review and statistical analysis

1. Presented by: Nurdalila Sahidan
October 2015

2. Contents
Vitamin C
Exercise Induce Bronchoconstriction (EIB)
The trials review

3. Vitamin C
 potent water-soluble antioxidant in humans
Inhibit oxidation by other molecules
Oxidation will poduce free radicals that can started
chain reaction causing harm
Antioxidant will terminate this chain reaction

4. 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

8. EIB
Common in Asthmatic
Occur in 10% of non-asthmatic
Common among competitive athletes:
-endurance sport :

9. Vitamin C level based on studies

10. Vitamin C
Level is high in lungs
Level in alveolar macrophages and alveolar type II cell
30x higher than plasma
 Reduce level of free radicals generated during
exercise

11. 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

12. Vitamin C
4 trials in human shows:
- Vit C reduce plasma level of histamine
Vit C reduce bronchoconstriction by histamine in
living guinea pig
Also reduce contraction caused by histamine in
isolated guinea pig trachea smooth muscle
Vit C decreased contraction by PGF2 α
(postaglandin- bronchoconstrictor) in guinea pig
tracheal tube preparation

13. 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

14. Trials
3 Randomized, double blinded, placebo-controlled
cross over trials
3 different decades and 2 different continents
Monitoring lung function test pre and post exercise
Effect of Vit C (0.5 to 2g/day) on exercise induce FEV1
decline

15. 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

16. 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

17. Result: 1)Post exercise FEV1 decline was 12.9% after placebo period
2) Post exercise FEV1 decline was 6.4% after Vitamin C period ( corresponds to
50% reduction in postexercise FEV1 decline

18. 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

19. 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

21. Result
On 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

22. 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 yr
Given 2g of ascorbic acid or a placebo 1 hour before
exercise
Exercise 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

23. Result
Vit 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.

24. 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

25. 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

26. 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

27. 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

28. 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

29. Conclusion
3 trials – 0.5 to 2 g/day vit c halved the postexercised
FEV1 decline
5 trials- vit c halved the incidence of respiratory sx
after physical stress
1 trial- vit c halved the duration of respiratory sx in
male swimmer
But 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

30. 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

31. Referrences
The 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.