High-Dose Zinc.ppt by tongxiamy

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									                  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…

   Valentine's day, 1979 my 3-year old daughter, Karen, was
    diagnosed with acute T-cell lymphocytic leukemia (ALL).

   Two weeks of chemotherapy (CCG protocol 161, regimen 2 ) and
    zinc gluconate = zero blasts

   Two weeks later, a massive proliferation of healthy reticulocytes.

   Two weeks more, ran 11 minute mile.

   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
   Discovery of the benefit of zinc gluconate lozenges in curing
    colds was also accidental.

   Developed a cold while on chemotherapy.

   Chewed, but did not swallow, zinc gluconate before afternoon
    nap.

   Two hours later, cold vanished and she went outside to play.

   No relapse of the cold.

   Totally immunosuppressed by chemotherapy, but the cold was
    completely gone.
       A few properties of zinc
   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.

   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.

   Ionic zinc: (zinc chloride, zinc acetate Zn 2+ only), zinc gluconate, zinc sulfate (Zn 2+
    and some positively charged ligand species)

   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
                                                            Zinc Gluconate
        60                              N=39                (23 mg)
   %
        40                                                  Placebo

        20
                                 N=41                   Total daily zinc = 207 mg
          0
                                                          P = 0.008 day 1
                0    1 2       3 4      5 6       7       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)
                                                              I tried for
No effect                                                     21 years
using 37 mg                                                   to get this
                                                              published.
zinc orotate
                                                              Editors said, “You
lozenges and                                                  expect me to
10 mmol zinc                                                  believe 200 mg of
                                                              zinc ‘cured’ colds
gluconate                                                     and 300 mg did
nasal spray.                                                  not?”

                                                              No understanding
P = 0.23 on                                                   of requirement for
                                                              ionic zinc
day 1, and
P = 0.57 on
day 7                                                          Total daily
                                                               zinc = 300 mg


     The difference in these studies? Ionic zinc at physiologic pH 7.4
         1984 – 2005 all studies: No relationship
         between high-dose zinc & reductions in
          median or average durations of colds
        7
        6
        5
        4
                                           Mean Reduction
        3
                                           in Duration
        2
                                           (Days)
Days




        1
        0                                  Median
       -1 0     100     200     300
                                           Reduction in
       -2                                  Duration (Days)
       -3                             Eby GA. Zinc Lozenges: Cold
                                      Cure or Candy? Solution
       -4                             Chemistry Determinants,
       -5                             Bioscience Reports, 2004, vol
                 mg zinc              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?
   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?
   Zinc acetate lozenges were flavor stable, pleasant-
    tasting 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?
   First use of intranasal zinc: nose drops of zinc sulfate – coryza
    (runny nose) (Merck - 1901)
   Many reports of use as decongestant early in 20 th 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?
   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 volt-
    ohm 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

   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
                                             Franklin,
two 15 minute
                                             BMJ - 1931
treatments
lasted one year.

Last mention of
this treatment
was in 1961.
WHY?
         Mast cell granules – storage sites
         for ionic zinc – role in immunity?

                                                           Ionic zinc
                                                           4 to 20 mMol –
                                                           Struckhoff -1986
   Does ionic zinc
   from mast cell                                          Considerable
   granules:                                               Zn2+ ions are
                                                           released during
   Stabilize                                               mast cell
   goblet cells?                                           degranulation
   Activate                                                of during colds
   T-cells?                                                & allergies
   Aid healing?                                            (inflammation).
   Reduce
   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                                                 Why are they
to have been                                                       no longer
shown efficacious                                                  marketed?
in two totally
independent                                                        Complaints
clinical trials of the                                             about oral
same formulation                                                   astringency,
against common                                                     no drug claims,
cold duration and                                                  FDA label rules,
symptom severity.                                                  and little or no
                         Good data: Prasad – 2000, Petrus - 1998   marketing
Petrus, 1998                                                       support
Prasad, 2000
         The really big fish that got away


“Zinc acetate
in hard candy
cooked with
oleates and
stearates to
eliminate                               Which is
objectionable                           more
mouthfeel…”                             important?
(& ionic zinc)
                                        Mouthfeel
Warner                                  or efficacy?
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      Weak data       No data
       No zinc ions    Few zinc ions    Few zinc ions
       due to citric   due to glycine   due to rapid
       acid additive   additive         Dissolution.
  What to do for colds and allergies?
                            What am I doing
After the initial           now?
commercial
interest subsided,          My Post Common
this is the only            Cold research:
zinc lozenge
remaining that              • Herpes
will actually               • Leukemia
shorten common              • Angina pectoris
colds by a week.            • 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.


   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?

   Ocular – Visine AC? Zinc sulfate? NO! Sodium citrate
    Hi George-
       I 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.
   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.

                                    She was an honors
Karen Eby, my A.L.L.                student at U T Austin
conquering daughter,                (3.9 GPA), and president
will be publishing her              of PSI CHI National
                                    Honors Society. She won
first neuroscience
                                    3 cash awards for her
research paper before               dogma-breaking chronic
she goes to graduate                stress research.
school.
                                    She wants to study
                                    effects of magnesium
Her paper is titled                 and other nutrients in
“Effects of Chronic                 traumatic brain injury
                                    and chronic stress,
Stress on Neurogenesis
                                    particularly from cranial
in Adult Golden                     radiation and
Hamsters”.                          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).

   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
      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.)

     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?

   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?

   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

								
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