Vitamin C as effective as combinations of anti-oxidant nutrients in reducing symptoms of upper respiratory tract infection in ultramarathon runners

Vitamin C as effective as combinations of anti-oxidant nutrients in reducing symptoms of upper respiratory tract infection in ultramarathon runners. Peters, EM* M.Sc.(Med) Goetzsche, JM* B. PhysJJd Joseph, LE* M.Ed. Noakes, TD**(MBBCh, MD, FACSM) Abstract The effect of anti-oxidant supplementation on the inci dence of symptoms of upper-respiratory-tract infection (URTI) was determined during the fortnight following the 1993 Comrades Marathon (90km). Runners (n=178) and sedentary matched controls (n=162) were randomly divided into groups receiving 500mg Vit C (C; n=86), 500mg Vit C and 4001U Vit E (CE; n=90) or 300IU Vit E, 300mg Vit C and 18mg Beta Carotene (CEB; n=73) or placebo (P; n=93) daily for 21 days prior to participation in the ultramarathon. Total pre-race dietary vitamin and mineral intakes and post-race selfreported URTI symptoms were recorded in all subjects (n=340). The incidence of the URTI symptoms in P run ners (40.4%) was significantly higher (p<0.05) than that in C (15,9%) and CEB (20,0%) runners, and also greater than that in matched, non-running controls receiving placebo (24,4%). The group of runners reporting the lowest incidence of URTI symptoms during the post race period, had the lowest mean age and the highest (i) total mean daily Vit C intake (1004 mg); (ii) pre-race training status and (iii) percentage of black runners. This study suggests that Vitamin C alone is as effec tive as combinations of Beta Carotene, Vitamin E and Vitamin C in reducing the incidence of post-race URTI symptoms and that age, training status and genetic make-up also may influence the susceptibility to the development of URTI symptoms in ultramarathon runners. Key Words: Anti-oxidant Vitamins, Upper Respiratory Tract Infections, Ultramarathon Runners. * Division of Physical Education, University of the Witwatersrand, Johannesburg, South Africa. * * MRC Bioenergetics of Exercise Research Unit in the Sport Science Institute of South Africa, Medical School, University of Cape Town, South Africa. Correspondence: Edith Peters Division of Physical Education, University of the Witwatersrand, Johannesburs, 2001, South Africa. Tel: (011) 716-5718 Introduction Two separate epidemiological surveys performed on ultradistance runners1 ~ have reported an increased inci dence of symptoms of upper respirator}' tract (URTI) following participation in ultrainarathon events. A sub sequent study5 found that daily administration of 600mg Vitamin C for three weeks prior to the 90km Comrades Marathon, resulted in a significantly lower (p<0.05) incidence of symptoms of infection in runners during the fortnight after the race, compared to runners ingesting placebo. This was attributed to the anti-oxi dant properties of Vitamin C, which suggests that ath letes participating in prolonged exercise have an increased daily Vitamin C requirement. ' . Evidence from more recent studies45 is that the anti oxidant nutrients may be more effective when used in combination. The aim of this study was therefore to compare the efficacy of supplementation with combina tions of Vitamin E, Vitamin C and Beta Carotene and Vitamin C alone in reducing the incidence of post race URTI in ultra marathon runners. Method The protocol was approved by the Committee for Research on Human Subjects of the University of the Witwatersrand. Two hundred and twenty entrants for the 1993 Comrades Marathon volunteered to partici pate in the study. Each runner was matched (n=220) with a control of similar age who resided with the run ner, but did not participate in running regularly. A dou ble-blind, placebo-controlled study design was used in which the runners, in addition to their matched, nonrunning controls, were randomly divided into four groups. Each group received either anti-oxidant supple ments or placebos for three weeks prior to the race. The pre-race training status, state of health and dietary vit amin and mineral intake of athletes and their agematched controls was recorded by means of a question naire which each runner and control subject completed prior to the race. Demographic data including running distance per week, average running speed, number of weeks spent training and the number of other ultrama rathons in which the athlete had recently participated were also recorded, hi addition, the pre-race incidence of self-reported symptoms of URTI was documented. Runners with a history7of sinusitis, hay-fever or both were excluded. Each runner and matched control (n=55) was required to take three tablets of similar appearance daily. These contained either 500mg Vit C (C), 500mg Vit C & 400IU Vit E (CE), 300mg Vit C & 300IU Vit E, 18 mg Beta SPORTS MEDICINE MARCH 1996 23 Reproduced by Sabinet Gateway under licence granted by the Publisher (dated 2012.) Carotene (CEB) or lactose as placebo (P). The total daily vitamin A, C and E intakes including that derived from any additional vitamin and mineral used by the athlete of all subjects was determined by using the Dietary Manager computer programme (Program Management, Randburg, South Africa). For the purpose of this study, the total vitamin A, C & E intake of each subject was thus calculated from the sum of the (i) daily dietary intake, (ii) additional supple ments used and (iii) the anti-oxidant supplements given to the subjects. Two weeks after the race all runners and controls who had originally volunteered to participate in the study were telephonically interviewed and questioned regarding: (i) whether the prescription of supplements had been adhered to or not; (ii) the race distance cov ered and the time taken by each athlete to complete this distance; (iii) the incidence and duration of symp toms of URTI. The number and duration of self-report ed symptoms including sneezing, running nose, sorethroat, cough and fever were documented. All reports of trivial symptoms were excluded by including in the final analysis only reports of single URTI symptoms which lasted >1 (lay or a combination of at least 2 URTI symp toms each of which lasted < I day. The training status ratio of each runner was calculat ed from the following formula: Weekly training distance (km) • no o) weeks spent in training average speed at which those kilometres were covered As in our previous study®, runners who reported a ratio of > 450 fell into the high-training status category, whereas those with a ratio < 300 were classified in the low training status category. Statistics A chi-square statistic was used to establish whether the incidence of symptoms of URTI was significantly differ ent between the four groups of runners and controls. Multivariate analysis of variance and several one-way analyses of variance were used to analyze the signifi cance of the difference between the four groups in terms of age, Vitamin C, E and Beta Carotene intake and training status ratio. For all statistical analyses the Statgraphics and Excel computer software programs were used and the level of significance were set at 0.05. Results Of the initial 220 runners and matched controls, 178 runners (23 female; 155 male) and 162 (116 female ; 46 male) controls compiled fully with the requirements of the study. Reasons for exclusion from the study includ ed a prev ious history of allergic rhinitis, failure to take the prescribed medications, failure to complete at least 60 km of the race and inability to establish contact with the subjects after the race. The size, gender distribution and mean age of the 4 groups of runners and their matched controls is given in Table 1. Among the runners who ranged in age from 19 to 65 years, 46 were < 30 y old, 119 were aged between 31 and 50 y and 13 were > 50 y in age. Although the two groups with the highest incidence of reports of URTI possessed the highest mean age, this was not signifi cantly different from the mean age of the groups with lower incidence of infection (p>0.05). Table 1: The size, gender distribution and age (+/- SD) of the 4 study groups (n=340) mean EXPERIMENTAL RUNNERS CONTROLS GROUP (n 178) (n = 162) NAge NAge MF(Years) M F (Years) Group C 44 34,3 41 33,1 36 8(5,2) 11 30 (9,5) Group CE 47 37,6 43 33,7 41 6(8,4) 11 32 (9,2) Group CEB 40 35,1 33 29,7 36 4• (10,0) 825 (11,9) Group P 47 39,2 45 32,8 42 5(9,5) 16 29 (11,8) The total mean Vitamin A, E and C intakes of the run ners in each of the four groups is shown in Table 2. The highest total mean intake of Vitamin C was reported in group C, whereas the P group reported a mean intake of 585mg of Vitamin C. Groups CE & CEB also reported high mean intakes of this Vitamin. Group CEB was the only group with a Vitamin A intake which exceeded the RDA for sedentary individuals'', whereas group CEB was the only group which exceeded the RDA0 of Vitamin E for sedentary7 individuals. The group with the lowest incidence of infection (C) reported a total mean Vitamin C intake of 1004mg. Table 2: The mean Vitamin A, C and E intakes of the runners (n=l 78) in the 4 groups. GROUP CGROUP CE GROUP CEB GROUP P Food Vit A (IU) 3170 4405 3915 3110 Sources Vit C (mg) 72 93 95 80 Vit E (IU) 25 22 26 18 Additional Vit A (IU) 1446 1737 2348 2992 Supplements Vit C (mg) 432 305 271 505 Vit E (IU) 12 22 843 Anti-oxidant Vit A (IU) -.30 000 - Supplements Vit C (mg) 500 500 300 - provided Vit E (IU) -400 300 - Total Vit A (IU) 4616 6142 36 263 6102 Vit C (mg) 1004 893 665 585 Vit E (IU) 37 444 334 61 24 SPORTS MEDICINE MARCH 1996 Reproduced by Sabinet Gateway under licence granted by the Publisher (dated 2012.) The incidence of symptoms of URTI in the runners and controls are given in Figure 1. The difference between the incidence of symptoms of infection in die runners ingesting placebo (40.4%) and their sedentary, matched controls (24.4%) was not significantly different (X2=1.99; p = 0.16). The lowest incidence of infection amongst the runners (15.9%) was reported in group C. This was significantly different (X2=5.54; p < 0.05) from the incidence of URTI symptoms in group P A 20% inci dence of infection was reported hi group CEB. The inci dence of symptoms of URTI in group CE was also sig nificantly lower than in group P (X2 = 6.24; p > 0.05). The incidence of symptoms of infection in group CE (25.6%>) was not significantly different (p > 0.05) than the incidence in group P (40.4%). The incidence, nature and mean duration of the symptoms of URTI among nmners and control subjects is presented in Table 3. The most common URTI symp toms reported by runners in the 4 groups were nasal (n = 35). Included in this category were reports of running noses and sneezing. Symptoms lasting more than 7 days occurred in 20 cases (nasal), 13 cases (sore throat) and 12 cases (coughing). Twelve of the runners reported fever in conjunction with their URTI symptoms. Only 24,2% of the reported runners symptoms lasting 1-3 days. The mean duration of symptoms in die runners was not significantly different from the mean duration of symptoms in the control subjects (p > 0.05). Although the mean duration of symptoms was higher in runners on placebo than in runners who received the different combinations of anti-oxidants, this difference was not statistically significant (p > 0.05). Table 3: Incidence, nature and duration of post race symptoms of URTI among runners and control subjects. EXPERIMENTAL GROUP 0/o MEAN (± SD) N SYMPTOMATIC TRArNING STATUS RATIO Group C Group CE Group CEB Group P 42 20,2* 311 (±150)** 47 25.8 274 (±127) 40 16,7* 328 (±166)** 47 40,4 236 (±111) * P < 0.05 vs Group P ** P <0.01 vs Group P The incidence of infection in the low, medium and high training status groups is shown in Figure 2. Those nm ners who reported a low pre-race training status (<250) group reported the highest incidence of infection symp toms. This finding was confirmed when the incidence of post-race URTI symptoms was related to the mean training status of die 4 groups of nmners (Table 4). The two groups with an incidence of URTI symptoms of more than 25%, reported the lowest mean training sta tus. The difference between the training status of groups C and CEB (possessing the lowest incidence of infection) and groups CE and P (possessing the highest Figure 1: Incidence of Symptoms of URTI in runners (n = 178) and controls (n post race period. 162) during the 14 day RUNNERS (n = 178) (x* = 8,20; p < 0,05) 60 50 (0 o ■<D. 5 * 40 cn o 30 o2010 60 5040 30 20 10 15.9%* I 25.5% 1 20.0% 40.4% CONTROLS (n = 162) (xz =3,01; p > 0,05) 12.2% I 23.3% I 15.1% 24.4% Group C Group CE Group CEB Group P Group C Group CE Group CEB Group P Symptomatic Asymptomatic * Significantly different from Group P (p<0,05) SPORTS MEDICINE MARCH 1996 25 Reproduced by Sabinet Gateway under licence granted by the Publisher (dated 2012.) Figure 2: The incidence of post-race URTI symptoms in low, medium and high training status groups (n=176) Number 50 — of Subjects 25 — 31,1% \ \ \ \ v 24,6% \ \ \ | \ \ ] Symptomatic □ Non-symptomatlc X2 = 2,21 p > 0,05 17,2%. <300 300-450 >450 LOW MED HIGH TRAINING STATUS RATIO incidence of infection) was highly significant (p > 0.01). When the incidence of URTI symptoms were related to weekly training distance completed in preparation for the race, this trend was confirmed. Once again, the run ners who had done the least pre-race training, reported the highest incidence of URTI symptoms. A total of 16 black runners participated in the study. None of these athletes reported symptoms of URTI. When excluding the black runners from their respective groups, the percentage incidence of infection symptoms in the respective groups was 25,7(C); 41,3(F); 26,7(CE) and 23 (CEB). The difference between the three groups receiving additional anti-oxidant supplementation was not significant (p > 0.05). Despite a substantial differ ence in percentage incidence in the placebo group and the groups receiving anti-oxidant supplementation, this difference was no longer significant ( p > 0.05). No relationship between running time and incidence of URTI symptoms in the four groups was found in this study. Although the incidence was highest (35,5%) in those runners who took >10hrs to complete the race, this incidence was not significantly greater than the incidence in groups taking 7-8 hrs (23.5%) and 8-9 hrs (27,8%) to finish the race. Discussion The data obtained in this study confirms our previous findings12 8,7 of a greater incidence of post-race symp toms of infection in ultramarathon runners compared to sedentary controls (Figure 2). The comparatively lower general incidence of symptoms in this study than in our previous study1 must be seen in the light of the fact that (i) in this study, reports of symptoms lasting one day or only part thereof were not included in the final calcula tion and (ii) prevailing virological or bacteriological counts may have varied greatly at the time that these two separate studies were undertaken. This study confirms previous findings3 that daily intake of an excess of lg of Vit C is effective in lowering the incidence of symptoms of URTI during the post race period. Although the incidence of symptoms of URTI was substantially lower in all three groups of run ners receiving anti-oxidant supplementation than in the group of runners receiving placebos, no correlation was obtained between the total amount of anti-oxidant nutrients ingested and the incidence of symptoms of URTI. Rather, it was the group with the highest total daily intake of Vit C which had the lowest incidence of URTI symptoms. Several factors could account for this. Table 4: The mean training status ratio and incidence of post race URTI symptoms in the 4 groups of runners (n=176) __________ _______ _ ___________ EXPERIMENTAL GROUP Post Race Symptoms Nasal Symptoms Sore Throat Cough Fever and URT Symptoms Total Symptomatic * * Mean Duration of Symptoms A : RUNNERS Group C Group CE Group CEB Group P (n=44) (n=47) (n=40) (n=47) 11 duration n duration n duration n duration 5,3 10 5,8 5,8 9,0 9 4,7 2 3,0 2 . 12 7,0 1,8 7 5 4 4 8 7,6 14 5,8 12 4,5 4,: 4,3 8 5 19 6 I 7,8 6,4 5,8 5,6 B : CONTROLS Group C Group CE Group CEB Group P (n=41) (n=43) (n=33) (n=45) n duration 11 duration 11 duration n duration 7,0 7,8 9.6 14.6 8 22,8 8 9,3 8 11,1 2 11 9,4 17,5 15,2 0 3 1 6 5 3.2 11 7,8 1.3 8 8,1 7 7,0 0,0 4 11 2,3 10,3 2,0 6,9 Nasal symptoms include runny nose and sneezing. ** No. of persons in the group who presented with 1 or more symptoms lastmg_ 1 day or 2 more symptoms lasting < 1 day Duration = mean no. of days 26 SPORTS MEDICINE MARCH 1996 Reproduced by Sabinet Gateway under licence granted by the Publisher (dated 2012.) Vitamin C is regarded as a first line anti-oxidant in the defence against phagocytederived reactive oxi dants8010. These immunosuppressive free radicals are known to be autotoxic, causing inhibition of chemotaxis, phagocytosis, the proliferation of T-lymphocytes and B -lymphocytes as well as the cytotoxic activity of natural killer cells 111213. Evidence is mounting in favour of Vitamin Cmediated neutralization of these reactive oxidants8910. The relatively smaller protective effect of vitamin E and Beta Carotene supplementation may, be partially attributable to the slow elevation in plasma Vitamin E and Beta Carotene levels15 and the fact that a 21 day supplementation period is too short to elevate plasma levels to reach protective levels. Secondly, variance in age14, training status15, environmental training condi tions'", and genetic make-up between the groups stud ied, may have obscured the effect of the other anti-oxi dant nutrients. As in our previous study3, age does not appear to have played a significant role in the risk of infection. Training status, however, appeared to be an important factor. The highest incidence of symptoms of URTI was found in those runners who fell into the low training status category (Figure 2). Further confirmation of a possible beneficial effect of training is found when examining the mean training status of the four groups. It was found that the two groups possessing the high est training status had the lowest incidences of infec tion symptoms (Table 4). These findings were further supported when the incidence of URTI symptoms was analysed as a function of weekly training distance. Two factors might support, this finding. First, endurance training results in a lower catecholamine levels at a given exercise workload. This is potentially important as catecholamines affect free radical produc tion16. Second, endurance training increases concentra tions of endogenous antioxidant enzymes in skeletal muscle15. That endurance training exerts a protective effect on oxidative stress thus warrants further investi gation in humans. The finding that Black runners who participated in this study did not develop infection symptoms, also requires further investigation. This difference might be explained by chance; socio-economic or hereditary fac tors may also have played a role. To conclude, the findings of this study appear to indicate that large intakes of Vitamin C alone OlOOOmg) are more effective than combinations of Vitamin E, Vitamin C and Beta Carotene in lowering the incidence of URTI in ultradistance runners. This study, however, also indicates that besides Vitamin C inges tion, training load and ethnic background, are impor tant variables which may influence the susceptibility to infection in ultramarathon runners. REFERENCES 1. Peters EM. Ultramarathon running fails to increase sus ceptibility of ultramarathon runners to infections. S. Afr. J. Sports. Med. 1990;5:4-8. 2. Peters EM, Bateman ED. Ultramarathon running and upper respiratory tract infections. S. Afr. Med. J. 1983;64:582584, 3. Peters EM, Goetzske JM, Grobbelaar B, Noakes TD : Vitamin C supplementation reduces the incidence of post-race symptoms of upper respiratory tract infections in ultradistance runners. Am J clin Nutr, 1993:57:170-174. 4. Packer JE, Slater TF, Wilson RI.. Direct observation of a free radical interaction between vitamin E. and vitamin C Nature. 1979;278:737-738. 5. Sharma MK, Buettner GR. Interaction of Vitamin C and Vitamin E During Free Radical Stress in Plasma: An ESR Study. Free Rad Biol & Med 1993;14:649-653. 6. Committee on Dietary Allowances, Food and Nutrition Board, National Research Council. Recommended Dietary Allowances. 10th Edition, Washington DC : National Academic Press, 1989. 7. Peters EM. Cambell A, Pawley L. Vitamin A fails to increase resistance to upper respiratory infection in distance runners. S. Afr. J. Sports Med. 1992;7:3-7. 8. Bendich A, Machlin LJ. Burton GW, Wayner DDM. The anti-oxidant role of Vitamin C. Adv Free Radical Biol Med. 1986;2:419-444. Irt'i B, England L, Ames BN. Ascorbate is an outstanding anti-oxidant in human blood plasma. Proc Nat Acad Sci1989;86:6377-6381. 10. Anderson R, Smit MJ, Joone GK, Van Staden AM. Vitamin C and cellular Immune Functions: Protection against hypochlorus dehydrogenase and ATP generation in human leukocytes as a possible mechanism of ascorbate immunostimulation. Ann N.Y. Acad. Sci. 1982;587:34-48. 11. Anderson R. Phagocyte-derived reactive oxidants as medi ators of inflammation-related tissue damaqe. S. Afr J Sri 1991;87:594-596. 12. Babior BM. Oxidants from Phagocytes: agents of defence and destruction. Blood 1984;64:959-964. 13. Herbaczynska-Cedro K, Wartanowicz M, PanceczenkoKresowska B, Cedro K, Klosiewicz-Wasek B, Wasek W: Inhibitory effect of vitamins C and E on the free radical produc tion in human polymorphonuclear leukocytes. Europ J Clin Invest. 1994;24:316-319. 14. Ji II/, Mitchell EW, Thomas DP. The Effect of exercise train ing on anti-oxidant and metabolic function in senescent rat skeletal muscle. Gerontology. 1991;37:317-325. 15. Machlin U , Bendich A : Free radical tissue damage: protective r°t(‘ °f anti-oxidant nutrients FASEBJ. 1981;51:44116. Fridowich I, Freeman B. Anti-oxidant defence in the lunq Ann Rev Physiol 1986;48:693-792. 17. Weiss SJ. Tissue destruction by neutrophils. New Enal J med 1989;320:365-376. 18. Viru A. Hormones in Muscular Activity. Boca Raton FI : CRC Press, 1985. ' r~i SPORTS MEDICINE MARCH 1996 27 Reproduced by Sabinet Gateway under licence granted by the Publisher (dated 2012.) m i: so rm afrk ax .khrxat, or SPORTS MEDICINE VOLUME 3 __________ NUMBER 1 _______ MARCH 1996 Editor Prof TD Noakes Dr MP Schwellnus Editorial Board Dr M E Maolla Dr P de Jager Dr J Skowno Dr P Schwartz ProfR Stretch Dr C de Ridder Prof B C Andrews Dr E \V Dermun Mr R H Farman Prof M Mars Dr C A Noble International Advisory Boar< Lyle J Micheli Associate Clinical Professor i Oithopaedic Surgery Boston, USA Chester R Kyle Research Director, Sports Equipment Research Associi California, USA Prof IIC Wildor Hollmann President des Deutschen Sport iirztebimdes Koln, West Gcnnany Howard J Green Professor, Department of Kinesiology Ontario, Canada George A Brooks Professor, Department of Physical Education California, USA Neil F Gordon Director, Exercise Physiology Texas, USA Edmund R Burke Associate Professor, Biology Department, University of Colorado Colorado. USA Graham N Smith Physiologist Glasgow, Scotland The views expressed in individual articles are the personal view's of the Authors and are not necessarily shared by the Editors, the Advertisers or the Publishers. No articles may be reproduced without the written consent of the Publishers. 1 [>f itcs CONTENTS Editorial L Weight Exercise and the immune system: A review L Weight Exercise and upper respiratory tract infections: A review EM Peters IIIV infection in sport: A review of current issues MP Schwellnus Vit C as effective as combinations of anti-oxidant nutrients in reducing symptoms of upper respiratory tract infection in ultramarathon runners EM Peters et al A social cognitive perspective on promotive and preventive health behaviour in postapartheid South Africa I Miller 9 16 23 29 THE EDITOR THE SOUTH AFRICAN JOURNAL OF SPORTS MEDICINE PO Box 115, Newlands 7725 PRODUCTION Andrew Thomas PUBLISHING Glenbarr Publishers cc Private Bag X14 Parklaiids 2196 Tel: (Oil) 442-9759 Fax: (Oil) 880-7898 ADVERTISING Marike de Waal/Andrew Thomas REPRODUCTION Output Reproductions PRINTING Horlors Cover sponsored by Ciba-Geigv SPORTS MEDICINE MARCH 1996 3 Reproduced by Sabinet Gateway under licence granted by the Publisher (dated 2012.)