Transcript High-Dose Zinc: - George Eby Research Institute

Zinc Signals - 2005
Hotel Galvez
Galveston, Texas
November 17 – 21, 2005
Drug Uses of Zinc in
Common Colds, Leukemia,
Angina Pectoris and…
George A. Eby, M.S.
George Eby Research
Austin, Texas
In the beginning…
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Valentine's day, 1979 my 3-year old daughter, Karen, was
diagnosed with acute T-cell lymphocytic leukemia (ALL).
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Two weeks of chemotherapy (CCG protocol 161, regimen 2 ) and
zinc gluconate = zero blasts
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Two weeks later, a massive proliferation of healthy reticulocytes.
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Two weeks more, ran 11 minute mile.
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Oncologist remarked, "Mr. Eby, her blood picture has set a new
standard in improvement. I wonder why. Perhaps one of those
enormous vitamin and mineral supplements you have been giving
her beneficially interacted with our chemotherapy. You might look
into that idea, because if you stop the operative supplement, she
might get worse. Who knows, and I am only guessing, but it
would keep you busy.”
How zinc as cure for common
colds was discovered
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Discovery of the benefit of zinc gluconate lozenges in curing
colds was also accidental.
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Developed a cold while on chemotherapy.
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Chewed, but did not swallow, zinc gluconate before afternoon
nap.
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Two hours later, cold vanished and she went outside to play.
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No relapse of the cold.
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Totally immunosuppressed by chemotherapy, but the cold was
completely gone.
A few properties of zinc
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Can be therapeutic
High-dose zinc = 50 to 300 mg per day of ionic zinc.
Doubling serum concentrations by IV for angina
Ten times serum – broadly antiviral.
Positively charged zinc species at pH 7.4.
Potentiates interferon 10-fold – Berg, 2001
Inhibits intercellular adhesion molecule (ICAM -1) – Novick, 1997.
Stabilizes cell/plasma membranes (2 to 100 X serum - including mast cells & goblet
cells) – Pasternak, 1986
Antirhinoviral – Korant, 1974
Anti-herpes (ocular – Merck, 1948) + many others
Astringent, and drying in common colds (nasal application – Merck, 1901).
Zinc lozenges releasing ionic zinc are astringent & drying.
Non-ionic zinc at physiologic pH is useless in biological systems & colds.
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NOTE: At this meeting, I learned that I was the first to distinguish between ionic
zinc and “zinc” in human medicine. No wonder people don’t understand.
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Ionic zinc: (zinc chloride, zinc acetate Zn2+ only), zinc gluconate, zinc sulfate (Zn2+
and some positively charged ligand species)
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Non-ionic zinc: zinc oxide, zinc orotate, zinc oleate, zinc sterate
First Eby study (1984): Percent with colds
using ionic zinc (zinc gluconate):
100
80
%
60
Zinc Gluconate
(23 mg)
Placebo
N=39
40
20
N=41
Total daily zinc = 207 mg
0
0
1 2
3 4
5 6
7
P = 0.008 day 1
P = 0.0005 day 7
Days
Eby GA, Davis DR & Halcomb WW. Reduction in Duration of Common colds by Zinc
Gluconate Lozenges in a Double Blind Study. Antimicrobial Agents and Chemotherapy,
1984, vol 25, no 1, pages 20-24.
Second Eby study (1984): Percent with colds
using non-ionic zinc (zinc orotate)
No effect
using 37 mg
zinc orotate
lozenges and
10 mmol zinc
gluconate
nasal spray.
P = 0.23 on
day 1, and
P = 0.57 on
day 7
I tried for
21 years
to get this
published.
Editors said, “You
expect me to
believe 200 mg of
zinc ‘cured’ colds
and 300 mg did
not?”
No understanding
of requirement for
ionic zinc
Total daily
zinc = 300 mg
The difference in these studies? Ionic zinc at physiologic pH 7.4
Days
1984 – 2005 all studies: No relationship
between high-dose zinc & reductions in
median or average durations of colds
7
6
5
4
3
2
1
0
-1 0
-2
-3
-4
-5
100
200
mg zinc
300
Mean Reduction
in Duration
(Days)
Median
Reduction in
Duration (Days)
Eby GA. Zinc Lozenges: Cold
Cure or Candy? Solution
Chemistry Determinants,
Bioscience Reports, 2004, vol
24, no 1, pages 23-39.
Why the mess?
Zinc solution chemistry
Ionic zinc must be measured at physiologic pH 7.4 in common colds
Physiologic pH
Effect of ionic zinc on common cold
median and mean duration
P=0.005
P = 0.02
Eby GA. Zinc Lozenges: Cold Cure or Candy? Solution Chemistry
Determinants, Bioscience Reports, 2004, vol 24, no 1, pages 23-39.
Eby’s U.S. Patents
Even though there were valuable
patents and successful clinical trials,
commercial failure occurred.
WHY?
Specifically, why did commercial
zinc gluconate lozenges fail?
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Clinical trial results were mixed and too confusing.
Zinc lozenges for colds were generally believed to
be bogus.
Zinc gluconate, which has a bland, drying taste, has
the strange property of becoming extremely bitter
when mixed with sweet carbohydrates (other than
fructose) in lozenges over time (low shelf life).
This property doomed zinc gluconate
lozenges for colds.
Zinc gluconate required additives that eliminated
both flavor issues and efficacy.
Why did commercial zinc
acetate lozenges fail?
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Zinc acetate lozenges were flavor stable, pleasanttasting and astringent, but major manufacturers
wanted a non-astringent, candy lozenge.
Major licensee found no efficacy from their own tests
of chemically modified zinc acetate lozenge products
having no astringency that passed their flavor tests.
MAIN PROBLEM! Licensees would not use
homeopathic drug claims, even though such
use was the main key to marketing success.
Lozenges are not a legal dietary supplement form
under DSHEA of 1994.
Why not nasal application?
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First use of intranasal zinc: nose drops of zinc sulfate – coryza
(runny nose) (Merck - 1901)
Many reports of use as decongestant early in 20th century.
The cure for common colds should have been discovered in earliest
part of 20th century (around 1901).
Nasal application – no effect in over 100 years of research reports,
exception - Hirt et al. – ENT, 2000, for Zicam zinc gluconate nasal
gel.
Nasal application of zinc - risk of permanent anosmia (contact with
olfactory organ - termination of sense of smell) Extremely painful.
Ionic zinc nasal sprays - preferred means to induce anosmia in
research animals.
Nasal application failed in our 2nd study. See: Eby GA.
Ineffectiveness of Zinc Gluconate Nasal Spray and Zinc Orotate
Lozenges in Common Cold Treatment and Potential for Harm: A
Double-Blind, Placebo-Controlled, Clinical Trial. 2006. Alternative
Therapies in Health and Medicine. In press.
Why lozenges? Its magic! The magical mouth-nose BCEC!
What is the mouth-nose BCEC?
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Biologically closed electric circuits (BCEC) – course
throughout the entire body
All except one (the mouth-nose BCEC) require
surgery to observe. (Nordenström, 1983)
The mouth-nose BCEC moves electrons from mouth
to nose. This circuit is readily observed with a voltohm meter.
Positively charged substances in the mouth, such as
zinc, migrate with electrons via this circuit into nose.
(natural electrophoresis)
Positively charged substances introduced into the
nose are repelled (like charges repel).
Opening of nares and olfactory region – exceptions!
Details of the mouth-nose BCEC
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Voltage between 60 and 120 millivolts.
Voltage rises and falls one to two millivolts with the
respiratory rhythm.
Individuals (like me) with frequent colds, allergies
and rhinitis have low resistance values between the
mouth and nose between 1 and 10 Kohms
Those with an average number of colds and few or
no allergies have resistances between mouth and
nose between 40 and 60 Kohms.
People (like physicians) who are immune to
common colds and have no allergies have mouth
and nose resistances between 100 and 500 Kohms.
Zinc ionization in treatment of allergy
(Reversing the mouth-nose BCEC)
Benefits from
two 15 minute
treatments
lasted one year.
Last mention of
this treatment
was in 1961.
WHY?
Franklin,
BMJ - 1931
Mast cell granules – storage sites
for ionic zinc – role in immunity?
Does ionic zinc
from mast cell
granules:
Stabilize
goblet cells?
Activate
T-cells?
Aid healing?
Reduce
inflammation?
Ionic zinc
4 to 20 mMol –
Struckhoff -1986
Considerable
Zn2+ ions are
released during
mast cell
degranulation
of during colds
& allergies
(inflammation).
Worsening of colds by negative zinc charge: a mast cell de-ionization effect?
Some no longer marketed highly
efficacious zinc acetate lozenges
These zinc acetate
lozenges were the
only products ever
to have been
shown efficacious
in two totally
independent
clinical trials of the
same formulation
against common
cold duration and
symptom severity.
Petrus, 1998
Prasad, 2000
Why are they
no longer
marketed?
Good data: Prasad – 2000, Petrus - 1998
Complaints
about oral
astringency,
no drug claims,
FDA label rules,
and little or no
marketing
support
The really big fish that got away
“Zinc acetate
in hard candy
cooked with
oleates and
stearates to
eliminate
objectionable
mouthfeel…”
(& ionic zinc)
Which is
more
important?
Mouthfeel
or efficacy?
Warner
Lambert
U.S. patent
6,242,019
Failed in trials
Currently marketed zinc lozenges
(not believed to be effective)
regardless of advertisements to the contrary
No data
No zinc ions
due to citric
acid additive
Weak data
Few zinc ions
due to glycine
additive
No data
Few zinc ions
due to rapid
Dissolution.
What to do for colds and allergies?
After the initial
commercial
interest subsided,
this is the only
zinc lozenge
remaining that
will actually
shorten common
colds by a week.
What am I doing
now?
My Post Common
Cold research:
• Herpes
• Leukemia
• Angina pectoris
• Arthritis
• Navicular disease
• Chronic sinusitis
• other
Eby GA, Halcomb WW. Use of topical zinc to prevent
recurrent herpes simplex infection: review of literature
and suggested protocols.
Medical Hypotheses. 1985 Jun;17(2):157-65.
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Zinc ions have been reported to be antiviral to herpes
simplex viruses. A number of treatments using zinc are
reviewed which illustrate the effects of topically applied
zinc in reducing the duration and severity of human oral
and genital infections. Long-term topical application of
zinc salts appears to greatly reduce or eliminate
recurrences of genital herpetic infections.
35 references cited. Why suffer?
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Ocular – Visine AC? Zinc sulfate? NO! Sodium citrate
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Hi GeorgeI want to say THANK YOU SO MUCH for making this information about zinc and
herpes public. I have had excellent results from use of topical zinc gluconate solutions,
although it is not a cure for me, at least so far. It is, however, an amazing reducer of both
the potency and recurrence of the virus.
For your continued research and to help others, I thought I should report my results to
you. I began using a 100 millimolar solution in January of this year. At the time I was
having continuous outbreaks that were severe.
My methodology was to mix 1 tsp of zinc gluconate. with 50 mL of hot tap water, stir
until it dissolved (which makes a strong 100 millimolar concentration), and keep the
measuring cup warm in a hot water bath in the sink. I then just applied the warm
aqueous solution to the affected area with a wet Kleenex, and timed the exposure to 15
minutes. Then I left the area wet and let it air dry (which extends the exposure time
another few minutes). This creates minor pain during an outbreak if the legions are
broken first, but even that goes away in a few minutes. Later, after the area begins to
heal, treatment is indeed ineffective, and in fact counter-productive, so I learned to not
apply it to the affected area after scabs form. Concerning frequency of use: In general I
used it once per day for about three months, except during outbreaks, and then I used it
twice a day. I kept it wet each time about 15 minutes, leaving it wet at the end.
You were right, never apply zinc gluconate powder to herpetic lesions
because they will make a big, nasty, painful hole.
The results have been a decrease in outbreaks from constant and severe to only about
once in 4 - 5 months (an amazingly tiny one), and duration has been reduced from
several weeks to 3 - 4 days. These results are against a backdrop of a much more
stressful job than most people have (very long hours, as I run a large company), a lot
less sleep than I should get, and eating poorly during the whole 9 month period. This
methodology is a big success and a helluva lot better than popping pills every day.
It has changed my life, I can sure tell you that. I owe you big time.
Dave
Eby GA. Treatment of acute lymphocytic leukemia using zinc
adjuvant with chemotherapy and radiation — a case history and
hypothesis. Medical Hypotheses. 2005;64(6):1124-6.
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Low blood levels of zinc are often noted in acute lymphocytic leukemia (ALL), but zinc is
not administered as part of any modern chemotherapy program in the treatment of ALL.
Upon noting low blood levels of zinc in a 3-year-old 11.3 kg girl, zinc at the rate of 3.18
mg/kg body weight/day was administered from the start of chemotherapy through the full
3 years of maintenance therapy. Dosage was split with 18 mg given at breakfast and 18
mg zinc with supper. The result was a bone marrow remission from 95+% blast cells to
an observed zero blast cell count in both hips within the first 14 days of treatment which
never relapsed. In addition to the reduction of blast cells to an observed count of zero
(not a single leukemic or normal blast), red blood cell production and other hemopoietic
functions returned to normal at a clinically remarkable rate. There were no side effects
from zinc or chemotherapy at any time, and zinc is hypothesized to have improved the
patient's overall ability to withstand toxic effects of chemotherapy. This report identifies
zinc treatment as being vital to rapid and permanent recovery from ALL. The extremely
broad role of zinc in pre-leukemic adverse health conditions, viral, fungal and tumoral
immunity, hemopoietics, cell growth, division and differentiation, genetics and
chemotherapy interactions are considered. If zinc could be shown to strengthen the
function of chemotherapy and immune function, then it could be hypothesized that the
relapse rate would be lessened since the relapse rate is related to both the rate at which
a remission is obtained and the thoroughness of the elimination of leukemic blasts.
Identical results also occurred in 13 other children with ALL whose parents chose to treat
with zinc adjuvant. Since treatment with zinc and other identified deficient nutrients,
particularly magnesium, did not appear injurious in ALL and they appear to be highly
beneficial, controlled clinical studies of zinc (3.18 mg/kg body weight/day) with
magnesium (8.0 mg/kg body weight/day) as adjuvants to chemotherapy in the treatment
of childhood ALL are suggested. Treatment with zinc adjuvant is hypothesized to
accelerate recovery from ALL, and in conjunction with chemotherapy, cure ALL. (76 ref)
This A.P. article brought in 13
zinc for A.L.L. success stories
Zinc for A.L.L. is worth it.
Karen Eby, my A.L.L.
conquering daughter,
will be publishing her
first neuroscience
research paper before
she goes to graduate
school.
Her paper is titled
“Effects of Chronic
Stress on Neurogenesis
in Adult Golden
Hamsters”.
She was an honors
student at U T Austin
(3.9 GPA), and president
of PSI CHI National
Honors Society. She won
3 cash awards for her
dogma-breaking chronic
stress research.
She wants to study
effects of magnesium
and other nutrients in
traumatic brain injury
and chronic stress,
particularly from cranial
radiation and
chemotherapy .
Eby GA, Halcomb WW. High-dose zinc to terminate angina
pectoris: A review and hypothesis for action by ICAM
inhibition. Med Hypotheses. 2005 Aug 3 (in press).
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We reviewed the literature related to the effects of high-dose zinc in arteriosclerosis-induced angina
pectoris. Lipid peroxidation and LDL oxidation are believed to be critical for arteriosclerosis, and
consequently angina pectoris. Administration of biologically available zinc was a beneficial treatment in
a significant percentage of patients with severely symptomatic, inoperable atherosclerotic disease. In
these patients, there was no difference in zinc concentration between patients with and without
atherosclerosis in whole blood, erythocytes or hair, but there was a major difference between normal
aorta and diseased aortas (40.6 ppm zinc in normal aorta vs. 23.2 ppm zinc in atherosclerotic aorta,
40.6 ppm zinc in normal aorta vs. 19.4 ppm zinc in atherosclerotic aneurysm aorta, and no difference
between normal and aneurysm aorta), although copper was low in aneurysm aorta. Medication with
high-dose zinc sulfate to raise zinc serum concentrations from 95 to 177 mug/dl resulted in objective
improvement in 12 of 16 of these patients, including a patient that also had Raynaud's disease. Long
term environmental exposure to zinc resulted in a 40% reduction in the incidence of angina of effort
compared to people not exposed to environmental zinc (P<0.01) and a 40% reduction in the
incidence of probable ischemia in exercise (P<0.001). The antioxidative action of zinc prevents
oxidation of LDL cholesterol and consequently stops the main mechanism of atherogenesis. Zinc
blocks calcium and its several actions on atherogenesis. Increased amounts of cytotoxic cytokines
such as TNF-alpha, IL-beta and IL-8, often produced in the elderly, are blocked by high-dose zinc. We
hypothesize that higher serum concentrations of LDL cholesterol resulting from 300 mg of zinc per
day is caused by a release of low density cholesterol from cardiovascular tissues, beneficially flushing
it into the serum where it is readily observed, thus decreasing arteriosclerosis, increasing circulation,
terminating angina pectoris and restoring more youthful cardiac function. Although prevention of
cholesterol-induced arteriosclerosis by zinc is predicted from findings related to oxidative stress and
lipid peroxidation, removal of LDL is attributable to action of ionic zinc on ICAM inhibition. In stark
contrast to current practice, high-dose zinc should be considered as basic in the strategy of
prophylaxis and therapy of the atherosclerosis process to terminate angina pectoris and restore
youthful cardiac function.
Other drug uses of ionic zinc research questions
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Chicken pox, shingles (topical 100 to 400 mmol)
Post herpetic neuralgia (topical 100 to 400 mmol)
Other cardiovascular: blood pressure, platelet
aggregation, sickle cell, inflammation, endothelial
function, cholesterol, carbonic anhydrase, P.A.D.
Anti-cadmium effect from tobacco (high-dose oral & IV)
Anti-mercury effects in autism (high-dose oral & IV)
Zinc acetate lozenges and allergies (colds in allergic people
Petrus - 1998, reversing BCEC – Franklin, 1931)
Menstrual cramps & bloating (30 - 90 mg/day
– start 3 to 4 days before menses)
Zinc acetate lozenges and mononucleosis (3-day cure)
(continued)
Other drug uses of ionic zinc research questions
(cont.)
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Venomous bites and stings (including brown recluse
spider bites, bee, yellow jacket, snake, scorpion &
Portuguese-Man-O-War) (topical, IV & oral)
Systemic scleroderma (high-dose oral – my sister-in-law)
Gangrene (topical, high-dose oral, IV)– Ellingwood 1919
Small pox (Paris 19th century), bird flu, SARS, hepatitis C,
(high-dose oral - IV)
Burns and wound healing generally (high-dose oral,
topical - IV)
Crohn's Disease, leaky gut, and other intestinal
inflammatory disorders
NOTE: IV = 2-100 X serum concentration – CA Pasternak
1989
Zinc and its commercialization?
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Need patents that are protectable. Patents for “use of zinc to
treat …” are usually worthless, because they are not protectable.
Need a gimmick. Clear zinc oxide, zinc lozenges, zinc condoms, zinc
test kits
Civil law enforces patents
Lawsuits necessary to enforce patents can be stressful and expensive
- not guaranteed to be successful.
Cultivate strong relations with decision makers in company to be
licensed.
Take vows of poverty, have a good wife, like my wife Patsy.
Patience, patience, patience. Good luck!
Side Effects from drug uses of zinc?
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Side effects from short-term zinc lozenges appear absent
Too much zinc: Stomach upset, nausea, vomiting, diarrhea and a
metallic taste
Avoid long term (>2 week) oral doses (copper and iron issues).
Iron depletion by zinc may be beneficial.
Zinc toxicity = dizziness, headache, drowsiness, immune
suppression, increased sweating, loss of muscle coordination,
alcohol intolerance, hallucinations and anemia.
With extreme over-dose or poisoning, loss of consciousness and
death.
Well people – low tolerance
Sick people – high tolerance
K. Brown, 2004