Acne
1. Endotoxin-induced changes in copper and zinc metabolism in the Syrian
hamster.
Etzel KR, Swerdel MR, Swerdel JN, Cousins RJ
J Nutr 1982 Dec;112(12):2363-73
The temporal response of zinc and copper metabolism to endotoxin administration
was examined in Syrian hamsters over a 144-hour period. Serum copper was
significantly elevated at 12, 24 and 72 hours after endotoxin, whereas
serum zinc was reduced 4-48 hours after treatment. A brief elevation (8
hours) in liver copper concentration and a sustained (72 hours) increase
in liver zinc concentration were also observed. The amount of zinc associated
with liver metallothionein (MT) progressively increased with time, to
a plateau by 24 hours and persisted at the elevated level until 72 hours
after endotoxin treatment. In vitro translation of poly (A)+ RNA from
liver polyribosomes showed that following endotoxin treatment MTmRNA activity
was maximally elevated 6 hours after endotoxin administration and remained
elevated 24 and 48 hours thereafter. Slab gel electrophoresis of serum
proteins indicated changes in a stainable protein comigrating with purified
ceruloplasmin after endotoxin administration. Pooled gingival tissue from
endotoxin-treated hamsters demonstrated a consistently elevated copper
content 12-144 hours after treatment. Endotoxin isolated from Bacteroides
melaninogenicus was more effective in elevating gingival and serum copper
and gingival zinc than Escherichia coli endotoxin. It was concluded that
endotoxin administration elicits responses that result in enhanced metaollthionein
mRNA activity. In addition, Cu and Zn concentrations in serum, liver and
gingival tissue are influenced by different endotoxins to different degrees.
2. [Current aspects about the role of zinc in nutrition]. [Article in
French]
Favier A Groupe de recherche sur les pathologies oxydatives, Universite
de Grenoble, La Tronche.
Rev Prat 1993 Jan 15;43(2):146-51
The role played by zinc in biology is now better known, and numerous
biochemical mechanisms, such as immunity or actions on several hormones
and more than 200 enzymes, have proved to be zinc-dependent. Thus, many
functions are disturbed when this trace metal is deficient, including,
for example, taste and appetite, cell multiplication, growth, pregnancy,
fertility, defence against bacteria and brain functions. Zinc intake has
been found to be unexcessive and indeed, at the limit of sufficiency in
the French population. Groups at risk, such as neonates, growing children,
pregnant women and elderly people, should have a higher zinc intake provided
by dietary measures or supplementation. Zinc supplementation has been
shown to exert a beneficial effect in randomized studies concerning children's
growth, acne, old people's immunity or low female fertility. Such supplementation
must be balanced and given in moderate doses since zinc interacts with
other foodstuffs, and an excess of zinc can be as bad as its deficiency
in our nutrition.
3. Effects of oral zinc and vitamin A in acne.
Michaelsson G, Juhlin L, Vahlquist A
Arch Dermatol 1977 Jan;113(1):31-6
The effects of oral zinc sulfate (corresponding to 135 mg of zinc daily)
alone and in combination with vitamin A (300,000 international units)
daily on acne lesions have been compared with those of vitamin A alone
and of a placebo. The number of comedones, papules, pustules, and infiltrates
were counted at each visit. After four weeks, there was a significant
decrease in the number of papules, pustules, and infiltrates in the zinc-treated
groups. The effect of zinc plus vitamin A was not better than zinc alone.
After 12 weeks of treatment, the mean acne score had decreased from 100%
to 15%. The mechanism for the effect of zinc therapy in acne, to our knowledge,
is not presently known.
4. Serum zinc and retinol-binding protein in acne.
Michaelsson G, Vahlquist A, Juhlin L
Br J Dermatol 1977 Mar;96(3):283-6
The serum levels of zinc and retinol-binding protein (RBP) have been
determined in 173 patients with acne and compared with those of a control
group. The RBP is a specific transport protein and its level in plasma
reflects the amount of vitamin A available to the tissues. Patients with
severe acne were found to have lower levels of RBP than either patients
with mild acne or healthy subjects of the same age. In the case of males
with severe acne, the mean serum zinc level was significantly lower than
that of the control group. No such difference was observed for girls.
The observed condition of low levels of zinc and vitamin A in the serum
of patients with severe acne may provide a rationale for the clinically
good effect of oral zinc treatment.
5. A double-blind study of the effect of zinc and oxytetracycline in
acne vulgaris.
Michaelsson G, Juhlin L, Ljunghall K
Br J Dermatol 1977 Nov;97(5):561-6
With a double-blind technique, the effects of oral zinc and tetracyclines
were compared in 37 patients with moderate and severe acne. No difference
in effect between the treatments was seen and no side-effects were noted
in any group. After 12 weeks of treatment, the average decrease in the
acne score was about 70% in both groups.
6. A double-blind controlled evaluation of the sebosuppressive activity
of topical erythromycin-zinc complex.
Pierard-Franchimont C, Goffin V, Visser JN, Jacoby H, Pierard GE Department
of Dermatopathology, University of Liege, Belgium.
Eur J Clin Pharmacol 1995;49(1-2):57-60
In a double-blind randomised study, 14 volunteers applied 4% erythromycin
plus 1.2% zinc (Zineryt lotion) and 4% erythromycin lotions, each on half
of the forehead twice daily for 3 months. The sebum output was evaluated
at 3-week intervals using the photometric and the lipid-sensitive film
methods. Evaluations of casual level (CL) and sebum excretion rate (SER)
were made with a Sebumeter, and total area of lipid spots (TAS) was measured
on Sebutapes. Compared to baseline values, the formulation of the erythromycin-zinc
complex induced significant reductions in SER after 6 and 9 weeks, and
in CL and TAS at 3, 6, 9 and 12 weeks. The mean reduction in TAS was over
20% for four successive 1-h samplings on completion of the study. Significant
reductions in CL, SER and TAS were observed for the erythromycin-zinc
formulation compared to the control lotion at 6 and 9 weeks, and also
at 3 weeks for SER and TAS, and at 12 weeks for CL and TAS. This study
indicates that sebum output is significantly reduced by the erythromycin-zinc
complex. This reduction is theoretically beneficial for the acneic patient.
7. Zinc sulfate in acne vulgaris.
Weimar VM, Puhl SC, Smith WH, tenBroeke JE
Arch Dermatol 1978 Dec;114(12):1776-8
The effects of orally administered zinc sulfate in 52 patients with mild
to moderate acne vulgaris were compared to those of a placebo capsule.
The numbers of comedones, papules, pustules, infiltrates, and cysts were
counted at each visit over a 12-week period. Forty patients completed
the study. Zinc appeared to have a somewhat beneficial effect on pustules
but not on comedones, papules, infiltrates, or cysts. Fourteen patients
(50%) in the zinc group had side effects of nausea, vomiting, or diarrhea.
Six patients (21%) in the zinc group could not tolerate the nausea and
withdrew from the study.
8. Inhibition of erythromycin-resistant propionibacteria on the skin
of acne patients by topical erythromycin with and without zinc.
Bojar RA, Eady EA, Jones CE, Cunliffe WJ, Holland KT Department of Microbiology,
University of Leeds, U.K.
Br J Dermatol 1994 Mar;130(3):329-36
Propionibacteria resistant to high concentrations of erythromycin [minimal
inhibitory concentration (MIC) > or = 0.5 mg/ml] are now commonly
isolated from the skin of antibiotic-treated acne patients. This double-blind
study was carried out to assess the ability of 4% w/v erythromycin with
and without 1.2% w/v zinc acetate to reduce the numbers of erythromycin-resistant
propionibacteria in vivo, and also to monitor the acquisition of resistant
strains de novo during therapy. Under laboratory conditions, erythromycin-resistant
propionibacteria were shown to be as sensitive to zinc acetate as fully
sensitive strains. In vivo, the erythromycin/zinc complex and erythromycin
alone produced highly significant reductions in total propionibacteria
(P < 0.001) and in the number of erythromycin-resistant strains
(P < 0.001 at 8 weeks). After 12 weeks, resistant propionibacteria
were reacquired, or acquired de novo, by three patients treated with erythromycin
alone and four patients treated with the erythromycin/zinc complex. In
contrast, changes in numbers of Micrococcaceae were slight and, after
12 weeks, erythromycin-resistant strains were predominant in both treatment
groups. In vitro MIC determinations suggested that this finding might
be explained by the exceptionally high degree of erythromycin resistance
displayed by some staphylococcal strains (MIC > 4 mg/ml) and by
the relative insensitivity of all staphylococcal strains to zinc acetate.
Erythromycin with and without zinc was clinically effective, and both
preparations produced significant reductions in acne grade, and inflamed
and non-inflamed lesion counts (P < 0.001).
9. Endotoxin-induced changes in copper and zinc metabolism in the Syrian
hamster.
Etzel KR, Swerdel MR, Swerdel JN, Cousins RJ
J Nutr 1982 Dec;112(12):2363-73
The temporal response of zinc and copper metabolism to endotoxin administration
was examined in Syrian hamsters over a 144-hour period. Serum copper was
significantly elevated at 12, 24 and 72 hours after endotoxin, whereas
serum zinc was reduced 4-48 hours after treatment. A brief elevation (8
hours) in liver copper concentration and a sustained (72 hours) increase
in liver zinc concentration were also observed. The amount of zinc associated
with liver metallothionein (MT) progressively increased with time, to
a plateau by 24 hours and persisted at the elevated level until 72 hours
after endotoxin treatment. In vitro translation of poly (A)+ RNA from
liver polyribosomes showed that following endotoxin treatment MTmRNA activity
was maximally elevated 6 hours after endotoxin administration and remained
elevated 24 and 48 hours thereafter. Slab gel electrophoresis of serum
proteins indicated changes in a stainable protein comigrating with purified
ceruloplasmin after endotoxin administration. Pooled gingival tissue from
endotoxin-treated hamsters demonstrated a consistently elevated copper
content 12-144 hours after treatment. Endotoxin isolated from Bacteroides
melaninogenicus was more effective in elevating gingival and serum copper
and gingival zinc than Escherichia coli endotoxin. It was concluded that
endotoxin administration elicits responses that result in enhanced metaollthionein
mRNA activity. In addition, Cu and Zn concentrations in serum, liver and
gingival tissue are influenced by different endotoxins to different degrees.
10. [Current aspects about the role of zinc in nutrition]. [Article in
French]
Favier A Groupe de recherche sur les pathologies oxydatives, Universite
de Grenoble, La Tronche.
Rev Prat 1993 Jan 15;43(2):146-51
The role played by zinc in biology is now better known, and numerous
biochemical mechanisms, such as immunity or actions on several hormones
and more than 200 enzymes, have proved to be zinc-dependent. Thus, many
functions are disturbed when this trace metal is deficient, including,
for example, taste and appetite, cell multiplication, growth, pregnancy,
fertility, defence against bacteria and brain functions. Zinc intake has
been found to be unexcessive and indeed, at the limit of sufficiency in
the French population. Groups at risk, such as neonates, growing children,
pregnant women and elderly people, should have a higher zinc intake provided
by dietary measures or supplementation. Zinc supplementation has been
shown to exert a beneficial effect in randomized studies concerning children's
growth, acne, old people's immunity or low female fertility. Such supplementation
must be balanced and given in moderate doses since zinc interacts with
other foodstuffs, and an excess of zinc can be as bad as its deficiency
in our nutrition.
11. Effects of oral zinc and vitamin A in acne.
Michaelsson G, Juhlin L, Vahlquist A
Arch Dermatol 1977 Jan;113(1):31-6
The effects of oral zinc sulfate (corresponding to 135 mg of zinc daily)
alone and in combination with vitamin A (300,000 international units)
daily on acne lesions have been compared with those of vitamin A alone
and of a placebo. The number of comedones, papules, pustules, and infiltrates
were counted at each visit. After four weeks, there was a significant
decrease in the number of papules, pustules, and infiltrates in the zinc-treated
groups. The effect of zinc plus vitamin A was not better than zinc alone.
After 12 weeks of treatment, the mean acne score had decreased from 100%
to 15%. The mechanism for the effect of zinc therapy in acne, to our knowledge,
is not presently known.
12. Serum zinc and retinol-binding protein in acne.
Michaelsson G, Vahlquist A, Juhlin L
Br J Dermatol 1977 Mar;96(3):283-6
The serum levels of zinc and retinol-binding protein (RBP) have been
determined in 173 patients with acne and compared with those of a control
group. The RBP is a specific transport protein and its level in plasma
reflects the amount of vitamin A available to the tissues. Patients with
severe acne were found to have lower levels of RBP than either patients
with mild acne or healthy subjects of the same age. In the case of males
with severe acne, the mean serum zinc level was significantly lower than
that of the control group. No such difference was observed for girls.
The observed condition of low levels of zinc and vitamin A in the serum
of patients with severe acne may provide a rationale for the clinically
good effect of oral zinc treatment.
13. A double-blind controlled evaluation of the sebosuppressive activity
of topical erythromycin-zinc complex.
Pierard-Franchimont C, Goffin V, Visser JN, Jacoby H, Pierard GE Department
of Dermatopathology, University of Liege, Belgium.
Eur J Clin Pharmacol 1995;49(1-2):57-60
In a double-blind randomised study, 14 volunteers applied 4% erythromycin
plus 1.2% zinc (Zineryt lotion) and 4% erythromycin lotions, each on half
of the forehead twice daily for 3 months. The sebum output was evaluated
at 3-week intervals using the photometric and the lipid-sensitive film
methods. Evaluations of casual level (CL) and sebum excretion rate (SER)
were made with a Sebumeter, and total area of lipid spots (TAS) was measured
on Sebutapes. Compared to baseline values, the formulation of the erythromycin-zinc
complex induced significant reductions in SER after 6 and 9 weeks, and
in CL and TAS at 3, 6, 9 and 12 weeks. The mean reduction in TAS was over
20% for four successive 1-h samplings on completion of the study. Significant
reductions in CL, SER and TAS were observed for the erythromycin-zinc
formulation compared to the control lotion at 6 and 9 weeks, and also
at 3 weeks for SER and TAS, and at 12 weeks for CL and TAS. This study
indicates that sebum output is significantly reduced by the erythromycin-zinc
complex. This reduction is theoretically beneficial for the acneic patient.
ADD – ADHD
14. Does zinc moderate essential fatty acid and amphetamine treatment
of attention-deficit/hyperactivity disorder?
Arnold LE, Pinkham SM, Votolato N. Department of Psychiatry, Ohio State
University, Columbus, USA. Arnold.6@osu.edu
J Child Adolesc Psychopharmacol 2000 SUMMMER;10(2):111-7
Zinc is an important co-factor for metabolism relevant to neurotransmitters,
fatty acids, prostaglandins, and melatonin, and indirectly affects dopamine
metabolism, believed intimately involved in attention-deficit/hyperactivity
disorder (ADHD). To explore the relationship of zinc nutrition to essential
fatty acid supplement and stimulant effects in treatment of ADHD, we re-analyzed
data from an 18-subject double-blind, placebo-controlled crossover treatment
comparison of d-amphetamine and Efamol (evening primrose oil, rich in
gamma-linolenic acid). Subjects were categorized as zinc-adequate (n =
5), borderline zinc (n = 5), and zinc-deficient (n = 8) by hair, red cell,
and urine zinc levels; for each category, placebo-active difference means
were calculated on teachers' ratings. Placebo-controlled d-amphetamine
response appeared linear with zinc nutrition, but the relationship of
Efamol response to zinc appeared U-shaped; Efamol benefit was evident
only with borderline zinc. Placebo-controlled effect size (Cohen's d)
for both treatments ranged up to 1.5 for borderline zinc and dropped to
0.3-0.7 with mild zinc deficiency. If upheld by prospective research,
this post-hoc exploration suggests that zinc nutrition may be important
for treatment of ADHD even by pharmacotherapy, and if Efamol benefits
ADHD, it likely does so by improving or compensating for borderline zinc
nutrition.
CARDIOVASCULAR DISEASE
15. Emerging concepts of neurohumoral modulation in the treatment of
congestive heart failure.
Mulder P, Thuillez Ch.
INSERM E9920, IFRMP No. 23, Rouen University Medical School, France.
paul.mulder@univ-rouen.fr
Arch Mal Coeur Vaiss. 2002 Sep;95(9):821-6.
The angiotensin converting enzyme (ACE), endothelin (ET) converting enzyme
(ECE) and neutral endopeptidase (NEP) are all zinc-metallopeptidases expressed
in almost all the organs, such as heart, vessels and kidneys. While ACE
and ECE are respectively involved in the transformation of angiotensin
I and Big-ET into angiotensin II and ET-1 respectively, which possess
vasoconstrictor and mitogenic properties, NEP is involved in the degradation
of atrial natriuric
factor (ANF), which possesses vasorelaxant, diuretic/natriuretic and
antihypertrophic properties. These three systems are activated in heart
failure
and modulate the progression of heart failure. This article will discuss
preliminary date concerning simultaneous inhibition of ACE, ECE and/or
NEP and their therapeutic potential interest in the treatment of heart
failure.
16. Magnesium and zinc status in survivors of sudden unexplained death
syndrome in northeast Thailand.
Pansin P, Wathanavaha A, Tosukhowong P, Sriboonlue P, Tungsanga K, Dissayabutr
T, Tosukhowong T, Sitprija V.
Department of Internal Medicine, Faculty of Medicine, Chulalongkorn University,
Bangkok, Thailand.
Southeast Asian J Trop Med Public Health. 2002 Mar;33(1):172-9.
Sudden Unexplained Death Syndrome (SUDS) is a major health problem in
rural
residents of Northeast Thailand. The cause of death in SUDS is suspected
to be
cardiovascular abnormalities. As magnesium (Mg) and zinc (Zn) deficiency
contribute significantly to several cardiovascular diseases, we investigated
the
Mg- and Zn-status of patients with sudden respiratory distress and cardiac
arrest who had survived resuscitation attempts or a near-SUDS episode
(N-SUDS). The following subjects were enrolled: 12 N-SUDS inhabitants
of rural Northeast Thailand (rural group 1, R1), 13 rural villagers with
no past history of N-SUDS (rural group 2, R2), 15 urban Northeasterners
(urban group 1, U1); 13
Bangkokians (urban group 2, U2). All subjects were free of structural
heart
disease. Magnesium and zinc were assessed by atomic absorption spectrophotometry
of samples of plasma, red blood cells (RBC), white blood cells (WBC),
and 24-hour urine. The mean levels of magnesium in the RBC, WBC, and 24-hour
urine of N-SUDS patients (R1) were significantly lower than those of the
urban groups (U1 and U2), while the plasma levels did not show any differences.
When comparing the Zn-status of R1 with that of the urban groups (U1 and
U2), the plasma, RBC, and WBC levels were found to be significantly lower
in R1 (except for the RBC-Zn of the U1 group), while the 24-hour urine
levels was higher. Although the magnesium and zinc parameters were not
significantly different between the rural groups R1 and R2, the prevalence
of hypomagnesuria (<2.2 mmol/day), hypozincemia (<9.7 micromol/l),
and hyperzincuria (>10.7 micromol/day) was higher in the R1 group.
These findings suggest that the homeostasis of both magnesium and zinc
is altered in N-SUDS patients. Similar alterations, to a lesser degree,
were observed in those people living in the same rural environment (R2).
17. Analysis of ionic ratios in myocardial tissue and their relation
to cardiac
damage.
Torres MC, Osuna E, Perez-Carceles MD, Gomez-Zapata M, Luna A.
Institute of Forensic Medicine of Murcia, Spain.
Am J Forensic Med Pathol. 2002 Jun;23(2):155-8.
The authors evaluated the usefulness of the postmortem biochemical analysis
of
ionic ratios in different parts of the heart and their relation to cardiac
damage caused by chest trauma, as observed by anatomopathologic study.
Fifty-nine 59 cases were studied, selected from routine necropsies, and
samples
were taken from different sites of cardiac tissue. The cause of death
was trauma
in 40 cases and nontraumatic causes in 19 cases. The object of this study
was to
analyze the levels of Na+, K+, Ca+2, Mg+2, and Zn+2 in different zones
of the
heart, and the relationship between intracellular and extracellular ion
ratios
and the different causes of death and any anatomopathologic alterations
observed. The biochemical tests revealed a possible relation between the
ionic
values and cause of death. Alterations in cell membrane permeability and
corresponding modification of the ionic ratios were produced earlier than
histologic alterations, which need longer to establish themselves whether
or not
they follow a traumatic process.
18. Influence of zinc on cardiac and serum biochemical parameters in
rabbits.
Bhaskar M, Madhuri E, Abdul Latheef SA, Subramanyam G.
Department of Zoology, S.V. University Post Graduate Centre, Kavali, India.
Indian J Exp Biol. 2001 Nov;39(11):1170-2.
The pattern of lipid profiles and organic constituents of cardiac and
serum
tissues of rabbits were studied on treatment with cholesterol, zinc and
zinc +
cholesterol. Total carbohydrate and total protein levels were decreased
with
elevated lipid levels in cholesterol fed rabbits. However, the zinc and
cholesterol + zinc fed rabbits showed decreased lipid fractions in cardiac
and
serum tissues leading to reduced atherosclerotic process in rabbits. These
results suggest that the zinc is acting as a hypolipidaemic and anti atherogenic
agent in experimental rabbits.
19. Diagnostic and therapeutic potential of the endothelin system in
patients with chronic heart failure.
Krum H, Denver R, Tzanidis A, Martin P.
Clinical Pharmacology Unit, Dept of Epidemiology & Preventive
Medicine/Department of Medicine, Monash University/Alfred Hospital, Prahran,
Victoria, Australia. henry.krum@med.monash.edu.au
Heart Fail Rev. 2001 Dec;6(4):341-52.
There is now considerable evidence to support a role for the endothelin
(ET)
system in the pathogenesis and progression of chronic heart failure (CHF).
As
such, the potential exists for this system to be useful in both diagnosis
(by
measurement of peptide levels in plasma and other body fluids) and treatment
(by pharmacological blockade) of this condition.Plasma levels of endothelin-1
(ET-1) are elevated in CHF and the magnitude of elevation correlates with
disease severity. ET-1 levels in plasma predict subsequent mortality in
patients with CHF. ET-1 may also contribute to symptoms associated with
CHF, such as exercise intolerance. In the diagnosis of CHF, plasma levels
of ET-1 appear to be a less powerful discriminator between patients with
mild disease and control subjects with normal ventricular function on
multivariate analyses, compared to brain natriuretic peptide (BNP), or
its N-terminal fragment. ET-1 concentrations are also elevated in the
saliva of patients with CHF and may represent an
alternative approach to assessment of the status of the ET system in these
patients.Specific ET receptor antagonists (both mixed and ET(A)-selective)
have
been developed. Studies with these agents in animal models of CHF have
demonstrated beneficial effects via both haemodynamic and non-haemodynamic
pathways. A number of short-term clinical studies have been performed
demonstrating improvements in haemodynamic parameters without neurohormonal
activation. Long-term clinical studies with ET receptor antagonists are
currently underway to definitively test the impact of blockade of this
system on mortality and major cardiovascular endpoints. Endothelin converting
enzyme (ECE) inhibitors represent an alternative strategy of ET blockade,
and early data from animal models suggest these agents may be of clinical
utility, either alone or, more likely, in combination with other zinc
metallopeptidases.
20. Antioxidant status in cerebrovascular accident.
Kocaturk PA, Akbostanci MC, Isikay C, Ocal A, Tuncel D, Kavas GO, Mutluer
N.
Departments of Pathophysiology, Faculty of Medicine, Ankara University,
Sihhiye, Turkey.
Biol Trace Elem Res. 2001 May;80(2):115-24.
Ischemia is associated with the pathological changes caused by the accumulation
of reactive oxygen metabolites (ROM) in cerebrovascular accident (CVA).
The aim of this study was to determine red cell copper/zinc-superoxide
dismutase (Cu/Zn-SOD) and catalase activities and copper and zinc concentrations
both in plasma and in red cells in CVA. Cu/Zn-SOD and catalase activities
of 16 patients, with an average age of 64 yr, were measured spectrophotometrically;
copper and zinc concentrations were determined by atomic absorption spectrophotometer.
The results showed that Cu/Zn-SOD activity was increased markedly in patients
compared to the young controls and reached a peak on the d 5 of the disease,
whereas the catalase activity of the patients on d 3 and d 5 were in the
normal range, but higher on d 10. The enzyme activities of the elderly
group were generally increased compared to the young controls. Copper
and zinc concentrations showed corresponding alterations. These findings
suggested that the effects of oxidative stress in CVA might be reflected
in red cell and plasma parameters.
21. Nutritional factors in the pathobiology of human essential hypertension.
Das UN.
EFA Sciences LLC, Norwood, Massachusetts 02062, USA. undurti@hotmail.com
Nutrition. 2001 Apr;17(4):337-46.
Endothelial cells produce vasodilator and vasoconstrictor substances.
Dietary
factors such as sodium, potassium, calcium, magnesium, zinc, selenium,
vitamins A, C, and E, and essential fatty acids and their products such
as eicosanoids can influence blood pressure, cardio- and cerebrovascular
diseases, and concentrations of blood lipids and atherosclerosis. There
might be a close
interaction between these dietary factors, sympathetic and parasympathetic
nervous systems, the metabolism of essential fatty acids, nitric oxide,
prostacyclin, and endothelium in human essential hypertension. A deficiency
in
any one factor, dietary or endogenous, or alterations in their interactions
with
each other, can lead to endothelial dysfunction and development of hypertension.
Therefore, alterations in the metabolism of essential fatty acids might
be a
predisposing factor to the development of essential hypertension and insulin
resistance.
22. Cardiovascular risk factors in relation to the serum concentrations
of copper and zinc: epidemiological study on children and adolescents
in the Spanish province of Navarra.
Elcarte Lopez T, Villa Elizaga I, Gost Garde JI, Elcarte Lopez R, Martin
Perez
A, Navascues Pujada J, Navarro Blasco I, Aparicio Madre MI.
Primary Health Care Center, Pamplona, Navarra, Spain.
Acta Paediatr. 1997 Mar;86(3):248-53.
This investigation was carried out to show the possible association between
groups of children with extreme values of copper and zinc concentrations
and
cardiovascular risk indicators. Serum copper and zinc concentrations were
analysed in a group of 3887 children from Navarra, Spain (both sexes.
aged 4-17
years). Hypertension, unfavourable serum lipid profile (total cholesterol,
high
density lipoprotein cholesterol, low density lipoprotein cholesterol,
triglycerides, and cholesterol/HDL and LDL/HDL ratios), and degree of
adiposity (weight, height, subcutaneous skinfolds, Quetelet's index and
mean of subcutaneous skinfolds) were evaluated. Positive correlation was
found between several lipid parameters and copper and zinc concentrations,
i.e. degree of correlation related with age, except for copper/HDL and
triglycerides/zinc ratios, where correlation remained negative at all
points. Copper levels were correlated with adiposity parameters in an
age-dependent fashion (Quetelet's index: r = 0.01 for ages 4-7 years to
r = 0.10, p < 0.01 for ages 14-17 years; mean skinfold thickness: r
= 0.05 for ages 4-7 years up to r = 0.18, p < 0.01 for ages 14-17 years).
Most correlations between lipid parameters and copper and zinc are markedly
amplified if adiposity parameters are taken into account. However, the
only significant association was the established relation between high
copper concentrations (> x + 2SD) and unfavourable serum lipid profile(LDL/HDL
> 2.2).
23. Serum calcium, magnesium, copper and zinc and risk of cardiovascular
death.
Reunanen A; Knekt P; Marniemi J; Maki J; Maatela J; Aromaa A
National Public Health Institute, Helsinki, Finland.
Eur J Clin Nutr (England) Jul 1996, 50 (7) p431-7
OBJECTIVE: To study the association of serum calcium, magnesium, copper
and zinc concentrations with cardiovascular mortality.
DESIGN: A nested case-control study within a prospective population study.
SUBJECTS AND METHODS: 230 men dying from cardiovascular diseases and 298
controls matched for age, place of residence, smoking and follow-up time.
Mean follow-up time was 10 years. Serum calcium, magnesium, copper and
zinc concentrations were determined from samples kept frozen at -20 degrees
C.
RESULTS: High serum copper and low serum zinc concentrations were significantly
associated with an increased mortality from all cardiovascular diseases
and from coronary heart disease in particular. The relative risk of coronary
heart disease mortality between the highest and lowest tertiles of serum
copper and zinc were 2.86 (P = 0.03) and 0.69 (P = 0.04), respectively.
Adjustment for social class, serum cholesterol, body mass index, hypertension
and known heart disease at baseline examination did not materially alter
the results. No significant differences were observed in concentrations
of serum calcium and magnesium between cases and controls. CONCLUSIONS:
High serum copper and low serum zinc are associated with increased cardiovascular
mortality whereas no association was found with serum calcium and magnesium
and mortality risk.
COMMON COLD
24. Zinc lozenges reduce the duration of common cold symptoms.
ANON [No Authors Listed]
Nutr Rev (United States) Mar 1997, 55 (3) p82-5
A randomized, double-blind, placebo-controlled clinical trial has shown
that treatment of the common cold with zinc gluconate lozenges resulted
in a significant reduction in duration of symptoms of the cold. Patients
received zinc-containing lozenges or placebo lozenges every 2 hours for
the duration of cold symptoms. The median time to complete resolution
of cold symptoms was 4.4 days in the zinc group compared with 7.6 days
in the placebo group. The mechanism of action of zinc in treating the
common cold remains unknown. (13 Refs.)
25. Zinc gluconate lozenges for treating the common cold. A randomized,
double-blind, placebo-controlled study
Mossad SB; Macknin ML; Medendorp SV; Mason P Cleveland Clinic Foundation,
Ohio, USA.
Ann Intern Med (United States) Jul 15 1996, 125 (2) p81-8, Comment in
Ann Intern Med 1996 Jul 15;125(2):142-4
BACKGROUND. The common cold is one of the most frequent human illnesses
and is responsible for substantial morbidity and economic loss. No consistently
effective therapy for the common cold has been well documented, but evidence
suggests that several possible mechanisms may make zinc an effective treatment.
OBJECTIVE. To test the efficacy of zinc gluconate lozenges in reducing
the duration of symptoms caused by the common cold. DESIGN. Randomized,
double-blind, placebo-controlled study. SETTING. Outpatient department
of a large tertiary care center. PATIENTS. 100 employees of the Cleveland
Clinic who developed symptoms of the common cold within 24 hours before
enrollment. INTERVENTION. Patients in the zinc group (n = 50) received
lozenges (one lozenge every 2 hours while awake) containing 13.3 mg of
zinc from zinc gluconate as long as they had cold symptoms. Patients in
the placebo group (n = 50) received similarly administered lozenges that
contained 5% calcium lactate pentahydrate instead of zinc gluconate. MAIN
OUTCOME MEASURES. Subjective daily symptom scores for cough, headache,
hoarseness, muscle ache, nasal drainage, nasal congestion, scratchy throat,
sore throat, sneezing, and fever (assessed by oral temperature). RESULTS.
The time to complete resolution of symptoms was significantly shorter
in the zinc group than in the placebo group (median, 4.4 days compared
with 7.6 days; P < 0.001). The zinc group had significantly fewer
days with coughing (median, 2.0 days compared with 4.5 days; P = 0.04),
headache (2.0 days and 3.0 days; P = 0.02), hoarseness (2.0 days and 3.0
days; P = 0.02), nasal congestion (4.0 days and 6.0 days; P = 0.002),
nasal drainage (4.0 days and 7.0 days; P < 0.001), and sore throat
(1.0 day and 3.0 days; P < 0.001). The groups did not differ significantly
in the resolution of fever, muscle ache, scratchy throat, or sneezing.
More patients in the zinc group than in the placebo group had side effects
(90% compared with 62%; P < 0.001), nausea (20% compared with 4%;
P = 0.02), and bad-taste reactions (80% compared with 30%; P <
0.001),
CONCLUSION. Zinc gluconate in the form and dosage studied significantly
reduced the duration of symptoms of the common cold. The mechanism of
action of this substance in treating the common cold remains unknown.
Individual patients must decide whether the possible beneficial effects
of zinc gluconate on cold symptoms outweigh the possible adverse effects.
DIABETES
26. Decreased serum magnesium and zinc levels: atherogenic implications
in type-2 diabetes mellitus in Nigerians.
Anetor JI, Senjobi A, Ajose OA, Agbedana EO.
Department of Chemical Pathology, College of Medicine, University College
Hospital, Ibadan, Nigeria.
Nutr Health. 2002;16(4):291-300.
Serum magnesium, zinc and total cholesterol were evaluated in 40 Nigerian
patients suffering from type-2 diabetes mellitus (21M, 19F) and 20 (14M,
6F)
apparently normal non diabetic control subjects. The mean age of the diabetic
patients was similar to that of controls (p > 0.05). The mean duration
of the
disease was (4.7 + 0.7 SEM) in these patients. Fasting blood glucose and
total
cholesterol were significantly higher in diabetics than in non diabetic
control
subjects (p > 0.001). The serum total cholesterol showed inter-group
variation
when the patients were classified into four different age groups. In contrast,
the serum level of magnesium (Mg) and zinc (Zn) were significantly lower
in
diabetics than in controls (p > 0.001). There were no significant correlation
between glucose and the minerals, Mg. and Zn. Serum total cholesterol
showed a significant positive correlation with magnesium (r = 0.6: p >
0.001), while the
correlation with zinc was not significant. In type-2 diabetic mellitus
the
concentration of both Mg and Zn levels were significantly reduced, probably
suggesting lower antioxidant status in this condition. The implication
is the
greater susceptibility to LDL-cholesterol oxidation. The attendant risk
of
development of premature Coronary Heart Disease is discussed. Magnesium
and zinc are nutritional minerals that play crucial roles in the regulation
of
carbohydrate and lipid metabolism.
27. Dietary zinc supplementation inhibits NFkappaB activation and protects
against chemically induced diabetes in CD1 mice.
Ho E, Quan N, Tsai YH, Lai W, Bray TM. Department of Human Nutrition,
The Ohio State University, Columbus 43210, USA.
Exp Biol Med (Maywood) 2001 Feb;226(2):103-11
Zinc status in patients with Type I diabetes is significantly lower than
healthy controls. Whether zinc supplementation can prevent the onset of
Type I diabetes is unknown. Recent studies have suggested that the generation
of reactive oxygen species (ROS) is a cause of beta cell death leading
to Type I diabetes. In addition, we found that activation of NFkappaB
(a ROS-sensitive transcription factor that regulates immune responses)
may be the key cellular process that bridges oxidative stress and the
death of beta cells. Zinc is a known antioxidant in the immune system.
Therefore, this study is designed to test whether an increase in dietary
zinc can prevent the onset of Type I diabetes by blocking NFkappaB activation
in the pancreas. The results show that high zinc intake significantly
reduced the severity of Type I diabetes (based on hyperglycemia, insulin
level, and islet morphology) in alloxan and streptozotocin-induced diabetic
models. Zinc supplementation also inhibited NFkappaB activation and decreased
the expression of inducible NO synthase, a downstream target gene of NFkappaB.
It is concluded that zinc supplementation can significantly inhibit the
development of Type I diabetes. The ability of zinc to modulate NFkappaB
activation in the diabetogenic pathway may be the key mechanism for zinc's
protective effect. Inhibition of the NFkappaB pathway may prove to be
an important criterion for choosing nutritional strategies for Type I
diabetes prevention.
28. Oral zinc therapy in diabetic neuropathy.
Gupta R, Garg VK, Mathur DK, Goyal RK.
Dept. of Medicine, JLN Medical College and Associated Group of Hospital,
Ajmer, Rajasthan-305 001.
J Assoc Physicians India. 1998 Nov;46(11):939-42.
The present double blind randomized study was conducted on 50 subjects;
20 age and sex matched healthy controls (Group--I); 15 patients of diabetes
mellitus
with neuropathy who received placebo for 6 weeks (Group--IIA); and 15
patients
of diabetes mellitus with neuropathy who were given supplemental zinc
sulphate
(660 mg) for 6 weeks (Group--IIB). Serum zinc level, fasting blood sugar
(FBS)
and post prandial blood sugar (PPBS) levels and motor nerve conduction
velocity
(MNCV) were estimated on day 0 and after 6 weeks in all subjects. Serum
zinc
levels were significantly low (p < 0.001) in group IIA and IIB as compared
to
healthy controls (Group--I) at baseline. After 6 weeks the change in pre
and
post therapy values of FBS, PPBS and MNCV (median and common peroneal
nerve) were highly significant (P = < 0.001) for group IIB alone with
insignificant
change (P = > 0.05) in group IIA. No improvement (P = > 0.05) in
autonomic
dysfunction was observed in either groups. Therefore, oral zinc supplementation
helps in achieving better glycemic control and improvement in severity
of
peripheral neuropathy as assessed by MNCV.
29. [Low zinc levels in metabolic X syndrome (mzX) patients measured
by hair zinc composition analysis] [Article in Polish]
Lukasiak J, Cajzer D, Dabrowska E, Falkiewicz B.
Pracownia Analizy Instrumentalnej, Katedra Chemii Fizycznej AM w Gdansku.
Rocz Panstw Zakl Hig. 1998;49(2):241-4.
The hair zinc content in 16 patients with metabolic X syndrome (mzX)
was
measured by means of atomic absorption spectrometry method. The mean
concentration (125.13 mg/kg) was lower than in the majority of other published
studies. The differences among groups of patients with different sex or
diseases
(e.g. coronary heart disease, hypertension, type II diabetes mellitus)
were not
significant. It seems to be probably that deficiency of zinc plays a role
in
pathogenesis of mzX or that it is a consequence of mzX.
30. [Influence of insufficient zinc on immune functions in NIDDM patients]
[Article in Chinese]
Wang P, Yang Z.
Department of Endocrinology, Second Affiliated Hospital, Hunan Medical
University, Changsha.
Hunan Yi Ke Da Xue Xue Bao. 1998;23(6):599-601.
The serum zinc level and immune functions were analyzed in 34 patients
with
NIDDM before and after the treatment with zinc gluconate supplement during
conventional therapy (after the blood glucose level stabilization). The
results
showed that before treatment the level of serum zinc and red cell C3b
receptor
rosette(RBCK-C3b RR), T-lymphocyte subgroup CD3, CD4, and CD4/CD8 were
decreased(P < 0.01), while CD8, red cell immune complex rosette(RBC-ICR)
were increased. After treatment with zinc gluconate for 1 month the serum
zinc level, RBC-C3b RR, RBC-ICR, CD3 and CD4/CD8 became normal, CD8 also
approached to normal. All the above figures were significantly different
before and after zinc therapy. The data showed that various degrees of
lowering of serum zinc and abnormal immune functions were present during
the conventional antidiabetic therapy. Thus, zinc supplement should be
used as an important adjunctive therapy for NIDDM patients.
31. Hyperzincuria in individuals with insulin-dependent diabetes mellitus:
concurrent zinc status and the effect of high-dose zinc supplementation.
Cunningham JJ, Fu A, Mearkle PL, Brown RG.
Department of Nutrition, University of Massachusetts, Amherst, MA 01003-1420.
Metabolism 1994 Dec;43(12):1558-62
The urinary excretion of zinc in individuals with insulin-dependent diabetes
mellitus (IDDM) is approximately doubled. In the absence of a compensatory
mechanism, this hyperzincuria should induce a deficient or marginal Zn
status. We examined parameters of Zn status in plasma and in blood cells
with respect to urinary Zn losses and Zn supplementation. We measured
Zn levels in the urine, plasma, and erythrocytes of 14 IDDM subjects and
15 nondiabetics who kept dietary records for 3 consecutive days. Subsequently,
six IDDM subjects and seven nondiabetics were supplemented with 50 mg
Zn daily for 28 days. We measured the above parameters, as well as mononuclear
leukocyte Zn (MNL-Zn) and the plasma subfraction of albumin-bound Zn (alb-Zn).
The total plasma Zn-binding capacity was also assessed. Plasma copper
and erythrocyte Cu were monitored as indicators of potential Zn toxicity.
Individuals with IDDM displayed the expected hyperzincuria, but had normal
blood Zn parameters. Zincuria increased by a similar amount in both groups
during supplementation, as did the MNL-Zn content. However, erythrocyte
Zn (e-Zn) was refractory, so a trend toward lower e-Zn among IDDM subjects
persisted during Zn supplementation. Hemoglobin A1c (HbA1c) increased
markedly in the Zn-supplemented IDDM group. Despite their chronic hyperzincuria,
individuals with IDDM appear not to be Zn-deficient. Large-dose Zn supplementation
increases MNL-Zn and induces an undesirable elevation of HbA1c in all
individuals. This is especially disconcerting for those with IDDM, and
may reflect an exacerbation of a chronic "Zn diabetes." These
data suggest a potential for toxicity from large-dose Zn supplementation.
32. Zinc and insulin sensitivity.
Faure P, Roussel A, Coudray C, Richard MJ, Halimi S, Favier A.
Laboratoire de Biochimie C, Hopital A. Michallon, Grenoble, France.
Biol Trace Elem Res 1992 Jan-Mar;32:305-10
Many studies have shown that zinc deficiency could decrease the response
to insulin. In genetically diabetic animals, a low zinc status has been
observed contrary to induced diabetic animals. The zinc status of human
patients depends on the type of diabetes and the age. Zinc supplementation
seems to have beneficial effects on glucose homeostasis. However, the
mechanism of insulin resistance secondary to zinc depletion is yet unclear.
More studies are therefore necessary to document better zinc metabolism
in diabetes mellitus, and the antioxidant activity of zinc on the insulin
receptor and the glucose transporter.
33. The influence of zinc supplementation on glucose homeostasis in NIDDM.
Raz I, Karsai D, Katz M.
Department of Medicine B, Hadassah University Hospital, Ein Karem, Israel.
Diabetes Res 1989 Jun;11(2):73-9
Decreased serum zinc levels and hyperzincuria occur in some non-insulin
dependent diabetic subjects (NIDDM). Zinc deficiency was demonstrated
in various tissues of animal models for NIDDM. Serum zinc and 24-hr urine
zinc of subjects with NIDDM were compared with that of age- and sex-matched
healthy volunteers. Zincuria was significantly increased in the diabetic
group. Thirteen diabetic subjects with hyperzincuria and hypozincemia
were supplemented with zinc sulfate 220 mg x 3/day for 7-8 weeks. At the
end of the study, glucose disposal (evaluated by kg) decreased significantly
from 0.562 +/- 0.03 to 0.414 +/- 0.05 (p less than 0.05) and fasting glucose
and fructosamine were significantly increased from 177 +/- 10 mg/dl to
207 +/- 15 mg/dl (p less than 0.05) and from 2.7 +/- 0.2% to 3.2 +/- 0.28%
(p less than 0.05), respectively. T-lymphocyte response to phytohemagglutinin
was increased significantly. We conclude that zinc supplementation to
NIDD patients with hypozincemia and hyperzincemia might aggravate their
glucose intolerance. More accurate methods to assess zinc deficiency in
NIDD patients is needed to justify the supplementation of zinc in these
patients.
ELDERLY
34. Zinc and immunoresistance to infection in aging: new biological tools.
Mocchegiani E, Muzzioli M, Giacconi R.
Immunology Centre, Research Department 'Nino Masera', Italian National
Research Centres on Aging (I.N.R.C.A.), Via Birarelli 8, 60121, Ancona,
Italy.
e.mocchegiani@inrca.it
Trends Pharmacol Sci. 2000 Jun;21(6):205-8.
Comment in:
Trends Pharmacol Sci. 2001 Mar;22(3):112-3.
Infections can cause mortality when the immune system is damaged. The
catalytic, structural (in zinc-finger proteins) and regulatory roles of
zinc mean that this ion is involved in the maintenance of an effective
immune response. Both zinc deficiency and impaired cell-mediated immunity
combine during aging to result in increased susceptibility to infection.
Dietary supplementation with the
recommended daily allowance of zinc for between one and two months decreases
the incidence of infection and increases the survival rate following infection
in the elderly. This article reviews the biochemical pathways through
which zinc might act to increase immunoresistance to infection in the
elderly.
35. Zinc and copper intakes and their major food sources for older adults
in the 1994-96 continuing survey of food intakes by individuals (CSFII).
Ma J, Betts NM.
Department of Nutritional Science and Dietetics, University of Nebraska,
Lincoln, NE 68583, USA.
J Nutr. 2000 Nov;130(11):2838-43.
Full text article
http://www.nutrition.org/cgi/content/full/130/11/2838
Zinc and copper are two trace minerals essential for important biochemical
functions and necessary for maintaining health throughout life. Several
national
food surveys revealed marginally to moderately low contents of both nutrients
in
the typical American diet. Using data from the respondents >/= 60 y
old in the
1994-96 Continuing Survey of Food Intakes by Individuals (CSFII), we examined
average dietary intakes of zinc, copper and relevant dietary factors;
primary
dietary contributors of zinc and copper; and Zn:Cu ratios of the primary
dietary
contributors. Data were analyzed with the use of a chi(2) test, Student's
t test
and multivariate analysis of covariance with Bonferroni correction. The
daily
zinc intake was 12 +/- 6.4 mg for men and 8.0 +/- 4.0 mg for women (P
< 0.05);
the daily copper intake was 1.3 +/- 0.7 mg for men and 1.0 +/- 0.5 mg
for women
(P < 0.05). Foods such as beef, ground beef, legumes, poultry, ready-to-eat
and
hot cereals, and pork constituted the major sources of zinc. Copper consumption
was contributed mainly by legumes, potato and potato products, nuts and
seeds,
and beef. The less-than-recommended intakes of zinc and copper by the
elderly
were likely associated with age, low income and less education. The intakes
of
zinc and copper could be improved by more frequent consumption of food
sources rich in these minerals. An inherent limitation of this study was
the use of the 24-h dietary recall method, which may underestimate usual
dietary intakes.
Nonetheless, this study affirms the need for assessment of zinc and copper
nutriture in the elderly.
36. [Zinc: pathophysiological effects, deficiency status and effects
of supplementation in elderly persons--an overview of the research]
[Article in German]
Abbasi A, Shetty K.
Medical College of Wisconsin, Milwaukee 53226, USA.
Z Gerontol Geriatr. 1999 Jul;32 Suppl 1:I75-9.
Zinc is an essential micronutrient. Several studies have shown that zinc
deficiency is common in older people. Zinc has been extensively studied
with
regard to its role in wound healing, infections, immune system, cardiovascular
disease, and several other medical conditions. Several investigators have
published intervention studies using zinc supplements in older people
with
favorable outcomes. This paper will briefly review the pathophysiologic
effects
of zinc, nutritional deficiency, and effects of zinc supplementation in
older
people.
37. Impact of trace elements and vitamin supplementation on immunity
and infections in institutionalized elderly patients: a randomized controlled
trial. MIN. VIT. AOX. geriatric network.
Girodon F, Galan P, Monget AL, Boutron-Ruault MC, Brunet-Lecomte P, Preziosi
P, Arnaud J, Manuguerra JC, Herchberg S.
Scientific and Technical Institute for Foods and Nutrition, Conservatiore
National des Arts et Mettiers, Paris, France.
Arch Intern Med. 1999 Apr 12;159(7):748-54.
BACKGROUND: Antioxidant supplementation is thought to improve immunity
and thereby reduce infectious morbidity. However, few large trials in
elderly people have been conducted that include end points for clinical
variables. OBJECTIVE: To determine the effects of long-term daily supplementation
with trace elements (zinc sulfate and selenium sulfide) or vitamins (beta
carotene, ascorbic acid, and vitamin E) on immunity and the incidence
of infections in institutionalized elderly people. METHODS: This randomized,
double-blind, placebo-controlled intervention study included 725 institutionalized
elderly patients (>65 years) from 25 geriatric centers in France. Patients
received an oral daily supplement of nutritional doses of trace elements
(zinc and selenium sulfide) or vitamins (beta carotene, ascorbic acid,
and vitamin E) or a placebo within a 2 x 2 factorial design for 2 years.
MAIN OUTCOME MEASURES: Delayed-type hypersensitivity skin response, humoral
response to influenza vaccine, and infectious morbidity and mortality.
RESULTS: Correction of specific nutrient deficiencies was observed after
6 months of supplementation and was maintained for the first year, during
which there was no effect of any treatment on delayed-type hypersensitivity
skin response. Antibody titers after influenza vaccine were higher in
groups that received trace elements alone or associated with vitamins,
whereas the vitamin group had significantly lower antibody titers (P<.05).
The number of patients without respiratory tract infections during the
study was higher in groups that received trace elements (P = .06). Supplementation
with neither trace elements nor vitamins significantly reduced the incidence
of urogenital infections. Survival analysis for the 2 years did not show
any differences between the 4 groups. CONCLUSIONS: Low-dose supplementation
of zinc and selenium provides significant improvement in elderly patients
by increasing the humoral response after vaccination and could have considerable
public health importance by reducing morbidity from respiratory tract
infections.
38. [Diagnosis of zinc deficiency] [Article in German]
Roth HP, Kirchgessner M.
Institut fur Ernahrungsphysiologie, Technischen Universitat Munchen.
Z Gerontol Geriatr. 1999 Jul;32 Suppl 1:I55-63.
Though far more common, particularly in elderly people, than was previously
assumed, marginal zinc deficiency does not lead to the classical manifestations
of zinc deficiency and is therefore difficult to diagnose. There is therefore
a
need for sensitive parameters that can reliably demonstrate even marginal
zinc
deficiency, as suboptimal zinc status can seriously impair human health,
performance, reproductive functions, and mental and physical development.
The
most important criteria for the diagnosis of zinc deficiency are critically
discussed. The laboratory parameters currently considered to be the most
useful
indicators of marginal zinc deficiency are zinc-binding capacity and
serum/plasma alkaline phosphatase activity before and after zinc supplementation
(zinc tolerance test!). In order to obtain a reliable assessment of a
patients zinc status, a number of different diagnostic parameters should
always be measured.
39. Effect of micronutrient supplementation on infection in institutionalized
elderly subjects: a controlled trial.
Girodon F, Lombard M, Galan P, Brunet-Lecomte P, Monget AL, Arnaud J,
Preziosi P, Hercberg S.
Institut Scientifique et Technique de la Nutrition et de l'Alimentation,
Paris, France.
Ann Nutr Metab. 1997;41(2):98-107.
To determine the impact of a trace element and vitamin supplementation
on infectious morbidity, a double-blind controlled trial was performed
on 81 elderly subjects in a geriatric center during a 2-year period. Subjects
were randomly assigned to one of four treatment groups, and received daily:
placebo; trace elements/zinc 20 mg; selenium 100 micrograms); vitamins
(vitamin C 120 mg; beta-carotene 6 mg; alpha-tocopherol 15 mg); or a combination
of trace elements and vitamins at equal doses. (1) Before supplementation,
low serum values in vitamin C, folate, zinc and selenium were observed
in more than two thirds of the patients. (2) After 6 months of supplementation,
a significant increase in vitamin and trace element serum levels was obtained
in the corresponding treatment groups: a plateau was then observed for
the whole study. (3) Subjects who received trace elements (zinc and selenium)
alone or associated with vitamins had significantly less infectious events
during the 2 years of supplementation. These results indicate that supplementation
with low doses of vitamins and trace elements is able to rapidly correct
corresponding deficiencies in the institutionalized elderly. Moreover,
zinc and selenium reduced infectious events.
40. [Zinc status evaluation in an elderly institutionalized population]
[Article in Spanish]
Meertens L, Solano L, Pena E.
Unidad de Investigaciones en Nutricion, Facultad de Ciencias de la Salud,
Universidad de Carabobo, Valencia, Venezuela.
Arch Latinoam Nutr. 1997 Dec;47(4):311-4.
Elderly people is at high nutritional risk for zinc, specially marginal
deficit,
which could contribute to complications of chronic diseases and undernutrition.
The aim of study was to know the zinc status of 83 elderly people (older
than
60), from both sexes, living in geriatric home. Zinc serum levels, alkaline
phosphatase serum levels; albumin serum levels, energy, proteins and zinc
dietary intake and gustative sensitivity were determined. Results expressed
as
mean +/- DS are the following: serum zinc: 90.89 +/- 19.0 micrograms/dl,
alkaline phosphatase: 125.41 +/- 24.2 IU/L, albumin serum: 3.9 +/- 0.76
g/dl
energy intake: 1643 +/- 309.9 Kcal/day, protein intake: 59.96 +/- 13.2
g/day,
zinc intake 7.9 +/- 3.0 mg/day, only energy and zinc intake were deficient.
18.1% had zinc values under 70 micrograms/dl. There was 54% of positive
responses to the taste acuity tests. This results qualify this group as
at risk,
specially for zinc nutritional.
41. Beneficial effects of oral zinc supplementation on the immune response
of old people.
Duchateau J, Delepesse G, Vrijens R, Collet H
Am J Med 1981 May;70(5):1001-4
Zinc is known to have beneficial effects on the immune response. In an
attempt
to modify age-associated immune dysfunction, supplemental zinc was administered
to 15 subjects over 70 years of age (220 mg zinc sulfate twice daily for
a month). As compared to 15 controls, matched for age and sex, there was
a
significant improvement in the following immune parameters in the treated
group:
(1) number of circulating T lymphocytes; (2) delayed cutaneous hypersensitivity
reactions to purified protein derivative, Candidin and streptokinase-streptodornase;
(3) immunoglobulin G (IgG) antibody response to tetanus vaccine. Zinc
treatment had no influence on the number of total circulating leukocytes
or lymphocytes, or on the in vitro lymphocyte response to
three mitogens: phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed
mitogen (PWM). The data suggest that the addition of zinc to the diet
of old persons could be an effective and simple way to improve their immune
function.
42. Effect of a two-year supplementation with low doses of antioxidant
vitamins and/or minerals in elderly subjects on levels of nutrients and
antioxidant defense parameters.
Girodon F, Blache D, Monget AL, Lombart M, Brunet-Lecompte P, Arnaud
J, Richard MJ, Galan P Laboratoire de Biochimie des Lipoproteines, Universite
de Bourgogne, Digon, France.
J Am Coll Nutr 1997 Aug;16(4):357-65
BACKGROUND: Eighty-one elderly hospitalized subjects (> 65 years)
were recruited for a double-blind placebo-controlled study to examine
low dose supplementation of antioxidant vitamins and minerals on biological
and functional parameters of free radical metabolism. Subjects were randomly
assigned to one of the four treatment groups, daily receiving for 2 years:
placebo group; mineral group: 20 mg zinc, 100 micrograms selenium; vitamin
group: 120 mg VITAMIN C (Vit C), 6 mg beta-carotene (beta CA), 15 mg vitamin
E (Vit E); mineral and vitamin group: Zn 20 mg, Se 100 micrograms, Vit
C 120 mg, beta CA 6 mg, Vit E 15 mg. RESULTS: Fifty-seven subjects completed
the study. A large frequency of Vit C, Zn and Se deficiencies were observed
at baseline. As early as 6 months of treatment, a significant increase
in vitamin and mineral serum levels was observed in the corresponding
groups. The increases ranged from 1.1-4.0 fold depending on the nutrient.
Antioxidant defense, studied in vitro with a test using red blood cells
in presence of 2,2'-azo-bis (2-amidinopropane) by hydrochloride, showed
an increase of cell resistance in patients receiving vitamins (p = 0.002);
it was positively correlated with serum Vit C (p < 0.0001), alpha-tocopherol/cholesterol
(p = 0.06), beta CA (p = 0.0014), serum Cu and Se (p < 0.05). Moreover,
red blood cell antioxidant defense was reduced in elderly compared with
young control subjects (50% hemolysis time: 69 +/- 14 mn and 109 +/- 12
mn, respectively). Erythrocyte glutathione peroxidase activity was enhanced
in groups receiving minerals, whereas no significant change was observed
for other indicators of oxidative stress (erythrocyte superoxide dismutase
activity, thiobarbituric acid-reactive substances, total glutathione,
reduced and oxidized forms). DISCUSSION: Our results provide experimental
evidence that a low dose supplementation with vitamins and minerals was
able to normalize biological nutrient status as early as 6 months of treatment.
In addition, our data indicate that antioxidant defense in elderly subjects
was improved with low doses of Vit C, vit E and beta CA as studied by
means of a functional test utilizing red blood cells challenged in vitro
with free radicals.
43. In vitro modulation of keratinocyte wound healing integrins by zinc,
copper and manganese.
Tenaud I, Sainte-Marie I, Jumbou O, Litoux P, Dreno B. Laboratory of
Immuno-Dermatology, CHU Hotel-Dieu, Place A. Ricordeau, 44035 Nantes Cedex
01, France.
Br J Dermatol 1999 Jan;140(1):26-34
Although the trace elements zinc, copper and manganese are used in vivo
for their healing properties, their mechanism of action is still only
partially known. Some integrins expressed by basal layer keratinocytes
play an essential part in healing, notably alpha2beta1, alpha3beta1, alpha6beta4
and alphaVbeta5, whose expression and distribution in epidermis are modified
during the re-epithelialization phase. This study demonstrates how the
expression of these integrins are modulated in vitro by trace elements.
Integrin expression was studied in proliferating keratinocytes in monolayer
cultures and in reconstituted skin that included a differentiation state.
After 48 h incubation with zinc gluconate (0.9, 1.8 and 3.6 microg/mL),
copper gluconate (1, 2 and 4 microg/mL), manganese gluconate (0.5, 1 and
2 microg/mL) and control medium, integrin expression was evaluated by
FACScan and immunohistochemistry. Induction of alpha2, alpha3, alphaV
and alpha6 was produced by zinc gluconate 1.8 microg/mL in monolayers,
of alpha2, alpha6 and beta1 by copper gluconate 2 and 4 microg/mL and
of all the integrins studied except alpha3 by manganese gluconate 1 microg/mL.
Thus, alpha6 expression was induced by all three trace elements. The inductive
effect of zinc was particularly notable on integrins affecting cellular
mobility in the proliferation phase of wound healing (alpha3, alpha6,
alphaV) and that of copper on integrins expressed by suprabasally differentiated
keratinocytes during the final healing phase (alpha2, beta1 and alpha6),
while manganese had a mixed effect.
44. Prevalence of magnesium and zinc deficiencies in nursing home residents
in Germany.
Worwag M, Classen HG, Schumacher E. Department of Pharmacology and Toxicology
of Nutrition, University of Hohenheim, Stuttgart, Germany.
Magnes Res. 1999 Sep;12(3):181-9.
In a multicentric study with 345 seniors over 70 years old we investigated
magnesium and zinc levels in serum together with the prevalence of their
typical symptoms of deficiency in nursing home residents (NHR) and non-nursing
home residents (nNHR). In addition calcium, sodium and potassium levels
in serum were determined as well as creatinine and albumin. Considering
all seniors 33 per cent exhibited hypomagnesemia and 19 per cent hypozincemia.
Zinc levels of female and male NHR were significantly lower than levels
of nNHR. Hypomagnesemia was significantly associated with calf cramps
and with diabetes mellitus. Hypozincemia was significantly associated
with impaired wound healing.
Hearing
45. [The serum zinc level in patients with tinnitus and the effect of
zinc treatment] [Article in Japanese]
Ochi K, Ohashi T, Kinoshita H, Akagi M, Kikuchi H, Mitsui M, Kaneko T,
Kato I. Department of Otorhinolaryngology, St. Marianna University School
of Medicine, Kyoto-fu.
Nippon Jibiinkoka Gakkai Kaiho 1997 Sep;100(9):915-9
We measured the serum zinc level in patients with tinnitus and evaluated
the effectiveness of zinc in the treatment of tinnitus. Blood zinc levels
were measured in 121 patients with tinnitus. All patients were examined
between 1995 and 1997 at the outpatient clinic of otorhinolaryngology
St. Marianna University Toyoko Hospital. Forty-seven patients who had
received any drug such as a calcium channel blocker and others or had
been affected by any diseases were excluded and therefore 74 patients
consisting of 46 females (62%) and 28 males (38%) were investigated. Twenty
two healthy volunteers served as a control group. The mean age and standard
deviations for the tinnitus group and the control group were 47.8 +/-
17.1 and 31.4 +/- 8.2 years, respectively. There was a significant decrease
(p < 0.0001) in serum zinc levels in patients with tinnitus compared
with the control group. Because there was a significant difference (p
< 0.0001) in age distribution between tinnitus and control groups,
patients were selected by their age in order to neglect the effect of
aging. In this situation, a significant difference (p < 0.01) was noted
between the tinnitus group and control group. Low blood zinc level was
defined by using the mean and standard deviation for the control group
(mean-1 S.D.). We treated patients with low blood zinc levels. A total
dose of 34-68 mg of Zn++ was administered daily for over 2 weeks. The
degree of tinnitus was expressed on a numeric scale from 0 to 10 before
and after treatment. Blood zinc levels were significantly elevated (p
< 0.05) after treatment. We found a significant decrease (p < 0.01)
in the numeric scale. These findings suggest that zinc is useful in at
least some patients suffering from tinnitus. It is possible to classify
patients with tinnitus by measuring serum zinc level and this leads to
improvement of the overall treatment effect.
46. Chemical anatomy of excitatory endings in the dorsal cochlear nucleus
of the rat: differential synaptic distribution of aspartate aminotransferase,
glutamate, and vesicular zinc.
Rubio ME, Juiz JM.
Instituto de Neurociencias, Universidad Miguel Hernandez, Alicante, Spain.
lrubio@pop.nidcd.nih.gov
J Comp Neurol 1998 Sep 28;399(3):341-58
In order to identify cytochemical traits relevant to understanding excitatory
neurotransmission in brainstem auditory nuclei, we have analyzed in the
dorsal cochlear nucleus the synaptic distribution of aspartate aminotransferase,
glutamate, and vesicular zinc, three molecules probably involved in different
steps of excitatory glutamatergic signaling. High levels of glutamate
immunolabeling were found in three classes of synaptic endings in the
dorsal cochlear nucleus, as determined by quantitation of immunogold labeling.
The first type included auditory nerve endings, the second were granule
cell endings in the molecular layer, and the third very large endings,
better described as "mossy." This finding points to a neurotransmitter
role for glutamate in at least three synaptic populations in the dorsal
cochlear nucleus. The same three types of endings enriched in glutamate
immunoreactivity also contained histochemically detectable levels of aspartate
aminotransferase activity, suggesting that this enzyme may be involved
in the synaptic handling of glutamate in excitatory endings in the dorsal
cochlear nucleus. There was also extrasynaptic localization of the enzyme.
Zinc ions were localized exclusively in granule cell endings, as determined
by a Danscher-selenite method, suggesting that this ion is involved in
the operation of granule cell synapses in the dorsal cochlear nucleus.
47. The role of zinc in the treatment of tinnitus.
Arda HN, Tuncel U, Akdogan O, Ozluoglu LN.
Department of Ear, Nose, Throat, Head and Neck Surgery, Ankara Numune
Research and Education Hospital, Turkey. nedard@yahoo.com
Otol Neurotol. 2003 Jan;24(1):86-9.
OBJECTIVE: This study was designed to investigate the role of zinc
administration in treatment of tinnitus.
STUDY DESIGN: Randomized, prospective, placebo-controlled study.
SETTING: Patients with tinnitus were admitted to the ear, nose, and throat
clinic of the authors' hospital.
PATIENTS: Patients with tinnitus with no know pathologic conditions of
the ear, nose, and throat; the mean age of 28 patients receiving zinc
was 51.2 years, and that of 13 patients given placebo was 55 years.
INTERVENTION: Blood zinc levels were measured. Frequency was detected
by audiometry, and loudness of tinnitus was screened by tinnitus match
test. A questionnaire that scored tinnitus subjectively between 0 and
7 was given to patients before zinc treatment. After 2 months of treatment
(zinc 50 mg daily to zinc group, placebo pill containing starch to placebo
group), all of the tests were performed again. There was no difference
in age, sex, duration of tinnitus, and affected ears between the patients
treated with zinc and those treated with placebo. Blood zinc levels were
lower than normal in 31% of patients before treatment.
MAIN OUTCOME MEASURES: A decrease in tinnitus loudness by at least 10
dB was accepted as clinically favorable progress. A decrease of more than
1 point in subjective tinnitus scoring was accepted as valid.
RESULTS: Clinically favorable progress was detected in 46.4% of patients
given zinc. Although this decrease was not statistically significant,
the severity of subjective tinnitus decreased in 82% of the patients receiving
zinc. The mean of subjective tinnitus decreased from 5.25 +/- 1.08 to
2.82 +/- 1.81 (< 0.001). However, the decrease in severity of the tinnitus
was not significant in patients receiving placebo.
CONCLUSION: It can be concluded that patients with tinnitus may have
low blood zinc levels (31%) and clinical and subjective improvement can
be achieved by oral zinc medication. However, it remains to be seen whether
the longer duration of treatment has more significant results.
48. The role of zinc in management of tinnitus.
Yetiser S, Tosun F, Satar B, Arslanhan M, Akcam T, Ozkaptan Y.
Department of ORL and HNS, Gulhane Medical School, Etlik, 06018 Ankara,
Turkey. syetiser@yahoo.com
Auris Nasus Larynx. 2002 Oct;29(4):329-33.
OBJECTIVE: Several therapeutic modalities have been tried in patients
with
tinnitus. These trials have given rise to unsatisfactory results in most
of the
patients since the etiology and pathophysiology of tinnitus is unclear.
Significant correlation between tinnitus and decreased zinc level and
also
reduction in severity of tinnitus after zinc therapy has been reported
in some
clinical studies. The aim of this study is to find out the prevalence
of
hypozincemia in patients suffering from tinnitus of various origins
(presbyacusis, acoustic trauma and ototoxicity) at young and elderly population
and to investigate the effect of zinc therapy upon the severity of tinnitus.
METHODS: Forty consecutive patients with severe tinnitus were included
in this
study between April 1998 and May 2000. There were 32 men (80%) and eight
women (20%) with an age ranging between 19 and 67 (mean 40.6 years). Eleven
patients were over the age of 50. The zinc level was measured in non-diluted
serum by flame atomic absorption spectrophotometry (normal values; 50-120
microg/dl) from fasting blood samples. All the patients were given zinc
pills 220 mg each, once a day and 2 h before lunch for 2 months. The patients
were required to fulfill a tinnitus scoring scale and a handicap questionnaire
before and after treatment. The Wilcoxon rank sum test and McNemar test
were used for the statistical analysis.
RESULTS: Six patients were hypozincemic and seven patients had decreased
serum zinc levels. No significant change has been observed in frequency
and severity of tinnitus measured by audiologic tests after zinc therapy.
Twenty-three (57.5%) of these patients reported some relief of tinnitus
in the tinnitus scoring scale but the rate of improvement was minor (P>0.05).
Decrease in severity of tinnitus after zinc therapy in elder group was
better than the younger ones.
CONCLUSION: Our study could not confirm the high incidence of hypozincemia
in patients with tinnitus as reported previously. Zinc therapy for 8 weeks
presented no promising effect on tinnitus in three groups of patients
and the difference between the rate of improvement in severity of tinnitus
after zinc intake in patients with normal and low serum zinc level was
not significant. Zinc supplement provided relief of tinnitus in some of
the elder people who apparently had dietary zinc deficiency.
49. Zinc: the neglected nutrient.
Shambaugh GE Jr.
Shambaugh Hearing and Allergy, Hinsdale, IL 60521.
Am J Otol 1989 Mar;10(2):156-60
Zinc was first recognized as essential for animals at the University
of Illinois School of Agriculture in 1916, when it was found that zinc-deficient
baby pigs were runty, developed dermatitis on their legs, and were sterile.
Zinc deficiency was first recognized in man by Dr. Ananda Prasad of Detroit
26 years ago when he measured serum and hair zinc levels in young male
Egyptian dwarfs who had failed to mature and were small in stature. By
simply adding zinc to their regular diet, they grew in height and became
sexually mature. It is now recognized that dwarfism in males is frequent
around the Mediterranean, where wheat is the staple of life and has been
grown for 4,000 years on the same soil, thereby resulting in the depletion
of zinc. Professor Robert Henkin first suggested that zinc deficiency
might cause hearing-nerve impairment. Assay of the soft tissues of the
cochlea and vestibule revealed a zinc level higher than that of any other
part of the body. Previously, the eye was considered to have the highest
level of zinc of any organ. To diagnose zinc deficiency clinically, we
use serum zinc assays made at the Mayo Clinic Trace Element Laboratory.
With zinc supplementation in patients who are marginally zinc deficient,
there has been improvement in tinnitus and sensorineural hearing loss
in about one-third of elderly adults. We believe zinc deficiency is one
causation of presbycusis; by recognizing and correcting it, a progressive
hearing loss can be arrested.
Hepatitis
50. Determination of hepatic zinc content in chronic liver disease due
to hepatitis B virus.
Gur G; Bayraktar Y; Ozer D; Ozdogan M; Kayhan B
Hacettepe University, Faculty of Medicine, Department of Internal Medicine,
Ankara-Turkey.
Hepatogastroenterology (Greece) Mar-Apr 1998, 45 (20) p472-6
BACKGROUND/AIMS: Zinc is an essential, mostly intracellular, trace element
which participates in many physiologic mechanisms. Some liver functions
like urea formation require the presence of zinc; thus the determination
of hepatic zinc content may contribute to the understanding of probable
zinc-related clinical consequences of chronic liver disease. In this study,
we aimed to determine the hepatic zinc concentrations in patients with
chronic liver disease due to the Hepatitis B virus and to ascertain the
relationship between the severity of liver disease and hepatic zinc content,
if one in fact exists.
METHODOLOGY: A total of 99 HBsAg positive subjects were included in the
study. We performed a liver biopsy on all subjects. Hepatic zinc concentrations
were determined by atomic absorption spectrophotometry.
RESULTS: The liver biopsies were normal in 25 subjects. There were 33
chronic active hepatitis (CAH), 34 cirrhosis and 7 chronic persistent
hepatitis (CPH) patients in the study group. In the control group, CAH,
cirrhosis and CPH groups, the mean liver zinc concentrations were 3.83
+/- 1.86, 1.86 +/- 0.92, 1.14 +/- 0.68 and 3.74 +/- 1.81 mumol/g dry weight,
respectively. Hepatic zinc in the CAH and cirrhosis groups were lower
than that of the control group (p < 0.05). We also found that liver
zinc in the cirrhosis group was lower than in the CAH group (p < 0.05).
CONCLUSION: According to these results, as the severity of liver damage
increases, the hepatic zinc concentration decreases. Therefore, it can
be suggested that zinc supplementation may improve hepatic encephalopathy
by increasing the efficiency of the urea cycle.
51. Zinc supplementation improves glucose disposal in patients with cirrhosis.
Marchesini G; Bugianesi E; Ronchi M; Flamia R; Thomaseth K; Pacini G
Dipartimento di Medicina Interna, Cardioangiologia, Epatologia, Universita
di Bologna, Italy.
Metabolism (United States) Jul 1998, 47 (7) p792-8
Zinc deficiency is common in cirrhosis, and was proved to affect nitrogen
metabolism. In experimental animals, zinc status may also affect glucose
disposal, and acute zinc supplementation improves glucose tolerance in
healthy subjects. This study was aimed at measuring the effects of long-term
oral zinc supplements on glucose tolerance in cirrhosis . The time courses
of glucose, insulin, and C-peptide in response to an intravenous (i.v.)
glucose load were analyzed by the minimal-model technique before and after
long-term oral zinc supplements (200 mg three times per day for 60 days)
in 10 subjects with advanced cirrhosis and impaired glucose tolerance
or diabetes. The test was performed using a simplified procedure, based
on 20 blood samples collected within 4 hours from the glucose load. Normal
values were obtained in 25 age-matched healthy subjects. Zinc levels were
low to normal or reduced before treatment, and were normalized by oral
zinc. Glucose disappearance improved by greater than 30% in response to
treatment. There were no changes in pancreatic insulin secretion and systemic
delivery, or in the hepatic extraction of insulin. Insulin sensitivity
(SI), which was reduced by 80% before treatment, did not change. Glucose
effectiveness (SG) was nearly halved in cirrhosis before treatment (0.013
[SD 0.007] min(-1) v. 0.028 [SD 0.009] in controls; P < .001), and
increased to 0.017 (SD 0.009) after zinc (P < .05 v. baseline). The
return to normal of plasma zinc levels after long-term zinc treatment
in advanced cirrhosis improves glucose tolerance via an increase of the
effects of glucose per se on glucose metabolism. Poor zinc status may
contribute to the impaired glucose tolerance and diabetes of cirrhosis.
52. Effect of dietary zinc deficiency on alkaline phosphatase and nucleic
acids in rats.
Okegbile EO, Odunuga O, Oyewo A. Department of Biochemistry, Ogun State
University, Ago-Iwoye, Nigeria.
Afr J Med Med Sci. 1998 Sep-Dec;27(3-4):189-92
Weanling male albino rats were randomly alloted to zinc deficient fed
(ZnDF) pair-fed (ZnPF) or ad libitum-fed (ZnAL) dietary treatments. The
rats were fed diets with either low (5 micrograms/g) or adequate (100
micrograms/g) zinc for 28 days. Zinc deficiency significantly reduced
growth rate by 60% and was associated with a significantly low feed intake
when compared with ZnPF and ZnAL groups. DNA and RNA contents of the liver
were used as indication of nitrogen metabolism. DNA content was similar
for both ZnPF and ZnAL groups (1.90 and 2.20 mg/g wet weight, respectively),
but significantly different from ZnDF (1.42 mg/g wet weight). Liver RNA
values of ZnAL, ZnPF and ZnDF groups similarly varied (25.0, 20.2 and
14.8 mg/g wet weight, respectively). Liver, muscle, spleen, femur and
serum zinc concentrations were lowest in rats fed ZnDF relative to adequate
zinc levels. The levels of the alkaline phosphatase activity was highest
in the serum and lowest in the brain (spleen value was greater than that
of the liver). Alkaline phosphatase activity was similar in ZnAL and ZnPF
groups, but significantly different from ZnDF. In conclusion, the constitutively
expressed growth rate, DNA level, RNA level, organ/serum zinc contents
and alkaline phosphatase activities were markedly affected by zinc deficiency
in rats.
HIV
53. Zinc status in human immunodeficiency virus type 1 infection and
illicit drug use.
Baum MK, Campa A, Lai S, Lai H, Page JB.
Florida International University, College of Health and Urban Affairs,
University Park, Rm. HLS 337, Miami, FL 33199, USA. baumm@fiu.edu
Clin Infect Dis. 2003;37 Suppl 2:S117-23.
Zinc deficiency is the most prevalent micronutrient abnormality seen
in human
immunodeficiency virus (HIV) infection. Low levels of plasma zinc predict
a
3-fold increase in HIV-related mortality, whereas normalization has been
associated with significantly slower disease progression and a decrease
in the
rate of opportunistic infections. Studies in Miami, Florida, indicated
that
HIV-positive users of illicit drugs are at risk for developing zinc deficiency,
at least partially because of their poor dietary intake. Zinc deficiency
characterized by low plasma zinc levels over time enhances HIV-associated
disease progression, and low dietary zinc intake is an independent predictor
of
mortality in HIV-infected drug users. The amount of zinc supplementation
in HIV
infection appears to be critical, because deficiency, as well as excessive
dietary intake of zinc, has been linked with declining CD4 cell counts
and
reduced survival. More research is needed to determine the optimal zinc
supplementation level in HIV-infected patients, to prevent further burden
on an
already compromised immune system.
54. Modulatory effects of selenium and zinc on the immune system.
Ferencik M, Ebringer L.
Institute of Immunology, Faculty of Medicine, Comenius University, Institute
of
Neuroimmunology, Slovak Academy of Sciences, Bratislava, Slovakia.
Folia Microbiol (Praha). 2003;48(3):417-26.
Almost all nutrients in the diet play a crucial role in maintaining an
"optimal"
immune response, and both insufficient and excessive intakes can have
negative
consequences on the immune status and susceptibility to a variety of pathogens.
We summarize the evidence for the importance of two micronutrients, selenium
and zinc, and describe the mechanisms through which they affect the immune
status and other physiological functions. As a constituent of selenoproteins,
selenium is needed for the proper functioning of neutrophils, macrophages,
NK cells, T lymphocytes and some other immune mechanisms. Elevated selenium
intake may be associated with reduced cancer risk and may alleviate other
pathological conditions including oxidative stress and inflammation. Selenium
appears to be a key nutrient in counteracting the development of virulence
and inhibiting HIV progression to AIDS. It is required for sperm motility
and may reduce the risk of miscarriage. Selenium deficiency has been linked
to adverse mood states and some findings suggest that selenium deficiency
may be a risk factor in cardiovascular diseases. Zinc is required as a
catalytic, structural and
regulatory ion for enzymes, proteins and transcription factors, and is
thus a
key trace element in many homeostatic mechanisms of the body, including
immune responses. Low zinc ion bioavailability results in limited immunoresistance
to infection in aging. Physiological supplementation of zinc for 1-2 months
restores immune responses, reduces the incidence of infections and prolongs
survival. However, in every single individual zinc supplementation of
food should be adjusted to the particular zinc status in views of the
great
variability in habitat conditions, health status and dietary requirements.
55. Nutrients and HIV: part two-vitamins A and E, zinc, B-vitamins, and
magnesium.
Patrick L.
Altern Med Rev 2000 Feb;5(1):39-51
There is compelling evidence that micronutrient deficiencies can profoundly
affect immunity; micronutrient deficiencies are widely seen in HIV, even
in asymptomatic patients. Direct relationships have been found between
deficiencies of specific nutrients, such as vitamins A and B12, and a
decline in CD4 counts. Deficiencies appear to influence vertical transmission
(vitamin A) and may affect progression to AIDS (vitamin A, B12, zinc).
Correction of deficiencies has been shown to affect symptoms and disease
manifestation (AIDS dementia complex and B12; diarrhea, weight loss, and
zinc), and certain micronutrients have demonstrated a direct anti-viral
effect in vitro (vitamin E and zinc). The previous article in this series
focused on selenium and beta carotene deficiencies in HIV/AIDS. This literature
review elucidates how deficiencies of the micronutrients zinc, magnesium,
vitamins A, E, and specific B vitamins relate to HIV symptomology and
progression, and clearly illustrates the need for nutritional supplementation
in HIV disease.
56. Zinc serum level in human immunodeficiency virus-infected patients
in relation to immunological status.
Wellinghausen N, Kern WV, Jochle W, Kern P. Section of Infectious Diseases
and Clinical Immunology, Medical University of Ulm, Germany.
Biol Trace Elem Res 2000 Feb;73(2):139-49
In human immunodeficiency virus (HIV) infection, serum level of zinc,
an important micronutrient for immune function, is frequently diminished.
The aim of this study was to determine the zinc status in relation to
immunological parameters and disease stage in 79 HIV-1 seropositive patients.
The median serum level of zinc was within normal limits (12.5 micromol/L)
but in 23% of patients, zinc deficiency was seen. Decreased serum zinc
was associated with a low CD4 cell count, high viral load, and increased
neopterin and IgA levels. According to current treatment recommendations,
the majority of patients received antiretroviral triple therapy. Zinc
levels in treated and untreated patients were comparable. Referring to
disease stage (CDC classification, 1993), the mean zinc level was highest
in stage C and lowest in stage A. In conclusion, even under antiretroviral
triple therapy, zinc deficiency is still of great importance in HIV infection,
and zinc substitution in zinc deficient individuals should be taken into
account to optimize therapeutical success.
57. Zinc serum level in human immunodeficiency virus-infected patients
in relation to immunological status.
Wellinghausen N, Kern WV, Jochle W, Kern P.
Section of Infectious Diseases and Clinical Immunology, Medical University
of
Ulm, Germany.
Biol Trace Elem Res. 2000 Feb;73(2):139-49.
In human immunodeficiency virus (HIV) infection, serum level of zinc,
an
important micronutrient for immune function, is frequently diminished.
The aim
of this study was to determine the zinc status in relation to immunological
parameters and disease stage in 79 HIV-1 seropositive patients. The median
serum level of zinc was within normal limits (12.5 micromol/L) but in
23% of patients, zinc deficiency was seen. Decreased serum zinc was associated
with a low CD4 cell count, high viral load, and increased neopterin and
IgA levels. According to current treatment recommendations, the majority
of patients received antiretroviral triple therapy. Zinc levels in treated
and untreated patients
were comparable. Referring to disease stage (CDC classification, 1993),
the mean zinc level was highest in stage C and lowest in stage A. In conclusion,
even under antiretroviral triple therapy, zinc deficiency is still of
great
importance in HIV infection, and zinc substitution in zinc deficient individuals
should be taken into account to optimize therapeutical success.
Hypertension
58. Free radical disease prevention and nutrition.
Krajcovicova-Kudlackova M, Ursinyova M, Blazicek P, Spustova V, Ginter
E,
Hladikova V, Klvanova J.
Institute of Preventive and Clinical Medicine, Bratislava, Slovakia.
Kudlackova@upkm.sk
Bratisl Lek Listy. 2003;104(2):64-8.
An improved antioxidant status (overthreshold plasma values of essential
antioxidants) minimizes the oxidative damage. The levels of antioxidant
vitamins
C and E, ,,antioxidant" trace elements selenium, zinc, copper and
iron were
measured in two groups of adults with different nutritional habits--alternative
(vegetarians; n=110) and traditional (mixed diet, control, n=101). The
prevalence of iron and zinc deficiencies was found in the alternative
group (20%
vs 11%--iron, 13% vs 9%--zinc) as a consequence of higher intake of plant
trace
element absorption inhibitors. As opposed to the latter, the control group
had
higher findings of iron and copper levels over the optimal range (18%
vs
8%--iron, 11% vs 2%--copper). The subjects on mixed diet was showed a
significant negative linear correlation between serum zinc and iron levels.
This
favourable relationship means a decrease in Fenton reaction by indirect
zinc
effect. Average plasma values of vitamin C, vitamin C/vitamin E, vitamin
E/
cholesterol (LDL protection), vitamin E/triacylglycerols (polyunsaturated
fatty
acid protection) in vegetarians are over the threshold with high number
of
individual overthreshold values (94% vs 17%--vitamin C, 100% vs 58%--vitamin
C/vitamin E, 89% vs 68%--vitamin E/cholesterol, 100% vs 64%--vitamin
E/triacylglycerols). Homocysteine levels in vegetarians (36% atherogenic
levels)
correlate significantly inversely to vitamin C levels, the fact of which
means a
positive vitamin C effect in free radical remove also in hyperhomocysteinemia.
Plant food is a rich source of antioxidants. A correct vegetarian nutrition
or
optimized mixed diets with regular and frequent consumption of protective
food
commodities may be an effective contribution to the age-related chronic
degenerative disease prevention. (Tab. 2, Fig. 2, Ref. 31.).
59. Angiotensin-I-converting enzyme and its relatives.
Riordan JF.
Center for Biochemical and Biophysical Sciences and Medicine, Harvard
Medical
School, One Kendall Square, Cambridge, MA 02139, USA.
james_riordan@hms.harvard.edu
Genome Biol. 2003;4(8):225. Epub 2003 Jul 25.
SUMMARY: Angiotensin-I-converting enzyme (ACE) is a monomeric, membrane-bound,
zinc- and chloride-dependent peptidyl dipeptidase that catalyzes the conversion
of the decapeptide angiotensin I to the octapeptide angiotensin II, by
removing a carboxy-terminal dipeptide. ACE has long been known to be a
key part of the renin angiotensin system that regulates blood pressure,
and ACE inhibitors are important for the treatment of hypertension. There
are two forms of the enzyme in humans, the ubiquitous somatic ACE and
the sperm-specific germinal ACE, both encoded by the same gene through
transcription from alternative promoters. Somatic ACE has two tandem active
sites with distinct catalytic properties, whereas germinal ACE, the function
of which is largely unknown, has just a single active site. Recently,
an ACE homolog, ACE2, has been identified in humans that differs from
ACE in being a carboxypeptidase that preferentially removes carboxy-terminal
hydrophobic or basic amino acids; it appears to be important in cardiac
function. ACE homologs (also known as members of the M2 gluzincin family)
have been found in a wide variety of species, even in those that neither
have a cardiovascular system nor synthesize angiotensin. X-ray structures
of a truncated, deglycosylated form of germinal ACE and a related enzyme
from Drosophila have been reported, and these show that the active site
is deep within a central cavity. Structure-based drug design targeting
the individual active sites of somatic ACE may lead to a new generation
of ACE inhibitors, with fewer side-effects than currently available inhibitors.
60. Studies of five microelement contents in human serum, hair, and fingernails
correlated with aged hypertension and coronary heart disease.
Tang YR, Zhang SQ, Xiong Y, Zhao Y, Fu H, Zhang HP, Xiong KM.
College of Chemistry and Molecular Science, College of Life Sciences,
Wuhan
University, 430072 Wuhan Hubei, China.
Biol Trace Elem Res. 2003 May;92(2):97-104.
Using atomic absorption spectrometry (AAS), five microelements in human
serum, hair, and fingernails of aged hypertension, coronary heart disease
(diseased group) and aged health control (healthy group) were detected.
Results of the t-test are as follows: The iron, zinc, and cadmium contents
and Zn/Cu (mol/mol) ratio of the diseased group were significantly higher
than that of the healthy group in serum (p<0.01, p<0.05, p<0.01,
and p<0.05, respectively); the chromium contents in the serum, hair,
and fingernails (p<0.05, p<0.01, and p<0.05, respectively); the
iron and zinc contents in the hair and fingernails (p<0.01, p<0.001,
p<0.05, and p<0.01 respectively) and Zn/Cu ratio in the hair (p<0.01)
of the diseased group were significantly lower than that of the healthy
group.
61. Zn deficiency aggravates hypertension in spontaneously hypertensive
rats:
possible role of Cu/Zn-superoxide dismutase.
Sato M, Yanagisawa H, Nojima Y, Tamura J, Wada O.
Department of Hygiene and Preventive Medicine, Faculty of Medicine, Saitama
Medical School, Iruma-gun, Japan.
Clin Exp Hypertens. 2002 Jul;24(5):355-70.
Using spontaneously hypertensive rats (SHR) fed a standard or a Zn-deficient
diet for 4 weeks, we examined whether Zn deficiency affects systemic blood
pressure (BP) levels in a genetically hypertensive state through a fall
in the
activity of Cu/Zn-superoxide dismutase (SOD). SHR fed a Zn-deficient diet
had a
progressive increase in systolic BP during the dietary conditioning.
Consequently, SHR fed a Zn-deficient diet exhibited significantly increased
levels of systolic BP by 2 weeks after the start of dietary treatment
when
compared with SHR fed a standard diet. Similarly, levels of basal mean
arterial
pressure (MAP) observed at the end of dietary treatment were SHR fed a
Zn-deficient diet > SHR fed a standard diet. Administration of the
nitric oxide
synthase (NOS) inhibitor, L-NAME, caused an increase in MAP levels in
the two
groups of rats, demonstrating the involvement of the vasodilator, nitric
oxide
(NO), in the regulation of systemic BP in a genetically hypertensive state.
The
expression of endothelial (e) NOS mRNA and protein in the thoracic aorta
paralleled basal MAP levels in the two groups of rats, suggesting the
counter-regulation of eNOS against the developed hypertensive state in
SHR fed a Zn-deficient diet. On the other hand, administration of the
superoxide
scavenger, tempol (a SOD mimetic compound), led to a decrease in MAP levels
in the two groups of rats, indicating the participation of the oxygen
free radical,
superoxide, in an increase in systemic BP in a genetically hypertensive
state.
As reported recently, the mechanism involved is due likely to a decrease
in the
action of the vasodilator, NO, based on the formation of peroxynitrite
coming
from the non-enzymatic reaction of superoxide and NO. In addition, tempol
treatment completely restored MAP levels in SHR fed a Zn-deficient diet
to
levels comparable to those observed in SHR fed a standard diet, indicating
that
a further increase in systemic BP levels seen in SHR fed a Zn-deficient
vs. a
standard diet is presumably brought by a reduction in the action of the
vasodilator, NO, resulting from an increase in the action of superoxide.
The
activity of the superoxide scavenger, Cu/Zn-SOD, in the thoracic aorta
was
significantly decreased in SHR fed a Zn-deficient diet relative to SHR
fed a
standard diet. It appears that a decrease in the activity of Cu/Zn-SOD
observed
in the thoracic aorta of SHR fed a Zn-deficient diet at least in part
plays a
role in an increase in the action of superoxide in this model. Thus, Zn
deficiency may be a factor to develop genetic hypertension presumably
through
the oxidative stress caused by superoxide.
62. Increased absorption of zinc from alimentary tract in primary arterial
hypertension.
Tubek S.
Department of Internal Diseases, Regional Hospital, Strzelce Opolskie,
Faculty
of Physical Education and Physiotherapy, Institute of Technology, Opole,
Poland.
szpital.strzelce-op.pl
Biol Trace Elem Res. 2001 Oct;83(1):31-8.
Zinc absorption from the alimentary tract, as revealed by serum zinc
concentration, was studied in a group of 10 patients (age 37.7+/-5.1 yr)
with
moderate and severe untreated primary arterial hypertension before and
after a
30-d treatment with perindopril 4 mg/d. Blood pressure was
177.33+/-16.24/111.33+/-15.26 mm Hg before and 143.41+/-17.34/91.29+/-12.54
mm Hg after treatment (p < 0.05/p < 0.05). Nine persons (age 37+/-6.2
yr) with
normal blood pressure (121.33+/-9.9/78+/-5.23 mm Hg) were the control
group.
Blood samples were taken from the ulnar vein at 8.00 AM (0 h), before
taking
zinc orally (one tablet of Zincas (zinc aspartate), containing 5 mg Zn2+)
and at
1, 3, and 6 h after the dose. Serum zinc concentration in control and
hypertensive group (before treatment) were initially 15.47+/-6.26 versus
15.99+/-5.65 (NS), 19.37+/-6.40 versus 20.83+/-4.48 (NS) after 1 h, 17.91+/-4.76
versus 31.32+/-10.49 (p < 0.003) after 3 h, and 15.32+/-5.47 versus
17.87+/-6.56
(NS) after 6 h. Maximal increase of Zn was 4.77+/-2.10 versus 17.53+/-4.13,
respectively (p < 0.001). In the hypertensive group, serum Zn before
and after
perindopril treatment was initially 15.98+/-5.65 versus 14.81+/-3.11 (NS),
20.83+/-4.48 versus 18.17+/-2.50 (NS) after 1 h, 31.32+/-10.49 versus
22.94+/-5.80 (NS) after 3 h, 17.53+/-4.13 (p < 0.001) after 6 h. Maximal
increase of Zn before treatment was 17.53+/-4.13 versus 9.17+/-4.67 (p
< 0.017)
after treatment. The following conclusions were reached: (1) In patients
with
primary arterial hypertension, an increased zinc absorption from alimentary
tract was found; (2) A 30-d perindopril treatment 4 mg/d orally decreased
zinc
absorption in these patients.
63. Zinc and copper status and blood pressure.
Bergomi M, Rovesti S, Vinceti M, Vivoli R, Caselgrandi E, Vivoli G.
Department of Biomedical Sciences, University of Modena, Italy.
J Trace Elem Med Biol. 1997 Nov;11(3):166-9.
Comment in:
J Trace Elem Med Biol. 1998 Mar;12(1):1.
In order to elucidate the relationships between Zn and Cu and blood pressure,
the present case-control study was carried out. Zn and Cu status was evaluated
in 60 subjects, pharmacologically untreated, affected by mild stable
hypertension and in 60 normotensives matched for sex, age and smoking
habits.
Different markers of Zn and Cu status, including serum, erythrocyte and
urine
levels of the two trace elements and activities of some Zn- or Cu-dependent
enzymes (alkaline phosphatase, lactic dehydrogenase, superoxide dismutase
and lysyl oxidase) were evaluated. No significant difference between hypertensives
and normotensives was observed in the mean levels of Zn and Cu as well
as in Zn- or Cu-dependent enzymes, though higher levels of serum copper
were associated with increased risk of hypertension. Interesting relationships
between the biological parameters investigated were observed in the hypertensive
subjects. Inverse correlations between blood pressures and serum Zn were
observed. Furthermore, blood pressure was inversely related to lysyl oxidase
activity. These findings give further support to the hypothesis that an
imbalance of Zn and Cu bioavailability may be associated to hypertensive
condition.
64. [Evaluation of selected parameters of zinc metabolism in patients
with primary hypertension]
Peczkowska M; Kabat M; Janaszek-Sitkowska H; PuLawska M
Kliniki Nadcisnienia Tetniczego Instytutu Kardiologii w Warszawie.
Pol Arch Med Wewn (Poland) Mar 1996, 95 (3) p198-204
The aim of the study was to investigate the role of zinc (Zn) in essential
hypertension (EH).
PATIENTS AND METHODS: Material of the study consisted of 31 patients
(12 female, 19 male) with mild and moderate EH and 20 healthy persons
(NT) (7 female, 13 male). Erythrocyte (ZnE) and serum (ZnS) zinc as well
as 24 hour urinary zinc excretion (ZuU) were assessed in both groups.
Zn parameters were measured by atomic absorption spectrophotomery.
RESULTS: ZnS was lower and ZnE was higher in EH (p < 0.001) than in
normotensives. ZnU did not differ between EH and NT. ZnE and ZnS negatively
correlated with age in NT but not in EH, ZnU negatively correlated with
age only in EH. BP positively correlated with ZnS in EH but not in NT.
In both groups negative correlations were found between BP and ZnU.
CONCLUSIONS: 1. Zinc probably plays a role in pathogenesis of essential
hypertension.
65. Zinc, cadmium, and hypertension in parturient women
Lazebnik N; Kuhnert BR; Kuhnert PM
Department of Obstetrics and Gynecology, Cleveland Metropolitan General
Hospital, OH 44109.
Am J Obstet Gynecol (United States) Aug 1989, 161 (2) p437-40
Zinc deficiency and cadmium toxicity have both been implicated in hypertension
during pregnancy. The goals of this study were twofold: first, to assess
the different zinc indices (plasma, red blood cell zinc, heat-labile alkaline
phosphatase, and placental zinc) in normotensive and hypertensive parturients
to determine whether they are altered in the different types of hypertension
that occur during pregnancy; second, to assess whole-blood cadmium and
placental cadmium with regard to hypertension and zinc status. Patients
were diagnosed as having chronic hypertension or preeclamptic toxemia
and were then further divided into groups on the basis of smoking status.
Each patient was matched with a normal control subject based on age, parity,
and smoking status. Forty-three hypertensive patients and their matched
control subjects were studied. No differences were found in the various
zinc indices between chronic hypertensive parturients and normal control
subjects. However, in parturients with preeclamptic toxemia, the plasma
zinc level was 19% lower than in control subjects (p less than 0.02);
these patients had the lowest plasma zinc level of the three groups. Placental
zinc was also 12% lower in patients with preeclamptic toxemia than in
control subjects (p less than 0.04). Whole-blood cadmium and placental
cadmium levels did not differ between control subjects or hypertensive
patients. However, a significant positive correlation was found between
whole-blood cadmium and plasma zinc levels in preeclamptic toxemia (r
= 0.53; p less than 0.05). The results support a marginal zinc deficiency
in parturients with preeclamptic toxemia but not in those with chronic
hypertension. The role of cadmium in the cause of preeclamptic toxemia
remains unclear.
Immune Enhancement
66. Zinc treatment prevents lipid peroxidation and increases glutathione
availability in Wilson's disease.
Farinati F, Cardin R, D'inca R, Naccarato R, Sturniolo GC.
Department of Surgical and Gastroenterological Sciences, University of
Padua,
Padua, Italy.
J Lab Clin Med. 2003 Jun;141(6):372-7.
Oxidative and reductive mechanisms are important in Wilson's disease.
In this
study, we sought to evaluate tissue levels of glutathione and cysteine,
an
important detoxification system, and of malondialdehyde, a marker of
lipoperoxidation, in patients with Wilson's disease receiving penicillamine
or
zinc treatment, in comparison with patients with chronic liver disease
of
different origin. Concentrations of cysteine, reduced/oxidized glutathione,
malondialdehyde, zinc, and copper were determined (with the use of high-pressure
liquid chromatography, fluorimetry and atomic-absorption spectrophotometry)
in liver-biopsy specimens from 24 patients with Wilson's disease (18 treated
with zinc, 6 with penicillamine), 34 patients with chronic viral hepatitis,
and 10 patients with alcoholic liver disease. In patients with Wilson's
disease, the concentration of reduced glutathione was lower than that
in patients with viral hepatitis and as high as that in subjects with
alcoholic liver damage. The cysteine level was significantly lower than
those in the control groups, and the percentage of oxidized glutathione/total
glutathione was higher than that in
viral or alcoholic disease. Malondialdehyde levels were low, but when
zinc- and
penicillamine-treated patients were considered separately, only the former
had
low malondialdehyde levels. Zinc-treated patients had higher concentrations
of
reduced glutathione and a lower percentage of oxidized glutathione. In
summary,
patients with Wilson's disease have relevant glutathione depression, with
low
levels of reduced glutathione and cysteine and high concentrations of
oxidized
glutathione: This is prevented by zinc administration, which inhibits
lipid
peroxidation and increases glutathione availability.
67. Zinc-altered immune function.
Ibs KH, Rink L.
Institute of Immunology, University Hospital, Technical University of
Aachen,
D-52074 Aachen, Germany.
J Nutr. 2003 May;133(5 Suppl 1):1452S-6S.
Zinc is known to be essential for all highly proliferating cells in the
human
body, especially the immune system. A variety of in vivo and in vitro
effects of
zinc on immune cells mainly depend on the zinc concentration. All kinds
of
immune cells show decreased function after zinc depletion. In monocytes,
all
functions |