Center
and Lab Med to provide the HPLC method as a semi-automated
low cost assay of blood Q10. It appears there are many ways
that the quality of care would improve and its cost would
be greatly decreased by this simple step (and the rest of
the US could follow).
[Peter Langsjoen,MD, is a biochemist as well as a cardiologist.
His wife is also a chemist. A few days ago, they sent me
a paper he has written recently for the clin/sci community
on Q10 (8pp incl 65 refs). For those who wish it, that paper
is now available herewith.] John Ely, Radiation Studies,
Box 351560
Author: Langsjoen-P-H. Folkers-K. Lyson-K. Muratsu-K. Lyson-T.
Langsjoen-P.
Title: Effective and safe therapy with coenzyme Q10 for
cardiomyopathy.
Source: Klin-Wochenschr. 1988 Jul 1. 66(13). P 583-90.
Journal Title: KLINISCHE WOCHENSCHRIFT.
Abstract: Coenzyme Q10 (CoQ10) is indispensable in mitochondrial
bioenergetics and for human life to exist. 88/115 patients
completed a trial of therapy with CoQ10 for cardiomyopathy.
Patients were selected on the basis of clinical criteria,
X-rays, electrocardiograms, echocardiography, and coronary
angiography. Responses were monitored by ejection fractions,
cardiac output, and improvements in functional classifications
(NYHA). Of the 88 patients 75%-85% showed statistically
significant increases in two monitored cardiac parameters.
Patients with the lowest ejection fractions (approx. 10%-30%)
showed the highest increases (115 delta %-210 delta %) and
those with higher ejection fractions (50%-80%) showed increases
of approx. 10 delta %-25 delta % on therapy. By functional
classification, 17/21 in class IV, 52/62 in class III, and
4/5 in class II improved to lower classes. Clinical responses
appeared over variable times, and are presumably based on
mechanisms of DNA-RNA-protein synthesis of apoenzymes which
restore levels of CoQ10 enzymes in a deficiency state. 10/21
(48%) of patients in class IV, 26/62 (42%) in class III,
and 2/5 (40%) in class II had exceptionally low control
blood levels of CoQ10. Clinical responses on therapy with
CoQ10 appear maximal with blood levels of approx. 2.5 micrograms
CoQ10/ml and higher during therapy.
Author: Langsjoen-P-H. Vadhanavikit-S. Folkers-K.
Title: Response of patients in classes III and IV of cardiomyopathy
to therapy in a blind and crossover trial with coenzyme
Q10.
Source: Proc-Natl-Acad-Sci-U-S-A. 1985 Jun. 82(12). P 4240-4.
Journal Title: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES
OF THE UNITED STATES OF AMERICA.
Abstract: Coenzyme Q10 (CoQ10), a biochemically established
redox component of respiration including the coupled mechanisms
of electron transfer and oxidative phosphorylation, is naturally
present in the human myocardium. A double-blind and double-crossover
trial has been conducted by administering CoQ10 and a matching
placebo orally to two groups of patients having class III
or IV cardiomyopathy (classification according to criteria
of the New York Heart Association). Group A received CoQ10
and then placebo; group B received placebo and then CoQ10.
Blood levels of CoQ10 and cardiac function were determined
at 0 and 4 weeks (control stabilization period) and at 16
and 28 weeks (after the 12-week CoQ/placebo-treatment periods).
For group A, significant increases in CoQ10 blood levels
and cardiac function occurred during CoQ10 treatment and
then decreased during crossover to placebo. For group B,
there was no change in CoQ10 blood levels and cardiac function
during placebo treatment, but increases in both parameters
occurred in crossover to CoQ10. These patients, steadily
worsening and expected to die within 2 years under conventional
therapy, generally showed an extraordinary clinical improvement,
indicating that CoQ10 therapy might extend the lives of
such patients. This improvement could be due to correction
of a myocardial deficiency of CoQ10 and to enhanced synthesis
of CoQ10-requiring enzymes.
Author: Langsjoen-P-H. Vadhanavikit-S. Folkers-K.
Title: Effective treatment with coenzyme Q10 of patients
with chronic myocardial disease.
Source: Drugs-Exp-Clin-Res. 1985. 11(8). P 577-9.
Journal Title: DRUGS UNDER EXPERIMENTAL AND CLINICAL RESEARCH.
Abstract: Nineteen patients with chronic myocardial disease
(NYHA Classes III and IV) were given Coenzyme Q10 in a controlled
double-blind cross-over study. All had either low or borderline
levels of CoQ10 in their blood, and showed a significant
change into the normal range with oral CoQ10 replacement.
Eighteen patients reported improvement in activity tolerance
with replacement therapy. Combined clinical observations,
stroke volume measured by impedance cardiography, and ejection
fractions calculated from systolic time intervals, all showed
significant improvement in parallel with CoQ10 administration.
This application of the principles of bioenergetics introduces
a promising new dimension to the study and treatment of
the complex problem of myocardial failure.
Author: Folkers-K. Langsjoen-P. Langsjoen-P-H.
Title: Therapy with coenzyme Q10 of patients in heart failure
who are eligible or ineligible for a transplant.
Source: Biochem-Biophys-Res-Commun. 1992 Jan 15. 182(1).
P 247-53.
Journal Title: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.
Abstract: Twenty years of international open and seven
double blind trials established the efficacy and safety
of coenzyme Q10 (CoQ10) to treat patients in heart failure.
In the U.S., ca. 20,000 patients under 65 years are eligible
for transplants, but donors are less than 1/10th of those
eligible, and there are many more such patients over 65,
both eligible and ineligible. We treated eleven exemplary
transplant candidates with CoQ10; all improved; three improved
from Class IV to Class I; four improved from Classes III-IV
to Class II; and two improved from Class III to Class I
or II. After CoQ10, some patients required no conventional
drugs and had no limitation in lifestyle. The marked improvement
is based upon correcting myocardial deficiencies of CoQ10
which improve mitochondrial bioenergetics and cardiac performance.
These case histories, and very substantial background proof
of efficacy and safety, justify treating with CoQ10 patients
in failure awaiting transplantation.
Author: Langsjoen-P-H. Langsjoen-P-H. Folkers-K.
Title: A six-year clinical study of therapy of cardiomyopathy
with coenzyme Q10.
Source: Int-J-Tissue-React. 1990. 12(3). P 169-71.
Journal Title: INTERNATIONAL JOURNAL OF TISSUE REACTIONS.
Abstract: One hundred and forty-three cases of chronic,
stable, non-secondary, non-hypertrophic cardiomyopathy,
98% of whom were in NYHA Classes III and IV, were given
100 mg of coenzyme Q10** orally in addition to their conventional
medical programme in an open-label long-term study. Blood
CoQ10 levels, clinical status, myocardial function and survival
have been recorded now for almost 6 years. Mean control/CoQ10
levels of 0.85 micrograms/ml rose to 2 micrograms/ml in
3 months and remained stable at that level. Mean ejection
fraction of 44% measured by systolic time interval analysis
rose to 60% within 6 months and stabilized at that level
with 84% of patients showing statistically significant improvement.
Eighty-five percent of patients improved by one or two NYHA
Classes. Survival figures were encouraging with an 11.1%
mortality in 12 months and 17.8% mortality in 24 months,
comparing favourably with several reports in the literature.
There was no positive evidence of toxicity or intolerance
in a total of 368.9 patient-years of exposure. Coenzyme
Q10 is safe and effective long-term therapy for chronic
cardiomyopathy. (**Ely estimate: $1/day retail!)
Author: Langsjoen-P-H. Folkers-K. Lyson-K. Muratsu-K. Lyson-T.
Langsjoen-P.
Title: Pronounced increase of survival of patients with
cardiomyopathy when treated with coenzyme Q10 and conventional
therapy.
Source: Int-J-Tissue-React. 1990. 12(3). P 163-8.
Journal Title: INTERNATIONAL JOURNAL OF TISSUE REACTIONS.
Abstract: During 1982-86, 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 3 months (range, 2-4 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.(**Ely:
Survival 3:1 !)
Author: Lockwood-K. Moesgaard-S. Yamamoto-T. Folkers-K.
Title: Progress on therapy of breast cancer with vitamin
Q10 and the regression of metastases.
Source: Biochem-Biophys-Res-Commun. 1995 Jul 6. 212(1).
P 172-7.
Journal Title: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.
Abstract: Over 35 years, data and knowledge have internationally
evolved from biochemical, biomedical and clinical research
on vitamin Q10 (coenzyme Q10; CoQ10) and cancer, which led
in 1993 to overt complete regression of the tumors in two
cases of breast cancer. Continuing this research, three
additional breast cancer patients also underwent a conventional
protocol of therapy which included a daily oral dosage of
390 mg of vitamin Q10 (Bio-Quinone of Pharma Nord) during
the complete trials over 3-5 years. The numerous metastases
in the liver of a 44-year-old patient "disappeared,"
and no signs of metastases were found elsewhere. A 49-year-old
patient, on a dosage of 390 mg of vitamin Q10, revealed
no signs of tumor in the pleural cavity after six months,
and her condition was excellent. A 75-year-old patient with
carcinoma in one breast, after lumpectomy and 390 mg of
CoQ10, showed no cancer in the tumor bed or metastases.
Control blood levels of CoQ10 of 0.83-0.97 and of 0.62 micrograms/ml
increased to 3.34-3.64 and to 3.77 micrograms/ml, respectively,
on therapy with CoQ10 for patients A-MRH and EEL.
Author: Lockwood-K. Moesgaard-S. Hanioka-T. Folkers-K.
Title: Apparent partial remission of breast cancer in 'high
risk' patients supplemented with nutritional antioxidants,
essential fatty acids and coenzyme Q10.
Source: Mol-Aspects-Med. 1994. 15 Suppl. P s231-40.
Journal Title: MOLECULAR ASPECTS OF MEDICINE.
Abstract: Thirty-two typical patients with breast cancer,
aged 32-81 years and classified 'high risk' because of tumor
spread to the lymph nodes in the axilla, were studied for
18 months following an Adjuvant Nutritional Intervention
in Cancer protocol (ANICA protocol). The nutritional protocol
was added to the surgical and therapeutic treatment of breast
cancer, as required by regulations in Denmark. The added
treatment was a combination of nutritional antioxidants
(Vitamin C: 2850 mg, Vitamin E: 2500 iu, beta-carotene 32.5
iu, selenium 387 micrograms plus secondary vitamins and
minerals), essential fatty acids (1.2 g gamma linolenic
acid and 3.5 g n-3 fatty acids) and Coenzyme Q10 (90 mg
per day). The ANICA protocol is based on the concept of
testing the synergistic effect of those categories of nutritional
supplements, including vitamin Q10, previously having shown
deficiency and/or therapeutic value as single elements in
diverse forms of cancer, as cancer may be synergistically
related to diverse biochemical dysfunctions and vitamin
deficiencies. Biochemical markers, clinical condition, tumor
spread, quality of life parameters and survival were followed
during the trial. Compliance was excellent. The main observations
were: (1) none of the patients died during the study period.
(the expected number was four.) (2) none of the patients
showed signs of further distant metastases. (3) quality
of life was improved (no weight loss, reduced use of pain
killers). (4) six patients showed apparent partial remission.
Author: Lockwood-K. Moesgaard-S. Folkers-K.
Title: Partial and complete regression of breast cancer
in patients in relation to dosage of coenzyme Q10.
Source: Biochem-Biophys-Res-Commun. 1994 Mar 30. 199(3).
P 1504-8.
Journal Title: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.
Abstract: Relationships of nutrition and vitamins to the
genesis and prevention of cancer are increasingly evident.
In a clinical protocol, 32 patients having -"high-risk"-
breast cancer were treated with antioxidants, fatty acids,
and 90 mg. of CoQ10. Six of the 32 patients showed partial
tumor regression. In one of these 6 cases, the dosage of
CoQ10 was increased to 390 mg. In one month, the tumor was
no longer palpable and in another month, mammography confirmed
the absence of tumor. Encouraged, another case having a
verified breast tumor, after non-radical surgery and with
verified residual tumor in the tumor bed was then treated
with 300 mg. CoQ10. After 3 months, the patient was in excellent
clinical condition and there was no residual tumor tissue.
The bioenergetic activity of CoQ10, expressed as hematological
or immunological activity, may be the dominant but not the
sole molecular mechanism causing the regression of breast
cancer.
Author: Folkers-K. Morita-M. McRee-J-Jr.
Title: The activities of coenzyme Q10 and vitamin B6 for
immune responses.
Source: Biochem-Biophys-Res-Commun. 1993 May 28. 193(1).
P 88-92.
Journal Title: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.
Abstract: Coenzyme Q10 (CoQ10) and vitamin B6 (pyridoxine)
have been administered together and separately to three
groups of human subjects. The blood levels of CoQ10 increased
(p < 0.001) when CoQ10 and pyridoxine were administered
together and when CoQ10 was given alone. The blood levels
of IgG increased when CoQ10 and pyridoxine were administered
together (p < 0.01) and when CoQ10 was administered alone
(p < 0.05). The blood levels of T4-lymphocytes increased
when CoQ10 and pyridoxine were administered together (p
< 0.01) and separately (p < 0.001). The ratio of T4/T8
lymphocytes increased when CoQ10 and pyridoxine were administered
together (p < 0.001) and separately (p < 0.05). These
increases in IgG and T4-lymphocytes with CoQ10 and vitamin
B6 are clinically important for trials on AIDS, other infectious
diseases, and on cancer.
Author: Folkers-K. Brown-R. Judy-W-V. Morita-M.
Title: Survival of cancer patients on therapy with coenzyme
Q10.
Source: Biochem-Biophys-Res-Commun. 1993 Apr 15. 192(1).
P 241-5.
Journal Title: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.
Abstract: Over ca. 25 years, assays in animal models established
the hematopoietic activities of coenzyme Q's in rhesus monkeys,
rabbits, poultry, and children having kwashiorkor. Surprisingly,
a virus was found to cause a deficiency of CoQ9. Patients
with AIDS showed a-"striking"-clinical response
to therapy with CoQ10. The macrophage potentiating activity
of CoQ10 was recorded by the carbon clearance method. CoQ10
significantly increased the levels of IgG in patients. Eight
new case histories of cancer patients plus two reported
cases support the statement that therapy of cancer patients
with CoQ10, which has no significant side effect, has allowed
survival on an exploratory basis for periods of 5-15 years.
These results now justify systematic protocols.
