Presented by: Nurdalila SahidanOctober 2015

ContentsVitamin CExercise Induce Bronchoconstriction (EIB)The trials review

Vitamin C potent water-soluble antioxidant in humansInhibit oxidation by other moleculesOxidation will poduce free radicals that can

started chain reaction causing harmAntioxidant will terminate this chain reaction

Exercise-induced Bronchoconstriction (EIB)Acute narrowing of the airway result from

vigorous exercise caused by loss water, oxidative stress

Depends on: type and level of physical activity, humidity and temperature of the inhaled air

Decline of 10% or greater in FEV1 after exercise

EIBCommon in AsthmaticOccur in 10% of non-asthmatic Common among competitive athletes: -endurance sport :

Vitamin C level based on studies

Vitamin CLevel is high in lungsLevel in alveolar macrophages and alveolar

type II cell 30x higher than plasma Reduce level of free radicals generated

during exercise

Mice and rats Guinea Pig-able to synthesis vit c-Increase level of VIT C in bronchoalveolar lavage fluid--serve as protective response

-unabe to synthesis vit c-effect; decrease level of VIT C in the lung-indicates comsumption to protect against oxidants-Vit C administration:reduce mortality in guinea pig due to ozone exposure

Exposure to ozone and nitrogen dioxide: A study on rats / mice

and guinea pig

Vitamin C4 trials in human shows:

- Vit C reduce plasma level of histamineVit C reduce bronchoconstriction by

histamine in living guinea pigAlso reduce contraction caused by histamine

in isolated guinea pig trachea smooth muscleVit C decreased contraction by PGF2 α

(postaglandin- bronchoconstrictor) in guinea pig tracheal tube preparation

Single dose of oral Vit C can rapidly elevate mucosal Vit C level

Nasal lavage fluid Vit C in human increase 3x in 2 hours after a single dose of 1 or 2 g Vit C

Thus rapid transport of ingested Vit C to respiratory tract lining fluid implies even single dose might be effective in protecting against acute increases in oxidative stress

Trials3 Randomized, double blinded, placebo-

controlled cross over trials3 different decades and 2 different continentsMonitoring lung function test pre and post

exerciseEffect of Vit C (0.5 to 2g/day) on exercise

induce FEV1 decline

Tecklenburg et al (2007)Selection: 8 subjects with Asthma from a

population of university students and the local community ,Indiana USA (FEV1 decline >10%)

Sex, age: 2males, 6 females ; mean age 24.5 yr

Given 2 weeks of ascorbic acid supplementation (1500 mg/day) or placebo

Exercise Test: ran on motorized treadmill which was elevated 1% per min until 85% of age predicted maximum heart rate and ventilation exceeding 40-60% of predicted max voluntary ventilation

Maintained exercise intensity until 6 min. Following steady 6-min exercise state, the grade of treadmill continued to increase 1%/min until volitional exhaustion

Pulmonary function was assessed post exercise at 1,5,10,15,20,30 min.

Outcome: maximum percentage fall in FEV1 from baseline calculated

Result: 1)Post exercise FEV1 decline was 12.9% after placebo period2) Post exercise FEV1 decline was 6.4% after Vitamin C period ( corresponds to

50% reduction in postexercise FEV1 decline

Schachter & Schlesinger (1982)Selection: 12 subjects with asthma, selected

among employees of Yale University USA. Decline in FEF60 at least 20%

Sex, age: 5 males, 7 females, mean age 26 yr

On two subsequent days, subjects ingest 500mg ascorbic acid or a placebo

Exercise test: on cycloergometer. Begun at constant speed of 20km/h against zero workload. Cardiac frequency measured by ECG was done every 1 min interval and workload was increased by 150 kilopondmeters per min, keeping pedalling speed constant . Larger workload was given until either heart rate reached 170 beats per min or fatigue. Pulmonary function was assessed post exercise at 0 and 5 min

ResultOn the basis of the slope of the linear regression

line, (Figure A) vit c decreased post exercise FEV1 decline by 55% ( 95%CI). The mean decline in placebo day is 18%

On the basis of the slope of the linear regression line, (Figure C) vit c decreased post exercise FEF60 decline by 58% ( 95%CI). The mean decline in placebo day is 35%

Figure D- Indicates that the effect of vit c may be restricted to those EIB pt who had postexercise FEF60 levels below 1L/s

Cohen et al (1997)Selection: 20 patients with asthma in Israel

(decline of FEV1 atleast 15%)Sex, age: 13 males, 7 females, mean age 14 yrGiven 2g of ascorbic acid or a placebo 1 hour

before exerciseExercise test: 7 minutes session on treadmill.

Exercise to submaximal effort at a speed and slope to provide 80% of motional oxygen consumption judge by a pulse oximeter. Pulmonary function was assessed after 8 min rest and repeat 1 week later

ResultVit C administration did not change the results

of pulmonary functions at rest after 1 hour. In 9 patients, a protective effect on exercise-

induced hyperreactive airways was documented.

Four of 5 patients who received Vit C and documented a protective effect on EIA continued to receive ascorbic acid, 0.5 g/d, for 2 more weeks with the same protective effect.

Reduction of postexercise FEV1 decline by vitamin C. The vertical lines indicate the 95% CI for the three trials that studied the effect of vitamin C administration on EIB and the squares in the middle of the lines indicate the point estimates of the studies. An effect of 100% would indicate full prevention of postexercise FEV1 decline. The diamond shape at the foot indicates the 95% CI for the pooled vitamin C effect: 48% (95% CI: 33% to 64%) reduction in postexercise FEV1 decline. For example, Tecklenburg et al. reported a 12.9% FEV1 decline after placebo, but only a 6.4% decline after the vitamin C period, which corresponds to a 50% reduction in FEV1 decline by vitamin C 

Studies focusing on symptoms

5 separate randomized placebo control trials, reported based on meta analysis: Vitamin C reduce incidence of respiratory sx after heavy physical stress by 52% (95%CI: 36% to 65%)

Symptoms include: cough, sorethroat, runny nose and dyspnoea

Studies Vitamin C Outcomes

Study on 92 marathon runners. Result monitor after 2 weeks of marathon

Given 600mg Vitamin C / placebo daily for 21 days before marathon

Reduce Incidence of postrace :

1)cough by 71% in Vit C group

2)Sore throat by 67%

-no significant effect on incidence of runny nose

Study on 39 Israel competitive swimmers in 3 winter months

Given 1g/day vitamin C/ placebo in 3 months

Vitamin C shortened the duration of URTI sx in male but no effect in female

All the trials of vitamin C show reduced incidence and duration of respiratory sx due to physical stress

Unfortunately possibility of infectious causes was not investigated

Irrespective of etiology, from EBM point of vie symptoms are more important than lab value

Two british based studies:- 1) 4 months trial on 154 British asthmatics

show: FEV1 not influenced by 1g/day Vit C- 2) A 5 year administration of 0.25g/day vit c

with vitamin E and β-carotene in large scale trial of 20536 adult : No influence towards FEV1

These british studies show:- Vit C does not influence pulmonary function of

stable asthma- But the needs of inhaled corticosteroids was

lower in vit C group

Conclusion3 trials – 0.5 to 2 g/day vit c halved the

postexercised FEV1 decline5 trials- vit c halved the incidence of

respiratory sx after physical stress1 trial- vit c halved the duration of

respiratory sx in male swimmerBut it is unclear how the effect depends on

type/ level of activity, temperature ,humidity of air, the dose,the level of dietary intake and various other fator

Since it is safe, low cost and consistent positive findings in the 9 randomized trial, reasonable to test the effect on individual basis if they have experienced EIB

ReferrencesThe effect of vitamin C on bronchoconstriction and

respiratory symptoms caused by exercise: a review and statistical analysis Harri Hemilä. Allergy, Asthma & Clinical Immunology 2014, 10:58

Schachter EN, Schlesinger A: The attenuation of exercise-induced bronchospasm by ascorbic acid.Ann Allergy 1982, 49:146-151.

Cohen HA, Neuman I, Nahum H: Blocking effect of vitamin C in exercise-induced asthma.Arch Pediatr Adolescent Med 1997, 151:367-370.

Tecklenburg SL, Mickleborough TD, Fly AD, Bai Y, Stager JM: Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma.Respir Med 2007, 101:1770-1778.