for Exercise Physiologists
Vol 1 No 2 July 1998
Nutrition and Exercise
C supplementation and upper respiratory tract infections in marathon runners
SHARON A. HIMMELSTEIN, ROBERT A. ROBERGS,
KATHLEEN M. KOEHLER, SHARON L. LEWIS, CLIFFORD R. QUALLS
Center for Exercise and
Applied Human Physiology, Clinical Nutrition Program, Nursing and Pathology,
and Clinical Research Center, University of New Mexico, Albuquerque, NM
S. A. , Robergs, R. A., Koehler, K. M., Lewis, S. L., & Qualls, C.
R. Vitamin C supplementation and upper respiratory tract infections in
marathon runners. JEPonline
1, No. 2, 1998.
This study was funded in
part by a grant from the University of New Mexico Clinical Research Center:
MO1-RR-00997 1994, and from the University of New Mexico, College of Education,
1994 Graduate Research, Project and Travel Grant. ABSTRACT The purpose
of this study was to determine whether vitamin C supplementation reduces
the incidence of upper respiratory tract infections (URTIs), and attempt
to explain the variability in URTIs among marathon runners and sedentary
subjects. Marathon runners (n=44) and sedentary subjects (n=48) were randomly
assigned either 1,000 mg vitamin C or a placebo daily for two months prior
to and one month following a marathon race. Baseline (pre-supplementation)
plasma vitamin C concentrations were higher among the vitamin C treated
runners (VR, n=30) and placebo treated runners (PR, n=14) (78.5 ±2.7
and 84.0 ±3.6 mmol/L, respectively) compared to vitamin C treated
sedentary (VS, n=23) and placebo treated sedentary (PS, n=25) subjects
(61.1±4.7 and 52.8 ±5.0 mmol/L, respectively). Vitamin C
concentrations increased with supplementation (81.0±2.1 mmol/L for
VR and 72.6 ±2.9 mmol/L for VS). No treatment differences were found
for URTI incidence (33.3%, 42.9%, 43.5%, and 32.0% among VR, PR, VS, and
PS, respectively). Multiple logistic regression revealed the following
factors to be significantly related to an increased risk of URTIs: (1)
faster training pace, (2) greater number of marathons run, (3) shorter
distance for the longest run of the week, and (4) female gender. The data
indicate that vitamin C supplementation of 1,000 mg/day did not decrease
the incidence of URTIs in marathon runners. Training and gender were more
influential than vitamin C supplementation in explaining the incidence
ASCORBIC ACID, RUNNING, GENDER, TRAINING
Exercise is accompanied by hormonal and
immunological changes that are associated with psychological stress. Psychological
stress has been associated with an increase in susceptibility to the common
cold (1,2). Similarly, prolonged exercise
results in an increased risk of upper respiratory tract infections (URTIs)
High intensity, long endurance exercise such as marathon running has been
shown to suppress immune function (6). In particular,
the incidence of URTIs has been shown to be dramatically increased among
marathon and ultramarathon runners prior to and following competition (4,5,7).
Currently, it is unclear what mechanism
is responsible for an increased risk of URTIs following heavy training
and competition. Endurance exercise results in a transient decrease in
natural killer cell activity which has been suggested as a potential mechanism
for the increased susceptibility to URTIs during the post-exercise period
Other potential mechanisms offer somewhat less satisfactory explanations
and less research evidence, such as findings of reduced salivary immunoglobulin
A levels in athletes (8) or decreased serum interferon
Many athletes and non-athletes alike take
vitamin C supplements in an attempt to ward off the common cold. In general,
studies of vitamin C supplementation by athletes and non-athletes have
shown mixed results, with little or no decrease in incidence of URTIs (10-14),
a decreased incidence of URTIs (7), and a relatively
small reduction in the duration of a cold (10-12,14,15).
Peters et al. (7) presented
the most convincing evidence for vitamin C supplementation to decrease
the incidence of URTIs. These authors presented data that indicated that
vitamin C supplementation of 600 mg decreased the incidence of URTIs in
ultrarunners by 50%. However, several faults were inherent in the design
of this study. Incidence of URTIs was based on telephone interview without
clinical substantiation, a moderate supplementation of 600 mg/day of vitamin
C was used without control of self-supplementation, only two female subjects
completed the study, and the high incidence of URTIs in the sedentary subjects
was not explained.
The conflicting research on vitamin supplementation
and the incidence of URTIs, combined with the many flaws evident in past
research, indicated to us that additional research was needed on whether
vitamin C supplementation influenced the incidence and duration of URTIs.
Therefore, the intent of the present study was to determine the effects
of vitamin C supplementation on the incidence of URTIs in marathon runners.
A secondary purpose of this study was to identify factors, other than vitamin
C supplementation or plasma vitamin C concentrations, that are associated
with increased risk of URTIs.
The participants were recruited from all
registered participants in the Duke City Marathon (Albuquerque, NM, elevation
= 5,000 ft above sea level), which was held on September 11, 1994. An age
and gender-matched sedentary group was obtained by including friends and
coworkers of the marathon runners whenever possible. Sedentary subjects
did not regularly participate in any aerobic exercise, as determined by
Initially, 104 potential marathon runners
and 87 sedentary subjects agreed to participate. Of these, 137 read and
signed an informed consent approved by the University Medical School Human
Subjects Review Committee prior to enrollment in the study. The subjects
were randomly assigned into either the vitamin C or the placebo treatment
(n = 52 for both VR and PR, n = 42 for VS and n = 45 for PS). Of the 137
subjects who consented to participate, only 92 subjects completed the study
(VR = 30, PR = 14, VS = 23, PS = 25). Reasons for drop out included injury,
relocation, side-effects to supplementation, time constraints, and poor
compliance with supplementation as determined from a pill count performed
at the end of the study.
A double-blind, placebo-controlled design
was used to determine the influence of vitamin C supplementation on the
incidence of URTIs among marathon runners and sedentary subjects during
the two months prior to and one month following the marathon. Data collected
during the study included demographic and training history data, vitamin
C intake, a training and URTI symptom log, plasma vitamin C concentrations,
and lymphocyte proliferation.
Data were collected at baseline (BL) which
corresponded to two months prior to the marathon, one week prior to the
marathon (PRE), and at two days (POST1) and 1 month (POST2) after the marathon.
Randomization of subjects to the vitamin C (VC) and placebo (PL) groups
was conducted at BL.
Questionnaires were distributed to the
subjects by a combination of mail delivery or in person at BL.
Vitamin C Intake
Usual dietary intake was determined at
BL using the Health Habits and History Questionnaire: Diet History and
Other Risk Factors Dietary Analysis System (HHHQ-DIETSYS Analysis Software,
Version 3.0, National Cancer Institute, 1993). Completed questionnaires
were computer scored by Survey & Ballot Systems, Inc. (Eden Prairie,
MN). The dietary questionnaire was modified to include foods commonly eaten
in the Southwest that are high in vitamin C (16-18).
Any vitamin C supplement use was also recorded.
Subjects were restricted to no more that
200 mg/day vitamin C self-supplementation during the study period. However,
vitamin C supplementation was not controlled prior to the start of the
Upper Respiratory Tract Infections
Symptoms and duration of URTIs were assessed
throughout the study period using a semi-quantitative list of respiratory
symptoms (Hoffman-LaRoche, Nutley, NJ). Subjects were asked to fill out
the respiratory symptoms report sheet on each day that they had a runny
nose, cough, or sore throat. In addition, subjects were encouraged to report
to the nurse practitioner at Urgent Care at the University Hospital for
diagnosis of URTI when they suspected that they had a cold to provide clinical
evidence of URTI. Only one subject pursued this option; therefore this
part of the study was not included in the analysis.
Incidence (total number of cases), duration,
and the percentage of subjects in each treatment group with at least one
URTI during the two months prior and one month following the marathon were
determined from the respiratory symptoms log data. The severity score was
determined by summing the severity of any symptoms present for each day
of a cold on a scale of 0 (not present), 1 (mild), 2 (moderate), and 3
(severe). Symptoms included: cough, nasal discharge, sneezing, stuffy nose,
sore throat, headache, malaise, chilliness, shaking chills, fever, hoarseness,
aching muscles or joints, or watery or burning eyes.
Running logs were developed based on similar
logs used by Nieman et al. (4) to determine training
mileage and intensity. Each subject was given a training log for the two
month period prior to and one month period following the race. Subjects
were instructed to log their training distances and running times daily.
Additional descriptive data, such as prior running history and marathon
experience were also collected.
Body fat was determined from anthropometric
measurements at BL for sedentary subjects using the equation of Durnham
and Womersley (19), and for runner subjects using the
equation of Jackson and Pollock (20,21).
Vitamin C Supplementation
Subjects were instructed to take two tablets
of either vitamin C (500 mg/tablet) or placebo (similar looking and tasting
tablets containing lactose) (Hoffman-La Roche, Nutley, NJ) each morning
with breakfast; and specifically at 8 a.m. on the mornings of the day immediately
prior to blood draws. Supplementation continued from BL to POST2.
Blood samples were only obtained from
a subset of volunteers from each research group, as only the local runners
had access to our testin facilities. Volunteer subjects reported to the
University Clinical Research Center (CRC) after a 12 hour fast and prior
to the ingestion of the daily supplement. Blood samples were obtained by
phlebotomy performed on an antecubital vein. Samples of 5 mL were used
for vitamin C, and a 7 mL sample was obtained from the subset of subjects
randomly selected for lymphocyte proliferation measurements. For subjects
from groups VS, PS, and PR, blood was obtained at BL and PRE. For subjects
from the VR group, blood was obtained at BL, PRE, and POST1.
Blood samples were immediately centrifuged
at 4 degrees C, and plasma was removed and stored at -80 degrees C for
subsequent assay for vitamin C. Plasma vitamin C was determined by an automated
procedure using 2,6 dichloroindophenol (22-23).
Blood samples for lymphocyte proliferation were delivered to Spectra Cell
Inc. (Houston, TX). Samples were exposed to the mitogen PHA (2 ug/mL) and
incubated for four days. Tritiated thymidine is then added and the lymphocytes
were cultured for 24 hours (24-26),
resulting in a measure of lymphocyte proliferation expressed as cpm x 10-3.
Assays of lymphocyte proliferation were performed on 8 VR and 8 PR subjects
at BL and PRE.
The Statistical Analysis System (SAS Institute,
Cary, NC) was used to perform the statistical analyses. McNemar's test
was used to determine whether subjects knew which treatment they were on.
Incidence (total number and % of subjects),
duration, and severity of URTIs in each subject group were assessed by
one-way ANOVA. Mean differences for URTIs were assessed by t-test. Fisher's
Exact Test was performed on the marathon runners and sedentary subjects
to determine whether there were any treatment differences in the number
Multiple logistic regression was used to
determine the factors associated with an increased incidence of URTI. While
the study subjects actually received the supplements for a total of 92
days (3 months), for analytical purposes, only days 7 through 90 of the
intervention were counted in the logistic regression. The entire 3 months
(BL to POST2) of the study was used in the determination of duration and
severity of colds. Finally, any colds which occurred on marathon day were
considered to occur after the race.
Repeated-measures three factor (runner
versus sedentary, vitamin C versus placebo, and PRE versus POST1) ANOVA
were performed on the plasma vitamin C data. Mean differences were either
performed using paired comparisons using specific error terms from ANOVA,
or by t-tests for variables at BL. Repeated-measures two factor (vitamin
C versus placebo, and PRE versus POST) ANOVA were performed on the lymphocyte
proliferation data. Mean differences were assessed as previously described.
Data are reported as mean ±SD.
Spearman partial correlation coefficeints
were used to determine the relationship between dietary, supplemental,
and total vitamin C intake and BL plasma vitamin C concentrations.
Demographics and Running History
Subject characteristics are shown in Table
1. Based on data of running history, the subjects of this study were moderately
trained marathon runners, with a large range of previous marathon experience
and performance times.
Table 1. Subject characteristics
at baseline (data are expressed as mean±SD).
|Vitamin C Treated
||42 ± 5.4
||24 - 64
||44 ± 4.9
||22 - 65
|177 ± 6
166 ± 7
157 - 175
|180 ± 6
167 ± 4
|168 - 198
157 - 175
|73.6 ± 10*
57.9 ± 3.9*
|55.3 - 97.5
51.3 - 63.5
|87.0 ± 20.8
67.7 ± 13.7
|59.0 - 130.0
49.9 - 94.3
|Body fat (%)
|14.3 ± 6.2*
22.6 ± 4.5*
|4.6 - 22.0
17.9 - 30.5
|27.3 ± 7.2
35.8 ± 6.9
|14.0 - 38.0
25.0 - 47.0
|47.4 ± 2.9
||13 - 113
|Longest Run of
|18.9 ± 7.7
||8.1 - 35.5
|11.0 ± 1.4
||6.0 - 15.3
|Years of Running
||13.4 ± 4.6
||3 - 32
|205.5 ± 29.6
||137 - 299
|16.9 ± 19.5
||0 - 140
^33 of the 44 runners had
previously completed a marathon
#data from training logs
completed during the study
Attrition and Compliance
Since fewer PR completed the study compared
to VR, an analysis of the number of dropouts (after giving informed consent)
was performed and revealed no significant treatment or running group differences
(Fisher's Exact test, p = 0.08).
Compliance with the study was determined
by performing a pill count for each subject (n = 94). The pill count revealed
that two subjects, both VS, had taken less than 60% of the study supplements.
This finding was vastly different from the remainder of the study subjects
and a post-hoc decision was made to drop them from the analysis (final
sample size = 92).
No significant differences between treatment
groups were found in the number of tablets left over at the end of the
study (beyond extras) (Kruskal-Wallis nonparametric test, p = 0.13). PR
and VR had 9.9 ± 16.3 and 4.0 ± 5.4 supplements left, respectively,
at the end of the study while PS and VS had 7.7 ± 11.4 and 14.9
± 18.5 tablets left, respectively. Subjects were queried regarding
which treatment they believed that they were taking during follow-up appointments
at the CRC or by questionnaire (data not shown). Subjects without any idea
which treatment they were on were excluded from this analysis. In the sedentary
group, no significant differences were found between actual and believed
treatment (McNamara's test, p = 0.51 for sedentary group). In contrast,
more of the marathon runners tended to be wrong when asked which treatment
they believed that they were on (p = 0.07 for runners). In particular,
more VR believed that they were on placebo.
Vitamin C Intake
Estimated usual dietary intake of vitamin
C over the past year was determined on the 135 subjects who were recruited
at BL. Six subjects were excluded from the dietary analysis due to questionable
accuracy of their responses.
ANOVA was performed for dietary, supplemental,
and total intake of vitamin C (Table 2). Logs of actual intake were used
due to unequal variances in the untransformed values. In order to avoid
performing logs on zeros, the log (x + 1) was used for supplemental vitamin
C. Supplemental vitamin C refers to self-selected vitamin C supplementation
prior to study intervention.
Table 2. Data of mean (±SD)
estimated usual dietary, supplemental, and total intake of vitamin C (mg/day)
for the year prior to the study.
||207 ± 131*
||169 ± 112*
||210 ± 203
||149 ± 80
||234 ± 423
||209 ± 518
||102 ± 293
||78 ± 212
||442 ± 457
||378 ± 518
||312 ± 360
||227 ± 226
Although no significant difference
was found for treatment group (vitamin C versus placebo), a treatment-by-gender
interaction was found for dietary vitamin C (p = 0.03) (153 ± 87
mg and 176 ± 126 mg for placebo-treated males and females respectively,
and 229 ± 176 mg and 149 ± 104 mg for vitamin C-treated males
and females, respectively). Thus, the placebo-treated females had a higher
intake of vitamin C than the placebo-treated males, whereas the vitamin-C
treated males had a higher intake of vitamin C than the vitamin C-treated
females. ANOVA of total vitamin C intake (supplemental plus dietary intake)
revealed a significant difference between the marathoners and the sedentary
subjects for total vitamin C intake (p = 0.02). As shown in Table 2, the
marathon runners had a higher total intake of vitamin C compared to sedentary
Plasma Vitamin C
Among the runners, 33 subjects had blood
drawn at BL, Post1, and Post2 (25 VR and 8 PR). ANOVA of BL and Post1 vitamin
C concentrations revealed a significant effect for running category (marathoners
versus sedentary subjects) (p = 0.0001) and for treatment-by-running category
(p = 0.03), whereas no effect was found for treatment alone (p = 0.10)
(Figure 1). Thus, a treatment effect was found, but it differed between
the runners and the sedentary subjects. For VR subjects, BL versus Post1
vitamin C concentrations were not significantly different (p = 0.12) whereas
Post1 vitamin C concentrations were significantly different from Post2
(repeated measures ANOVA, p = 0.04).
Figure 1. The
change in plasma vitamin C concentrations for the subjects of each group
during the study phases. At baseline, runners (VR and PR) had significantly
higher plasma vitamin C than sedentary subjects (* p<0.05). The change
in plasma Vitamin C from supplementation between baseline and post-race
was significantly different between VR and PR (* p<0.05). Note, that
pre-race blood samples were obtained between two to eight days pre-marathon,
and post-race data were collected two days following the marathon.
The relationship between usual dietary
intake and total intake of vitamin C and baseline plasma vitamin C concentrations
were examined in 92 subjects with available data (including dropouts from
the study). Dietary and total vitamin C intake were positively related
to BL plasma vitamin C concentrations (Spearman correlation coefficients
r = 0.32, p = 0.01 and r = 0.35, p = 0.001, respectively). However, supplemental
vitamin C intake was not significantly related to baseline plasma vitamin
C concentrations (r = 0.20, p = 0.006). The results were similar when the
data were adjusted for gender.
Upper Respiratory Tract Infections
Fifty-three cases of URTIs were reported
during the study, 31 among vitamin C-treated subjects (15 VR and 14 VS)
and 25 among placebo-treated subjects (12 PR and 12 PS). Fisher's Exact
Test revealed no differences in reported URTI incidence between the four
treatment groups (p = 0.79). When treatment alone was examined by combining
the runners and sedentary subjects, no differences were found in reported
URTI's (p = 1.0).
Duration and Severity of URTI Symptoms
The ANOVA of the duration of URTI symptoms
revealed no differences between running groups (marathoners versus sedentary
subjects) (p = 0.46) or treatment groups (p = 0.41). However, a significant
treatment-by-running group effect was found (p = 0.02). Among the marathon
runners, a significant treatment difference was found for the duration
of URTI symptoms (t-test, p = 0.01), with VR having a longer duration of
URTI symptoms than PR (Table 3). By contrast, no treatment difference was
found among the sedentary VS and PS subjects for duration.
Table 3. Data of the incidenceof
URTIs for the subject groups.
||5.4 ± 3.5*
||42.6 ± 28.7
||2.7 ± 2.1
||17.8 ± 26.0
||2.5 ± 1.1
||16.1 ± 14.6
||4.2 ± 3.5
||37.4 ± 52.7
See Table 2 for
the definitions of group code abbrevations.
*p<0.05 from PR
^some subjects had more
than one URTI
Analysis of the number of symptoms revealed
no running group effect (p = 0.83) or treatment difference (p = 0.43),
but did find a running group-by-treatment interaction (p = 0.02). A significant
treatment difference was found for the number of symptoms for runners (t-test,
p = 0.01), with VR reporting more symptoms than PR . Among the sedentary
subjects, no treatment difference was found for the number of symptoms
(t-test, p = 0.23).
URTI incidence was examined for the two
weeks immediately following the marathon. Seven marathon runners (15.9%
of the runners) reported URTIs during these two weeks, whereas only four
sedentary subjects (8.3% of the sedentary subjects) had cold symptoms during
this time period (Fisher's Exact test, p = 0.34). When the marathoners
and sedentary group were examined together 12.0% had cold symptoms during
the two weeks following the race (95% confidence interval from 6.1 to 20.4%).
However, no treatment differences were found in the number of reported
URTIs during the two weeks following the marathon when the marathoners
and sedentary group were examined together (Fisher's Exact test, p = 0.19).
Interestingly, no URTIs were reported among the sedentary group during
the week immediately following the marathon, whereas four (three VR and
one PR) marathon runners (9.1% of the runners) reported URTIs during this
week (95% confidence interval from 2.0 to 18.9%).
Logistic regression revealed an increased
risk of colds with increasing age, and a reduced risk with increased alcohol
intake (Table 4). However, the majority of the subjects (82.6%) reported
drinking less than one drink per day, and only 4.4% reported drinking more
than 2 drinks per day. Therefore, this finding does not imply that drinking
large amounts of alcohol is of any benefit. No relationship was found between
training mileage and risk of cold symptoms. However, marathon runners that
reported a faster average training pace during the 12 weeks of the study,
as determined by daily running logs, had a significant relationship to
risk of cold symptoms (p = 0.04).
Table 4. Data from logistic
regressionfor select variables likely to influence the incidence of URTI's,
adjusted for month of the study.
||0.4 - 3.1
||1.0 - 9.6
|Number of Prior Marathons
||1.0 - 1.04
|Longest Run of Week
||0.8 - 1.0
||1.0 - 5.1
Additional factors among the marathon
runners which were related to risk of cold symptoms included the number
of marathons previously run, marathon personal best time, and the distance
of the longest run of the week (Table 4). Specifically, the more marathons
previously run, the slower the marathon personal best, and the shorter
the distance of the longest run of the week were related to increased risk
of URTIs. In addition, females were at greater risk of URTIs compared to
males. However, marathon personal best was no longer significant when gender
was added to the model, implying a relationship between these two factors.
Therefore, marathon personal best was omitted from the model.
No treatment or running group differences
were significant in any of the regression analyses. Furthermore, plasma
vitamin C concentrations following two months of supplementation were not
related to the incidence of URTIs using multiple logistic regression among
the sub-sample (n = 69, p = 0.22 for one week pre-marathon and p = 0.20
for two days post-marathon for marathon runners, p = 0.65 for sedentary
Vitamin C Supplementation and URTIs
The major finding of this study was that
vitamin C supplementation did not reduce the incidence of colds in VR compared
to PR during the two months prior to and one month following a marathon.
Similarly, vitamin C supplementation did not reduce the incidence of colds
among the sedentary subjects. However, comparison between R and S subjects
is complicated by additional differences such as body composition, as identified
in Table 1.
Our finding that vitamin C supplementation
had no effect on the incidence of colds is in agreement with the vast majority
of the literature (10,13,14,27-29).
In general, vitamin C appears to be ineffective in reducing the incidence
of colds, with the possible exception in cases of severe stress (7,28,30),
whereas it does seem to modify cold symptoms and severity (10,29,31).
Some authors have described this benefit of vitamin C supplementation as
marginal at best and not adequate to justify supplementation
(13,14). However, other researchers have stated
that the risks of vitamin C supplementation are negligible and the benefits,
including chronic disease prevention as well as possible effects against
the common cold, may warrant supplementation (32-34).
Nevertheless, no recommendation for vitamin C supplementation for the prevention
of URTIs prior to or after a marathon can be made based on results of the
Our findings are in contrast with those
of Peters et al. (7) who found that vitamin C supplements
reduced the incidence of URTIs by 50% in ultramarathoners. However, the
ultramarathoners had a much greater incidence of cold symptoms (68% in
the placebo group and 33% in the vitamin C group during the two weeks following
an ultramarathon) and a larger sample size (92 runners and 92 sedentary
subjects). Peters et al. (7) found no differences in
the duration of symptoms between the vitamin C-treated runners and the
placebo-treated runners, which is contrary to most of the literature on
vitamin C. In addition, the incidence of colds among non-runners was extraordinarily
high. In fact, there were more colds among vitamin C-supplemented non-runners
(53% of subjects) than vitamin C-supplemented runners (33% of subjects).
However, the duration of cold symptoms was shorter in the vitamin-C supplemented
non-runners compared to placebo-treated non-runners. The findings of Peters
et al. (7) are also surprising since they provided only
600 mg of vitamin C, did not control additional vitamin C supplementation,
and relied on subject recall of cold symptoms in a telephone interview
two weeks following the ultramarathon to determine incidence of URTIs.
On the other hand, the ultramarathoners ran greater distances than the
marathoners in the present study, and participated in a winter race, which
may have made them more prone to URTIs. In addition, the higher stress
of training among the ultramarathoners may have increased the likelihood
of benefiting from supplemental vitamin C.
In the present study, seven runners (15.9%)
and four sedentary subjects (8.3%) reported URTI symptoms during the two
weeks following the marathon. While not significantly different, this finding
suggests the possibility of increased cold symptoms following the marathon,
which is in agreement with other studies of marathon and ultramarathon
For example, Nieman et al. (4) found that 12.9% of marathoners
had cold symptoms during the week following the Los Angeles Marathon, while
9.1% of the runners in the present study reported cold symptoms during
the week following the marathon. Nieman et al. (4) reported
that 43.2% of the marathoners had URTIs during the two months before the
marathon, which is similar to our findings (33.3% of the vitamin C-treated
runners and 42.9% of the placebo-treated runners had cold symptoms during
the three month study). The finding that the runners in the present study
were not overtraining (Table 1) may also have reduced the likelihood of
finding any benefits with vitamin C supplementation.
Vitamin C Supplementation and Plasma
Vitamin C Concentration
Dietary and supplemental vitamin C intake
are shown in Table 2. Mean dietary intake of vitamin C was at or above
2.5 times the RDA for each of the groups. Runners had a significantly higher
mean dietary vitamin C intake compared to sedentary subjects. Runners also
tended to have a higher supplemental intake of vitamin C compared to sedentary
subjects, although there was greater variation in these data.
Another important finding of this study
was that usual estimated dietary and total vitamin C intake for the year
prior to the study were positively related to BL plasma vitamin C concentrations,
thus validating the food frequency questionnaire (HHHQ-DIETSYS).
An additional finding of this study was
that after supplementation VR and VS subjects had plasma vitamin C concentrations
in excess of 68.1 mmol/L (Figure 1). Levine et al. (35,36) showed a dietary
intake of about 200 mg/day produced about 80% plasma saturation. Further,
Levine et al. (35,36) also reported
that neutrophils, monocytes, and lymphocytes were saturated with only 100
mg of vitamin C. Data of vitamin C intake, including supplemental intake,
for all subjects revealed that average vitamin C intake was above 200 mg/day
and therefore would be close to plasma saturation. Therefore, since mean
plasma vitamin C was near plateau, additional vitamin C intake from the
intervention would not be expected to raise plasma concentrations substantially.
This was seen in Figure 1. Consequently, it is not surprising that supplementation
did not influence URTIs. Unfortunately, plasma vitamin C data were not
provided by Peters et al. (7). However, the subjects
of their study also had mean vitamin C intakes in excess of 200 mg/day.
Once again, based on the data of Levine et al. (35,36)
and also Garry et al. (23) it would seem unlikely that
the vitamin C supplemented subjects of the Peters et al.
(7) study should have benefitted from such large additional doses of
Other Factors Related to URTI Symptoms
In addition to vitamin C, other factors
have been reported to influence the incidence of URTIs in runners
(7,3,4). Therefore, the present
study examined demographic, dietary, and training parameters in an attempt
to explain the variation in incidence of URTIs in runners and sedentary
Logistic regression revealed an increased
risk of colds with increasing age, and a reduced risk with increased alcohol
intake. However, the majority of the subjects (82.6%) reported drinking
less than one drink per day, and only 4.4% reported drinking more than
2 drinks per day. Therefore, this finding does not imply that drinking
large amounts of alcohol is of any benefit.
No relationship was found between training
mileage and risk of cold symptoms, which is in contrast with other studies
For example, Nieman et al. found a two-fold increase in risk of URTIs in
runners that ran more than 97 km per week compared to runners who ran under
32 km per week. Our sample size may have been too small to find such an
effect (there were 2,016 runners in the study by Nieman et al.). In addition,
running mileage was noted to be rather low for marathon runners in the
present study (median 47 km , 75th percentile = 56 km). Nieman et al. (37)
proposed a U-shaped curve for the risk of acquiring colds versus exercise
level, where both very low and very high levels of exercise compromise
immune function while moderate exercise enhances immune function. Thus,
the moderate amount of training our subjects reported may have actually
improved their immune function.
Logistic regression showed that a faster
average training pace during the 12 weeks of the study, as determined by
daily running logs, was significantly related to risk of cold symptoms
(p = 0.04). As noted above with running mileage, the marathon runners did
not appear to be training excessively hard. The median running pace was
11.1 km/hr (with 50% of the subjects running between 10.2 and 11.9 km/hr).
Additional factors among the marathon runners
which were related to risk of cold symptoms included the number of marathons
previously run, marathon personal best time, and the distance of the longest
run of the week (Table 4). Specifically, the more marathons previously
run, the slower the marathon personal best, and the shorter the distance
of the longest run of the week were related to increased risk of URTIs.
In contrast, Nieman et al. (4) reported that runners
who had fewer years of running experience were at greater risk of colds
(p < 0.05). However, Nieman et al. (4) also found
that runners who ran fewer miles per week (NS) and (as in the present study)
ran a shorter distance during the average longest weekly run had a greater
risk of URTIs (p < 0.05).
Finally, it should be noted that this study
was conducted at moderate altitude (5,000 ft above sea level), and in a
hot and dry environment. Although subjects differed in their residential
altitude most participants in the marathon were local and resided between
3,000 to 7,000 ft. In remains unclear how the interaction between training
and chronic altitude exposure influences URTIs.
In summary, we found no apparent benefit
of vitamin C supplementation on the incidence of URTIs, despite excellent
compliance of the subjects with taking their supplements during the three
month study. Vitamin C supplementation did not significantly affect the
incidence of colds among marathon runners or sedentary subjects. In addition,
vitamin C supplementation did not decrease the duration or severity of
cold symptoms in the marathon runners, although it did reduce the severity
of colds in the sedentary subjects. However, only about 40% of the study
subjects succumbed to colds during the study and the marathon runners were
moderately trained, which may have enhanced rather than impaired immune
Based on the present study, vitamin C appears
to offer no benefit against the common cold in marathon runners. However,
the current study was based on a group of middle-aged New Mexican runners
who were not over-training based on an average weekly mileage of about
33 miles per week in the year prior to the study. Thus these results should
not be applied to people who are exposed to extraordinary amounts of physical
or psychological stress, such as elite athletes or ultramarathoners. Thus,
future research on the effect of vitamin C on colds should focus on more
highly stressed subjects, and ideally should include a larger sample size
and fewer dropouts. In addition, the inclusion of a higher proportion of
female subjects is desirable.
Other populations that warrant further
study to determine whether vitamin C might improve resistance against the
common cold or improve immunity include the elderly and the immune-compromised.
For example, recent studies have shown improved resistance against colds
in the elderly with a multivitamin/mineral supplement, but have not determined
which nutrients might be responsible (38-41). In addition,
vitamin C supplementation might play a role in other respiratory conditions
besides the common cold, such as in the treatment of asthma or bronchitis
authors gratefully acknowledge Hoffman-La Roche for providing the study
supplements, the staff of the University of New Mexico Clinical Research
Center for collecting blood samples and anthropometric data, Patricia Stauber,
M.P.H. and the staff of the Clinical Nutrition Program for conducting plasma
ascorbate assays, Beth Gautier for her assistance in organizing and running
the study, Bruce Hendrickson, Ph.D. for his excellent help with computer
programming, and the marathon runners and sedentary subjects for participating
in this study.
to: Robert A. Robergs,
Ph.D., c/o Center For Exercise and Applied Human Physiology, Johnson Center,
B 143, The University of New Mexico, Albuquerque, NM 87131; phone: (505)
277-2658; FAX: (505) 277-9742.
Note: No reprints
will be available from the authors.
This study was funded
in part by a grant from the University of New Mexico Clinical Research
Center: MO1-RR-00997 1994, and from the University of Nex Mexico, College
of Education, 1994 Graduate Research, Project and Travel Grant.
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