Olin and Wechsler review novel drugs for asthma treatment. I would like to propose vitamin C to the list of drugs that should be investigated in more detail.
Vitamin C is involved in the metabolism of histamine and prostaglandins, which are involved in bronchoconstriction [1]. In asthmatics, vitamin C decreased post-exercise nitric oxide and cysteinyl leukotriences {2].
There is strong evidence indicating that, in some conditions, vitamin C can reduce bronchoconstriction. Three RCTs assessed the effect of vitamin C on asthmatics who suffered from exercise-induced bronchoconstriction (EIB), and found that vitamin C reduced postexercise FEV1 decline by 48% (95% CI: 33% to 64%)[1,3]. No long-term supplementation was necessary, since in two studies vitamin C
was administered as a single dose 1 to 1.5 hours before the exercise session.
The total number of participants in the three EIB studies was only 40, but the studies were carried out in three different decades on two different continents, and the criteria for EIB differed. We do not know
how far the results can be extrapolated, but the consistency in the findings suggests that vitamin C may also be effective for other asthmatics.
In five RCTs, vitamin C halved the frequency of respiratory symptoms after strenuous exercise, e.g., a marathon run [4,5]. The original authors assumed that the respiratory symptoms after the marathon were
the result of virus infections, however, it was merely a guess, as no etiological investigations were carried out. A cough after a marathon run can as well originate from non-viral irritation of the airways, such as with an EIB-kind of etiology [1]. Thus, in eight RCTs with subjects under physical stress, vitamin C decreased both objective pulmonary function outcomes and subjective respiratory symptoms.
Over two dozen controlled trials have shown that vitamin C shortens the duration and alleviates the symptoms of the common cold. Doses of ≥1 g/day of regularly administered vitamin C shortened the duration of colds in adults by 8% (3% to 12%) and in children by 18% (9% to 27%) [4,5]. The common cold is, in turn, a common cause of asthma exacerbations.
A systematic review found three studies providing direct information on vitamin C and common cold-induced asthma [6]. An RCT in Nigeria examined patients whose asthma exacerbations resulted from respiratory infections. Vitamin C at a dosage of 1 g/day lowered the incidence of severe and moderate asthma attacks by 89% (52% to 98%; based on 3/22 vs. 23/19). An RCT in former East Germany on patients with infection-related asthma found that 5 g/day of vitamin C decreased the prevalence of bronchial hypersensitivity to histamine by 52 percentage points (25 to 71 pp; decrease in prevalence from 91% to 39%). The third study compared participants while they suffered from the common cold and after they had recovered. While they suffered from the cold, vitamin C raised histamine PC20 levels 3.2-fold, thereby reducing bronchial hypersensitivity. The effect of vitamin C was significantly smaller after recovery from the common cold. These findings support the hypothesis that vitamin C might benefit some people who suffer from asthma exacerbation during colds.
A 4-month trial on 154 British asthmatics showed that the FEV1 level was not influenced by 1 g/day of vitamin C [7]. Nevertheless, the need for inhaled corticosteroids was lower in the vitamin C group [8]. Even if vitamin C may not be effective for patients with permanent stable asthma, it may beneficially influence pulmonary functions of some asthmatics under certain forms of acute stress, such as when they endure heavy physical activity or suffer from a viral respiratory tract infection [1-3,6].
A Cochrane review on vitamin C and asthma was published in 2001 [9] and it was updated in 2004 and 2009. In 2009, I pointed out that the Cochrane review contained substantial errors in the data extraction and analysis [10]. The authors replied to my criticism in 2012 and even then their reply was loaded with of errors [11]. With the first version published in 2001, the sloppy Cochrane review misled readers
about the evidence on vitamin C and asthma for a decade.
Evidently, vitamin C should also be included in the list of potential asthma drugs that should be examined in much more detail.
References
1. Hemila H. The effect of vitamin C on bronchoconstriction and respiratory symptoms caused by exercise: a review and statistical analysis. Allergy
Asthma Clin Immunol 2014;10:58
2. Tecklenburg SL, Mickleborough TD, Fly AD, Bai Y, Stager JM. Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma.
href="http://dx.doi.org/10.1016/j.rmed.2007.02.014">Respir Med 2007;101:1770–1778
3. Hemila H. Vitamin C may alleviate exercise-induced bronchoconstriction: a meta-analysis. BMJ Open
2013;3:e002416
4. Douglas RM, Hemila H. Vitamin C for preventing and treating the common cold. PLoS Med 2005;2:e168
7. Fogarty A, Lewis SA, Scrivener SL, Antoniak M, Pacey S, Pringle M, Britton J. Oral magnesium and vitamin C supplements in asthma: a parallel group randomized placebo-controlled trial.
href="http://dx.doi.org/10.1046/j.1365-2222.2003.01777.x">Clin Exp Allergy 2003;33:1355–1359
8. Fogarty A, Lewis SA, Scrivener SL, Antoniak M, Pacey S, Pringle M, Britton J. Corticosteroid sparing effects of vitamin C and magnesium in asthma: a randomised trial. Respir Med 2006;100:174–179
Rapid Response:
Vitamin C and asthma
Olin and Wechsler review novel drugs for asthma treatment. I would like to propose vitamin C to the list of drugs that should be investigated in more detail.
Vitamin C is involved in the metabolism of histamine and prostaglandins, which are involved in bronchoconstriction [1]. In asthmatics, vitamin C decreased post-exercise nitric oxide and cysteinyl leukotriences {2].
There is strong evidence indicating that, in some conditions, vitamin C can reduce bronchoconstriction. Three RCTs assessed the effect of vitamin C on asthmatics who suffered from exercise-induced bronchoconstriction (EIB), and found that vitamin C reduced postexercise FEV1 decline by 48% (95% CI: 33% to 64%)[1,3]. No long-term supplementation was necessary, since in two studies vitamin C
was administered as a single dose 1 to 1.5 hours before the exercise session.
The total number of participants in the three EIB studies was only 40, but the studies were carried out in three different decades on two different continents, and the criteria for EIB differed. We do not know
how far the results can be extrapolated, but the consistency in the findings suggests that vitamin C may also be effective for other asthmatics.
In five RCTs, vitamin C halved the frequency of respiratory symptoms after strenuous exercise, e.g., a marathon run [4,5]. The original authors assumed that the respiratory symptoms after the marathon were
the result of virus infections, however, it was merely a guess, as no etiological investigations were carried out. A cough after a marathon run can as well originate from non-viral irritation of the airways, such as with an EIB-kind of etiology [1]. Thus, in eight RCTs with subjects under physical stress, vitamin C decreased both objective pulmonary function outcomes and subjective respiratory symptoms.
Over two dozen controlled trials have shown that vitamin C shortens the duration and alleviates the symptoms of the common cold. Doses of ≥1 g/day of regularly administered vitamin C shortened the duration of colds in adults by 8% (3% to 12%) and in children by 18% (9% to 27%) [4,5]. The common cold is, in turn, a common cause of asthma exacerbations.
A systematic review found three studies providing direct information on vitamin C and common cold-induced asthma [6]. An RCT in Nigeria examined patients whose asthma exacerbations resulted from respiratory infections. Vitamin C at a dosage of 1 g/day lowered the incidence of severe and moderate asthma attacks by 89% (52% to 98%; based on 3/22 vs. 23/19). An RCT in former East Germany on patients with infection-related asthma found that 5 g/day of vitamin C decreased the prevalence of bronchial hypersensitivity to histamine by 52 percentage points (25 to 71 pp; decrease in prevalence from 91% to 39%). The third study compared participants while they suffered from the common cold and after they had recovered. While they suffered from the cold, vitamin C raised histamine PC20 levels 3.2-fold, thereby reducing bronchial hypersensitivity. The effect of vitamin C was significantly smaller after recovery from the common cold. These findings support the hypothesis that vitamin C might benefit some people who suffer from asthma exacerbation during colds.
A 4-month trial on 154 British asthmatics showed that the FEV1 level was not influenced by 1 g/day of vitamin C [7]. Nevertheless, the need for inhaled corticosteroids was lower in the vitamin C group [8]. Even if vitamin C may not be effective for patients with permanent stable asthma, it may beneficially influence pulmonary functions of some asthmatics under certain forms of acute stress, such as when they endure heavy physical activity or suffer from a viral respiratory tract infection [1-3,6].
A Cochrane review on vitamin C and asthma was published in 2001 [9] and it was updated in 2004 and 2009. In 2009, I pointed out that the Cochrane review contained substantial errors in the data extraction and analysis [10]. The authors replied to my criticism in 2012 and even then their reply was loaded with of errors [11]. With the first version published in 2001, the sloppy Cochrane review misled readers
about the evidence on vitamin C and asthma for a decade.
Evidently, vitamin C should also be included in the list of potential asthma drugs that should be examined in much more detail.
References
1. Hemila H. The effect of vitamin C on bronchoconstriction and respiratory symptoms caused by exercise: a review and statistical analysis. Allergy
Asthma Clin Immunol 2014;10:58
2. Tecklenburg SL, Mickleborough TD, Fly AD, Bai Y, Stager JM. Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma.
3. Hemila H. Vitamin C may alleviate exercise-induced bronchoconstriction: a meta-analysis. BMJ Open
2013;3:e002416
4. Douglas RM, Hemila H. Vitamin C for preventing and treating the common cold. PLoS Med 2005;2:e168
5. Hemila H, Chalker E. Vitamin C for preventing and treating the common cold. Cochrane Database Syst Rev 2013;CD000980
6. Hemila H: Vitamin C and common cold-induced asthma: a systematic review and statistical analysis. Allergy Asthma Clin Immunol 2013;9:46
7. Fogarty A, Lewis SA, Scrivener SL, Antoniak M, Pacey S, Pringle M, Britton J. Oral magnesium and vitamin C supplements in asthma: a parallel group randomized placebo-controlled trial.
8. Fogarty A, Lewis SA, Scrivener SL, Antoniak M, Pacey S, Pringle M, Britton J. Corticosteroid sparing effects of vitamin C and magnesium in asthma: a randomised trial. Respir Med 2006;100:174–179
9. Kaur B, Rowe BH, Ram FS. Vitamin C supplementation for asthma. Cochrane Database Syst Rev 2001;CD000993
10. Hemila H. Feedback, 2009
11. Hemila H. Vitamin C and exercise-induced bronchoconstriction: further problems in the Cochrane review "vitamin C for asthma", 2013
Competing interests: No competing interests