NEW CoQ10 Breakthrough: Our

In Focus
I n n o v a t i v e
NutriCology® Newsletter
®
N u t r i t i o n
November 2007
NEW CoQ10 Breakthrough: Our
Most Potent Fat-Soluble Antioxidant Now
Available in its Natural Reduced Form
In This Issue
CoQ10 Breakthrough: Our Most
Potent Fat-Soluble Antioxidant
Now Available in its Natural
Reduced Form . . . . . . . . . . . 2
A Matter of Life and Death:
Antioxidants and the Morbidity Index . . . . . . . . . . . . . . . . 8
Oxidation and Antioxidants:
A Key to the Most Baffling
Illnesses of Our Time. . . . . .10
Germanium for Energy and
Immunity . . . . . . . . . . . . . . 12
Coenzyme Q10 has been called one of the miracle nutrients of our time, and
for good reason. Interest in this nutrient is now skyrocketing, with large, multicenter Phase III clinical trials scheduled in Parkinson’s, Huntington’s and Alzheimer’s diseases, and the publication this past June of a 200 page special issue
of the journal Mitochondrion entirely devoted to coenzyme Q10. And yet for the
last 30 years coenzyme Q10 has only been available as a supplement in its oxidized form, called ubiquinone. Now the antioxidant form, ubiquinol, has been
made available as a stable, effective supplement for the first time.
Ubiquinol is highly bioavailable and seems to have even more striking effects
than regular CoQ10. Just 150 mg per day of ubiquinol may provide the same
high CoQ10 blood levels as 1200 mg of enhanced-delivery ubiquinone. When
healthy volunteers in their fifties took regular CoQ10 for a year, they could not
attain the plasma levels that similar volunteers attained in a mere 3 months with
the new CoQ10.
Turn to page 2 for more on Ubiquinol.
A Matter of Life & Death: The Morbidity Index
The ratio of antioxidant and oxidized molecules predicts recovery from disease. We call this “the morbidity index.” See how vitamin C and CoQ10 ratios
are key indicators of health and fitness.
Turn to page 8 for more on Antioxidants and the Morbidity Index.
New Data Supports The Revolutionary Theory
of Antioxidant Adaptation
A fresh look at Stephen Levine's landmark theory, presented in his classic text, Antioxidant Adaptation, along with the newest findings and innovations in the field.
Turn to page 10 for more on Antioxidant Adaptation.
NutriCology®
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Germanium for Energy and Immunity
Organic germanium may be a promising and safe agent to offset hypoxia, create
energy and support immunity. New research is ongoing for this amazing and
under-utilized oxygen nutrient.
Turn to page 12 for more on Germanium, Energy and Immunity.
CoQ10 Breakthrough: Our Most Potent
Fat-Soluble Antioxidant Now Available
in its Natural Reduced Form
Reduced, Electron-Rich Coenzyme Q10 is Now Here
Coenzyme Q10.
It’s a key molecule in one of the 20th
century’s most significant Nobel Prize
winning discoveries—solving the
puzzle of how our cells make energy.
It’s in every single one of the fifty trillion cells in our bodies, inside the mitochondria. It’s a potent antioxidant—
the only fat-soluble antioxidant our
bodies make—and there’s more of it
in our cell membranes than any other
lipid-based antioxidant.
It’s powerfully protective
against
cardiovascular
disease, and can be of astonishing help to patients
suffering heart failure.
It may slow the onset of
Parkinson’s and Huntington’s disease, and is
an indispensable antiaging nutrient.
• Ubiquinol is so readily bioavailable
in comparison to ubiquinone (oxidized CoQ10) that plasma levels increased from .59 µg/ml to .91 µg/ml
in young people, and from .82 µg/ml
to 1.33 µg/ml in older healthy people
after supplementation.
is a major biochemical feat that will have
far-reaching health consequences, and allow
us to study CoQ10’s impact on aging and
disease much more effectively.
And yet until now—in fact, for the last
30 years—CoQ10 has only been available as a supplement in its oxidized
form. That form is called ubiquinone.
To replenish our bodies by taking the
supplement, we’ve had to swallow
oxidized coenzyme Q10 and convert
it to the antioxidant form, known as
ubiquinol. Only a small percentage of
a standard oral dose of regular CoQ10
In Focus November 2007
In brief, here are a few impressive highlights of the new research:
• When healthy volunteers in their
fifties took regular CoQ10 for a year,
they could not attain the
plasma levels that simiInitial studies and impressive word-oflar volunteers attained
a mere 3 months with
mouth suggest the manufacture of ubiquinol in
the new CoQ10.
It has been called one of the miracle
nutrients of our time, and for good
reason. Interest in this nutrient is now
skyrocketing, with large, multi-center
Phase III clinical trials scheduled in
Parkinson’s, Huntington’s and Alzheimer’s diseases, and the publication this past June of a 200 page special issue of the journal Mitochondrion
entirely devoted to CoQ10 (1).
2
is actually bioavailable, according to
cardiologist Salvatore Pepe of the Department of Cardiothoracic Surgery at
Alfred Hospital and Monash University in Australia (2). Even so, CoQ10 is
so potent that the oxidized supplement
alone has been the subject of over 1500
peer-reviewed studies on the supplement’s powerful protective health effects. In some studies, individuals have
needed doses as high as 3,000 milligrams a day of ubiquinone to increase
blood levels enough to make a difference in disease.
But now all that has changed. A new
form of stable ubiquinol, the actual
antioxidant form of coenzyme Q10,
has been made available in a stable
form for the first time. Ubiquinol is
the form that is found 95% of the time
in our blood, the form that actually
quenches free radicals and helps prevent disease. It is also seems to have
a higher degree of bioavailability.
Initial studies and impressive wordof-mouth suggest the manufacture
of ubiquinol is a major biochemical
feat that will have far-reaching health
consequences, and allow us to study
CoQ10’s impact on aging and disease
much more effectively.
level.
• When
individuals
were given 300 milligrams daily of ubiquinol for four weeks, their
blood levels increased
eleven-fold over baseline, a remarkably high
• In a recent study, ubiquinol was
given to children at both low and high
doses—1 mg/kilogram of weight and
10 mg/kilogram of weight per day for
one month. Blood levels were comparable to data from studies involving
much higher doses of regular CoQ10
(2400 to 3000 mg/day).
• The highest net increase in blood levels in any study to date occurred using
ubiquinol at a dose of 600 milligrams
daily. Levels of 10.7 umol/L were
achieved—higher than in any previous
study of CoQ10.
• Early case reports indicate that
ubiquinol packs a powerful punch and
may save lives. In one report, a Class
IV heart patient dying of heart failure,
with an ejection fraction of only 15%,
and little response to regular CoQ10,
took ubiquinol and nearly tripled his
ejection fraction.
The Power of CoQ10:
Highlights of 30 Years of
Remarkable Research
a carrier in the mitochondrial electron
transport chain.
Interestingly, white blood cells contain high amounts of CoQ10, while
red blood cells have very little. In one
study it was found that there was a
clear, dose-dependent relationship be-
scientist Randar S. Sohal and his colleagues at the University of Southern
California note in the June issue of Mitochondrion (3), “Oxygen is the basis of
our life on earth. And yet, paradoxically, it is a very toxic substance under a number of conditions. Oxygen
You probably know it well: that orange
colored powder or gel supplement
called coenzyme Q10, one of the most
popular nutritional supplements of
the last few decades, so effective that
in 2006 health-conscious individuals
bought over $400 million worth of the
supplement. The nutrient has a remarkable safety profile, and as remarkable a
history of benefiting individuals with
heart disease, diabetes, and neurodegenerative diseases like Parkinson’s
and Huntington’s. In a major NIHfunded study on Parkinson’s patients,
CoQ10 supplements slowed disability
by 44%.
CoQ10 is best known for its protective
effect on the heart, with over 35 placebo
controlled trials in cardiovascular disease. It contributes to 95% of the cellular ATP production to the heart muscle.
In Japan it has been an approved drug
for congestive heart failure for the last
30 years.
Even aging skin seems linked to decreased CoQ10. Between the ages of
30 and 80, levels of CoQ10 in the epidermis drop dramatically. CoQ10 may
protect the skin against damage from
UV radiation.
Figure 1. CoQ10 Distribution in the Body
The concentration of coenzyme Q10 is higher in such organs as the
heart, kidney, liver, muscle, pancreas, and thyroid gland.
tween CoQ10 and ATP in white blood
cells. Scientists looked at ascorbic acid,
vitamin E, riboflavin, thiamine, niacin,
vitamin K and carnitine. But none had
a significant effect on ATP synthesis.
Only CoQ10 did.
radicals, such as hydrogen peroxide,
singlet oxygen, and ozone, are called
reactive oxygen species (ROS). But all
organisms have antioxidant defense
systems to limit ROS.”
Like all antioxidants, CoQ10 exists in
an electron-rich (called “reduced”)
Just as important is its lipid antioxi- form, which donates electrons to highdant ability, especially because it is ly reactive, unstable molecules like perCoenzyme Q10 has two pivotal roles inside the cell, the mitochondria, and
oxides—and stabilizes
in our bodies: energy
them. That’s ubiquinol.
metabolism and lipidOnce it has donated its
soluble antioxidant pro"We have now repeated and are continuing electrons, it is oxidized.
tection. CoQ10 is a key
That’s
ubiquinone.
factor in producing ATP, to treat several other patients with end-stage Then it needs to be rethe universal energy curor far advanced congestive heart failure
cycled so it once again
rency of all living cells.
becomes electron rich
with similar remarkable findings"
In 1978, scientist Peter
(“reduced” back to the
Mitchell was awarded the
ubiquinol form).
Nobel Prize for deciphering how electron transfer in cells is in our cell membranes. It is the most Because of its energy-rich, antioxidantcoupled to ATP synthesis. CoQ10 is an important antioxidant nutrient in the rich ability, there can hardly be a more
essential co-factor in this process. It is mitochondria. As pharmaceutical significant impact than CoQ10’s on agContinued next page
For more information call 800-545-9960 or visit www.nutricology.com
3
cording to Barry, levels start declining
around age 20 and by age 40 the drop
is noticeable. Peak values in the lungs,
heart, spleen, liver, and kidneys are observed at 20 years of age (Figure 2).
“A steady, lifetime decrease in CoQ10
is far more common than we may have
assumed,” states biochemist Magnus
Bentinger of Stockholm University and
the Rolf Luft Center for Diabetes and
Endocrinology in Stockholm (6).
Figure 2. Age-Related Decrease in Coenzyme Q10
The concentration of coenzyme Q10 in the body decreases year
by year, indicating that it has a close relationship with aging.
ing and health. Biosynthesis of CoQ10
occurs in all tissues and cells in animals
and is present in all membranes. It is
found in particularly high levels in the
heart, kidney, and liver, as well as the
muscle, pancreas and thyroid (Figure 1).
When we are young and healthy, we
synthesize CoQ10 entirely ourselves.
As we age, we make less and less. And
if we’re chronically ill, we rapidly deplete this essential substance. It’s hard
to get CoQ10 from our diet (15 pounds
of peanut butter contains 100 milligrams, a reasonable daily supplement;
three pounds of sardines, a food ‘rich’
in CoQ10, provides 100 milligrams
as well). And as we lose our ability to
synthesize enough of it, we end up vulnerable to aging and ill health (Figure
2). As our CoQ10 stores fall because of
increased metabolic demand, disease,
deficiency of precursors and enzymes
that synthesize it, and oxidative stress,
we suffer. That slow, continuous decline
becomes apparent around forty years
of age, and according to Robert J. Barry,
Ph.D., a former advisor for the National
Institute of Health, and currently in Scientific Affairs at Kaneka Nutrients, the
world’s leading supplier of CoQ10, is
linked to age-related conditions such as
4
In Focus November 2007
heart disease, neurodegenerative diseases, cancer, diabetes, and the profound
loss of stamina and energy that we all
associate with growing old (4).
As Dr. Barry states: “It is very important
to note that CoQ10 concentrations in the
body decrease steadily as we age, and
this decrease has been associated with
the aging process itself, as well as agerelated degenerative diseases”(5). Ac-
CoQ10 is the only lipid-soluble antioxidant we make, present in all membranes.
Forty years of research has shown that
CoQ10 prevents both lipid and protein
oxidation, and even DNA oxidation (3).
And it prevents both the initiation and
the propagation of lipid peroxidation
(unlike, for instance, vitamin E, which
only inhibits propagation).
Because CoQ10 is essential for the production of cellular energy, supplementing it enhances stamina and health.
Millions of people have taken CoQ10
supplements with no reported toxicity
in over a thousand human and clinical
trials. According to Dr. Barry, “Some
reports say this decline in coenzyme
Q10 becomes apparent around 40 years
of age, some reports say as early as 20
years with slow but continuous decline.
The result is less cellular energy, slower
conversion to the reduced form and subsequently diminished protection against
oxidative insult.”
Figure 3. Reported Plasma Ubiquinol: Ubiquinone
Ratio in Humans
As blood glucose rises in diabetic patients, the amount of
ubiquinol drops.
Ubiquinol: Why the
Antioxidant Form of
CoQ10 is So Potent
The antioxidant action of the reduced
form of CoQ10 (ubiquinol) is now considered to be one of its most important
protective functions in cellular systems.
As pure as snow (because it is not oxidized, the familiar orange color of regular
CoQ10), ubiquinol was first manufactured and commercially available in stable form in 2006, by Kaneka Pharmaceuticals, the world’s primary manufacturer
of ubiquinone. Ubiquinol carries two additional hydrogen atoms—two extra electrons. Biologically, the difference between
the two is therefore enormous.
Autopsies and fresh animal dissection
show that ubiquinol is the main form
of CoQ10 in tissues. And similarly,
about 95% of CoQ10 in the blood is
in the form of ubiquinol. In the blood,
CoQ10 helps regenerate vitamin E. It
protects against the oxidation of cholesterol—more powerfully than other
major antioxidants including lycopene,
beta-carotene, and tocopherol (7).
2005 study found that diabetics have
an astounding 75% less ubiquinol
overall compared to healthy individuals (Figure 3). The same profound loss of
ubiquinol was found in people with
chronic liver disorders such as hepatitis, cirrhosis and hepatoma.
Disorders marked by oxidative stress
cause large shifts in the amounts
of ubiquinol and ubiquinone in the
body. This is referred to as the ratio
(ubiquinol:ubiquinone). In a 2005
Japanese study of diabetics, oxidative
stress increased over the course of the
day, while the ratio declined. Another
Perhaps the most impressive aspect
of the new ubiquinol data is how bioavailable the supplement is. It is absorbed quickly and in high amounts
in older people—far higher than
regular CoQ10. This is an extremely
strong indication that the body needs
and wants to assimilate ubiquinol.
Based on recently published absorp-
Ubiquinol: Uniquely
Bioavailable
A Cardiologist’s Firsthand Report: I have not seen this
in 25 years of cardiology practice
A noted U.S. cardiology group (currently submitting their research to a peer-reviewed medical journal, so must
remain anonymous until the article is accepted and published) has this to say about ubiquinol: “It is my strong feeling that this ubiquinol product is a major breakthrough. I have carefully reviewed our experience with ubiquinol
beginning last summer when we initially evaluated this product in healthy subjects. I will briefly summarize this
as follows:
In September 2006, a healthy 52 year old woman on 100 mg three times per day of CoQ10 oxidized formulation in
soybean oil, had plasma CoQ10 level of 2.5 µg/ml with 0.7% oxidized and the ratio of CoQ10 to cholesterol was
0.5 µmol/mmol. After one month of taking ubiquinol 100 mg three times per day, plasma CoQ10 was rechecked in
October 2006, and had more than doubled to 5.2 µg/ml with 0.5% oxidized, and CoQ10 to cholesterol ratio had essentially doubled up to 1.1 µmol/mmol. This very encouraging improvement in plasma level in healthy individuals led us to further evaluate the reduced CoQ10 product in critically ill patients with advanced congestive heart
failure with life expectancy less than six months, and actually in several cases, less than three months.
Our first patient was a 65-year-old gentleman with advanced ischemic cardiomyopathy who was on maximal
medical therapy with diuretics, digitalis, beta-blocker, coumadin, and a biventricular implantable cardiac defibrillator, who was steadily going downhill requiring frequent admissions for Class IV congestive heart failure with
severe recurrent pulmonary edema and lower extremity edema….This gentleman’s evaluation in June 2006, on
450 mg of soybean oil based CoQ10 revealed a plasma CoQ10 level that was sub-therapeutic at 1.6µg/ml, and an
echocardiogram on that date revealed a 15% ejection fraction with moderately severe mitral regurgitation. The patient was then changed to the ubiquinol formulation at exactly the same dosage of 450 mg daily, and by September
2006, approximately three months later, the plasma CoQ10 level increased dramatically up to 6.4 µg/ml with an
echocardiogram performed the following month October 2006, showing an improvement in ejection fraction up to
the 35%-40% range and a reduction in the degree of mitral regurgitation down to moderate. By this time, the patient was no longer requiring any diuretics and his functional status was markedly improved. By January 2007, his
echocardiogram showed further improvement up to a 45% ejection fraction and continued clinical improvement
to the point of becoming quite active, and he has required no further hospitalizations. This single case represents
very striking improvement that I have not seen before in 25 years of cardiology practice. We have now repeated and
are continuing to treat several other patients with end-stage or far advanced congestive heart failure with similar
remarkable findings” (Figure 6).
Continued next page
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5
Figure 4. Comparison Ubiquinol and Ubiquinone Absorption in
Older Health Subjects
In older, healthy individuals, ubiquinol absorption is more than
twice as high.
tion studies, just 150 mg per day of
ubiquinol would provide virtually
the same high CoQ10 blood levels as
1200 mg of enhanced-delivery ubiquinone CoQ10. Human studies show
that ubiquinol increases blood CoQ10
levels several times more efficiently
than ubiquinone (8,9) (Figure 4).
According to a review in Mitochondrion by Hemmi Bhagavan and Raj
Chopra (7), individuals taking 300
milligrams of ubiquinol for four
weeks daily reached “a markedly
high value of 8.413 umol/L, an 11fold increase over baseline.” And
according to the authors, when children were given either 1 milligram
per kilogram of body weight per day,
or a high dose of 10 milligrams per
kilogram of body weight per day, after one month their blood levels were
comparable to the levels achieved by
much higher doses of ubiquinone (up
to 3000 milligrams a day).
CoQ10 is better absorbed with fat
(this was first discovered by asking
patients to consume it with peanut
butter). Soluble gel forms of CoQ10
are better absorbed overall. According to Bhagavan and Chopra, solubilized ubiquinone is “far superior to
the powder-based” supplements, and
“solubilized ubiquinol is even better.”
In other words, solubilized ubiquinol
seems to be best of all.
6
In Focus November 2007
Aging is Dramatically
Slowed by Ubiquinol in
Special Mice Studies
Sometimes a picture literally is worth a
thousand words. And this picture of 3
“senescence-accelerated mice” at age
14 months is just that (Figure 5) (10).
These are mice bred to age quickly, so
that we can study markers of aging
more effectively. Senescence-accelerated mice grow normally, but show
early signs of aging, including markedly reduced physical activity, loss of
hair glossiness, coarse skin, hair loss,
lesions in and around the eye, and curvature of the spine. The control mouse
looks painfully hunched and aged, the
victim of severe degenerative changes.
The mouse given regular CoQ10 looks
a bit better, but still has aged rapidly.
However, the mouse given ubiquinol is
in far better shape than its peers.
It turns out that ubiquinol is 40% more
effective than conventional CoQ10 in
slowing aging markers in middle-aged
senescent-accelerated mice, and over
50% more effective than no supplementation at all. At around three months of
age, aging started to spike in the control group. When middle age set in (at
about eight months), both ubiquinol
and ubiquinone were helpful, slowing
aging by about 45%.
It was at 10 months of age that the
remarkable data showed up. By ten
months, mice receiving ubiquinol aged
51% slower than the control group and
Figure 5. Anti-Aging Activity of Ubiquinol
This illustrates the powerful anti-aging impact of ubiquinol
supplementation on 14 month old SAM (senescence-accelerated mice).
shows that for the first two or three
weeks, if you take 2-300 milligrams per
day, the levels in your plasma plateau
out during this period of time, and
then 50-100 milligrams a day is a good
maintenance dose. If you’re over age 40
or have any type of metabolic disease
that would indicate an ongoing level
of oxidative stress, ubiquinol may be
more effective.”
Figure 6. Ubiquinol Supplementation in Stage IV CHF Patient
This patient, critically ill and in Stage IV heart failure, improved
remarkably on ubiquinol supplementation. His ejection fraction
tripled in a mere 3 months.
40% slower than the group receiving
ubiquinone. And by twelve months, according to the researchers, the control
mice were immobile and unresponsive, showing lesions in and around
the eye, with spinal and limb deformities and a patchy, discolored coat. In
contrast, the aging mice supplemented with ubiquinol were reported to be
alert, responsive and energetic with no
physical lesions or deformities, and a
glossy coat resembling that of a young,
healthy mouse (10).
In other unpublished research, the same
scientists looked at the anti-fatigue effects of the ubiquinol and ubiquinone
in aged rats. A control group receiving
no CoQ10 showed a slight decline in
treadmill running time. In a group receiving regular CoQ10, running times
increased 60%. But the ubiquinol group
outshone them all: their treadmill times
increased a remarkable 150%.
This is impressive news considering
regular CoQ10’s already remarkable efficacy profile: A meta-analysis of the use
of CoQ10 in randomized clinical trials
in patients with congestive heart failure
showed a significant and clinically relevant improvement of heart function, in
some cases doubling the survival rate.
What even more remarkable news might
ubiquinol hold for the heart? According
to Dr. Barry, “A cardiology group is submitting a case report to a refereed medical journal. Look at Figure 6: the patient
was already on regular CoQ10, which
helped to some degree. Three months
later, after 450 milligrams of ubiquinol
daily, his ejection fraction had almost
tripled. The doctors said they had never
seen this type of recovery before. Now
other cardiology groups in the U.S. are
interested and will be initiating their
own studies.”
The Future: How Much
Ubiquinol to Take
The importance of CoQ10 (ubiquinone) should not be disqualified and has
nearly 30 years of research and clinical
evaluation demonstrating its considerable health benefits and excellent safety profile, according to Dr. Barry. As a
healthy twenty year old you are likely
to readily biosynthesize all the ubiquinol (reduced CoQ10) you can use. But
as you age, he says, “you produce less,
and the result is less cellular energy,
slower conversion to the reduced form
and subsequently diminished protection against oxidative insult. Ubiquinol
provides a strong first stage defense
against cellular oxidative insult/disease and needs to be replenished to
maintain optimum health.”
“In terms of dosages,” says Dr. Barry,
“of course patients should always consult with their healthcare provider first
before taking any supplement. Just as a
general rule, and everyone is different,
if you’ve never taken CoQ10 and are
going to start taking ubiquinol, research
If you are already on CoQ10, Dr.
Barry notes that, “Case studies with
cardiology patients show that higher
levels of ubiquinol may be useful.
The cardiology study used 450 milligrams a day. Doctors can have plasma levels taken.”
References
1. Mitochondrion: The official journal of the
Mitochondria Research Society, Affiliated
with the Japanese Society of Mitochondrial
Research and Medicine. Special Issue, The
Role of Coenzyme Q in Cellular Metabolism:
Current Biological and Clinical Aspects, Richard H. Haas, Guest Editor. Volume 7S (2007),
pp. 1-186.
2. Pepe S, Marasco SF, Haas SJ, Sheeran FL,
Krum H, Rosenfeldt FL. Coenzyme Q10 in
Cardiovascular Disease. Mitochondrion 2007,
June; Vol. 7S: 154-167.
3. Sohal RS, Forster MJ. Coenzyme Q, oxidative stress and aging. Mitochondrion 2007,
June; Vol.7S: 103-111.
4. Powerpoint Presentation, Robert J. Barry,
Ph.D., Scientific Affairs, Kaneka Nutrients, LLC.
5. Personal interview with Robert J. Barry, Ph.D.
6. Bentinger M, Brismar K, Dallner G. The antioxidant role of coenzyme Q. Mitochondrion
2007, June, Vol. 7S: 41-50.
7. Bhagavan HN, Chopra RK. Plasma coenzyme Q10 response to oral ingestion of coenzyme Q10 formulations. Mitochondrion 2007,
June; Vol. 7S: 78-88.
8. Hosoe K, Kitano M, Kishida H, et al. Study
on safety and bioavailability of ubiquinol after
single and 4-week multiple oral administration to healthy volunteers. Regul Toxicol Pharmacol 2007 Feb;47(1): 19-28.
9. Shults CW, Oakes D, Kieburtz K, et al. Effects of coenzyme Q10 in early Parkinson disease: evidence of slowing of the functional decline. Arch Neurol. 2002 Oct;59(10):1541-50.
10. Yan J, Fujii K, Yao J, et al. Reduced coenzyme Q10 supplementation decelerates senescence in SAMP1 mice. Exp Gerontol 2006
Feb;41(2): 130-40.
For more information call 800-545-9960 or visit www.nutricology.com
7
A Matter of Life & Death: Antioxidants
and the Morbidity Index
The Ratio of Reduced and Oxidized Molecules
Predicts Recovery from Disease
Disorders marked by oxidative stress
cause large shifts in the amounts of reduced (antioxidant) and oxidized nutrients. The antioxidant form plummets,
and the oxidized form rises. Recovery
is marked by a shift toward the antioxidant form. This has already been demonstrated in the case of vitamin C, and
it now appears to be the case with coenzyme Q10. This simple and powerful
truth has been overlooked by medicine
and science.
Millions of molecules move swiftly between oxidizing and reducing (antioxidant) states in our bodies all the time.
An oxidizing agent receiving electrons
becomes a reducing agent (thus, for example, coenzyme Q10 in its antioxidant
form can donate electrons to vitamin E
after it has been oxidized and recycle
that vitamin E so that it is once again
in its electron-rich, antioxidant form).
A reducing agent offering electrons becomes an oxidizing agent once it has
given up its electrons. Thus, oxidizing
and reducing agents form what science
calls a redox couple. They do a dance
of giving and receiving. The terminology can be a bit confusing to a layperson, but to sum it up: antioxidants are
electron-rich and in that antioxidant
form they are called “reduced”, and
can donate those electrons to stabilize
free radicals. Oxidized substances have
already lost their electrons. Free radicals are generally unstable, oxidized
compounds. They need electrons to
become stable. In their unstable, freeradical form, some of them are powerful killers of pathogens.
8
In Focus November 2007
Interestingly, the ratio of antioxidant
(reduced) to oxidant (free radical) in
the body seems to be a very important
marker of health or illness. Take ascorbic acid, perhaps our most potent water-soluble antioxidant, as an example.
Disease lowers the reduced form of
ascorbic acid to such a degree that one
may predict morbidity and mortality
based on the ratio of antioxidant (ascorbic acid) to oxidized (dehydroascorbic
acid) alone. It’s of great interest that we
now know the ratio of reduced (ubiquinol) to oxidized (ubiquinone) CoQ10
also changes radically in disease.
With vitamin C this ratio is so predictive we can predict, in very ill patients,
those who will recover from life threatening illness. We need more data on coenzyme Q10 to expand this picture to
lipid soluble antioxidants. When you
see data as consistent as this, you begin to get the sense that health and longevity depend on keeping the reduced
form of antioxidants at high levels,
with continuous and effective recycling
of the oxidized form.
Back in 1985, Stephen Levine, Ph.D.
& Paris Kidd, Ph.D. published a landmark text called Antioxidant Adaptation: Its Role in Free Radical Pathology.
Many of the insights in that 400 page
text, now in its fourth printing, have
been supported and confirmed again
and again by subsequent research. As
the authors noted then, ascorbic acid
is a diagnostic and prognostic tool.
As far back as the 1930’s, researchers
were able to determine the amount of
reduced (the electron-rich, antioxidant
form) ascorbic acid in the blood. But in
1943, new research methods were introduced that measured the total level of
ascorbic acid. This was deceptive, because it included not only the reduced
form, but also the oxidized (dehydroascorbic acid), along with other decomposition products of vitamin C. In
1955, researchers pointed out that both
the antioxidant and the oxidized form
of vitamin C could protect from scurvy
at low levels, but that at high levels the
oxidized form was toxic. In fact, as sick
patients became sicker, and finally died
from illnesses such as meningitis, tetanus, pneumonia, and typhoid fever, the
antioxidant form of ascorbate plummeted while the oxidized form rose. In
fact, many dying patients had higher
“total” levels of ascorbate (both forms)
than survivors. The magical “key” lay
in the ratio, which the authors termed
the morbidity index.
Look closely at Figure 7. The difference
in the ratio is astounding. Healthy individuals had a morbidity index of about
14—which means approximately 95%
of the vitamin C is in the antioxidant,
reduced form. This is parallel to the
new findings on CoQ10, although a
healthy individual taking high levels
of ascorbic acid would have an even
higher index. In contrast, those who
were critically ill but survived, had a
morbidity index of about 1, while those
who died had even less—a mere 0.3 to
0.5. During convalescence, the morbidity index tripled or even quintupled,
rising to 3.0 to 5.0.
Now take a look again at the ratio of
ubiquinol (reduced) to ubiquinone
(oxidized) in common diseases where
oxidative stress is high. In diabetes,
the percentage of ubiquinol plummets
from about 95% to 29% as blood glucose rises (Figure 3). Diabetics have an
astounding 75% less ubiquinol overall
compared to healthy individuals.
There is an elegant logic to this striking
correlation, and we are likely to find it
with other significant antioxidants as
well. Both ubiquinol and ubiquinone,
and ascorbic acid and dehydroascorbic acid, are part of the body’s oxidation-reduction system. Ascorbic acid
is known to be one of the most potent
redox stabilizers in the body. In turn,
CoQ10 is our most potent lipid-soluble
antioxidant, and the key antioxidant
in the mitochondria. The fact that in
both cases, healthy individuals seem to
maintain 95% of Vitamin C and coen-
zyme Q10 in their reduced, antioxidant
form is compelling data. To maintain
health, we believe the ratio must favor
high amounts of reduced, or antioxidant, forms of nutrients. Vitamin C had
long been available as a supplement in
its reduced form, and now we have the
reduced form of coenzyme Q10 available as a new supplement. Armed with
these and other important nutrients, we
may be on the verge of truly utilizing
the power of antioxidant adaptation.
Number
of
Patients
"Total"
Ascorbic
Acid
(mg/100 ml)
"Reduced"
Ascorbic
Acid
(AA)
(mg/100 ml)
"Oxidized"
Ascorbic
Acid
(DHAA)
(mg/100 ml)
Morbidity
Index
AA
DHAA
Normal
Meningitis
died
survived
convalescent
Tetanus
died
Survived
convalescent
Pneumonia
died
survived
convalescent
Typhoid fever
died
survived
convalescent
Chronic
tubercular
meningitis
28
0.93
0.87
0.06
14.0
8
17
11
1.22
1.04
0.72
0.27
0.43
0.53
0.95
0.61
0.19
0.3
0.7
2.8
13
12
12
1.09
0.93
0.89
0.36
0.52
0.74
0.73
0.41
0.15
0.5
1.3
5.0
7
19
15
0.98
0.83
0.75
0.30
0.43
0.59
0.68
0.40
0.16
0.4
1.0
4.0
4
19
15
0.80
0.80
0.83
0.24
0.45
0.68
0.56
0.35
0.15
0.4
1.3
4.5
17
0.83
0.50
0.33
1.5
Normal
Cholera
Smallpox
Pyogenic
Meningitis
Tubercular
Meningitis
Gonorrhea
Syphilis
16
21
16
0.95
0.99
1.07
0.89
0.62
0.51
0.06
0.37
0.56
14.8
1.7
0.9
16
0.80
0.35
0.45
0.7
16
16
16
0.92
0.79
0.92
0.74
0.53
0.74
0.18
0.26
0.18
4.2
2.0
4.2
Disease
and
Condition
Figure 7. Morbidity Index as a Prognostic Tool and Index of Survival
The figures for the last seven entries in the above table were calculated from the data of
Bhaduri et al. (1), while the rest are from Chakrabarti et al. (2).
1. Bhaduri JN, Banerjee S. Ascorbic acid, dehydroascorbic acid and glutathione levels in
blood of patients suffering from infectious diseases. Indian J Med Res 1960;48:208-11.
2. Chakrabarti B, Banerjee S. Dehydroascorbic acid levels in blood of patients suffering
from various infectious diseases. Proc Soc Exp Biol Med 1955;88(4):581-3.
For more information call 800-545-9960 or visit www.nutricology.com
9
Oxidation and Antioxidants:
A Key to the Most Baffling Illnesses of Our Time
by Stephen Levine, Ph.D.
In our last issue of Nutricology’s In
Focus newsletter, we addressed the
critical importance of the antioxidant
defense system and the crucial role
oxidative stress plays in many of the
most mystifying diseases of our age.
In particular, we covered the landmark
work of Dr. Martin Pall, Ph.D., who has
gathered substantial evidence that nitric oxide, superoxide, and ultimately
peroxynitrite (all are either free radicals or lead to free radicals) play a key
role in inflammatory cytokine activity
and oxidative cell damage central to
many of today’s baffling illnesses. Dr.
Pall’s new book is: Explaining “Unexplained Illnesses”: Disease Paradigm
for Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromyalgia,
Post Traumatic Stress Disorder, Gulf
War Syndrome and Others (1).
Think of metabolism as like a fire. We
burn energy to live. Food is our fuel.
Oxygen is our elixir, because it’s required for the burning to occur. Optimizing tissue oxygenation is necessary
for optimal health. But fires send out
dangerous sparks, or in our metabolic
fire, free radicals. Unchecked, fires burn
to excess, and turn houses and forests
into smoldering ash – or damaged tissue. And fires need water to quench
and cool the damage, and keep it contained. Antioxidants are our metabolic
water, as they cool out the side effects
of our burning metabolism.
dative stress, especially from toxins in
our environment.
• The ability to quench oxidative
stress with a potent store of antioxidants, so that we do not end up with
damaged tissue, either from excess free
radicals from stress or metabolism, or
from free-radical associated hypoxia.
I Sing The Body Electric
At the most fundamental level, the
ability to generate energy is electrical.
Electron transfer in the mitochondria
allows us to produce energy. The oxidative burst of immune cells results
in highly unstable oxygen species,
such as peroxides and free radicals, to
kill pathogens.
But the oxidative burst needs to be just
that—a burst, not a continuous fireworks. Free radicals, when chronically
elevated, damage cell membranes, enzymes, receptors, and proteins. Rapidly
proliferating oxidative reactions initiated by radicals and other activated species of oxygen liberated from damaged
blood vessels wreak serious havoc.
Much chemical toxicity is due to the
oxidative damage from those chemicals. This includes heavy metals, halogenated hydrocarbons, photochemical
oxidants in smog, and many therapeutic drugs. It is the body’s response to
the foreign chemical that leads to the
free radical damage and disease.
For good health we need:
• Oxygen. Our tissues need to be well- Chronic oxidative stress so damages tisperfused with oxygen, and our immune
system needs to effectively utilize the
oxygen in the oxidative ‘burst’ to kill
pathogens. I believe that the oxidative
burst is critical in immune function.
• The ability to adapt to chronic oxi-
10
In Focus November 2007
sues that they cannot effectively utilize
oxygen, and become hypoxic. The authoritative text, Robbins & Cotran The
Pathologic Basis of Disease (2), states,
“Hypoxia is probably the most common cause of cell injury and may also
be the ultimate mechanism of damage
initiated by a variety of physical, biological and chemical agents. Ironically
oxidative injury appears to occur from
hypoxia.” Halocarbon toxicity studies have consistently shown that if the
experimental animal is hypoxic during
the halocarbon insult, the resultant liver necrosis is much more extensive. By
itself, severe hypoxia produces hepatic
cell killing that resembles halocarbon
necrosis or alcohol necrosis. Thus a
hypoxic tissue state even moderate in
degree shifts the halocarbon dose response curve so that halogenated hydrocarbons are far more toxic under
hypoxic conditions. This is very relevant to all chronic disease.
A very powerful if tragic example of
chronic oxidative stress is mesothelioma—the lung cancer caused by
asbestos exposure. Asbestos itself is
inert. The lung cancer resulting from
exposure is caused by years of free
radical damage. Immune cells called
phagocytes spew out free radicals to
destroy pathogens. These free radicals are a key defense of our immune
system. When confronted with asbestos, the phagocytes do their job, and
spew out the free radicals, attempting
to destroy it. But they can’t. They are
actually known in science as “frustrated phagocytes.” It’s the free radical
damage over many years that actually leads to the lung cancer—not the
fibers themselves. This example demonstrates that even an inert fiber can
become toxic via oxidative damage.
Adapt or Die:
What Does Darwin’s
Insight Really Mean?
Adaptation is associated with an increase in antioxidant function. Stun-
ning research in the 1950’s and early
1960’s found that exposure to one toxic
chemical not only led to tolerance to
that chemical, but tolerance to other
similar chemicals. Rodents made tolerant to ozone also were rendered tolerant to ketene, nitrogen dioxide, nitrosyl
chloride, and phosgene. All of these are
oxidizing toxins. Upon re-exposure to
ozone or a new exposure to any of these
other compounds, animals previously
made tolerant could now survive levels
of exposure that would otherwise be lethal. In short, a prior exposure could be
life saving and only one exposure was
enough. In contrast, continuous exposure of mice to high, toxic levels of ozone
was more injurious than intermittent
exposures to the same levels. The intermittent exposures allowed the animals
to undergo adaptive processes. So, as
stress proceeds to affect us biologically,
oxidative damage is a key mechanism.
And much of our adaptation to stress
occurs via antioxidant adaptation.
A quick review of these powerful key
concepts: oxygen is a double edged
sword. Optimum levels are required
for health, but chronic oxidative stress
leads to permanent tissue damage via
free radical damage. I suggested over
20 years ago, in my first publications
about free radical damage, aging, and
disease that any serious stress could
increase free radical production and
that if we could monitor the amount
of free radicals we were generating we
would have a powerful diagnostic tool
in chronic illness (3).
The Conclusion: What
Really Counts
Living creatures have evolved a marvelous, ingenious antioxidant defense
system since the time, eons ago, when
the earth began to shift to an aerobic
rather than anaerobic atmosphere. We,
air breathing mammals, must have
sufficient antioxidants to contain the
havoc created by free radical damage.
In fact, here we have a distinct advantage. Pathogens, whether viral, bacterial, protozoan, or fungal, are generally
more sensitive to free radical damage
than we are. For instance, current research into three major classes of antibiotics that kill bacteria by completely
different mechanisms found that all
three kill bacteria in part via free radical damage. The research, published in
the journal Cell in September (4), used
a fluorescent dye that lights up in the
presence of hydroxyl molecules. The
researchers discovered that all three
classes of bactericidal drugs ramp up
the production of harmful free radicals.
Because those different types of antibiotics each initially hit different targets,
it had been believed they worked by
independent means. The fact is, pathogens don’t have the same sophisticated antioxidant defenses that we do.
Therefore there is a large window for
therapy. That’s why oxygen therapies
are extremely powerful and effective.
It’s my opinion that the wise use of both
oxidative and antioxidative therapies
are our best doorways to health and
healing. Using these polarities wisely,
Now Available! The New
we have some of our strongest tools in
medicine to prevent stress and aging,
and to treat acute illness with pulses of
targeted oxidizing therapies.
With an intact antioxidant defense, we
can successfully adapt, survive and
flourish. If we deplete our antioxidant
stores over time, we may suffer mightily over the long run.
It is wonderful to see this work on free
radical damage and antioxidants come
full circle with new breakthroughs such
as Marty Pall’s research, or the latest
studies on coenzyme Q10. In sum, we
need a fine balance between the oxidative burst and the antioxidant defense.
We need to move quickly and effectively between these two polarities and
to understand the value of each for a
healthy life.
References
1. Pall ML. Explaining “Unexplained Illnesses”: Disease Paradigm for Chronic Fatigue Syndrome, Multiple Chemical Sensitivity, Fibromyalgia, Post Traumatic Stress
Disorder, Gulf War Syndrome and Others.
Harrington Park Press, 2007. 446 p.
2. Kumar V, Abbas A, Fausto N. Robbins
and Cotran Pathologic Basis of Disease.
7th ed. Elsevier; 2004. 1552 p.
3. Levine SA, Kidd PM. Antioxidant Adaptation: Its Role in Free Radical Pathology. San Leandro: Allergy Research Group,
1985. 367 p.
4. Kohanski MA, Dwyer DJ, Hayete B,
Lawrence CA, Collins JJ. A common
mechanism of cellular death induced by
bactericidal antibiotics. Cell 2007 Sep
7;130(5):797-810.
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11
Germanium for Energy & Immunity
It was a mere three years ago that Bonnie Kaplan, Ph.D., of the University of
Calgary in Canada and her colleagues
published a paper asking why studies
on germanium sesquioxide (Ge-132),
a promising anticancer treatment, had
languished. As Kaplan and her colleagues note in the article, published in
The Journal of Alternative and Complementary Medicine (1), the organic form
of the compound is unique and animal
studies have shown it to not only have
anticancer properties, but to be safe
and nontoxic. It may be a powerful ally
to our innate immune system.
There is also abundant clinical data
showing that germanium improves energy and immunity. As far back as 1988,
Gerald Faloona, Ph.D., and Stephen
Levine, Ph.D., published an article in
the Journal of Orthomolecular Medicine (2) offering clinical reports showing that germanium dramatically improved fatigue in patients with chronic
fatigue syndrome (then often called
Chronic Epstein-Barr Virus Syndrome).
According to Faloona and Levine, psychotherapist Arnold Horowitz was
disabled for 18 months with chronic
fatigue, and responded dramatically
to Ge-132. A Vancouver physician, Ron
Greenberg, M.D., reported that 25% of
his severely fatigued patients showed
“substantive clinical improvement”
with 300 milligrams of Ge-132 per day.
A New York physician, George Maslen,
M.D., also reported that most of his patients had significant relief from chronic
fatigue at doses of 150-300 milligrams
a day. As the authors noted, “Organic
germanium has many remarkable biological properties. The best studied effects have been on the mammalian immune system on which it has a number
of augmenting effects, at least some of
which are a consequence of host production of interferon.” Blood levels of
12
In Focus November 2007
gamma interferon increased in animals
and humans taking Ge-132.
Also remarkable, notes Levine, is its
seeming ability to enhance oxygen
uptake or lower the body’s requirement for oxygen consumption. Ge-132
has been used anecdotally for years to
treat or prevent altitude sickness and
combat fatigue. Dr. Kazuhiko Asai,
Ph.D. author of Miracle Cure: Organic
Germanium (3) postulates that Ge-132
plays the same role as oxygen in the
body, and can help protect against conditions linked with oxygen starvation,
from stroke to Raynaud’s disease. Asai
was impressed with germanium’s beneficial effects because he experienced
it himself, and he called it a blessing:
“I was in a state of virtual disability.
Doctors had diagnosed my illness as a
severe case of polyrheumatism complicated by arthritis and had given little
hope of improvement…I decided that
my own illness would be its (germanium’s) first real test…Improvement
was slow at first…gradually, I began to
feel better and in ten days I was up and
walking around the house—at times
feeling robustly healthy.”
Asai postulated that diseases like his
own were characterized by oxygen
deficiency and the accumulation of
tissue-damaging positive hydrogen
ions. To remove the hydrogen ions,
he thought, a large quantity of oxygen
was needed. Instead, the germanium
itself might be combining with hydrogen to neutralize it and allow the
body to eliminate it. In this way, Ge132 might substitute for oxygen, and
allow the body itself a greater supply
of naturally available oxygen.
And so we circle back to the original
question posed by researchers at the
University of Calgary in 2004: why
hasn’t this remarkable substance been
studied further? The answer is, it is finally being studied. Arizona Oncology
Services Foundation is currently conducting an IRB-approved double-blind
placebo controlled study on 101 early
stage breast and prostate cancer patients receiving radiation, according to
Theresa Thomas, M.S., CCRC, Director
of Research. The effect of germanium
on fatigue is being evaluated. We hope
this new research on germanium will
trigger further studies.
If Levine is right, this compound can
function as the oxygen boost that many
people need, because hypoxia is so
common in chronic health issues. As
the classic medical textbook, Robbins
& Cotran Pathologic Basis of Disease
notes (4), hypoxia leads to much chronic illness. Germanium may be a promising and safe agent to offset hypoxia.
Weaving the themes of this entire
newsletter together, antioxidants, oxygen radicals, and oxygen deficiency are
all important factors in health and illness. Germanium may be a key player
in oxygen and immunity.
References
1. Kaplan BJ, Merrill AG, Parish WW.
Germane Facts About Germanium Sesquioxide: II. Scientific Error and Misrepresentation. The Journal of Alternative
and Complementary Medicine 2004; 10
(2): 345-8.
2. Faloona GR, Levine SA.The Use of Organic Germanium in Chronic EpsteinBarr Virus Syndrome (CEBVS): An Example of Interferon Modulation of Herpes
Reactivation. Journal of Orthomolecular
Medicine 1988; 3 (1): 29-31.
3. Asai K. Miracle Cure: Organic Germanium. Japan Publications, 1980. 171 p
4. Kumar V, Abbas A, Fausto N. Robbins
and Cotran Pathologic Basis of Disease.7th
ed. Elsevier; 2004.1552 p.
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they are involved in.”
- Stephen Levine, Ph.D.
In Focus on Nutricology®
Editor-in-Chief: Stephen A. Levine, Ph.D.
Executive Editor: Jill Neimark
Medical Editor: Jeffry L. Anderson, M.D.
Assistant Editors: Rick Bierman, LAc, Daniel Milosevich, CN, Diane Raile, CNC and Luba Voloshko, Ph.D.
Graphic Design & Layout: Christian Northcott
FOCUS publishes emerging nutritional science and scientific theories that should not be construed to be conclusive scientific proof of any specific cause, effect, or relationship. The publication is for the educational use of healthcare practitioners and physicians. The articles in the publication are the independent scientific views and theories
of the authors. FOCUS takes no position on the views and theories expressed but offers them for candid inquiry and debate. The articles are not intended for use in support
of the sale of any commercial product and should not be construed as indicative of the use or efficacy of any commercial product. Emerging science and scientific theories
do not constitute scientific proof of any specific cause, effect, or relationship. Copyright © 2007. NutriCology. Special permission is required to reproduce by any manner, in
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