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Immune-Enhancing Role of Vitamin C and Zinc and Effect on Clinical Conditions

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Abstract

Vitamin C concentrations in the plasma and leukocytes rapidly decline during infections and stress. Supplementation of vitamin C was found to improve components of the human immune system such as antimicrobial and natural killer cell activities, lymphocyte proliferation, chemotaxis, and delayed-type hypersensitivity. Vitamin C contributes to maintaining the redox integrity of cells and thereby protects them against reactive oxygen species generated during the respiratory burst and in the inflammatory response. Likewise, zinc undernutrition or deficiency was shown to impair cellular mediators of innate immunity such as phagocytosis, natural killer cell activity, and the generation of oxidative burst. Therefore, both nutrients play important roles in immune function and the modulation of host resistance to infectious agents, reducing the risk, severity, and duration of infectious diseases. This is of special importance in populations in which insufficient intake of these nutrients is prevalent. In the developing world, this is the case in low- and middle-income countries, but also in subpopulations in industrialized countries, e.g. in the elderly. A large number of randomized controlled intervention trials with intakes of up to 1 g of vitamin C and up to 30 mg of zinc are available. These trials document that adequate intakes of vitamin C and zinc ameliorate symptoms and shorten the duration of respiratory tract infections including the common cold. Furthermore, vitamin C and zinc reduce the incidence and improve the outcome of pneumonia, malaria, and diarrhea infections, especially in children in developing countries.
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Review
Ann Nutr Metab 2006;50:85–94
DOI: 10.1159/000090495
Immune-Enhancing Role of Vitamin C
and Zinc and Effect on Clinical Conditions
Eva S. Wintergerst
a
Silvia Maggini
a
Dietrich H. Hornig
b
a
Bayer Consumer Care Ltd., Basel , and
b
Reinach , Switzerland
quate intakes of vitamin C and zinc ameliorate symptoms
and shorten the duration of respiratory tract infections
including the common cold. Furthermore, vitamin C and
zinc reduce the incidence and improve the outcome of
pneumonia, malaria, and diarrhea infections, especially
in children in developing countries.
Copyright © 2006 S. Karger AG, Basel
Nutritional and Physiological Aspects of
Vitamin C and Zinc
Vitamin C (ascorbic acid) and zinc are essential nutri-
ents and play important roles in nutrition and mainte-
nance of human health. Both have profound effects on
cellular growth and differentiation, and are vital for the
optimal functioning of the immune system. Inadequacy
and clinical defi ciency of vitamin C and/or zinc lead to
impaired immune response with altered resistance to in-
fections, impaired growth, and weakened collagenous
structures with delayed wound healing.
The nutritional and physiological aspects of these es-
sential nutrients have been widely reviewed and a large
number of comprehensive publications on vitamin C [1,
2] and zinc [3, 4]
are available. Therefore, the nutritional
and physiological aspects of these essential nutrients are
only briefl y summarized here.
Vitamin C has direct antioxidant capacity and con-
tributes to the protection of cells from the damaging ef-
fects of endogenously produced or exogenous reactive
Key Words
Vitamin C Zinc Oxidative stress Effects on immune
response Risk of infections
Abstract
Vitamin C concentrations in the plasma and leukocytes
rapidly decline during infections and stress. Supplemen-
tation of vitamin C was found to improve components of
the human immune system such as antimicrobial and
natural killer cell activities, lymphocyte proliferation,
chemotaxis, and delayed-type hypersensitivity. Vitamin
C contributes to maintaining the redox integrity of cells
and thereby protects them against reactive oxygen spe-
cies generated during the respiratory burst and in the
infl ammatory response. Likewise, zinc undernutrition or
defi ciency was shown to impair cellular mediators of in-
nate immunity such as phagocytosis, natural killer cell
activity, and the generation of oxidative burst. Therefore,
both nutrients play important roles in immune function
and the modulation of host resistance to infectious
agents, reducing the risk, severity, and duration of infec-
tious diseases. This is of special importance in popula-
tions in which insuffi cient intake of these nutrients is
prevalent. In the developing world, this is the case in low-
and middle-income countries, but also in subpopula-
tions in industrialized countries, e.g. in the elderly. A
large number of randomized controlled intervention tri-
als with intakes of up to 1 g of vitamin C and up to 30 mg
of zinc are available. These trials document that ade-
Published online: December 21, 2005
Eva Wintergerst
International Medical Manager, Speciality Vitamins, Bayer Consumer Care Ltd.
Peter-Merian-Strasse 84
CH–4002 Basel (Switzerland)
Tel. +41 58 272 76 72, Fax +41 58 272 76 04, E-Mail eva.wintergerst.ew@bayer.ch
© 2006 S. Karger AG, Basel
0250–6807/06/0502–0085$23.50/0
Accessible online at:
www.karger.com/anm
Wintergerst /Maggini /Hornig
Ann Nutr Metab 2006;50:85–94
86
oxygen radicals and reactive nitrogen species, e.g. during
immune activation. Vitamin C was shown to protect neu-
trophils from reactive oxygen species generated during
phagocytosis [2] , to prevent endogenous oxidative dam-
age to lymphocytes and sperm DNA [5–7] , and vitamin
C supplementation decreased signifi cantly H
2
O
2
-induced
DNA damage in lymphocytes in healthy male and female
nonsmokers [5] . Vitamin C prevents oxidative damage to
lipids, proteins, and DNA, which has been implicated as
a major contributing factor in the development of chron-
ic diseases such as cardiovascular disease, cancer, and
cataract, respectively [2, 8] . Evidence further suggests
that vitamin C provides indirect antioxidant protection
by regenerating other biologically important antioxidants
such as glutathione and vitamin E to their active state [9] .
Vitamin C functions as an electron donor involving either
monooxygenase or dioxygenase activities in a number of
important enzymes: dopamine-
-hydroxylase (biosyn-
thesis of the catecholamines norepinephrine and epi-
nephrine), peptidyl-glycine monooxygenase (amidation
of peptide hormones) and is involved in tyrosine metab-
olism (4-hydroxyphenylpyruvate dioxygensase) [1, 2] . Vi-
tamin C further acts as a cofactor for hydroxylases and
oxygenase metalloenzymes. Proline and lysine hydroxy-
lase catalyze the posttranslational hydroxylation of pep-
tide-bound proline and lysine residues, which is essential
for the development of functionally active collagen in its
triple helical structure and thus for effective wound heal-
ing [10] . Further, it functions as a reducing agent for
mixed-function oxidases, which are of importance in the
drug-metabolizing system in the microsomes, and as a
consequence, in vitamin C defi ciency, the activity of the
drug-metabolizing enzymes and the cytochrome P-450
electron transport are lowered [2] . Ascorbic acid stimu-
lates non-hem iron absorption from the intestine and
modulates iron transport and storage [11] .
Zinc is important in cellular growth and differentia-
tion with profound effects on antioxidant defense, col-
lagen synthesis, and the immune system [3, 4] . A large
number of enzymes depend on zinc for catalytic activity
(e.g. alcohol dehydrogenase; zinc containing metallo-en-
zymes such as RNA polymerases, carbonic anhydrase,
and alkaline phosphatases), and removal of zinc results
in loss of the enzymatic activity without affecting the
enzyme protein irreversibly [12] . By its antioxidant ca-
pacity, zinc contributes to the protection of cells from the
damaging effects of reactive oxygen radicals and reactive
nitrogen species produced during e.g. immune activa-
tion. Zinc antagonizes the catalytic properties of the re-
dox-active metals iron and copper with regard to the for-
mation of hydroxyl radicals from H
2
O
2
and superoxide
by competing with certain types of binding sites for cop-
per and iron, and blocking the initiation of destructive
processes [13] .
Elevated levels of superoxide anions cause increased
formation of reactive oxygen species that can damage lip-
ids, proteins and DNA which has been implicated as a
major contributing factor in chronic diseases such as car-
diovascular disease, cancer and cataract [8] . The antioxi-
dant properties of zinc have recently been reviewed [13] .
The antioxidant enzyme Cu, Zn-superoxide dismutase
catalyzes the reduction of two superoxide anions to mo-
lecular oxygen and hydrogen peroxide. However, in this
enzyme, copper provides the catalytic activity whereas
the role of zinc is structural. Zinc is essential for the in-
tracellular binding of tyrosine kinase to T cell receptors,
which are required for T lymphocyte development and
activation [14, 15] . The mechanism that underlies the
antioxidant action causes acute and chronic effects. The
acute effect may involve protection of protein sulfhydryl
groups against oxidation and oxidative damage to mem-
branes, or reduction in the formation of hydroxyl radicals
from H
2
O
2
through the antagonism of redox-active tran-
sition metals such as copper and iron [16] . Thiol-depen-
dent enzymes and proteins containing thiol groups have
been shown to be protected by zinc from oxidation, e.g.
-aminolevulinate dehydratase, DNA-zinc binding pro-
teins (zinc fi ngers) or tubulin [13] . Studies in zinc-defi -
cient animals and cell systems have shown an increased
free radical production and enhanced injury from expo-
sure to oxidative stress [14] .
Zinc is important for structural integrity by facilitating
protein folding to generate biologically active molecules.
Structural sites or zinc fi ngers have a broad cellular dis-
tribution and are present in transcription and replication
factors, in nuclear hormonal receptors, and in signal
transduction factors. Examples for zinc fi nger transcrip-
tion factors are retinoic acid receptors and vitamin D
receptors. Nuclear hormone receptors include those for
estrogen, testosterone, and vitamin D. Zinc fi nger pro-
teins have a broad cellular distribution and are involved
in protein-protein interaction affecting cellular differen-
tiation and proliferation [17] . Removal of zinc from zinc
nger proteins with apometallothionein in vitro has been
shown for a transcription factor to result in loss of func-
tion [18] . Zinc fi ngers contribute to zinc requirement and
support the fundamental and critical physiological role of
zinc, such as the intracellular binding of tyrosine kinase
to T cell receptors, which are required for T lymphocyte
development and activation [19, 20] .
Potential of Vitamin C and Zinc in
Immune Function
Ann Nutr Metab 2006;50:85–94
87
This overview attempts to demonstrate that suffi cient
intakes of vitamin C and zinc are essential to support ad-
equate immune response, to elaborate on the clinical con-
sequences, such as the risk, severity and duration of infec-
tious diseases, and to demonstrate the relevance of the
immune response modulated by these nutrients to vari-
ous population groups.
Immune Function and Oxidative Stress
The immune system protects the organism from inva-
sion and damage from a wide range of microorganisms,
such as viruses, bacteria, fungi or parasites, by a highly
complex biological response, which involves cellular pro-
liferation, enhanced protein synthesis and infl ammatory
mediator production as well as physiological changes. In
the activation of the immune system, the process of cell
proliferation is most active among T lymphocytes. Con-
currently, protein synthesis, immunoglobulin synthesis
by B lymphocytes, and acute phase protein synthesis in
the liver are enhanced. Infl ammatory mediators such as
the proinfl ammatory cytokines (IL 1; IL 6) and tumor
necrosis factor-
(TNF-
), prostaglandins, leukotrienes,
and reactive oxygen and nitrogen species, are increased
[21] .
The generation of reactive oxygen species is part of the
physiological function of cells involved in host defense,
such as activated neutrophils and macrophages, especial-
ly during chemotactic locomotion and phagocytosis. The
reactive oxygen species play an essential role in the intra-
cellular killing of bacteria and other invading organisms.
Whereas this microbicidal activity is a benefi cial activity,
on the other side the immune system is particularly vul-
nerable to oxidative stress, since immune cells rely on
cell-cell communication via membrane receptors and any
damage to the signaling systems has been shown to impair
the ability to build up an immune response [22, 23] . How-
ever, besides the antimicrobial and therefore protective
properties of these oxidants, other biomolecules may be
vulnerable to free radical attack. Especially, cell mem-
branes rich in long-chain polyunsaturated fatty acids are
susceptible to oxidative destruction, which could lead to
a loss of membrane integrity, altered membrane fl uidity,
and may result in alterations of cell-cell communication,
herewith contributing to degenerative disorders such as
cancer and cardiovascular diseases [8] . Antioxidants,
such as vitamin C and zinc, could play an immunomod-
ulatory role by preventing tissue damage mediated by im-
mune-system-generated reactive oxidant species, espe-
cially in population groups with poor dietary habits. Mar-
ginal or clinical nutrient defi ciency may impair the
proper functioning of the immune system, suppressing
various immune functions, which are critical determi-
nants of host resistance. As a consequence, the defi cient
individual becomes more susceptible to infections. In
many cases, by supplying the defi cient nutrient, immune
function may be normalized and resistance to infections
restored [22, 23] .
Furthermore, vitamin C is involved as an antioxidant
in the maintenance of the endothelial function, mainly
by preventing or reversing endothelial dysfunctions lead-
ing to the development of cardiovascular diseases [24–
26] . Mechanisms discussed include suppression of the
induction of endothelial cell apoptosis [24] , protection of
nitric oxide against oxidative inactivation [26] , stimula-
tion of nitric oxide synthesis [27] , intracellular reduction
of oxidized glutathione [28] , and prevention of the forma-
tion of atherogenic oxidized phospholipids [29] .
Vitamin C and the Immune System
The high cellular concentration of vitamin C and its
rapid decline in plasma and leukocytes during stress and
infection suggest a role in the process of immune response
[30–32] . Vitamin C was found to be a stimulant of leuko-
cyte functions, especially of neutrophil and monocyte
movement. Supplementation of healthy adults (1–3 g/
day) and children (20 mg/kg/day) enhanced neutrophil
chemotaxis in vivo, but bactericidal activity was not en-
hanced [32] . Lymphocyte proliferation was not impaired
in vitamin C defi ciency in humans and the number of
circulating CD4+ or CD8+
cells was not altered [33] . Vi-
tamin C in doses of 1–5 g/day for 3 days and over sev-
eral weeks increased human T lymphocyte proliferation
and neutrophil motility towards lipopolysaccharide-acti-
vated autologous serum [34, 35] . In vitro treatment of
peritoneal macrophages with antioxidant vitamins, in-
cluding vitamin C, was shown to stimulate the entire pro-
cess of phagocytosis. The observed decrease of vitamin C
in plasma and leukocytes during infective periods sug-
gests that the increased generation of oxidizing agents is
counteracted by reaction with vitamin C, and herewith
the host is protected against any harmful oxidative action
[31] .
In studies in healthy subjects, administration of vita-
min C resulted in improvement of several components of
human immune parameters, such as antimicrobial and
natural killer cell activities, lymphocyte proliferation,
Wintergerst /Maggini /Hornig
Ann Nutr Metab 2006;50:85–94
88
chemotaxis, and DTH [35–38] . The effect of vitamin C
intake with the diet on immune function was studied in
young, healthy nonsmokers. The volunteers consumed a
vitamin-C-defi cient diet and then increased their vitamin
C intake from 5 to 250 mg/day. Upon ingestion of the
vitamin-C-defi cient diet, plasma and leukocyte vitamin
C concentrations were decreased by about 50%, and DTH
response to several antigens was decreased as well. With
higher doses (60 and 250 mg/day) the DTH response was
normalized, but lymphocyte proliferation was not affect-
ed [37] . In older people, known to have reduced vitamin
C plasma and leukocyte concentrations even if they are
not institutionalized, vitamin C supplementation result-
ed in enhanced cell-mediated immunity [39] . Intracellu-
lar concentrations of vitamin C in human leukocytes have
been shown to decline with increasing age, accompanied
by neutrophil function impairment. Oral administration
of vitamin C resulted in improved neutrophil functions
and serum immunoglobulin levels [40] . An earlier inves-
tigation showed that administration of 1 g of vitamin C
together with 200 mg of vitamin E for 16 weeks to healthy
elderly women enhanced neutrophil chemotaxis and
phagocytosis, and decreased concentrations in serum lip-
id peroxides, which is indicative of improved resistance
to oxidative stress [41] . Other studies, however, did not
show any alterations in indices of immune function fol-
lowing vitamin C administration, which may be due to
the fact that individuals participating in these studies had
already adequate vitamin C baseline concentrations [1] .
Vitamin C stimulated interferon production in vitro
when incubated with cultured mouse cells and in vivo
when administered to mice [42] . There is evidence that
ascorbic acid may also have antiviral activity in vivo [43,
44] . Topical application of ascorbic acid in patients with
herpes simplex virus infections decreased the duration of
the lesions and viral shedding [45] .
Zinc and the Immune System
The immune-related functions of zinc have been re-
viewed recently [46] . The innate or nonspecifi c immu-
nity as the fi rst line of defense is disturbed by altered zinc
concentrations. Lowered zinc status, such as in subclini-
cal defi ciency and zinc defi ciency impairs cellular media-
tors of innate immunity such as phagocytosis by macro-
phages and neutrophils, natural killer cell activity, gen-
eration of the oxidative burst, and complement activity
[47] . These alterations are considered to be important
contributors to increased susceptibility to infections, es-
pecially during childhood. Patients on total parenteral
nutrition without zinc supplementation showed reduced
resistance to infections that was corrected by addition of
zinc to their nourishment [48] . Zinc plays an essential role
in cell-mediated and humoral immunity, as observed in
in vitro studies and in studies in zinc-defi cient subjects
[46, 49] .
Consistent fi ndings in zinc defi ciency are a decrease in
lymphocyte numbers (lymphopenia), impaired lympho-
cyte development, reduced proliferation, increased apop-
tosis, and thymic atrophy [50] . Zinc defi ciency in experi-
mental animals is associated with low thymic weight, a
progressive loss of T lymphocytes and macrophages, de-
layed hypersensitivity and cytotoxic activity, impaired B
and T cell function, and reduced antibody recall respons-
es. Zinc is an essential cofactor for the thymic hormone
thymulin, which induces several T cell markers, and pro-
motes T cell function, including allogenic cytotoxicity,
suppressor functions, and interleukin-2 production. It
also modulates cytokine release by peripheral blood nu-
clear cells and induces the proliferation of CD8+ T cells,
which function as cytotoxic cells able to recognize and kill
pathogens [49] . In experimentally induced zinc defi cien-
cy, subjects show low serum thymulin activity, impaired
T cell and natural killer cell activities, and decreased in-
terleukin-2 and interferon production [51] .
Vitamin C and Zinc and Infectious Diseases
Vitamin C and zinc have been demonstrated to sup-
port important functions, which are essential in main-
taining health. Especially, their role in modulating host
resistance to infectious agents is considered of impor-
tance. Thus, undernutrition and defi ciency of these nu-
trients may already result in profound effects on overall
immune function with increased susceptibility to oxida-
tive stress and subsequent respiratory infections. Micro-
nutrient defi ciencies are quite common in the elderly and
even apparently healthy elderly, e.g. in European coun-
tries, were shown to have low dietary intake of at least
one nutrient [52] . Vitamin C intakes were reported in the
SENECA study to be insuffi cient in about 5–10% of the
elderly population in Europe [53] . But, also heavy chron-
ic smokers, exposed to continuous increased oxidative
stress, are known to have a reduced vitamin C status. The
NHANES III study showed signifi cantly lower leukocyte
vitamin C concentrations in smokers than in nonsmokers
[54] . This may be of importance, since the immune sys-
tem also becomes activated by environmental pollutants,
Potential of Vitamin C and Zinc in
Immune Function
Ann Nutr Metab 2006;50:85–94
89
burns, injury, exposure to radiation, and the presence of
chronic infl ammation. The proinfl ammatory cytokines
will indirectly ensure that vitamin C, and other antioxi-
dants, are released from host tissues and made available
for antioxidant defense. If not re-supplied, the host is at
risk of developing a defi ciency state.
Similarly to vitamin C, the body has no storage system
for zinc; a steady intake of zinc is thus necessary. Zinc
defi ciency in developed countries is rather seldom, but
risk groups for zinc undernutrition and zinc defi ciency
include vegetarians (decreased absorption), elderly (in-
suffi cient dietary intake), patients with intestinal diseases
(causing decreased absorption), children, pregnant and
nursing women, and patients with chronic infections or
infl ammatory diseases often seen especially in the elderly
(increased requirement) [55] . The NHANES III study in
the US reported groups at greatest risk of inadequate zinc
intake to be children aged 1–3 years, adolescent females
aged 12–19 years, and elderly people aged 1 71 years [56] .
In developing countries, infections very often coexist
with multiple nutritional defi ciencies which may be the
result of general malnutrition. Especially children, in the
case of zinc, and the elderly for both nutrients are af-
fected.
Vitamin C as well as zinc supplementation has been
shown to be of therapeutic value in specifi c clinical con-
ditions. In Chediak-Higashi syndrome, which is charac-
terized by clinical phagocytic cell dysfunction, in chronic
granulomatous disease, and in recurrent furunculosis, vi-
tamin C supplementation increases neutrophil chemo-
taxis, improves bactericidal activity and reduces the
length of clinical illness [36, 57, 58] . The rare autosomal
recessively inherited disease acrodermatitis enteropathi-
ca, caused by impaired absorption of zinc from the
gastrointestinal tract, is characterized by dermatitis, in-
termittent diarrhea, recurrent infections, growth retarda-
tion, impaired immune function and increased suscep-
tibility to infections [59] . Zinc defi ciency was shown to
result in impaired immune function and increased sus-
ceptibility to infections [60] .
Respiratory Infections and the Common Cold
Based on its immunostimulatory properties, vitamin
C has been postulated to be effective in ameliorating
symptoms of upper respiratory tract infections, especial-
ly the common cold, and a large number of placebo-con-
trolled studies in large cohorts have been carried out to
evaluate the potential role of vitamin C supplementation
in their prevention of the common cold. The most recent
overall review evaluated whether oral vitamin C in doses
of 200 mg or more daily reduces the incidence, duration
or severity of the common cold when used either as con-
tinuous prophylaxis or as therapy after the onset of symp-
toms [61] . A meta-analysis of 29 trials involving 11,077
study participants indicated that routine prophylaxis
with high-dose vitamin C in the normal population did
not result in a reduction in the incidence of colds (RR
0.96; 95% CI 0.92–1.00), whereas a subgroup of 6 trials
involving 642 marathon runners, skiers, and soldiers on
sub-arctic exercise showed a 50% reduction in the risk of
colds (RR 0.50; 95% CI 0.38–0.66). A consistent and sta-
tistically signifi cant benefi t in reduction of cold duration
during prophylaxis with vitamin C of 8% (95% CI 3–13%)
for adults and 13.5% (95% CI 5–21%) for children was
observed in 30 comparisons involving 9,676 respiratory
episodes. The meta-analysis of severity of episodes while
on prophylaxis with vitamin C was based on 15 trial com-
parisons with 7,054 respiratory episodes. When taking
days confi ned to home and off work or school as measure
of severity (p = 0.02) or including only studies which used
symptom severity scores (p = 0.16), the pooled results re-
vealed a difference favoring vitamin C prophylaxis, which
is of great economic importance. No signifi cant differ-
ence in cold duration or cold severity was seen versus
placebo during therapy with up to 4 g of vitamin C when
started at onset of cold symptoms, but one large trial re-
ported benefi t from an 8 g therapeutic dose at onset of
cold symptoms. The authors concluded that prophylactic
vitamin C supplementation may not be justifi ed for com-
munity use, but could be of benefi t in persons exposed to
brief periods of severe physical exercise and/or cold en-
vironment. The consistent and statistically signifi cant
small benefi ts for duration and severity in those on regu-
lar vitamin C prophylaxis point to a role for vitamin C in
respiratory defense mechanisms [61] . Elderly patients
hospitalized with acute respiratory infections (pneumo-
nia; chronic bronchitis) showed a better overall status
measured as a ‘total respiratory clinical score’ when re-
ceiving 200 mg/day of vitamin C over 4 weeks [62] .
Following exercise, increased reactive oxygen species
are produced that may exceed antioxidant defense, result-
ing in oxidative damage and the stimulation of an infl am-
matory response with increased proinfl ammatory cyto-
kine production. Ultramarathon runners may therefore
benefi t from antioxidant supplementation. Subjects sup-
plemented with 600 mg vitamin C per day showed a sig-
nifi cant decrease in the incidence of postrace upper respi-
ratory infections and were able to cope better with the
oxidative stress response resulting from strenuous exer-
cise [63] . In a more recent study, it was shown that anti-
Wintergerst /Maggini /Hornig
Ann Nutr Metab 2006;50:85–94
90
oxidant supplementation of a mixture of 1 g vitamin C
and 300 mg vitamin E over 6 weeks prevented exercise-
induced oxidative stress, measured as F2-isoprostane as
marker for lipid peroxidation [64] .
Earlier in vitro studies have shown that zinc salts, at
concentrations of about 0.1 mmol/l, possess antiviral
properties and inhibit rhinovirus replication [65] . The
effects of zinc on rhinovirus replication were found to be
related to the concentration of Zn
2+
ions and were unre-
lated to total amount of zinc. The antiviral effect of Zn
2+
ions was found to be as effective as that of interferon [66] .
Alternatively, zinc salts may protect plasma membranes
against lysis by cytotoxic agents, such as microbial toxins
[67] .
On the basis of antiviral interaction, several random-
ized and placebo-controlled clinical trials were carried
out, mainly with lozenges of zinc gluconate. Several meta-
analyses were conducted, including 8 clinical trials [68] ,
and 7 clinical trials [69] . The summary odds ratio for the
presence of any cold symptoms at day 7 was 0.50 (95%
CI 0.19–1.29), and the authors concluded that convincing
evidence for the effectiveness of zinc gluconate lozenges
in reducing the common cold is lacking, but methodolog-
ical fl aws and small sample size made a defi nitive conclu-
sion diffi cult [68] . The meta-analysis by the Cochrane
Collaboration also concluded that there was no convinc-
ing evidence for zinc gluconate lozenges, since 4 trials
have shown that zinc may be effective in the treatment
of the common cold by reducing the duration and sever-
ity of symptoms, whereras 4 other trials have shown no
benefi t. But it was stated that due to diffi culties with re-
spect to blinding and bioavailability of zinc from the loz-
enges better designed studies are necessary before a fi nal
conclusion can be drawn [69] . Whereas most trials were
carried out on patients with community-acquired infec-
tions, in two studies volunteers were inoculated with rhi-
novirus, but the authors reported opposite fi ndings [70,
71] . As a treatment, zinc gluconate lozenges (containing
23 mg; 1 lozenge/2 waking hours for a total of 12 lozeng-
es/day for 4.5 days; 12 volunteers) shortened experimen-
tally induced rhinovirus-2 colds by a statistically signifi -
cant average of 4.8 days [70] . The other trial was carried
out in 55 individuals with zinc gluconate lozenges (con-
taining 23 mg of zinc gluconate and 90 mg citric acid; 1
lozenge every 2 h for a total of 8 lozenges/day for 5 days).
The treatment actually was found to prolong the cold by
1 day compared to placebo [71] .
Since the Cochrane review, three trials have been re-
ported [72–74] . Prevention and treatment of rhinovirus
infection with intranasal zinc gluconate in 91 subjects did
not show any effect [72] . The effi cacy of zinc acetate and
zinc gluconate lozenges in a study on 273 subjects chal-
lenged with rhinovirus and in 281 patients with sponta-
neous colds treated by intranasal application of zinc glu-
conate signifi cantly reduced the duration of the cold from
3.5 to 2.5 days in the rhinovirus-challenged group versus
placebo. No effects were seen in the zinc acetate group.
Likewise, no effect was observed on duration and sever-
ity with both treatments in those subjects with spontane-
ous colds [73] . In the third study, the effect of zinc acetate
in reducing the duration of symptoms of the common
cold was investigated in a randomized, double-blind, and
placebo-controlled trial in 50 volunteers. The partici-
pants were recruited within 24 h of developing symptoms
and received zinc acetate lozenges containing 12.8 mg of
zinc acetate every 2–3 h while awake as long as the symp-
toms prevailed. Measurements recorded daily for 12 days
included subjective scores for sore throat, nasal discharge,
nasal congestion, hoarseness, muscle ache, fever, and
headache. Compared with the placebo group, the zinc
acetate group showed a signifi cantly shorter overall dura-
tion of cold symptoms (4.5 vs. 8.1 days; p ! 0.005), cough
(3.1 vs. 6.3 days), nasal discharge (4.1 vs. 5.8 days) and
signifi cantly decreased total severity scores for all symp-
toms (p ! 0.002). The authors concluded that zinc acetate
may be effi cacious in reducing the duration of common
cold symptoms and should be preferred over zinc gluco-
nates [74] .
Overall, the available trials on the effect of zinc on
common colds report confl icting results. However, the
observation that prospective effi cacy of zinc lozenges
might be predicted based on the zinc ion availability from
chemically different zinc lozenge formulations, may at
least partly explain the differences in clinical outcome
[75] . Zinc ion availability identifi es the potential for ab-
sorption of Zn
2+
ions at physiological pH 7.4 into oral and
oropharyngeal mucosal membranes, which is infl uenced
by components in the lozenges (chelating substances;
food acids). The analyses of zinc lozenge formulations
used with regard to their zinc ion availability showed a
linear relationship with the reduction in the duration of
common colds in days, and suggests that the lozenges
containing zinc acetate without substances minimizing
zinc ion availability (e.g. chelators such as citric acid or
tartaric acid, EDTA, amino acids; salicylic acid) should
be investigated, since 100% of zinc acetate is released as
Zn
2+
ions at physiological pH [75] . Unfortunately, these
aspects were not considered so far by any meta-analysis
of the effect of zinc on the common cold. However, the
recent effective trial with zinc acetate lozenges to reduce
Potential of Vitamin C and Zinc in
Immune Function
Ann Nutr Metab 2006;50:85–94
91
duration and severity of symptoms actually seems to sup-
port the importance of the availability of zinc ions [74] .
Thus, further carefully conducted clinical trials are neces-
sary to prove or disprove the effi cacy of zinc acetate loz-
enges against the common cold, and such trials may be of
high economic value. Nevertheless, the mechanism un-
derlying a potential effect of zinc acetate in the treatment
of the common cold is still unclear.
The Zinc Investigators’ Collaborative Group [76] eval-
uated the effect of zinc supplementation in doses ranging
from 10 to 30 mg/day in children aged 3–36 months, on
the incidence of pneumonia in a meta-analysis including
4 randomized controlled trials and found a 41% reduc-
tion (95% CI 17–59%). This fi nding was confi rmed in
children, in whom recent trials showed a 26% reduction
in the risk of pneumonia [77] . The revised pooled analy-
sis of all 5 trials showed a 34% reduction in the incidence
of pneumonia infections (95% CI 17–47%) [76, 78] . Zinc
supplementation together with antibiotics resulted in a
30% reduction versus placebo with regard to the duration
of severe pneumonia and individual markers of disease
severity (fast breathing, hypoxia), and a mean reduction
of 25% with regard to the duration of hospital stays [79] .
A benefi t of daily zinc supplementation to Bangladeshi
children with diarrhea (20 mg for 14 days) showed a sta-
tistically nonsignifi cant downward trend in the incidence
and in hospital admission for acute lower respiratory in-
fection in the intervention group [80] . A recent study
showed that zinc treatment (10 mg zinc as acetate twice
daily for 4 days) of 153 children aged 2–24 months with
acute respiratory infection signifi cantly reduced the dura-
tion of fever (p = 0.003) and very ill status (p = 0.004) in
boys, but not in girls [81] .
Effect of Nutritional Status
Viral and bacterial infections are the most common
causes of acute diarrhea. Worldwide, acute infectious di-
arrhea has a huge impact, causing over 5 million deaths
per year. The clinical condition of diarrhea does not seem
to be related to decreased vitamin C status. Zinc defi -
ciency is highly prevalent in children in developing coun-
tries due to inadequate dietary intake, lack of intake of
animal foods, and reduced bioavailability of zinc due to
a high phytate:zinc ratio in the diet [82] . The adverse ef-
fects of zinc defi ciency on the immune response are like-
ly to increase the susceptibility of children to infectious
diarrhea, and chronic or persistent diarrhea may further
compromise the zinc status and many children become
zinc defi cient due to increased fecal losses of zinc during
diarrhea [83] .
Diarrhea is clearly established to increase the rate of
loss of endogenous zinc from the intestinal mucosa [84] .
Results are available from a large number of randomized
controlled intervention trials in developing countries as-
sessing the effect of zinc supplementation in the preven-
tion of diarrhea. The Zinc Investigators’ Collaborative
Group performed a pooled analysis of trials in children
to assess the effects of zinc supplementation in the pre-
vention of diarrhea and pneumonia and found an 18%
reduction in the incidence of diarrhea. Zinc also had a
positive therapeutic effect in the treatment of acute and
persistent diarrhea (34 and 27% reduction, respectively).
Overall, zinc was found to have signifi cant therapeutic
effects in persistent diarrhea by decreasing the duration
of episodes, lowering stool frequencies, and reducing
treatment failures or deaths by 40%. These trials were
conducted in children aged between 6 months and 3 years
and zinc treatment ranged from 10 to 30 mg/day [76, 78] .
Subsequent trials in Bangladesh [85, 86] , India [87, 88] ,
and Brazil [89] replicated these fi ndings. It is thus sug-
gested that zinc supplementation could be an important
adjuvant therapy for treating acute diarrhea in children
in developing countries [85] .
Zinc is essential for several lymphocyte functions
which have been related to resistance to malaria infec-
tions, such as production of immunoglobulin IgG, inter-
feron-
, and tumor necrosis factor-
, and just like vita-
min C, it is also most important in the microbicidal activ-
ity of macrophages [31, 49]. In children with acute
malaria infection, baseline plasma zinc concentrations
are very low ( ! 9.2
mol/l) and were found to be inverse-
ly correlated with C-reactive protein and the degree of
parasitemia [90] . Cross-sectional studies showed an as-
sociation between low zinc status and increased incidence
of malaria [91] . The Zinc Against Plasmodium Study
Group evaluated the therapeutic effect of zinc adminis-
tered as an adjuvant to standard treatment in large dou-
ble-blind controlled trials and was not able to fi nd any
effect [92] , whereas zinc supplementation in patients suf-
fering from malaria infections showed on average a 36%
decrease in the incidence of febrile illness [93] .
Conclusion
Adequate intakes of vitamin C and zinc are essential
for health. These nutrients interact with the human im-
mune system by supporting immune responses and by
providing antioxidant protection to exogenously derived
and endogenously generated reactive oxygen species pro-
Wintergerst /Maggini /Hornig
Ann Nutr Metab 2006;50:85–94
92
duced during the infl ammatory response. Vitamin C
stimulates neutrophil chemotaxis and contributes to
maintaining the redox integrity of cells thereby protecting
them against reactive oxygen species. The latter are gen-
erated during the respiratory burst to kill pathogens and
are elevated in the infl ammatory response. Likewise, zinc
undernutrition or defi ciency was shown to impair cellular
mediators of innate immunity such as phagocytosis, nat-
ural killer cell activity, and the generation of oxidative
burst.
Both vitamin C and zinc have been investigated to
determine their role in the amelioration of the common
cold. Zinc salts as lozenges have been investigated for
their potential therapeutic effect on the common cold on
the basis of their direct anti-viral activity. Available trials
on the effect of oral administration of zinc salts as loz-
enges reported confl icting results and the available evi-
dence is inconclusive. However, a recent therapeutic tri-
al with zinc acetate showed a signifi cant reduction in the
overall duration of symptoms and overall severity score.
The discrepancies in clinical outcome with zinc salts on
the common cold have recently been suggested to be due
to the different zinc ion availability from these formula-
tions to the oral and oropharyngeal mucosal membranes.
Therefore, more studies are required, especially with zinc
acetate.
The current belief is that regular prophylactic intakes
of vitamin C at doses of 200 mg or more daily have no
effect on the incidence of the common cold, but may be
benefi cial in the reduction of the severity and duration of
the symptoms, suggesting that vitamin C plays some role
in the respiratory defense mechanisms. However, the el-
derly, who have been shown to have a lowered vitamin C
status and may therefore be more prone to infections,
persons exposed to continuous oxidative stress, such as
chronic smokers, and persons exposed to heavy physical
exercise and/or cold environment may benefi t from a
moderate continuous vitamin C intake.
Other vulnerable population groups include children.
Due to the high prevalence of zinc defi ciency, especially
in children in developing countries, and to the impaired
immune status, susceptibility to infectious diarrhea, ma-
laria, and pneumonia is found to be substantially in-
creased. Large intervention trials with daily intakes of
10–30 mg of zinc have shown that zinc supplementation
could be an important adjuvant therapy for treating
these infectious diseases in children in developing coun-
tries.
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... Vitamins cannot be synthesized within the body; therefore, they must be supplemented in the diet to obtain healthy levels [28]. The water-soluble Vitamin C and Vitamin B (thiamine, riboflavin, niacin, pantothenic acid, B6, biotin, B9, and cobalamin) have been reported in kombucha [29]. ...
... Water-soluble vitamins are less likely to be stored within the body like fat-soluble vitamins (Vitamins A, D, E or K) because they are quickly transported through the blood stream following consumption [29]. Vitamin C supports human health by using defensive antioxidants, the formation of collagen to aid in connective tissue, and during an immune response. ...
... Vitamin C supports human health by using defensive antioxidants, the formation of collagen to aid in connective tissue, and during an immune response. At the height of an infection, levels of Vitamin C are quickly depleted [29]. The mechanism behind this action can be explained by the fact that Vitamin C does not require a coenzyme, although it acts as a cofactor for an enzyme called "prolyl hydrolase", which aids in the formation of collagen [30]. ...
Article
Kombucha is a fermented sweetened tea with a mixed fermenting culture of yeast and acetic acid bacteria. While the history of kombucha is not completely clear, it is now available around the world and has shown an increase in availability and demand in the United States market. The proponents of kombucha consumption tout the varied health benefits it can provide. The final kombucha flavor and composition is a function of both the initial tea used and the fermentation process. While the ascribed benefits are varied and numerous, the number of direct studies has been limited. This review focuses on the current state of understanding of the chemical composition and the potential health effects both positive and negative reported in the literature.
... Poor nutrition in children may interfere with the development and function of the immune system. The immune regulatory mechanisms become impaired both quantitatively and qualitatively due to altered immune cell populations (7,19,(24)(25)(26) as a result the whole immune response pathway from innate to adaptive antibody response including cellular responses is said to be affected (7,(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38). In malaria endemic areas, the impact of the disease may even be aggravated. ...
... The philosophy underlying the immune dysfunctionmalnutrition connection informs the cause-consequence idea such that each may be a cause or consequence of the other (40). Several other reviews and studies (31,(35)(36)(37)(38)(41)(42)(43)(44)(45)(46)(47) have explored the association between micronutrients, particularly zinc deficiencies, with infections but only a few have specifically focused on the association with malaria (41,44). Even those studies that have extensively investigated the factors associated with a protective role of IgG subclasses have been limited to individual effects of age, exposure, transmission intensity, ethnicity, geographical location of the parasite, seasonality on the dynamics (13,42), and fine specificity (13) of antibodymediated protection to malaria. ...
Article
Full-text available
Immunoglobulin G (IgG) subclasses have been suggested to confer naturally acquired immunity to Plasmodium falciparum malaria. Cytophilic IgG1 and IgG3 with their potential for opsonization, phagocytosis, and antibody-dependent cellular inhibition in association with monocytes have been suggested to have a critical role in malaria. The potential for production of antibodies is influenced by micronutrient status. This study aimed at exploring the effect of micronutrients, particularly zinc status, on the profiles of IgG subclasses in 304 Tanzanian children aged ≤ 5 years. An enzyme-linked immunosorbent assay was performed using whole asexual blood stage malaria antigens to determine plasma malaria-specific antibody titers. This baseline cross-sectional study was done from 2005 – 2010 prior to the larger randomized control trial of the Micronutrient and Child Health (MACH) Study. Plasma concentrations of zinc and magnesium were measured by inductively coupled plasma atomic emission spectrometry and results correlated with plasma IgG subclass levels. The findings reveal zinc deficiency to possibly influence the production of IgM, total IgG, and several IgG subclasses in a malaria status-dependent manner. Among IgG subclasses, IgG3 and partly IgG2 displayed a remarkable association with zinc deficiency, particularly IgG3 which was predominant in children with malaria. Nevertheless, zinc, magnesium, and malaria status did not influence the association between IgG3 and IgG4. The study leads to the conclusion that, under conditions of micronutrient deficiency and malaria status, an imbalance in IgG subclass production may occur leading to predominantly higher levels of IgG3 and IgG2 that may not confer sufficient protection from infection. The profile of both cytophilic and non-cytophilic IgG subclasses has been shown to be variably influenced by zinc status; the effects vary with age at least in under-fives. These results provide insight for inclusion of micronutrients, particularly precise amounts of zinc, in future malaria interventional programs in endemic areas.
... COVID-19 infection can result in oxidative damage in several different organs and tissues. However, vitamin C maintains the cell redox integrity to protect the lungs against oxidative stress [76]. Recent studies spotted deficient levels of vitamin C in COVID-19 patients. ...
Article
COVID-19 is a rapidly spreading disease, which has caught the world by surprise. Millions of people suffer from illness, and the mortality rates are dramatically high. Currently, there is no specific and immediate treatment for this disease. Remedies are limited to supportive regiments and few antiviral and anti-inflammatory drugs. The lack of a definite cure for COVID-19 is the reason behind its high mortality and global prevalence. COVID-19 can lead to a critical illness with severe respiratory distress and cytokine release. Increased oxidative stress and excessive production of inflammatory cytokines are vital components of severe COVID-19. Micronutrients, metalloids, and vitamins such as iron, manganese, selenium, Zinc, Copper, vitamin A, B family, and C are among the essential and trace elements that play a pivotal role in human nutrition and health. They participate in metabolic processes that lead to energy production. In addition, they support immune functions and act as antioxidants. Therefore, maintaining an optimal level of micronutrients intake, particularly those with antioxidant activities, is essential to fight against oxidative stress, modulate inflammation, and boost the immune system. Therefore, these factors could play a crucial role in COVID-19 prevention and treatment. In this review, we aimed to summarize antiviral properties of different vitamins and minerals. Moreover, we will investigate the correlation between them and their effects in COVID-19 patients.
... Although studies of the individual carotenoids have given inconsistent results (6,25). Serum carotenoids are powerful antioxidants that are important for the immune system (26). One of the most plentiful dietary carotenoids, alpha-carotene, inhibit the proliferation of human cancer cells (27). ...
Article
Full-text available
Objective The purpose of this study was to evaluate the associations of serum biomarkers of fruit and vegetable intake (vitamin C and carotenoids) with cause–specific mortality and all–cause mortality in a nationally representative sample of US adults. Methods We analyzed data from 12,530 participants from the National Health and Nutrition Examination Survey III (1988–1994). The Cox proportional hazards models with restricted cubic spline were used for the analysis. Results During 246,027 person–years of follow–up, 4,511 deaths occurred, including 1,395 deaths from cardiovascular disease, 1,072 deaths from heart disease, 323 deaths from cerebral disease, and 954 deaths from cancer. The serum vitamin C was significantly associated with the cancer and all–cause mortality, with hazard ratios (HRs) (95% CIs) for each one SD of 0.80 (0.71–0.91) and 0.91 (0.86–0.96). The serum alpha–carotene was significantly associated with the cancer mortality, with HRs (95% CIs) of 0.70 (0.54–0.90), 0.68 (0.48–0.95), 0.64 (0.43–0.95), and 0.44 (0.33–0.60) for comparisons of groups 2–5 with group 1 in model 2, respectively. The change for each one SD in the composite biomarker score, equivalent to a 0.483 times/month difference in total fruits and vegetables intake, gave an HR of 0.79 (0.69–0.90) for cancer mortality. Conclusion Inverse associations were found between serum vitamin C, carotenoids, and composite biomarker score and outcomes expect for cerebral disease, heart disease, and cardiovascular disease mortality. This finding supports an increase in dietary fruit and vegetable intake as a primary prevention strategy for cancer and all–cause mortality.
... This pathological condition is characterized by gingival hemorrhagic-ulcerative manifestations, cachexia, skin hemorrhage and extensive hemorrhagic manifestations. Vitamin C plasma levels can decrease, not only due to food deficits, but also from infections and post-surgical stress [116], because, as described previously, this vitamin is involved in tissue repair processes [117][118][119]. The diagnosis of scurvy is based on the typical clinical signs of hypovitaminosis and on the resolution of these signs after the intake of vitamin C. Vitamin C serum levels lower than 0.2 mg/dL indicate scurvy [120] and its treatment relies on an appropriate intake from diet and/or correct vitamin C supplementation [120]. ...
Article
Full-text available
Several studies have demonstrated a strong relation between periodontal diseases and chronic kidney disease (CKD). The main mechanisms at the base of this link are malnutrition, vitamin dysregulation, especially of B-group vitamins and of C and D vitamins, oxidative stress, metabolic acidosis and low-grade inflammation. In particular, in hemodialysis (HD) adult patients, an impairment of nutritional status has been observed, induced not only by the HD procedures themselves, but also due to numerous CKD-related comorbidities. The alteration of nutritional assessment induces systemic manifestations that have repercussions on oral health, like oral microbiota dysbiosis, slow healing of wounds related to hypovitaminosis C, and an alteration of the supporting bone structures of the oral cavity related to metabolic acidosis and vitamin D deficiency. Low-grade inflammation has been observed to characterize periodontal diseases locally and, in a systemic manner, CKD contributes to the amplification of the pathological process, bidirectionally. Therefore, CKD and oral disease patients should be managed by a multidisciplinary professional team that can evaluate the possible co-presence of these two pathological conditions, that negatively influence each other, and set up therapeutic strategies to treat them. Once these patients have been identified, they should be included in a follow-up program, characterized by periodic checks in order to manage these pathological conditions.
... 192 A daily intake of 1 g vitamin C and 30 mg Zn can help to prevent viral symptoms in flu patients. 193 The other study indicated that dietary-rich vitamin C enhances macrophage function. 194 Furthermore, combining vitamin C, curcumin, and glycyrrhizic acid can protect against viral infection by boosting interferon synthesis, modulating the innate immune response, activating and balancing T-cells. ...
Article
Full-text available
Due to the absence of successful therapy, vaccines for protection are continuously being developed. Since vaccines must be thoroughly tested, viral respiratory tract infections (VRTIs), mainly coronaviruses, have seriously affected human health worldwide in recent years. In this review, we presented the relevant data which originated from trusted publishers regarding the practical benefits of functional foods (FFs) and their dietary sources, in addition to natural plant products, in viral respiratory and COVID-19 prevention and immune-boosting activities. As a result, FFs were confirmed to be functionally active ingredients for preventing COVID-19 and VRTIs. Furthermore, the antiviral activity and immunological effects of FFs against VRTIs and COVID-19 and their potential main mechanisms of action are also being reviewed. Therefore, to prevent COVID-19 and VRTIs, it is critical to identify controlling the activities and immune-enhancing functional food constituents as early as possible. We further aimed to summarize functional food constituents as a dietary supplement that aids in immune system boosting and may effectively reduce VRTIs and COVID-19 and promote therapeutic efficacy.
... This can contribute to the increased susceptibility to viral respiratory infections. Zinc is critical in the fast growth, differentiation, and activation of immune cells [101]. Not only does this increase immune cell proliferation, but it can also enhance cellular resistance to apoptosis by inhibiting caspases and increasing the Bcl-2/Bax ratio [102]. ...
Article
Full-text available
The coronavirus disease 2019 (COVID-19) has caused a pandemic and upheaval that health authorities and citizens around the globe are still grappling with to this day. While public health measures, vaccine development, and new therapeutics have made great strides in understanding and managing the pandemic, there has been an increasing focus on the potential roles of diet and supplementation in disease prevention and adjuvant treatment. In the literature, the impact of nutrition on other respiratory illnesses, including the common cold, pneumonia, and influenza, has been widely demonstrated in both animal and human models. However, there is much less research on the impact related to COVID-19. The present study discusses the potential uses of diets, vitamins, and supplements, including the Mediterranean diet, glutathione, zinc, and traditional Chinese medicine, in the prevention of infection and severe illness. The evidence demonstrating the efficacy of diet supplementation on infection risk, disease duration, severity, and recovery is mixed and inconsistent. More clinical trials are necessary in order to clearly demonstrate the contribution of nutrition and to guide potential therapeutic protocols.
... From a preclinical perspective, the importance of various micronutrients for a functioning immune system has been well Nutrients 2022, 14, 1862 2 of 12 documented [7][8][9]. For example, it has been shown that vitamin A plays an important role in maintaining mucosal integrity [10], while zinc plays an essential role in protecting against reactive oxygen and nitrogen species [11,12]. Furthermore, vitamin D increases the excretion of antimicrobial peptides in epithelial lining cells in the respiratory tract [13] and is involved in the modulation of pro-and anti-inflammatory cytokine production [14]. ...
Article
Full-text available
Background: A higher risk for severe clinical courses of coronavirus disease 2019 (COVID-19) has been linked to deficiencies of several micronutrients. We therefore studied the prevalence of deficiencies of eight different micronutrients in a cohort of hospitalized COVID-19-patients. Methods: We measured admission serum/plasma levels of vitamins A, B12, D, and E, as well as folic acid, zinc, selenium, and copper in 57 consecutively admitted adult patients with confirmed COVID-19 and analyzed prevalence of micronutrient deficiencies and correlations among micronutrient levels. Further, we studied associations of micronutrient levels with severe disease progression, a composite endpoint consisting of in-hospital mortality and/or need for intensive care unit (ICU) treatment with logistic regression. Results: Median age was 67.0 years (IQR 60.0, 74.2) and 60% (n = 34) were male. Overall, 79% (n = 45) of patients had at least one deficient micronutrient level and 33% (n = 19) had ≥3 deficiencies. Most prevalent deficiencies were found for selenium, vitamin D, vitamin A, and zinc (51%, 40%, 39%, and 39%, respectively). We found several correlations among micronutrients with correlation coefficients ranging from r = 0.27 to r = 0.42. The strongest associations with lower risk for severe COVID-19 disease progression (adjusted odds ratios) were found for higher levels of vitamin A (0.18, 95% CI 0.05-0.69, p = 0.01), zinc (0.73, 95% CI 0.55-0.98, p = 0.03), and folic acid (0.88, 95% CI 0.78-0.98, p = 0.02). Conclusions: We found a high prevalence of micronutrient deficiencies in mostly older patients hospitalized for COVID-19, particularly regarding selenium, vitamin D, vitamin A, and zinc. Several deficiencies were associated with a higher risk for more severe COVID-19 courses. Whether supplementation of micronutrients is useful for prevention of severe clinical courses or treatment of COVID-19 warrants further research.
Article
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Background and aims: Over-the-counter (OTC) dietary supplements gained popularity during the COVID-19 pandemic as a preventive measure. Lack of complete understanding among the general population of the pathophysiologic mechanisms underlying the severity and progression of infection with coronavirus disease 2019 (COVID-19) has further encouraged the use of supplements. The present study aimed to assess the perceptions of the general public toward the efficacy and safety of the use of OTC dietary supplements as immune enhancers during the COVID-19 pandemic. The factors impacting these perceptions were also explored. Methods: This was an online survey-based, cross-sectional study conducted in Jordan over 4 months. A validated survey which comprised 28 questions covering aspects related to the respondents' demographic characteristics, their perceptions toward the efficacy of OTC dietary supplements and their awareness regarding the safety of popular OTC supplements and healthy dietary habits was used to collect responses. Associations between patient characteristics with perception and awareness were explored. Results: A total of 1487 responses were included in the analysis. Ascorbic acid, zinc, and vitamin D were the most popular OTC supplements, as indicated by the percentages of users (48.8%, 38.6%, and 34.6%, respectively). Perceptions toward OTC supplement use were suboptimal, with a reported mean perception score of 27.82 ± 8.56 (range 0-45). The multivariate analysis showed that participants who were of older age (>65 years) (AOR = 6.29, 95% CI = 2.2-17.9), had an income level >1500 (AOR = 1.84, 95% CI = 1.80-3.56), and used chronic medications had better perceptions than did younger participants, those with no income, and non-users of chronic medications, respectively. The mean safety awareness score was 5.36 ± 1.58 (maximum 7), with a significant direct relationship identified between perceptions and safety awareness scores (Spearman's correlation = 0.136, p < 0.001). Conclusion: This study highlighted the needs to organize educational campaigns that promote general public perceptions toward the safe use of OTC supplements to enhance immunity during COVID-19.
Article
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Background: Zinc supplementation in young children has been associated with reductions in the incidence and severity of diarrheal diseases, acute respiratory infections, and malaria. Objective: The objective was to evaluate the potential role of zinc as an adjunct in the treatment of acute, uncomplicated falciparum malaria; a multicenter, double-blind, randomized placebo-controlled clinical trial was undertaken. Design: Children (n = 1087) aged 6 mo to 5 y were enrolled at sites in Ecuador, Ghana, Tanzania, Uganda, and Zambia. Children with fever and greater than or equal to 2000 asexual forms of Plasmodium falciparum/muL in a thick blood smear received chloroquine and were randomly assigned to receive zinc (20 mg/d for infants, 40 mg/d for older children) or placebo for 4 d. Results: There was no effect of zinc on the median time to reduction of fever (zinc group: 24.2 h; placebo group: 24.0 h P = 0.37), a greater than or equal to 75% reduction in parasitemia from baseline in the first 72 h in 73.4% of the zinc group and in 77.6% of the placebo group (P = 0.11), and no significant change in hemoglobin concentration during the 3-d period of hospitalization and the 4 wk of follow-up. Mean plasma zinc concentrations were low in all children at baseline (zinc group: 8.54 +/- 3.93 mumol/L; placebo group: 8.34 +/- 3,25 mumol/L), but children who received zinc supplementation had higher plasma zinc concentrations at 72 h than did those who received placebo (10.95 +/- 3.63 compared with 10.16 +/- 3.25 mumol/L, P < 0.001). Conclusion: Zinc does not appear to provide a beneficial effect in the treatment of acute, uncomplicated falciparum malaria in preschool children.
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: Plasma concentrations of some micronutrients are altered in the setting of acute infectious or inflammatory stress. Previous studies have provided conflicting evidence concerning the extent and direction of changes in plasma zinc concentrations during the acute phase response. We carried out an observational cohort study in 689 children enrolled in a randomized trial of zinc supplementation during acute falciparum malaria in order to evaluate the relation between plasma zinc concentration and the acute phase response. Plasma zinc was measured by atomic absorption spectrophotometry. On admission, 70% of all subjects had low plasma zinc (<9.2 micromol/L). Multivariate analysis of predictors of admission plasma zinc showed that admission C-reactive protein (CRP), parasite density, and study site were the most important predictors. Predictors of changes in plasma zinc from admission to 72 h included baseline CRP, change in CRP, treatment group, study site, and baseline zinc concentration. In children with acute malaria infection, baseline plasma zinc concentrations were very low and were inversely correlated with CRP (r = -0.24, P < 0.0001) and the degree of parasitemia (r = -0.19, P < 0.0001). Even when CRP and time were taken into account, zinc supplementation increased plasma zinc concentration from admission to 72 h. When available, plasma zinc concentrations should be interpreted with concurrent measures of the acute phase response such as CRP. In children whose age, diet, and/or nutritional status place them at risk of zinc deficiency, those with low plasma zinc levels should be supplemented with oral zinc and followed for clinical and/or biochemical response.
Chapter
This book contains 18 chapters discussing the roles of specific nutrients in maintaining the immune response and protection against infection and non-communicable diseases, and the influence of various factors, such as exercise and aging, on the interaction between nutrition and immune function. The contents include methods for studying nutrient-immune function interactions, the impact of undernutrition on immune function and infection, the influences of fatty acids, amino acids, antioxidant vitamins, various minerals and probiotics on immunity, food allergies, immunological effects of changes throughout the life cycle, and public health policy implications.
Article
Background: Zinc supplementation in young children has been associated with reductions in the incidence and severity of diarrheal diseases, acute respiratory infections, and malaria. Objective: The objective was to evaluate the potential role of zinc as an adjunct in the treatment of acute, uncomplicated falciparum malaria; a multicenter, double-blind, randomized placebo-controlled clinical trial was undertaken. Design: Children (n = 1087) aged 6 mo to 5 y were enrolled at sites in Ecuador, Ghana, Tanzania, Uganda, and Zambia. Children with fever and ≥2000 asexual forms of Plasmodium falciparum/μL in a thick blood smear received chloroquine and were randomly assigned to receive zinc (20 mg/d for infants, 40 mg/d for older children) or placebo for 4 d. Results: There was no effect of zinc on the median time to reduction of fever (zinc group: 24.2 h; placebo group: 24.0 h; P = 0.37), a ≥75% reduction in parasitemia from baseline in the first 72 h in 73.4% of the zinc group and in 77.6% of the placebo group (P = 0.11), and no significant change in hemoglobin concentration during the 3-d period of hospitalization and the 4 wk of follow-up. Mean plasma zinc concentrations were low in all children at baseline (zinc group: 8.54 ± 3.93 μmol/L; placebo group: 8.34 ± 3.25 μmol/L), but children who received zinc supplementation had higher plasma zinc concentrations at 72 h than did those who received placebo (10.95 ± 3.63 compared with 10.16 ± 3.25 μmol/L, P < 0.001). Conclusion: Zinc does not appear to provide a beneficial effect in the treatment of acute, uncomplicated falciparum malaria in preschool children.
Article
OBJECTIVE: To evaluate the effect on morbidity and mortality of providing daily zinc for 14 days to children with diarrhoea. DESIGN: Cluster randomised comparison. SETTING: Matlab field site of International Center for Diarrhoeal Disease Research, Bangladesh. PARTICIPANTS: 8070 children aged 3-59 months contributed 11 881 child years of observation during a two year period. INTERVENTION: Children with diarrhoea in the intervention clusters were treated with zinc (20 mg per day for 14 days); all children with diarrhoea were treated with oral rehydration therapy. MAIN OUTCOME MEASURES: Duration of episode of diarrhoea, incidence of diarrhoea and acute lower respiratory infections, admission to hospital for diarrhoea or acute lower respiratory infections, and child mortality. RESULTS: About 40% (399/1007) of diarrhoeal episodes were treated with zinc in the first four months of the trial; the rate rose to 67% (350/526) in month 5 and to >80% (364/434) in month 7 and was sustained at that level. Children from the intervention cluster received zinc for about seven days on average during each episode of diarrhoea. They had a shorter duration (hazard ratio 0.76, 95% confidence interval 0.65 to 0.90) and lower incidence of diarrhoea (rate ratio 0.85, 0.76 to 0.96) than children in the comparison group. Incidence of acute lower respiratory infection was reduced in the intervention group but not in the comparison group. Admission to hospital of children with diarrhoea was lower in the intervention group than in the comparison group (0.76, 0.59 to 0.98). Admission for acute lower respiratory infection was lower in the intervention group, but this was not statistically significant (0.81, 0.53 to 1.23). The rate of non-injury deaths in the intervention clusters was considerably lower (0.49, 0.25 to 0.94). CONCLUSIONS: The lower rates of child morbidity and mortality with zinc treatment represent substantial benefits from a simple and inexpensive intervention that can be incorporated in existing efforts to control diarrhoeal disease.