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
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
20.
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.
Editor's Notes
-Unlike guinea pig and human, rats and mice able to synthesis vitamin c. Thus able to increase to rates of vit c synthesis
FEF= forced expiratory flow, -flow or speed of air coming out of the lung during middle portion of a forced expiration.
FEF was used during this study because the deccline is twice as great as FEV1
PEF was not recommended for assessing EIB because it is less repeateble than FEV1