Coenzyme Q:The Ubiquitous Quinone
Part III
This article first appeared in the
November, 1993
issues of VRP's newsletter
Coenzyme Q:
The Ubiquitous Quinone Part I
Coenzyme
Q: The Ubiquitous Quinone Part II
Coenzyme Q: The Ubiquitous Quinone Part III
by A.S. Gissen
In part 2 of our review of Coenzyme
Q10 (CoQ10), we examined the broad spectrum of research into CoQ's
role in varied conditions such as cancer, muscular dystrophies, physical
performance and athletics, diabetes, and periodontal disease. In the third
and final part of our look at CoQ, we will explore the role that CoQ10 plays
in immune function, antioxidant protection, and brain function.
CoQ and Immune Function
Vitamin and nutritional deficiencies are well known to be common causes of
immunodeficiencies. Persons having nutritional and vitamin deficiencies have
impaired cell-mediated immunity, as well as decreased microbicidal activity
of immune cells and increased susceptibility to infections. Being vitally
important to the generation of cellular energy, it is not surprising that
deficiencies of CoQ result in suppression of the immune system. However, the
result of supplemental CoQ10 is quite provocative, as it produces a
significant enhancement of the immune system in both normal and
immuno-depressed animals.
In 1970, it was first reported that CoQ6 and CoQ10, when administered to
rats, significantly enhanced the activity of immune cells' ability to kill
bacteria, as well as elevating their antibody response.(44) By 1982, more
than half a dozen studies had documented significant immunological
enhancement following the administration of CoQ10. These results included
decreasing the number of tumors, and increasing the number of survivors,
following exposure to carcinogens;(45) increasing the number of survivors
following exposure of rats to a leukemia-inducing virus, which interestingly
caused a CoQ deficiency after infection;(46) and reversing an age-related
decrease in CoQ levels in the thymus of aging animals.(47) The immune
potentiating activity of CoQ was paralleled by a protection of
immune-suppressed animals against otherwise lethal infections.(48) When
compared to other antioxidants like vitamin E, it was found that these
immune-enhancing properties were specific to CoQ, as the antioxidants did not
stimulate the immune system to an equal degree.(49) A similar activity of
CoQ10 was also found in human patients with conditions such as diabetes,
cancer, and cardiovascular disease, with CoQ10 administration resulting in
significantly enhanced levels of immunoglobulins (IgG).(50)
At a 1981 conference on Coenzyme Q, several reviews were presented that
documented the significant role that CoQ has on immune function.(51) The
conclusions of these researchers were that:
1. In extensive studies, using many experimental models which evaluated
various parameters of immune function (phagocytic rate, antibody level,
cancer, viral, and parasitic infections), a role of CoQ as an
immuno-modulating agent was established.
2. During some infections and aging, an organism develops a Coenzyme Q-
enzyme deficiency.
3. Results indicate that CoQ is an important component, probably at the
mitochondrial level, for the optimal function of the immune system.
4. The lack of toxicity, as demonstrated in clinical and experimental tests,
indicates that CoQ10 is an appropriate candidate for clinical application in
disease states where the immune system is not functioning at an optimal
level.
5. Research indicates that tumors, infections, and some of the
immunity-related "diseases of aging" should be included in a new
entity, "diseases of bioenergetics."
CoQ and AIDS
While the above results are certainly provocative, the most exciting
immune-related research on CoQ10 has been in the area of Acquired Immune
Deficiency Syndrome (AIDS). In the early 1990's, a series of reports were
published showing that CoQ10 deficiency could play a role in the development
of AIDS. These investigations were begun after the observation that, among
other things, many AIDS patients have significant heart-function failure,
similar to persons with CoQ10-deficiency related heart-failure.(52)
Subsequent measurements of blood CoQ10 levels revealed that Human
Immunodeficiency Virus (HIV) positive patients that were asymptomatic had
normal levels of CoQ10, Aids Related Complex (ARC) patients had significantly
lower levels, and full- blown AIDS patients had the lowest levels. Thus, AIDS
was associated with CoQ10 levels that were severely and significantly
depressed, while HIV-positive persons without symptoms had normal levels that
declined as they progressed to ARC, and further declined as they developed
AIDS. Based on these investigations, a small pilot-study was begun to
investigate the effects of CoQ10 supplementation on patients with ARC and
AIDS. The results of this study showed that ARC patients on CoQ10 therapy
remained free of opportunistic infections and didn't progress to AIDS over a
period of more than 4 years. The authors concluded that this excellent
clinical response was possibly because, "... the delicate equilibrium
between host and virus has been tipped in favor of the host in this disease
state through the use of oral CoQ10."(52)
CoQ and Peroxidation
Free-radical mediated lipid-peroxidation appears to be of critical importance
in various degenerative diseases, including atherosclerosis. Studies have
suggested that the oxidative modification of low-density lipoprotein (LDL) is
central to the induction of atherosclerotic changes in blood vessels. In
research comparing the relative effectiveness of various antioxidants in
preventing free-radical induced peroxidation of LDL, CoQ10 was found to be
more effective than either lycopene (a carotenoid), beta- carotene, or
vitamin E.(53) This effect was specific to the reduced form of CoQ10
(ubiquinol), and not oxidized CoQ10 (ubiquinone). Although oxidized CoQ10
(ubiquinone) is the only supplemental form of CoQ10, other studies have shown
that dietary supplementation with CoQ10 results in increased levels of
reduced CoQ10 (ubiquinol) within circulating lipoproteins, as well as
increased resistance of LDL to the initiation of lipid peroxidation.(54) It
appears that after oral supplementation, CoQ10 appears mainly in its reduced,
antioxidant form in the body. Not surprisingly, research has shown that the
ratio LDL to CoQ10 is an important indicator of the risk of developing
atherosclerosis, being even more important than the often cited ratio of HDL
to total cholesterol.(55) Indeed, while CoQ10 has been repeatedly shown to be
a physiologically important lipid-soluble antioxidant, it may be the most
important lipid-soluble antioxidant.
CoQ and Brain Function
It is well established that deficiencies of myocardial CoQ10 results in
derangements of cardiac energy production, eventually leading to cardiac cell
death. This is the biochemical basis for the success in using CoQ10 in
cardiomyopathy. Recent evidence now shows that a similar mechanism may be
involved in degenerative brain disorders. In the case of Parkinson's disease,
research has shown that deficiencies in CoQ10-dependant enzymes may play a
part in the development of the cell death that results in Parkinson's
disease.(56) In Alzheimer's disease, as well, deficiencies of CoQ10-dependent
enzymes have been found.(57) Attempts to improve the mental functions in
Alzheimer's patients have been very encouraging, with reversals of mental
deterioration being documented in several studies, including those using
genetically-confirmed Alzheimer's patients.(58) Although these preliminary
studies await confirmation, it is not surprising that CoQ10 deficiencies,
leading to cellular energy deficiencies, would result in the cell death that
is a hallmark of both Parkinson's and Alzheimer's disease In fact, the use of
supplemental CoQ10 to prevent brain deterioration has been an indicated use
of CoQ10 for many years in Japan.(59)
Using Coenzyme Q10
With the vast amount of positive results that have been published about CoQ10
in the last three decades, it is not surprising that CoQ10 has become one of
the best- selling supplements in the United States. Few dietary supplements
are as well proven, or hold as much potential for improving health, as does
CoQ10. However, as with any biologically-active dietary supplement, how CoQ10
is used is important in order to attain maximum benefit from supplementation.
CoQ10 is fat-soluble, and like most other fat-soluble compounds, is poorly
absorbed from the gastrointestinal tract, especially when taken on an empty
stomach. For this reason it is important to take CoQ10 with meals to ensure
maximum absorption. The dosage of CoQ10 is also a very important
consideration. Although small dosages of CoQ10 will ensure a good dietary
amount of CoQ, and prevent the decrease in blood levels seen when purified
diets free of CoQ are consumed, they will not significantly raise blood
levels in persons with depressed CoQ10 levels due to disease or aging. Human
research has found that doses of at least 30 milligrams are needed to
significantly raise blood levels of CoQ10.(60) Due to the vast amount of
research that has been conducted on CoQ10 supplementation, dosages have
varied over a wide range. In most of these studies CoQ10 was administered in
two or three divided doses, with meals, throughout the day. The usual dosages
used to correct CoQ10 deficiency in disease states has been from 60 to 200
milligrams a day. Also, the increase in blood levels seen after
supplementation is not uniform, as some people seem to absorb CoQ10 poorly
and require larger doses to attain maximum benefit. One important
consideration to keep in mind when determining the appropriate dosage is that
despite rarely occurring nausea or gastrointestinal upset, toxicity and
side-effects have not been encountered in several decades of clinical use at
doses up to several hundred milligrams a day. Younger persons, as well as
persons with no CoQ10-related deficiency disease, may wish to supplement with
CoQ10 in doses of 10-30 milligrams in one daily dose, or even consider taking
30 milligrams with one meal every other day. CoQ10 is fat-soluble, and has a
half-life in the body of several days, so healthy persons can benefit from
less frequent supplementation than those who have CoQ10-related diseases, and
should take CoQ10 in several doses throughout the day.
When purchasing CoQ10,
the purity of the material should be carefully considered. Very few companies
in the world manufacture CoQ10, and the pharmaceutical- grade product in its
pure state is a bright yellow to orange color. CoQ10 has a very long
shelf-life when protected from light and excessive heat, with little
deterioration occurring over periods of up to several years at room
temperature. When exposed to light, however, CoQ10 will degrade quite
rapidly. If a CoQ10 product is being sold at a price that seems to good to be
true, it probably is. Production of CoQ10 can barely meet the world-wide demand.
Prices are relatively uniform between the different primary manufacturers,
and should be among the different retailers.
The following book offers a good general review of CoQ research for the
layperson:
E. Bliznakov, Coenzyme Q: The Miracle Nutrient. Bantam Books, NY. 1986.
The following six volume set offers a good review of CoQ research for the
scientist:
K. Folkers, et al.(eds): Biomedical and Clinical Aspects of Coenzyme Q, Vol.
1-6, Elsevier Science Publishers, Amsterdam. 1976 - 1991.
References: Part 3
44) E.G. Bliznakov, A.C. Casey, E. Premuzic, Experentia 1970; 26: 953-954.
45) E.G. Bliznakov, Proc Nat Acad Sci USA 1973; 70: 390-394.
46) E.G. Bliznakov, A.C. Casey, T. Kishi, et al, Internat J Vitam Nutr Res
1975; 45: 388-395.
47) E.G. Bliznakov, T. Watanabe, S. Saji, et al, J Med 1978; 9: 337-346.
48) G. Hogenauer, P. Mayer, J. Drews, In: K. Folkers and Y. Yamamura (eds.),
Biochemical and Clinical Aspects of Coenzyme Q, Vol. 3. Elsevier / North
Holland Biomedical Press, Amsterdam. 1981, p. 325-334.
49) A.C. Casey, E.G. Bliznakov, Chem-Biol Interactions 1972; 5: 1-12.
50) K. Folkers, S. Shizukuishi, K. Takemura, et al, Res Commun Chem Path
Pharm 1982; 38: 335-338.
51) E.G. Bliznakov, In: K. Folkers and Y. Yamamura (eds.), Biochemical and
Clinical Aspects of Coenzyme Q, Vol. 3. Elsevier / North Holland Biomedical
Press, Amsterdam. 1981, p. 311-323.
52) P.H. Langsjoen, P.H. Langsjoen, K. Folkers, In: K. Folkers, G.P.
Littarru, and T. Yamagami (eds.), Biochemical and Clinical Aspects of
Coenzyme Q, Vol. 6 Elsevier Science Publishers, Amsterdam. 1991, p. 409-415.
53) R. Stocker, V.W. Bowry, B. Frei, Proc Natl Acad Sci USA 1991;
88:1646-1650.
54) D. Mohr, V.W. Bowry, R. Stocker, Biochem Biophys Acta 1992; 1126:
247-253.
55) Y. Hanaki, et al, N Engl J Med 1991; 325: 814-815.
56) T. Matsubara, T. Azuma, S. Yoshida, et al, In: K. Folkers, G.P Littarru,
and T. Yamagami (eds.), Biochemical and Clinical Aspects of Coenzyme Q, Vol.
6. Elsevier Science Publishers, Amsterdam. 1991, p. 159-166.
57) C. Edlund, M. Soderberg, K. Kristensson, et al, Biochem Cell Biol 1992;
70: 422-428.
58) M. Imagawa, et al, Lancet 1992; 340: 671.
59) K. Anderson: Orphan Drugs. New York: The Linden Press / Simon &
Schuster, 1983, p. 238-239.
60) T. Kishi, T. Okamoto, N. Kanamori, et al, In: K. Folkers and Y. Yamamura
(eds.), Biochemical and Clinical Aspects of Coenzyme Q, Vol. 3. Elsevier /
North Holland Biomedical Press, Amsterdam. 1981, p. 67-70.