A Combination of High-Dose Vitamin C plus Zinc for the Common Cold

Abstract

Vitamin C and zinc play important roles in nutrition, immune defence and maintenance of health. Intake of both is often inadequate, even in affluent populations. The common cold continues to place a great burden on society in terms of suffering and economic loss. After an overview of the literature on the effects of the separate administration of either vitamin C or zinc against the common cold, this article presents data from two preliminary, double-blind, randomized, placebo-controlled trials, conducted with a combination of 1000 mg vitamin C plus 10 mg zinc in patients with the common cold. In both studies, a nonsignificant reduction of rhinorrhoea duration (range 9-27%) was seen. In pooled analyses of both studies (n=94), vitamin C plus zinc was significantly more efficient than placebo at reducing rhinorrhoea over 5 days of treatment. Furthermore, symptom relief was quicker and the product was well tolerated. In view of the burden associated with the common cold, supplementation with vitamin C plus zinc may represent an efficacious measure, with a good safety profile, against this infectious viral disease.

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DOI: 10.1177/147323001204000104
2012 40: 28Journal of International Medical Research
S Maggini, S Beveridge and M Suter
A Combination of High-Dose Vitamin C plus Zinc for the Common Cold
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The Journal of International Medical Research
2012; 40: 28 – 42 [first published online ahead of print as 40(1) 13]
28
A Combination of High-dose Vitamin C
Plus Zinc for the Common Cold
S MAGGINI1, S BEVERIDGE1AND M SUTER2,a
1Bayer Consumer Care Ltd, Basel, Switzerland; 2Basel, Switzerland
Vitamin C and zinc play important roles in
nutrition, immune defence and
maintenance of health. Intake of both is
often inadequate, even in affluent
populations. The common cold continues
to place a great burden on society in terms
of suffering and economic loss. After an
overview of the literature on the effects of
the separate administration of either
vitamin C or zinc against the common
cold, this article presents data from two
preliminary, double-blind, randomized,
placebo-controlled trials, conducted with a
combination of 1000 mg vitamin C plus 10
mg zinc in patients with the common cold.
In both studies, a nonsignificant reduction
of rhinorrhoea duration (range 9 – 27%)
was seen. In pooled analyses of both
studies (n= 94), vitamin C plus zinc was
significantly more efficient than placebo
at reducing rhinorrhoea over 5 days of
treatment. Furthermore, symptom relief
was quicker and the product was well
tolerated. In view of the burden associated
with the common cold, supplementation
with vitamin C plus zinc may represent an
efficacious measure, with a good safety
profile, against this infectious viral disease.
KEY WORDS: VITAMIN C; ZINC; MICRONUTRIENTS; COMMON COLD; RESPIRATORY INFECTIONS;
IMMUNE SYSTEM
Vitamin C and zinc
Vitamin C (ascorbic acid) and zinc are two
essential micronutrients that play important
functional roles in nutrition, immune
support and maintenance of health. Vitamin
C is a cofactor for several enzymes involved
in the biosynthesis of collagen, carnitine and
neurotransmitters.1,2 It is a highly effective
antioxidant that protects proteins, lipids,
carbohydrates and nucleic acids from
damage by free radicals generated during
normal metabolism, as well as through
exposure to toxins and pollutants (e.g.
smoking).1 – 3 Marginal vitamin C deficiency
results in fatigue, lack of well-being and poor
concentration.2Severe vitamin C deficiency
has been known for many centuries as the
potentially fatal disease, scurvy. Scurvy
causes weakening of collagenous structures,
resulting in tooth loss, joint pain, bone and
connective tissue disorders (e.g. impaired
bone growth and disturbed ossification),
poor wound healing and compromised
immunity. 1 – 3 Zinc is a component of over
1000 transcription factors, including DNA-
binding proteins with zinc fingers, and is
required in over 300 metalloenzymes.2,3 Zinc
plays a central role in cellular differentiation
and proliferation, and its deficiency causes
growth retardation, skin changes, impaired
immune response, increased susceptibility to
infections, delayed wound healing,
aM Suter is a retired employee of Roche Consumer Health,
Basel, Switzerland.

29
S Maggini, S Beveridge, M Suter
High-dose vitamin C plus zinc for the common cold
abnormal dark adaptation, delayed sexual
maturation and impaired fertility.2 – 5 Zinc
deficiency is an important public health
problem affecting 2 billion people
worldwide,2,5 including a considerable
proportion of the Western population.2,3
Among the micronutrients required to
ensure proper immune function, vitamin C
and zinc hold central positions through their
complementary roles in supporting
components of both innate and adaptive
immunity, such as epithelial barriers, cellular
proliferation and antibody production.2
Vitamin C is mainly necessary for cell-
mediated immune responses including
leucocyte and macrophage functions,
neutrophil motility and phagocytosis, but
also for antimicrobial activity, interferon
synthesis and antihistamine properties.2,3 It is
further required for collagen synthesis and
wound healing, with collagen being
important to the physical infection barrier
provided by the skin and the linings of all of
the body openings.2,3,6 – 11 Vitamin C
generally has a limited effect on humoral
immune responses such as antibody
production.2,3,12
Zinc is necessary for optimal functioning
of both innate and adaptive immunity;
impaired immune function due to
inadequate zinc status may be the most
common cause of secondary immuno -
deficiency in humans.13 – 15 Zinc status
strongly affects T- and B-lymphocyte function
and antibody formation, and is required by
the thymus for the production of thymic
hormone.2,3,16,17 Finally, both vitamin C and
zinc provide complementary antioxidant
protection against exogenously derived and
endogenously generated reactive oxygen
species.2,3 Immune cells are frequently
exposed to alterations in the oxidant–
antioxidant equilibrium, due to the high
number of reactive oxygen species they
produce in order to incapacitate pathogens
as part of their normal function.18 Immune
cells need to protect themselves from reactive
oxygen species in order to preserve their
structure and function, and the oxidant–
antioxidant balance is, therefore, an
important determinant of immune function.
Immune cells are particularly sensitive to
changes in this balance because of the high
levels of polyunsaturated fatty acids in their
plasma membranes.19
Deficiencies of vitamin C3,9,12,20,21 and
zinc13 – 15 both severely depress immune
responses. Vitamin C deficiency results in
decreased resistance to disease.3,9,12,20 – 22 Zinc
deficiency can have marked effects on
virtually all components of the immune
system, increasing susceptibility to a number
of bacterial, viral and parasitic
challenges.13,23 Overall, there is a sound
scientific rationale for taking a combination
of vitamin C and zinc to support immune
function, in order to realize better the body’s
potential for defence.2,3
The common cold
Viral respiratory tract infections, such as the
common cold and influenza, are among the
most common illnesses in humans. Despite
great advances in medicine, the common cold
continues to place a great burden on society
in terms of suffering and economic loss.24,25
The common cold is caused by a large variety
of viruses that mutate frequently during
reproduction, resulting in constantly
changing viral strains.2 5 Thus, successful
immunization is highly improbable.
The occurrence of the common cold shows
clear seasonality. In temperate regions of the
northern hemisphere, the frequency of
respiratory infections increases rapidly in the
autumn, remains fairly high throughout the
winter, and decreases again in spring.25 In
tropical areas, most colds arise during the

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S Maggini, S Beveridge, M Suter
High-dose vitamin C plus zinc for the common cold
rainy season.25 Adults have around two to
four common-cold episodes annually,
whereas children may have six to 10 colds per
year (and up to 12 colds per year for school
children).25,26 Even if the common cold is
mostly an uncomplicated disease, its social
costs are important because of its frequency.
The best way to avoid a cold is to stay
away from existing sufferers, to wash hands
thoroughly and regularly, and to avoid
touching the face. Antibacterial soap has no
effect on the cold virus; it is the mechanical
action of hand washing that removes virus
particles from the skin.25,27,28 Tobacco
smoking has been shown to reduce
antioxidant levels (vitamin C status, in
particular)3,29 and also weakens the immune
system. Thus, smokers may experience colds
more frequently than nonsmokers. Smokers
are known to take more days off work with
illness than nonsmokers.30,31 As there is no
clinically proven ‘gold standard’ medication
directly targeting the causative pathogen for
the common cold, there is no cure for this
condition. Treatment is limited to
symptomatic supportive options that
maximize the comfort of the patient by
reducing symptom severity and limiting the
occurrence of complications.25,27 The most
frequent symptoms linked to the common
cold are shown in Table 1.27 Nasal symptoms
including congestion, runny nose
(rhinorrhoea) and sneezing are most
common, occurring in 45 – 75% of
patients.27 The duration of these symptoms
has been reported to vary between 4 days
and up to 3 weeks.27
In addition to classical drugs (e.g.
decongestants, analgesics), dietary supple -
ments including echinacea,32propolis,33
ginseng,34,35 β-glucans,36,37 vitamin E,38 and
especially vitamin C2,3 and zinc,26 have been
studied for the prevention and treatment of
the common cold and cold-related
symptoms.
This article provides an overview of the
available published data on the effects of the
separate administration of either vitamin C
or zinc against the common cold. In addition,
it presents the results of two preliminary
placebo-controlled studies carried out with a
combination effervescent tablet containing
high-dose (1000 mg) vitamin C plus 10 mg
zinc (Redoxon®Double Action; Bayer
Consumer Care Ltd, Basel, Switzerland) in
patients with symptoms of a common cold.
Effects of vitamin C against
the common cold
Based on its immunostimulatory properties,
high doses of vitamin C have been
postulated to be effective in ameliorating
TABLE 1:
Frequency of the usual symptoms of the common cold27
Location Symptom Incidence, %
Nasal Rhinorrhoea 75
Sneezing 60
Nasal congestion/obstruction 45
Pharyngeal Dry throat 50
Throat irritation 30
Tracheal Cough 40
General Headache 40
Fever 15
Myalgia 15

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S Maggini, S Beveridge, M Suter
High-dose vitamin C plus zinc for the common cold
and speeding the recovery from the common
cold.39 Endogenous vitamin C concentration
falls rapidly with the onset of infection and
tends to return to normal with the
disappearance of symptoms, suggesting that
its administration may be beneficial for the
recovery process.40,41
The notion that vitamin C has no effect
on the common cold seems to be based
largely on a review article written in 1975 by
Chalmers,42 which was criticized as
unreliable by Hemilä in the 1990s.43,44
Chalmers’ review showed several systematic
flaws (such as not considering the amount of
vitamin C used in the studies and including
a trial administering only 25 – 50 mg/day
ascorbic acid) and inconsistencies when
compared with the original publications.42
Since the publication of the Chalmers review,
a large number of placebo-controlled,
double-blind studies have been carried out.
The results of these studies, summarized
below, consistently support the conclusion
that vitamin C supplementation has an
effect in alleviating the symptoms of the
common cold.
The results of 21 placebo-controlled
studies performed between 1971 and 1988
were reviewed by Hemilä.45 The main
objective of these studies was to establish
whether vitamin C given regularly at doses
≥ 1 g/day had any effect on the course of the
common cold. Despite large variations in
each of the 21 studies, regular vitamin C use
consistently and significantly reduced both
the duration of episodes and the severity of
symptoms of the common cold by 23%.45
Furthermore, regular vitamin C use also
reduced the incidence of the common cold by
9% in the general population, although
evidence for this reduction was not seen
consistently in all 21 studies.45 A further
analysis of 23 studies, in which patients had
been taking vitamin C ≥ 1 g/day regularly,
was carried out to determine factors
contributing to the variation in benefits
observed in the above trials.46 It appeared
that the higher the dose per kg body weight,
the greater the benefit; vitamin C produced a
greater benefit in terms of cold duration for
children than adults, and the magnitude of
the benefit of vitamin C was greater with
doses of ≥ 2 g/day than 1 g/day.46The trials
analysed in this review used preventive
vitamin C supplementation, but it is
conceivable that therapeutic supplement -
ation starting at the onset of a cold episode
could produce comparable benefits.46
Over 60 studies (involving widely varying
dosages) have examined the effects of
vitamin C on the common cold. A 2007
Cochrane review evaluated whether oral
doses of ≥ 200 mg/day of vitamin C reduced
the incidence, duration or severity of the
common cold when used either as
continuous prophylaxis or after the onset of
symptoms.47 That review concluded there
was a benefit of high-dose vitamin C
(exceeding the recommended dietar y
allowance) in reducing the duration of cold
symptoms.47
The meta-analysis of common-cold
duration during prophylactic vitamin C
intake included 30 studies involving 9676
respiratory episodes.47 A consistent benefit
was observed, representing a reduction in
cold duration of 8% (95% confidence
interval [CI] 3%, 13%) for adults and 13.6%
(95% CI 5%, 22%) for children.47 The
reduction of cold duration in adults was
lower than the 23% reduction reported by
Hemilä,45 but the Hemilä review included
only studies using ≥ 1 g vitamin C; the
higher vitamin C dose may explain the
different findings.
The Cochrane review47 revealed that
vitamin C supplementation (≥ 200 mg/day)
has not been shown to offer a preventive

32
S Maggini, S Beveridge, M Suter
High-dose vitamin C plus zinc for the common cold
effect regarding the incidence of the
common cold in the general population.
However, a subgroup of six trials – involving
a total of 642 marathon runners, skiers and
soldiers on subarctic exercises – showed that
the pooled relative risk of developing a
common cold was 0.50 (95% CI 0.38, 0.66)
while taking prophylactic vitamin C.47
The meta-analysis of cold duration during
therapy with vitamin C initiated after the
onset of symptoms included seven trials
involving 3294 respiratory episodes.47 No
significant differences from placebo were
seen in these cases,47 but the treatment
period in some of the studies evaluated may
have been too short (3 days) to detect a
significant effect.47Again, the dose of
vitamin C may also have contributed to the
negative findings. Gorton and Jarvis48
treated students (aged 18 – 32 years)
reporting cold and flu symptoms with 1000
mg/h of vitamin C for 6 h, repeating the
treatment for up to 3 days, followed by 1000
mg three times daily.48 This treatment
protocol resulted in an 85% reduction of
reported flu and cold symptoms compared
with the control group.48 In another trial,
either 4 g/day or 8 g/day of vitamin C was
administered on the first day of illness.49 The
mean duration of cold episodes was 3.17
days in the 4 g/day group, 2.86 days in the 8
g/day group and 3.52 days in the placebo
group.49 The reduction seen with both
vitamin C doses reached statistical
significance.49 The relationship between
vitamin C dose and treatment benefits needs
further exploration, and it is important to
note that none of the studies analysed in the
Cochrane or Hemilä reviews44,45,47 took into
account the patients’ dietary intake of
vitamin C or their vitamin C status.50
Overall, these data indicate that vitamin
C supplementation plays a role in
respiratory defence mechanisms. It appears
that the elderly (who have been shown to
have a lowered vitamin C status) may be
more prone to infections than younger
people,3,12 and that patients exposed to
continuous oxidative stress (such as chronic
smokers1 – 3 and persons exposed to heavy
physical exercise and/or stress due to low
temperatures3) may benefit from a moderate
continuous vitamin C intake, in relation to
respiratory infections such as the common
cold.
Effects of zinc against the
common cold
The immunostimulatory properties of zinc
may also contribute to the management of
the common cold. Zinc salts have been
found to inhibit rhinovirus replication in
vitro,51and it has been suggested that zinc
salts may protect plasma membranes
against lysis by cytotoxic agents (such as
microbial toxins and components of
activated complement).52 Analyses of trials
conducted between 1984 and 2000,
investigating the role of zinc for alleviating
symptoms of the common cold, yielded
mixed results in terms of efficacy.52,53
Inadequate treatment masking, reduced
bioavailability of zinc from some
formulations and overall dose have been
cited as possible influencers of the results.3,54
A Cochrane review on zinc and the
common cold was undertaken in 2011.26 The
review identified 15 randomized controlled
trials enrolling 1360 participants of all age
groups, comparing zinc (irrespective of the
zinc salt or formulation used) versus
placebo.26 The Cochrane review in 2000 had
assessed seven trials, involving 754 cases.53
Zinc administered either as lozenges or syrup
within 24 h of symptom onset was found to
reduce the duration and severity of the
common cold in otherwise healthy people.26
In these therapeutic trials, 1.5 – 2-hourly

33
S Maggini, S Beveridge, M Suter
High-dose vitamin C plus zinc for the common cold
treatments with zinc (at doses of 10 – 23 mg)
or placebo lozenges during waking hours were
applied for > 6 h per day, for ≥ 5 consecutive
days.26 When supplemented for ≥ 5 months in
the form of syrup (10 – 30 mg/day),55,56 zinc
further reduced the incidence of common
colds, school absenteeism and the prescription
of antibiotics in children.26In contrast, people
taking zinc lozenges (not syrup or tablet form)
were more likely to experience adverse events,
including a bad taste and nausea.26 Given the
variability in the populations studied, dose,
formulation and duration of administration
in the included studies, more research is
required to determine the optimal duration of
treatment (as well as the dosage and
formulations of zinc) that will produce clinical
benefits without increasing adverse effects.
Hemilä54analysed a subset of studies from
the Cochrane review, consisting of 13
placebo-controlled trials exclusively using
zinc lozenges. This analysis considered both
the type of zinc salts as well as the total
amount of zinc used on the therapeutic effect
of common-cold episodes of natural origin.54
Five of the trials used a total daily zinc dose
of < 75 mg and uniformly found no effect.54
Three trials used zinc acetate in daily doses
of > 75 mg, the pooled result indicating a
42% reduction in the duration of colds (95%
CI 35%, 48%). Five trials used zinc salts other
than acetate in daily doses of > 75 mg, the
pooled result indicating a 20% reduction in
the duration of colds (95% CI 12%, 28%).54
Both the type of zinc salt used and the dose
of zinc in the lozenges impacted on the
benefits of supplementation in relation to
the common cold.54 These findings help to
explain the mixed results observed in the
reviews published in 2000.52,53
The postulated local mechanism of action
of zinc lozenges (e.g. gluconate, acetate),
differs in general from the well-documented,
important actions of systemic zinc on
immune defences.57 This indicates a
potential dual mode of action (i.e. local and
systemic) for zinc, related to immune support.
Due to the broad geographical distribution
and high prevalence of zinc deficiency and
the resulting impairment of immune
function, individuals at risk of deficiency
may benefit from a moderate continuous
zinc intake to maintain respiratory health.3
Taken together, data from a number of
clinical studies demonstrate that the
separate administration of vitamin C or zinc
results in a reduction of the duration and
severity of common-cold symptoms in
healthy individuals. To elicit these effects,
vitamin C at doses > 200 mg is typically
consumed as a prophylactic measure,
whereas zinc is administered in the form of
lozenges (10 – 23 mg of zinc at least six times
daily) or syrup (10 – 30 mg/day) and taken
within 24 h after symptom onset. There is
also evidence showing that the prophylactic
use of vitamin C or zinc may reduce the
incidence of the common cold in some
special populations.
Effect of combined vitamin
C and zinc supplement
against the common cold
RATIONALE
Redoxon®Double Action is a dietary
supplement in the form of an effervescent
tablet, typically consisting of 1000 mg
vitamin C (ascorbic acid) and 10 mg zinc (as
zinc citrate), sold as an over-the-counter drug
in many countries of the world. It is indicated
for the prevention and treatment of vitamin
C and zinc deficiencies, during situations and
conditions with increased requirements or
increased risk of deficiencies. Symptoms of
the common cold are closely related to the
immune status of the host, and evidence
supports the separate administration of

34
S Maggini, S Beveridge, M Suter
High-dose vitamin C plus zinc for the common cold
vitamin C and zinc. Therefore, an evaluation
of the effect of 1000 mg vitamin C plus 10 mg
zinc on the duration of the common cold and
the intensity of cold-related symptoms
appeared to be appropriate. Consequently,
two preliminary, double-blind, randomized,
parallel-group, placebo-controlled clinical
studies were carried out to evaluate
effervescent tablets containing a daily dose of
1000 mg vitamin C plus 10 mg zinc (as zinc
citrate) in patients with the common cold.b,c
Details of the two studies are summarized in
Table 2. Both studies were conducted in
accordance with the principles outlined in the
Declaration of Helsinki, and with Good
Clinical Practice.
STUDY 1
Aims
A double-blind, randomized, placebo-
controlled pilot study was conducted in
patients with common-cold symptoms, who
received either 1000 mg vitamin C plus 10 mg
zinc (one effervescent tablet daily, consumed
in the morning) or a matching placebo.b
Patients and methods
Participants were enrolled consecutively by
general practitioners, and treatment lasted
for 5 days (Table 2). Standard demographic
data were collected at baseline. Each day,
between day 0 and day 5, participants were
required to fill in a self-evaluation booklet.
Self-assessment
Patients were required to evaluate the
intensity of the usual symptoms of the
common cold (rhinorrhoea, sneezing, cough,
laryngeal irritation, myalgia, headache,
overall nasal obstruction/congestion and eye
watering) every day in a self-evaluation
booklet. Global assessment of the discomfort
due to their symptoms was to be documented
every day using a visual analogue scale
(VAS) of 100 mm (0 mm, no discomfort; 100
mm, maximum possible discomfort).
Discomfort caused especially by rhinorrhoea,
sneezing, cough, laryngeal irritation,
myalgia, headache, overall nasal
obstruction/congestion, and watering of the
eyes, was additionally assessed daily on a
verbal rating scale (very severe; severe;
moderate; mild and none).
Investigator assessment
Common-cold symptoms (rhinorrhoea,
cough, laryngeal irritation, myalgia,
headache, rectal temperature) were
evaluated on day 0 and day 6 by the
investigator (rectal temperature was
measured; other symptoms evaluated with
‘Yes’ or ‘No’).
Tolerance of the investigational product
was assessed by the incidence of adverse
events; this was researched by asking open
questions. If any adverse events were
observed during the course of the study, the
investigator had to note these in the case
report form including the nature, onset,
intensity, evolution, causality assessment
and actions taken.
Results
The study included 30 patients: 13 males and
17 females. The 1000 mg vitamin C plus 10
mg zinc group included 14 patients (five
males, nine females; mean ± SD age 37 ± 17
years; mean ± SD body mass index [BMI],
22.15 ± 2.90 kg/m2). The placebo group
included 16 patients (eight males, eight
females; mean ± SD age, 43 ± 15 years; mean
bData on file – Roche Consumer Health: Comparison of
the efficacy and tolerance of REDOXON ZINC and
placebo in the treatment of common cold. A double blind,
parallel groups, pilot study on 30 patients for 5 days;
1997. Clinical Report No. 16 51 55.
cData on file – Roche Consumer Health: Comparison of
the efficacy and tolerance of REDOXON ZINC and
placebo in the treatment of common cold. A double blind,
parallel groups, placebo controlled study on 64 patients
for 10 days; 1999. Clinical Report No. 16 52 12.

35
S Maggini, S Beveridge, M Suter
High-dose vitamin C plus zinc for the common cold
TABLE 2:
Summary of study protocol details from two preliminary studies with an effervescent
tablet containing 1000 mg vitamin C plus 10 mg zinc
Study 1 Study 2
Locations Study conducted by general Study conducted by general
practitioners in Saint Martin d’Hères, practitioners in Marseille and Angers
Domène and Meylan (France) (France)
Randomization • Treatment allocation according to randomization list provided by sponsor
method • Each treatment designated by its number
Inclusion criteria • Men or women > 18 years of age
• Symptoms of a simple, uncomplicated, without superinfection, common cold
with a bilateral and clear rhinorrhoea for < 3 days
• Rectal temperature < 38 °C
• Able to understand aims and constraints of study and complete self-evaluation
booklet
• Informed consent given
Exclusion criteria • Superinfected common cold (rectal temperature > 38 °C; and/or purulent
rhinorrhoea; and/or purulent expectoration)
• Pregnancy or breast-feeding, or delivery within 1 month before study
commenced
• Women of child-bearing potential who did not use any effective
contraceptive method
• Diagnosis of any disease that could decrease absorption or metabolism of trial
drugs
• Participation in another clinical study in previous 12 weeks
• Diagnosis of a psychological disease or disorder that could interact with
ability to understand aims and constraints of study, to give informed consent
or to present good compliance
• Currently taking any of the following drugs: aspirin, carbasalate calcium,
nonsteroidal anti-inflammatory drugs, steroids including inhaled steroids,
inhaled vasoconstrictors, antihistamines, anticongestants, parasympatholytics,
modulators of immunity, treatments containing zinc or vitamin C
Patient consent • Written, informed consent obtained during enrolment, after a clear
explanation of study aims and constraints, and before treatment allocation
Ethics committee • Reviewed and approved by Independent Ethics Committee of Nantes (France)
approval
Statistical • Nonparametric variables described by absolute and relative frequencies
analyses • Parametric variables described by means, standard deviation, minimum,
maximum and median
Intergroup comparisons tested by:
• Wilcoxon’s rank sum test for categorical variables
• χ2-test or Fisher’s exact test for Boolean variables
Evolution of symptoms and global discomfort tested by:
• Analysis of variance on ranks for repeated measures with two factors (time
and treatment)
Details of statistical software were not available for either study

36
S Maggini, S Beveridge, M Suter
High-dose vitamin C plus zinc for the common cold
± SD BMI 23.25 ± 3.32 kg/m2). No
demographic differences between the two
groups were observed at baseline. An
effervescent tablet containing 1000 mg
vitamin C plus 10 mg zinc was found to
reduce the mean duration of rhinorrhoea by
27% when compared with placebo (mean ±
SD 4.14 ± 1.88 versus 5.25 ± 1.34 days,
respectively). The difference did not reach
statistical significance due to the small
number of patients studied and the short
treatment period. The course of other local
symptoms was not different between the two
groups. The tolerance was very good.
STUDY 2
Aims
A larger double-blind, randomized, placebo-
controlled, pilot study was conducted in
patients with common-cold symptoms who
were given either 1000 mg vitamin C plus 10
mg zinc or placebo.c
Patients and methods
Participants were enrolled by general
practitioners and treatment lasted for 10 days.
Inclusion criteria and standard assessments
were identical to those of Study 1 (Table 2).
Participants were required to complete, daily,
the same self-evaluation booklet as in Study
2, between day 0 and day 10.
Self-assessment
Patients carried out the same self-
assessments as those in Study 1. In addition,
in Study 2 the intensities of rhinorrhoea,
sneezing and cough were assessed on a VAS
of 100 mm (0 mm, no discomfort; 100 mm,
maximum possible discomfort).
Investigator assessment
Common-cold symptoms (rhinorrhoea,
cough, laryngeal irritation, myalgia,
headache, rectal temperature) were
evaluated on day 0 and day 11 by the
investigator (rectal temperature was
measured; other symptoms evaluated with
‘Yes’ or ‘No’). Tolerance was assessed by the
incidence of adverse events, recorded by
asking open questions.
Results
The study enrolled 64 patients: 25 males and
39 females. The 1000 mg vitamin C plus 10
mg zinc group included 32 patients (15
males, 17 females; mean ± SD age 37 ± 12
years; mean ± SD BMI 24.16 ± 4.56 kg/m2).
The placebo group included 32 patients (10
males, 22 females; mean ± SD age 41 ± 15
years; mean ± SD BMI 23.39 ± 4.24 kg/m2).
No demographic differences were observed
between the two groups at baseline.
Although 1000 mg vitamin C plus 10 mg
zinc reduced the mean duration of
rhinorrhoea by 9% when compared with
placebo (mean ± SD 5.63 ± 2.54 versus 6.13
± 2.20 days, respectively), the difference did
not reach statistical significance. With
TABLE 2 (continued):
Summary of study protocol details from two preliminary studies with an effervescent
tablet containing 1000 mg vitamin C plus 10 mg zinc
Study 1 Study 2
Statistical Additional intergroup comparisons
analyses tested by:
(continued) • Student’s t-test or Wilcoxon’s rank sum
test in case of continuous variables
depending on the distribution

37
S Maggini, S Beveridge, M Suter
High-dose vitamin C plus zinc for the common cold
regard to the relief of discomfort due to nasal
obstruction, active treatment was more
effective than placebo at day 3 (P= 0.05).
The discomfort due to rhinorrhoea was also
significantly lower in the active treatment
than the placebo group at day 3 (P= 0.04).
POOLED ANALYSES
Since the protocols of the two pilot studies
were similar,b,c individual data were pooled
and overall analyses were performed
retrospectively.dThere were 46 patients in the
active treatment (1000 mg vitamin C plus 10
mg zinc) group and 48 in the placebo group
at day 0 in the pooled analyses. The groups
were comparable at day 1 and each
participant was diagnosed with an
uncomplicated common cold with clear,
bilateral, rhinorrhoea.
It was found that the rate of definite relief
from rhinorrhoea was significantly higher in
the active treatment group than in the
placebo group over the 5-day assessment
period (P= 0.03, Cox proportional hazards
model). The percentages of asymptomatic
patients with respect to rhinorrhoea (i.e.
definite relief) are plotted in Fig. 1. Active
treatment began to show a benefit relative to
placebo at day 3, and the difference between
groups continued to widen at days 4 and 5.
The relief was quicker in the active treatment
group, reaching statistical significance (P=
0.001, Cox proportional hazards model at
day 4).
The course of the other local symptoms
(i.e. relief from laryngeal irritation, cough,
sneezing, headache and overall nasal) was
not different between the two groups over the
5 days. Nevertheless, the active treatment
group had significantly greater relief from
dData on file – Roche Consumer Health: An overview of two
randomised placebo controlled studies to determine the
efficacy and tolerance of REDOXON ZINC in the treatment
of common cold; 1999. Clinical Report No. 16 52 13.
FIGURE 1: Pooled analysis showing the percentage of patients with a common cold
who did not experience rhinorrhoea (i.e. asymptomatic) during once-daily treatment
with either placebo effervescent tablets or effervescent tablets containing 1000 mg
vitamin C plus 10 mg zinc. Rate of definite relief from rhinorrhoea was significantly
higher in the active treatment group than in the placebo group over the 5-day
assessment period (P= 0.03, Cox proportional hazard model)
1000 mg vitamin C + 10 mg zinc
Placebo
60
50
40
30
20
10
00 1 2
Treatment period (days)
Asymptomatic patients (%)
345

38
S Maggini, S Beveridge, M Suter
High-dose vitamin C plus zinc for the common cold
some related symptoms, e.g. nasal
obstruction at day 2, overall discomfort due
to sneezing and overall evolution of eye
watering (P= 0.02 for all three symptoms,
analysis of variance; data not shown).
Table 3 shows the number of patients in
each treatment group, the severity of
rhinorrhoea symptoms (very severe, severe,
moderate, mild and none) and the
percentage of patients with no rhinorrhoea
from day 0 to day 5.
In the pooled analyses,d active treatment
was more effective than placebo in terms of
the relief of rhinorrhoea during the first 5
days of treatment. Discomfort due to nasal
obstruction, sneezing and eye watering was
also less pronounced in the active treatment
group. Although the pooled analyses were
retrospective, their findings strongly suggest
the benefits of combination treatment with
1000 mg vitamin C and 10 mg zinc on the
most obvious symptom of upper respiratory
infection, namely rhinorrhoea. In both pilot
studies,b ,c a reduction of rhinorrhoea
duration was seen (between 9% and 27%),
but this reduction did not reach statistical
significance compared with placebo. These
findings are in contrast to the 2011
Cochrane review, which reported that the
therapeutic use of vitamin C after the onset
of the common cold did not ameliorate its
symptoms.47 The difference may be due to
the short duration of some of the studies in
the Cochrane meta-analysis (3 days only),47
the high dose of vitamin C (1000 mg) used in
the two pilot studies and/or the presence of
zinc in the active treatment used in these two
studies. While supportive data for zinc
lozenges and syrup on cold symptoms exist,
no such data for zinc administered in the
1000 mg vitamin C plus 10 mg zinc, n= 46
Severity of rhinorrhoea Day 0 Day 1 Day 2 Day 3 Day 4 Day 5
Very severe 16 9421 1
Severe 14 11 642 1
Moderate 13 21 21 20 15 12
Mild 2210 11 11 9
None 135917 23
Asymptomatic patients, % 2.2 6.5 10.9 19.6 37.0 50.0
Placebo, n= 48
Day 0 Day 1 Day 2 Day 3 Day 4 Day 5
Very severe 10 52211
Severe 13 13 9745
Moderate 24 27 25 21 20 11
Mild 02513 16 18
None 1175713
Asymptomatic patients, % 2.1 2.1 14.6 10.4 14.6 27.1
Statistical significanceaNS NS NS NS P= 0.04 P= 0.05
Data presented as number of patients unless stated otherwise.
a1000 mg vitamin C plus 10 mg zinc versus placebo; analysis of variance.
TABLE 3:
Severity of rhinorrhoea in patients with a common cold receiving once-daily treatment
with either placebo effervescent tablets or effervescent tablets containing 1000 mg
vitamin C plus 10 mg zinc for 5 days (pooled analyses, two preliminary studies)

39
S Maggini, S Beveridge, M Suter
High-dose vitamin C plus zinc for the common cold
form of an effervescent tablet have been
reported to date. Thus, these findings for
1000 mg vitamin C plus 10 mg zinc merit
further investigation.
The active treatment was very well
tolerated in both pilot studies. This is in line
with the results from the general
literature26,47,58 and was expected, since the
levels of vitamin C and zinc in the product
(i.e. 1000 mg vitamin C plus 10 mg zinc) are
below the respective upper tolerable levels
for chronic intake.58 – 60
Health issues in the 21st
Century
Old, new or re-emerging infectious diseases
continue to be major health issues, despite
great advances in medicine (including the
establishment of strong healthcare systems
in various parts of the world, the
development of vaccines and a number of
other therapeutic options).61 Infectious
disease is the leading cause of death
worldwide and is the third leading cause of
death in the USA.62 In recent decades,
pathogenic infectious diseases have emerged
including acquired immunodeficiency
syndrome, multidrug-resistant tuberculosis,
avian63 – 67 and swine68,69 flu and tick-borne
diseases,70 – 72 all of which represent
substantial global threats to human health.
While multiple factors determine whether
an individual will become unwell, the
immune system remains the first line of
defence against all external pathogens and
noxious insults. Immune defences constantly
protect the human body against fungi,
bacteria, viruses and internal threats such as
cancer cells. Over millions of years, the
human-defence arsenal has coevolved to
meet various attackers and now ranges from
simple physical barriers (e.g. skin, mucosa)
to sophisticated cells as well as biological
and chemical defences (e.g. antibodies,
cytokines and free radicals).73 – 76
Vitamin C and zinc hold central positions
among the micronutrients required to ensure
proper immune function.2,3 Data from
clinical studies demonstrate that the separate
administration of either vitamin C47or zinc26
results in a reduction in the duration and
severity of common-cold symptoms in
otherwise-healthy individuals. Vitamin C is
typically consumed at doses > 200 mg as a
prophylactic measure, and this regimen
consistently leads to a reduction in cold
duration.47 There appears to be no preventive
effect of vitamin C regarding the incidence of
the common cold, with the exception of
patients undergoing heavy physical stress
(i.e. work, sport, those working in low
temperatures).3,47 Zinc is beneficial for
alleviating symptoms of the common cold
when administered in the form of lozenges
(10 – 23 mg, 5 – 8 times daily) or syrup (10 –
30 mg/day) and taken within 24 h of the
onset of symptoms.26 However, some
formulations – particularly lozenges –
produce adverse events such as nausea.26
The functional interdependence of vitamin
C and zinc – and their complementary roles
in immune support, resistance to infectious
diseases and health maintenance – indicate
that there is a strong rationale for using them
in combination. The effects of a combination
product containing 1000 mg vitamin C and
10 mg zinc were investigated in two
preliminary, double-blind, randomized,
placebo-controlled clinical studies conducted
in patients with symptoms of the common
cold. There were a number of reasons for
choosing the common cold as a model for
infectious disease. First, it is the most
common human disease. Secondly, it is self-
limited, is in general uncomplicated and is
effectively dealt with by the host’s immune
system. Thirdly, considerable support is
available in the literature for the separate use

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• Revised accepted 18 November 2011
Copyright © 2012 Field House Publishing LLP
40
S Maggini, S Beveridge, M Suter
High-dose vitamin C plus zinc for the common cold
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Conflicts of interest
S Maggini and S Beveridge are employed by
Bayer Consumer Care Ltd, a manufacturer of
multivitamins. M Suter is a retired employee of
Roche Consumer Health, a company acquired
by Bayer Consumer Care Ltd in 2005.

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Author’s address for correspondence
Dr Silvia Maggini
Bayer Consumer Care Ltd, Peter-Merian-Strasse 84, Postbox 4002, Basel, Switzerland.
E-mail: silvia.maggini@bayer.com