This paper was written fourteen years ago, yet
CoQ 10 is not used as a universal miracle treatment because the drug
companies cannot patent it and doctors are not needed to buy
prescriptions: we can buy it off the shelf.
I use 150 mg of CoQ 10 divided into three 50mg
doses taken with each meal. My cholesterol and blood pressure, as
well as my complexion and skin, have improved remarkably.
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.
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 also synthesized 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).
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
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
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
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
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. Asimprovement 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
4. If CoQ10 is so effective in the
treatment of heart failure, why is it not more generally used in
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
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
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
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
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.
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
Peter H. Langsjoen, M.D., F.A.C.C.,
P.A. 1120 Medical Dr.
Tyler, Tx 75701
1. Gian Paolo Littarru (1994) Energy and Defense. Facts and
perspectives on CoenzymeQ10 in biology and medicine. Casa
Editrice Scientifica Internazionale, pp 1-91.
2. Crane F.L., Hatefi Y., Lester R.I., Widmer C. (1957)
Isolation of a quinone from beef heart mitochondria. In:
Biochimica et Biophys. Acta, vol. 25, pp 220-221.
3. Morton R.A., Wilson G.M., Lowe J.S., Leat W.M.F. (1957)
Ubiquinone. In: Chemical Industry, pp 1649.
4. Mellors A., Tappel A.L. (1966) Quinones and quinols as
inhibitors of lipid peroxidation. Lipids, vol. 1, pp 282-284.
5. Mellors A., Tappel A.L. (1966) The inhibition of
mitochondrial peroxidation by ubiquinone and ubiquinol. J.
Biol. Chem., vol. 241, pp 4353-4356.
6. Littarru G.P., Ho L., Folkers K. (1972) Deficiency of
Coenzyme Q10 in human heart disease. Part I and II. In:
Internat. J. Vit. Nutr. Res., 42, n. 2, 291:42, n. 3:413.
7. Mitchell P. (1976) Possible molecular mechanisms of the
protonmotive function of cytochrome systems. In: J.
Theoret. Biol., vol. 62, pp 327-367.
8. Mitchell P. (1991) The vital protonmotive role of coenzyme
Q. In: Folkers K., Littarru G.P., Yamagami T. (eds)
Biomedical and Clinical Aspects of Coenzyme Q, vol. 6,
Elsevier, Amsterdam, pp 3-10.
9. Mitchell P. (1988) Respiratory chain systems in theory and
practice. In: Advances in Membrane Biochemistry and
Bioenergetics, Kim C.H., et al. (eds), Plenum Press, New
York, pp 25-52.
10. Mitchell P. (1979) Kelin's respiratory chain concept and its
chemiosmotic consequences. In: Journal Science, vol. 206,
11. Ernster L. (1977) Facts and ideas about the function of
coenzyme Q10 in the Mitochondria. In: Folkers K.,
Yamamura Y. (eds) Biomedical and Clinical Aspects of
Coenzyme Q. Elsevier, Amsterdam, pp 15-8.
12. Littarru G.P., Lippa S., Oradei A., Fiorni R.M., Mazzanti L.
Metabolic and diagnostic implications of blood CoQ10 levels.
In: Biomedical and Clinical Aspects of Coenzyme Q, vol. 6
(1991) Folkers K., Yamagami T., and Littarru G. P. (eds)
Elsevier, Amsterdam, pp 167-178.
13. Ghirlanda G., Oradei A., Manto A., Lippa S., Uccioli L.,
Caputo S., Greco A.V., Littarru G.P. (1993) Evidence of
Plasma CoQ10 - Lowering Effect by HMG-CoA Reductase
Inhibitors: A double blind , placebo-controlled study. Clin.
Pharmocol., J. 33, 3, 226-229.
14. Folkers K., Langsjoen Per H.,Willis R., Richardson P., Xia
L.,Ye C., Tamagawa H. (1990) Lovastatin decreases
coenzyme Q levels in humans. Proc. Natl. Acad Sci. Vol.
15. Folkers K., Vadhanavikit S., Mortensen S.A. (1985)
Biochemical rationale and myocardial tissue data on the
effective therapy of cardiomyopathy with coenzyme Q10. In:
Proc. Natl. Acad. Sci., U.S.A., vol. 82(3), pp 901-904.
16. Mortensen S.A., Vadhanavikit S., Folkers K. (1984)
Deficiency of coenzyme Q10 in myocardial failure. In:
Drugs Exptl. Clin. Res. X(7) 497-502.
17. Hiasa Y., Ishida T., Maeda T., Iwanc K., Aihara T., and Mori
H. (1984) Effects of coenzyme Q10 on exercise tolerance in
patients with stable angina pectoris. In: Biomedical and
Clinical Aspects of Coenzyme Q, vol. 4 (1984) Folkers K.,
Yamamura Y., (eds) Elsevier, Amsterdam, pp 291-301.
18. Kamikawa T., Kobayashi A., Yamashita T., Hayashi H., and
Yamazaki N. (1985) Effects of coenzyme Q10 on exercise
tolerance in chronic stable angina pectoris. In: Am. J.
19. Langsjoen Per.H., Vadhanavikit S., Folkers K. (1985)
Response of patients in classes III and IV of cardiomyopathy
to therapy in a blind and crossover trial with coenzyme Q10.
In: Proc. Natl. Acad. of Sci., U.S.A., vol. 82, pp 4240-4244.
20. Judy W.V., Hall J.H., Toth P.D., Folkers K. (1986) Double
blind-double crossover study of coenzyme Q10 in heart
failure. In: Folkers K., Yamamura Y. (eds) Biomedical and
clinical aspects of coenzyme Q, vol. 5. Elsevier,
Amsterdam, pp 315-323.
21. Rossi E., Lombardo A., Testa M., Lippa S., Oradei A.,
Littarru G.P., Lucente M. Coppola E., Manzoli U. Coenzyme
Q10 in ischaemic cardiopathy. In: Biomedical and Clinical
Aspects of Coenzyme Q, vol. 6 (1991) Folkers K., Yamagami
T., and Littarru G. P. (eds) Elsevier, Amsterdam, pp 321-326.
22. Morisco C., Trimarco B., Condorelli M. Effect of coenzyme
Q10 therapy in patients with congestive heart failure: A
long-term multicenter randomized study. In: Seventh
International Symposium on Biomedical and Clinical Aspects
of Coenzyme Q Folkers K., Mortensen S.A., Littarru G.P.,
Yamagami T., and Lenaz G. (eds) The Clinical Investigator,
(1993) 71:S 34-S 136.
23. Schneeberger W., Muller-Steinwachs J., Anda L.P., Fuchs
W., Zilliken F., Lyson K., Muratsu K., and Folkers K. A
clinical double blind and crossover trial with coenzyme Q10
on patients with cardiac disease. In: Biomedical and
Clinical Aspects of Coenzyme Q, vol. 5 (1986) Folkers K.,
Yamamura Y., (eds) Elsevier, Amsterdam, pp 325-333.
24. Schardt F., Welzel D., Schiess W., and Toda K. Effect of
coenzyme Q10 on ischaemia-induced ST-segment depression:
A double blind, placebo-controlled crossover study. In:
Biomedical and Clinical Aspects of Coenzyme Q, vol. 6
(1991) Folkers K., Yamagami T., and Littarru G. P. (eds)
Elsevier, Amsterdam, pp 385-403.
25. Swedberg K., Hoffman-Berg C., Rehnqvist N., Astrom H.
(1991) Coenzyme Q10 as an adjunctive in treatment of
congestive heart failure. In: 64th Scientific Sessions
American Heart Association, Abstract 774-6.
26. Biomedical and Clinical Aspects of Coenzyme Q. (1977)
Folkers K., Yamamura Y. (eds) Elsevier, Amsterdam, pp 1-315.
27. Biomedical and Clinical Aspects of Coenzyme Q, Vol. 2
(1980) Yamamura Y., Folkers K., and Ito Y. (eds) Elsevier,
Amsterdam, pp 1-456.
28. Biomedical and Clinical Aspects of Coenzyme Q, Vol. 3
(1981) Folkers K., Yamamura Y., (eds) Elsevier,
Amsterdam, pp 1-414.
29. Biomedical and Clinical Aspects of Coenzyme Q , Vol. 4
(1983) Folkers K., Yamamura Y., (eds) Elsevier,
Amsterdam, pp 1-432.
30. Biomedical and Clinical Aspects of Coenzyme Q, Vol. 5
(1986) Folkers K., Yamamura Y., (eds) Elsevier,
Amsterdam, pp 1-410.
31. Biomedical and Clinical Aspects of Coenzyme Q, Vol. 6
(1991) Folkers K., Yamagami T., and Littarru G. P. (eds)
Elsevier, Amsterdam, pp 1-555.
32. Seventh International Symposium on Biomedical and Clinical
Aspects of Coenzyme Q (1993) Folkers K., Mortensen S.A.,
Littarru G.P., Yamagami T., and Lenaz,G. (eds) The Clinical
Investigator, Supplement to Vol.71 / Issue 8, pp S51-S177.
33. Eighth International Symposium on Biomedical and Clinical
Aspects of Coenzyme Q (1994) Littarru G.P., Battino M. ,
Folkers K. (Eds) The Molecular Aspects of Medicine, Vol.
15 (Supplement), pp S1-S294.
34. Spigset O. (1994) Reduced effect of warfarin caused by
ubidecarenone. Lancet Nov 12 Vol. 344, pp. 8933.
35. Mortensen S.A., Vadhanavikit S., Folkers K. (1984)
Deficiency of coenzyme Q10 in myocardial failure. In: Drugs
Exptl. Clin. Res., vol. X(7), pp 497-502.
36. Mortensen S.A., Vadhanavikit S., Baandrup U., Folkers K.
(1985) Long term coenzyme Q10 therapy: a major advance in
the management of resistant myocardial failure. In: Drugs
Exp. Clin. Res., vol.11(8), pp 581-593.
37. Langsjoen P.H., Folkers K., Lyson K., Muratsu K., Lyson T.,
Langsjoen P. H. Effective and safe therapy with coenzyme
Q10 for cardiomyopathy. In: Klin. Wochenschr. (1988)
38. Langsjoen P. H., Langsjoen, P. H., Folkers, K. (1989) Long
term efficacy and safety of coenzyme Q10 therapy for
idiopathic dilated cardiomyopathy. In: The American
Journal of Cardiology, Vol. 65, pp 521 - 523.
39. Mortensen S.A., Vadhanavikit S., Muratsu K., Folkers K.
(1990) Coenzyme Q10: Clinical benefits with biochemical
correlates suggesting a scientific breakthrough in the
management of chronic heart failure. In: Int. J. Tissue
React., Vol. 12 (3), pp 155-162.
40. Ursini T., Gambini C., Paciaroni E., and Littarru G.P.
Coenzyme Q10 treatment of heart failure in the elderly:
Preliminary results. In: Biomedical and Clinical Aspects of
Coenzyme Q, vol. 6 (1991) Folkers K., Yamagami T., and
Littarru G. P. (eds) Elsevier, Amsterdam, pp 473-480.
41. Poggessi L., Galanti G., Comeglio M., Toncelli L., Vinci M.
(1991) Effect of coenzyme Q10 on left ventricular function in
patients with dilative cardiomyopathy. Curr. Ther. Res.
42. Langsjoen H.A., Langsjoen P. H., Langsjoen P. H., Willis R.,
Folkers K. (1994) Usefulness of coenzyme Q10 in clinical
cardiology, a long-term study. In: Eighth International
Symposium on Biomedical and Clinical Aspects of
Coenzyme Q, Littarru G.P., Battino M. , Folkers K. (Eds)
The Molecular Aspects of Medicine, Vol. 15 (Supplement),
43. Baggio E., Gandini R., Plancher A.C., Passeri M., Carmosino
G. Italian multicenter study on safety and efficacy of
coenzyme Q10 adjunctive therapy in heart failure. In: Eighth
International Symposium on Biomedical and Clinical Aspects
of Coenzyme Q (1994) Littarru G.P., Battino M. , Folkers K.
(Eds) The Molecular Aspects of Medicine, Vol. 15
(Supplement), pp S287-S294.
44. Langsjoen Per H., Langsjoen Peter H., Folkers K. Isolated
diastolic dysfunction of the myocardium and its response to
CoQ10 treatment. In: Seventh International Symposium on
Biomedical and Clinical Aspects of Coenzyme Q. Folkers,
K., Mortensen S.A., Littarru G.P., Yamagami T., and Lenaz
G. (eds) The Clinical Investigator, (1993) 71:S 140-S 144.
45. Oda T. Recovery of the Frank-Starling mechanism by
coenzyme Q10 in patients with load-induced contractility
depression. In: Eighth International Symposium on
Biomedical and Clinical Aspects of Coenzyme Q (1994)
Littarru G.P., Battino M., Folkers K. (Eds) The Molecular
Aspects of Medicine, Vol.15 (Supplement), pp S149-S154.
46. Langsjoen P. H., Langsjoen P. H., Willis R., Folkers K.
(1994) Treatment of essential hypertension with coenzyme
Q10. In: Eighth International Symposium on Biomedical and
Clinical Aspects of Coenzyme Q (1994) Littarru G.P.,
Battino M. , Folkers K. (Eds) The Molecular Aspects of
Medicine, Vol. 15 (Supplement), pp S287-S294.
47. Pihko H., Saarinen U., and Paetau A. (1989) Wernicke
encephalopathy - a preventable cause of death: Report of 2
children with malignant disease. Pediatric Neurology vol. 5
no. 4, pp 237-242.
48. Hansen I.L. (1976) Bioenergetics in clinical medicine.
Gingival leucocytic deficiencies of coenzyme Q10 in patients
with periodontal disease. In: Research Communications in
Chemical Pathology and Pharmacology, vol. 14, no. 4,
49. Iwamoto Y., Watanabe T., Okamoto H., Ohata N., Folkers K.
Clinical effect of coenzyme Q10 on periodontal disease. In:
Folkers, K., Yamamura, Y., (eds) Biomedical and Clinical
Aspects of Coenzyme Q10, (1981) vol. 3, Elsevier,
Amsterdam, pp 109-119.
50. Folkers K., Langsjoen P. H., et al. (1988) Biochemical
deficiencies of coenzyme Q10 in HIV-infection and the
exploratory treatment. Biochemical and Biophysical
Research Communications vol. 153, no. 2, pp 888-896.
51. Langsjoen P. H., Langsjoen P. H., Folkers K., Richardson P.
Treatment of patients with human immunodeficiency virus
infection with coenzyme Q10. In: Folkers K., Littarru G.P.,
and Yamagami, T., (eds) Biomedical and Clinical Aspects of
Coenzyme Q, (1991) vol. 6, pp 409-415.
52. Cortes E.P, Mohinder G., Patel M., Mundia A., and Folkers
K. Study of Administration of coenzyme Q10 to Adriamycin
treated cancer patients. In:Biomedical and Clinical Aspects
of Coenzyme Q (1977). Folkers K., Yamamura Y. (eds)
Elsevier, Amsterdam, pp 267-273.
53. Combs A.B., Faria D.T., Leslie S.W., and Bonner H.W.
(1981) Effect of coenzyme Q10 on Adriamycin induced
changes in myocardial calcium. In: Biomedical and Clinical
Aspects of Coenzyme Q, vol. 3 Folkers, K., Yamamura Y.,
(eds) Elsevier, Amsterdam, pp 137-144.
54. Judy W.V. Hall J., H., Dugan W., Toth P.D., and Folkers K.
Coenzyme Q10 reduction of Adriamycin toxicity. In:
Biomedical and Clinical Aspects of Coenzyme Q (1983),
vol. 4 Folkers K., Yamamura Y., (eds) Elsevier, Amsterdam,
55. Lockwood K., Moesgaard S., Yamamoto T., Folkers K.
Progress on therapy of breast cancer with vitamin Q10 and
the regression of metastases. Biochem Biophys Res Commun
1995 Jul 6;212(1):172-7.
56. Lockwood K., Moesgaard S., Hanioka T., Folkers K.
Apparent partial remission of breast cancer in 'high risk'
patients supplemented with nutritional antioxidants, essential
fatty acids and coenzyme Q10. Mol Aspects Med 1994;15
57. Lockwood K., Moesgaard S., Folkers K. Partial and
complete regression of breast cancer in patients in relation to
dosage of coenzyme Q10. Biochem Biophys Res Commun
1994 Mar 30;199(3):1504-8.
58. Folkers K., Brown R., Judy W.V., and Morita M. (1993)
Survival of cancer patients on therapy with coenzyme Q10.
Biochem. Biophys. Res. Comm., Ms. No. G-8658.
59. Mellstedt H., Osterborg A., Nylander M., Morita M., and
Folkers K. A deficiency of coenzyme Q10 (CoQ10) in
conventional cancer therapy and blood levels of CoQ10 in
cancer patients in Sweden. In: Eighth International
Symposium on Biomedical and Clinical Aspects of
Coenzyme Q (1994) The Molecular Aspects of Medicine, in
60. Bowry V.W., Mohr D., Cleary J., Stocker R. (1995)
Prevention of tocopherol-mediated peroxidation in
ubiquinol-10-free human low density lipoprotein. J Biol
Chem 1995 Mar 17;270(11):5756-63.
61. Ingold K.U., Bowry V.W., Stocker R., Walling C. (1993)
Autoxidation of lipids and antioxidation by alpha-tocopherol
and ubiquinol in homogeneous solution and in aqueous
dispersions of lipids: unrecognized consequences of lipid
particle size as exemplified by oxidation of human low
density lipoprotein. Proc Natl Acad Sci U S A 1993 Jan
62. Sun I.L., Sun E.E., Crane F.L., Morre, V.J., Lindgren A., and
Low H. Requirement for coenzyme Q in plasma membrane
electron transport. In: Proc. Nat. Acad. Sci. U SA 89,
63. Linnane A.W., Zhang C., Baumer A., Nagley P. (1992)
Mitochondrial DNA mutation and the aging process:
bioenergy and pharmacological intervention. Mutation
Research 275, pp. 195-208.
64. Martinius R.D., Linnane A.W., Nagley P. (1993) Growth of
human namalwa cells lacking oxidative phosphorylation can
be sustained by redox compounds potassium ferricyanide or
coenzyme Q10 putatively acting through the plasma
membrane oxidase. In: Biochem. Mol. Biol. Internat. 31,
65. Lawin A., Martinius R.D., McMullen G., Nagley P., Vaillant
F., Wolvetang E. J., Linnane A.W. The universality of
bioenergetic disease: The role of mitochondrial DNA
mutation and the putative inter-relationship between
mitochondria and plasma membrane NADH oxidases. In:
Eighth International Symposium on Biomedical and Clinical
Aspects of Coenzyme Q (1994) Littarru G.P., Battino M. ,
Folkers K. (Eds) The Molecular Aspects of Medicine, Vol.
15 (Supplement), pp S13-S27.