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Medical Hypotheses (2006) 66, 169–172
http://intl.elsevierhealth.com/journals/mehy
High-dose zinc to terminate angina pectoris:
A review and hypothesis for action by
ICAM inhibition
a,* b
George A. Eby , William W. Halcomb
a
George Eby Research, 14909-C Fitzhugh Road, Austin, TX 78704, United States
b
William W. Halcomb Clinic, 4323 E. Broadway, Suite 109, Mesa, AZ 85206, United States
Received 3 June 2005; accepted 9 June 2005
Summary 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 lg/dl resulted in objective improvement in 12 of 16
of these patients, including a patient that also had Reynard’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). Lead had no effect while
cadmium exposure resulted in more than tripling the incidence of angina of effort (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-a, IL-b 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 administration of 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 might be 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.
c 2005 Elsevier Ltd. All rights reserved.
* Corresponding author. Tel.: +1 512 263 6968; fax: +1 512 263 0805.
E-mail address: [email protected] (G.A. Eby).

0306-9877/$ - see front matter c 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.mehy.2005.06.013
170 Eby and Halcomb
Introduction common colds [10], a 65-year-old man with severe,
disabling angina pectoris evaded our selection cri-
Angina pectoris (coronary chest pain) occurs when teria and received zinc. His cold did not respond
the myocardium does not get as much oxygen as to zinc and he consumed 300 mg of zinc on the first
it needs usually when one or more of the heart’s day and 276 mg of zinc on the following days of the
arteries is narrowed or blocked by low density lipo- 7 day trial. No copper supplements were given to
protein (LDL) cholesterol-induced arteriosclerosis alter the effects of high-dose zinc.
(hardening of the arteries). Lipid peroxidation
and LDL oxidation are believed to be critical for
arteriosclerosis. Increased amounts of cytotoxic Results
cytokines such as TNF-a, IL-b and IL-8 are often
produced in the elderly. These cytokines affect The patient returned a few days after the trial was
the vascular endothelium and they generate acti- over and wanted to know whether he had received
vated endothelial cell molecules, such as ICAM, zinc or placebo. He reported that after 5 days on
VCAM and E-Selectin, etc. These molecules trap zinc, his angina pectoris pain, very poorly con-
platelets, red cells, neutrophil, monocytes, etc. trolled with any medication including nitroglycerin,
and plug up the blood vessels, thus producing vanished for the first time in 15 years. Indeed, his
angina pectoris. Furthermore, the monocytes– blood pressure was normal and he showed no out-
macrophages become activated and produce free ward evidence of coronary damage. After his zinc
radicals and reactive oxygen species (ROS) which therapy, he went snow skiing in the mountains of
lead to DNA oxidation and lipid peroxidation. Zinc Colorado for the first time in over 15 years and
has beneficial molecular effects in regulating these had no cardiac discomfort. He obtained a new job
events [1]. working for a railroad and felt fine working hard
Zinc deficiency is found in elderly hospitalized all day.
patients, and higher proportions of respiratory This effect was soon reproduced in a heavy
infections, cardiac failure, and depression were 150 kg man with severe angina pectoris. After
observed among zinc deficient patients as com- about a year of freedom from angina pectoris and
pared with the group of patients with normal zinc resumption of an active lifestyle, this man’s cardi-
status [2]. Today, the elderly tend to avoid meat ologist, while remarking his great pleasure with his
and other high zinc-content foods due to fears of progress, told him to discontinue zinc because
cholesterol [3]. Rather, they increase consumption 300 mg of zinc per day would significantly decrease
of refined wheat products. Wheat was a main serum high-density lipoprotein concentration and
source of zinc in the historical diet, but today zinc, would increase low-density lipoprotein. The pa-
magnesium and other critical nutrients have been tient died of congestive heart failure within a
depleted by the refining process [4]. Therefore, month of cessation of zinc treatment.
zinc deficiency may play a major, perhaps the dom- The observation of zinc benefit to angina pecto-
inant role, in causing most adverse cardiac events. ris was incorporated into clinical practice by one of
High-dose zinc (50–300 mg/day) significantly us (WWH) but records of these results are no longer
decreases serum high-density lipoprotein concen- available. Nearly all persons that made dietary
tration and increases low-density lipoprotein modifications (reduced refined carbohydrate and
[5–7]. while lower doses or biologically unavailable fat intake), stopped smoking and supplemented
zinc compounds such as zinc oxide do not [8,9]. It is with 180 mg of zinc per day in split doses favorably
hypothesized that transient increases in low den- responded to treatment. In a recent case (2005) of
sity serum cholesterol result from release of tissue chronic, severe Raynaud’s Disease affecting tops of
bound low density lipoprotein by action of zinc. We both hand, face and the nose, 180 mg of zinc per
coincidentally found that zinc could benefit angina day from zinc gluconate terminated Raynaud’s dis-
pectoris during a zinc gluconate lozenge for com- ease within 7 days.
mon cold clinical trial.
Discussion
Methods and procedures
There are several reports that show zinc was used
In 1981, while conducting a clinical trial using to both prevent angina pectoris and effectively
23 mg of zinc from zinc gluconate each 2 h to treat treat it in humans, some animal research and
much biochemical and molecular biology research
High-dose zinc to terminate angina pectoris 171
showing means to prevent atherosclerosis. How- Hennig et al. [15] in 1996 pointed out that there
ever, we found no insight as to how zinc might is evidence that zinc can provide antiatherogenic
treat it. properties by preventing metabolic physiologic
According to a report by Henzel et al. [11] in derangements of the vascular endothelium. Be-
1968, administration of zinc sulfate was a beneficial cause of its antioxidant and membrane-stabilizing
treatment in a significant percentage of patients properties, zinc appears to be crucial for the pro-
with severely symptomatic, inoperable atheroscle- tection against cell-destabilizing agents such as
rotic disease. They found that there was no differ- polyunsaturated lipids and inflammatory cytokines.
ence in zinc concentration between patients with Zinc also may be antiatherogenic by interfering
and without atherosclerosis in whole blood, erytho- with signaling pathways involved in apoptosis. Cer-
cytes or hair, but there was a major difference be- tain lipids and zinc deficiency may potentiate the
tween normal aorta and diseased aortas (40.6 ppm cytokine-mediated inflammatory response and
zinc in normal aorta vs. 23.2 ppm zinc in atheroscle- endothelial cell dysfunction in atherosclerosis.
rotic aorta, 40.6 ppm zinc in normal aorta vs. Thus, the antiatherogenic role of zinc appears to
19.4 ppm zinc in atherosclerotic aneurysm aorta be in its ability to inhibit oxidative stress-respon-
and no difference between normal and aneurysm sive factors involved in disruption of endothelial
aorta), although copper was low in aneurysm aorta. integrity and atherosclerosis. In 2000, Hennig
They medicated with zinc sulfate to raise zinc et al. [16] suggested that zinc requirements of
serum concentrations from 95 to 177 lg/dl. Objec- the vascular endothelium are increased during
tive patient evaluation included treadmill walking, inflammatory conditions such as atherosclerosis.
electrocardiography, plethysmography, and posi- Clemons et al. [17] showed that age-related macu-
tional photography of ischemic limbs. Objective lar degeneration patients randomly assigned to re-
improvement was observed in 12 of their 16 pa- ceive zinc (80 mg zinc from zinc oxide) had lower
tients, however, 6 of the 12 improved patients were mortality than those not taking zinc over a 6.5-year
discounted since factors such as weight loss and period (RR, 0.73; 95% CI, 0.61–0.89). Dietary sup-
cessation of smoking may have contributed to plements of copper or zinc both inhibited aortic
improvement. One of these patients also had Rey- atherogenesis in the cholesterol-fed rabbits
nard’s disease, which promptly vanished. They [18,19].
suggested that zinc acts as a therapeutic pharma- Variant angina (Princemetal’s angina) [20–22]
ceutical (rather than as a nutrient) in those patients has been shown to benefit from prompt magnesium
with occlusive vascular disease who experience sulfate administration, and IV magnesium sulfate
improvement when medicated with zinc. Under- terminated variant angina in one of us (GAE), who
wood [12] in 1971 also reported beneficial effects after 8 years of previous high-dose zinc treatment
of high-dose zinc in angina pectoris. showed no coronary artery blockage.
Giec et al. [13] in 1980 reported on 1000 physical Although the mechanisms by which zinc can pre-
workers (900 males, 100 females) aged 21–60 years vent arteriosclerosis are defined, we are only left
with the professional exposure to zinc, lead or cad- with the hypothesis that higher serum concentra-
mium. They showed that environmental exposure tions of LDL cholesterol resulting from administra-
to zinc in mines in Poland resulted in a 40% reduc- tion of 300 mg of zinc per day results from release
tion in the incidence of angina of effort compared of LDL cholesterol from cardiovascular tissues. Zinc
to people not exposed to environmental zinc appears to flush LDL cholesterol, perhaps by action
(P < 0.01) and a 40% reduction in the incidence of of ionic zinc on intracellular adhesion molecule
probable ischemia in exercise (P < 0.001). Lead (ICAM) inhibition, into the serum where LDL choles-
had no effect while cadmium exposure resulted in terol is readily observed, thus decreasing arterio-
more than tripling the incidence of angina of effort sclerosis, increasing circulation, terminating
(P < 0.001). angina pectoris and restoring more youthful car-
Ripa and Ripa [14] in 1994 argued that the anti- diac function. We suggest that the increase in low
oxidative action of zinc prevents oxidation of LDL density lipoprotein shown by Chandra and others
and consequently stops the main mechanism of with administration of 300 mg of zinc per day is ex-
atherogenesis. Zinc blocks calcium and its several tremely beneficial rather than harmful as sug-
favorable actions on atherogenesis. In stark con- gested by Chandra.
trast to current practice, they pointed out that zinc Caution with high-dose zinc treatment is advised
in suitable doses, should be considered as basic in for two reasons. First, 300 mg of zinc per day for 30
the strategy of prophylaxis and therapy of the ath- days suppresses primary immunity in young healthy
erosclerosis process. adults [5], while 200 mg per day enhances primary
immunity in old people [23]. Second, high-dose
172 Eby and Halcomb
zinc will lower copper serum concentrations [24], [8] Bonham M, O’Connor JM, McAnena LB, Walsh PM, Downes
which might increase incidence of aneurysms. CS, Hannigan BM, et al. Zinc supplementation has no effect
on lipoprotein metabolism, hemostasis, and putative indi-
Copper (from copper chloride) treatment, starting ces of copper status in healthy men. Biol Trace Elem Res
14 days before zinc treatment (4–6 mg copper/ 2003;93(1–3):75–86.
day) should be given to help prevent aneurysms. [9] Age-Related Eye Disease Study Research Group. The effect
To further minimize side effects, treatment with of five-year zinc supplementation on serum zinc, serum
high-dose zinc to terminate angina pectoris should cholesterol and hematocrit in persons randomly assigned to
treatment group in the age-related eye disease study:
not be given for longer than 14 days. AREDS Report No. 7. J Nutr. 2002;132:697–702.
High-dose zinc treatment of atherosclerosis- [10] Eby GA, Davis DR, Halcomb WW. Reduction in duration of
induced angina pectoris should be studied imme- common colds by zinc gluconate lozenges in a double-blind
diately and extensively in nationally supported study. Antimicrob Agents Chemother 1984;25:20–4.
clinical trials of daily 300 mg zinc (from a biologi- [11] Henzel JH, Holtmann B, Keitzer FW, DeWeese MS, Lichti E.
Trace elements in atherosclerosis, efficacy of zinc medi-
cally available source such as zinc gluconate, chlo- cation as a therapeutic modality. In: Trace substances in
ride, acetate, glycinate, histidinate or sulfate). environmental health, conference 2nd proceedings; 1967–
Taurine (8–16 g/day in split doses), to help treat 68.
angina pectoris [25], regulate cardiac rhythm [12] Underwood EJ. Trace elements in human and animal
[25], eliminate extrasystoles [25] and prevent con- nutrition. New York: Academic Press; 1971.
[13] Giec L, Wnuk-Wojnar A, Trusz-Gluza M, Szulc A, Kargul W.
gestive heart failure [26], should also be given. Epidemiological evaluation of the coronary risk in physical
We suggest that widespread consumption of re- laborers in nonferrous metallurgy. Part II: coronary dis-
fined grains depleted of their minerals is a principal ease. Przegl Lek 1980;37:507–10.
underlying cause of cardiovascular disease. We sug- [14] Ripa S, Ripa R. Zinc and atherosclerosis. Minerva Med
gest that the practice of refining grain should be 1994;85:647–54.
[15] Hennig B, Toborek M, McClain CJ. Antiatherogenic proper-
abolished world-wide. To eliminate angina pecto- ties of zinc: implications in endothelial cell metabolism.
ris, patients should eat whole grains, seeds and Nutrition 1996;12:711–7.
nuts, stop eating refined carbohydrates, reduce ani- [16] Hennig B, Meerarani P, Ramadass P, Toborek M, Malecki A,
mal fat intake, stop smoking and receive high-dose Slim R, et al. Zinc nutrition and apoptosis of vascular
zinc treatment for 14 days. Ironically, in the United endothelial cells: implications in atherosclerosis. Nutrition
1999;15:744–8.
States, marketing nutrients to treat, cure, diagnose [17] Clemons TE, Kurinij N, Sperduto RD, AREDS Research
and prevent diseases is essentially illegal under the Group. Associations of mortality with ocular disorders and
overly broad Dietary Supplement Health Education an intervention of high-dose antioxidants and zinc in the
Act of 1994. Age-Related Eye Disease Study: AREDS Report No. 13. Arch
The English translation of the Polish Giec article Ophthalmol. 2004;122:716–26.
[18] Alissa EM, Bahijri SM, Lamb DJ, Ferns GA. The effects of
and the difficult to find Henzel article, and links to coadministration of dietary copper and zinc supplements
the other articles are on the Internet at . peroxidation in the cholesterol-fed rabbit. Int J Exp Pathol
2004;85:265–75.
[19] Bhaskar M, Madhuri E, Abdul Latheef SA, Subramanyam G.
Influence of zinc on cardiac and serum biochemical
References parameters in rabbits. Indian J Exp Biol 2001;39:1170–2.
[20] Prikryl P. Positive therapeutic effect of K–Mg asparaginate
[1] Bao B, Prasad AS, Beck FW, Godmere M. Zinc modulates in Prinzmetal’s angina pectoris and Adams–Stokes syn-
mRNA levels of cytokines. Am J Physiol Endocrinol Metab drome. Cas Lek Cesk 1973;112:186.
2003;285(5):E1095–102. [21] Cohen L, Kitzes R. Prompt termination and/or prevention
[2] Pepersack T, Rotsaert P, Benoit F, Willems D, Fuss M, of cold-pressor-stimulus-induced vasoconstriction of dif-
Bourdoux P, et al. Prevalence of zinc deficiency and its ferent vascular beds by magnesium sulfate in patients with
clinical relevance among hospitalised elderly. Arch Geron- Prinzemetal’s angina. Magnesium 1986;5(3–4):144–9.
tol Geriatr 2001;33:243–53. [22] Gertz SD, Wajnberg RS, Kurgan A, Uretzky G. Effect of
[3] AlAteeqi N, Allard J. Zinc deficiency in the elderly. Geriatr magnesium sulfate on thrombus formation following partial
Aging 2002;5:14–7. arterial constriction: implications for coronary vasospasm.
[4] Unknown. Harvard heart letter; 2002. pp. 2–4. Magnesium 1987;6(5):225–35.
[5] Chandra RK. Excessive intake of zinc impairs immune [23] Duchateau J, Delepesse G, Vrijens R, Collet H. Beneficial
responses. JAMA 1984;252:1443–6. JAMA. effects of oral zinc supplementation on the immune
[6] Xiang Y, Yang X, Bian J, Wang L. Effects of high level Zn response of old people. Am J Med 1981;70:1001–4.
intake on metabolism in man. Wei Sheng Yan Jiu [24] Willis MS, Monaghan SA, Miller ML, McKenna RW, Perkins
2004;33:727–31. WD, Levinson BS, et al. Zinc-induced copper deficiency: a
[7] Chevalier CA, Liepa G, Murphy MD, Suneson J, Vanbeber report of three cases initially recognized on bone marrow
AD, Gorman MA, et al. The effects of zinc supplementation examination. Am J Clin Pathol 2005;123:125–31.
on serum zinc and cholesterol concentrations in hemodi- [25] Chazov EI, Malchikova LS, Lipina NV, et al. Taurine and
alysis patients. J Ren Nutr 2002;12:183–9. electrical activity of the heart. Circ Res 1974;34 and
35(Suppl. 3):11–21.


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