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Canadian Asthma Prevention Institute |
Latest Studies on the Influence of Nutrition on Asthma
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| Asthma and the Influence of Nutritional Science. | ||||
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Gastroesophageal Reflux,
Asthma and Infants Gastroesophageal reflux (GER) has been linked with an increase in asthma symptoms. In a study reported in September of 1999, by S Sheikh and associates, 84 otherwise healthy patients referred to the Pediatric Pulmonary Medicine Division at Kosair Children’s Hospital for evaluation of daily wheezing 54% tested positive for GER. 64.8% of these infants were able to discontinue all daily asthma medications within 3 months of starting treatment with an H2 receptor antagonist and a prokinetic agent. The researchers concluded that silent GER is common in infants with wheezing and controlling GER improves morbidity and decreases the need for daily asthma medications.98 Coughing may be produced by a number of different disorders in distinct anatomic sites. Seventy-eight nonsmoking patients of both genders who complained of cough for greater than or equal to 3 weeks and had normal findings on plain chest radiographs were studied prospectively by BC Palombini and colleagues. The patients’ histories were obtained, and physical examinations were performed. The diagnostic workup included pulmonary function tests, CT of the paranasal sinuses and chest, carbachol provocation test, fiberoptic rhinoscopy, fiberoptic bronchoscopy, and 24-h esophageal pH monitoring. The final diagnosis depended on clinical, radiologic, and laboratory findings; a successful response to therapy was required for confirmation. The causes of chronic cough were determined in all patients. Coughing was due to a single cause in 30 patients (38.5%) and multiple causes in 48 patients (61.5%). The five most important causative factors were asthma (46 patients; 58.9%), postnasal drip syndrome (PNDS; 45 patients; 57.6%), gastroesophageal reflux disease (GERD; 32 patients; 41.1%), bronchiectasis (14 patients; 17.9%), and tracheobronchial collapse (11 patients; 14.1%). The researchers concluded that asthma, PNDS, and GERD, alone or in combination, were responsible for 93.6% of the cases of chronic cough.99 Leukotrienes and Lipo-oxygenase Inhibitors Today's oral asthma medications inhibit lipo-oxygenase, meaning they interfere with the action of leukotrienes (LTs). Leukotrienes are biochemicals that sustain inflammatory conditions once they are triggered, and thus play a role in asthmatic bronchial inflammation. Some LTs are also strong stimulators of bronchial constriction, and mucus production--they are 1,000 times more potent than histamine. This means just a small amount of LTs can narrow the breathing passages and precipitate an asthma attack. Many medicinal plants contain phytochemicals that inhibit lipo-oxygenase without the dangerous side effects of pharmaceutical prescriptions. The commonly used inhalers are beta-adrenergic stimulators that relax bronchial smooth muscle, thereby mechanically opening the airway. Designed for emergency use only, they do nothing to reduce underlying inflammation. Overuse of inhalers--more than two canisters weekly--increases the risk of death from asthma by increasing side effects, which include desensitization to the medication, increased heart rate and blood pressure, headaches and blurred vision. Steroids used for asthma can cause or exacerbate diabetes, glaucoma, obesity, liver damage, abnormal cholesterol levels and heart disease. Naturally occurring lipo-oxygenase inhibitors caffeic acid, catechin, chlorogenic acid, hydroxycinnamic acids, kaemp-ferol, procyanidin-D2, quercetin and cinnamic acid, all have potential benefits to asthmatics, without the side-effects associated with drugs. Benefits
of Proanthocyanidins - Antihistamine, Antioxidant and Antiinflammatory Flavonoids have been found to be beneficial in a number of areas associated with asthma. Reduction of histamine levels, either at source or at histamine receptors, has been noted in numerous studies on flavonoids. One of the most beneficial groups of plant flavonoids is the proanthocyanidins (also called procyanidins). These flavonoids provide many health-promoting benefits. The most potent proanthocyanidins are those bound to other proanthocyanidins. Collectively, mixtures of proanthocyanidin dimers, trimers, tetramer, and larger molecules are referred to as procyanidolic oligomers, or PCO for short. Although PCO exists in many plants and red wine, commercially available sources of PCO include extracts from grape seeds. Some of the most important properties of PCO’s are that they are antihistamic, antiinflammatory, antioxidant, and have the ability to “saturate” the body at dose-dependent levels. They are extremely bioavailable and are immediately absorbed from the stomach into the bloodstream. They are completely safe, and, significantly, are one of the few antioxidants that can cross the blood-brain barrier to protect neural tissue. Not only do they neutralize free radicals themselves, but they conserve and regenerate vitamins C and E. Vitamin E is a powerful free-radical scavenger, and flavonols and vitamin C regenerate vitamin E.100 Proanthocyanidins and Potential Chronotherapeutic Use in Asthma Proanthocyanidins
are efficient in neutralizing free radicals, are distributed to virtually every organ and
tissue, and remain in the body for up to 72 hours.101 As a result, once saturation is reached at a particular dose, that level can be maintained by daily supplementation. The suggested resulting benefit for asthmatics is the ability to control the level of antihistamine action, 24 hours a day. This constant antihistamine action
relates positively to recent studies indicating the importance of chronotherapeutic use of
antihistamine drugs in controlling asthma. Published asthma consensus reports now acknowledge that asthma is a nocturnal disease in as many as 75% of those afflicted by this medical condition. Nonetheless, the treatment of this chronic obstructive pulmonary disease in the clinic continues to be based primarily on homeostatic considerations in that it relies on long-acting bronchodilator and other therapies formulated and scheduled to ensure constant or near-constant levels of medication during the 24h. The need of asthma patients prone to nighttime attacks is not the same during the day and night; the therapeutic requirements of patients who experience nocturnal asthma, especially ones with the more severe forms of the disease, are often not satisfied by conventional medications. The therapeutic response and patient tolerance to bronchodilator medications can be improved markedly when the medications are proportioned during the 24h as a chronotherapy, that is, when more medication is delivered during nighttime sleep than daytime activity, as verified by numerous studies.102 Curcumin
(Turmeric) and Hesperidin as Anti-inflammatories Curcumin, a dietary pigment responsible for the yellow color of curry, is a natural product of plants obtained from Curcuma longa (turmeric). Curcumin has been used for the treatment of inflammatory diseases and exhibits a variety of pharmacological effects such as anti-inflammatory, anti-tumor, anti-oxidant and anti-viral activity. In a study by Kobayashi, et al.,
results indicated curcumin may have a potential effect on controllying allergic diseases
through inhibiting the production of cytokines affecting eosinophil function and IgE
synthesis.162 Galati, and colleagues conducted a
study to define in vivo the antiinflammatory and analgesic activities of hesperidin, and important flavanone of Citrus
sp.. They used hesperidin obtained from the
solid residue of orange peel after and acidic pretreatment. Their results showed that hesperidin possesses significant
antiinflammatory and analgesic effects.163 Jean and Bodinier reported that each step of an inflammatory reaction is triggered by one or several chemical or biological mediators such as arachidonic acid derivatives (prostaglandins (PG), leukotrienes (LT), or thromboxanes (TX), vasoactive amines (histamine or serotonin), and oxygen free radicals (superoxide ion, O2-, or hydrogen peroxide, H2O2). In perivenous inflammation, these mediators play a prominent role in favoring vasodilation (histamine), increasing membrane permeability (PGE2, histamine, free radicals) and providing a chemotactic signal for specialized cells, ie, neutrophil polynuclears, macrophages, lymphocytes (LTB4, free radicals). The researchers reported that Daflon 500 mg (a purified flavonoid fraction - 90% diosmin, 10% hesperidin) behaves as a potent protective agent against inflammatory disorders.164 Gastroesphogeal reflux (GER) is common in those with asthma, with 77% of asthmatics complaining of heartburn and 41% experiencing reflux-associated respiratory symptoms. A number of studies have shown that flavonoids are capable of reducing GER, leading to improvement in asthma symptoms. The increased production of stomach acid in asthmatics with GER may be attributable to the increased levels of histamine in the blood and it’s resulting effect on the acid-forming glands in the stomach. Since asthmatics have a higher IgE levels (which has also been associated with GER) it would appear that higher histamine levels may account for the increase in abnormal esophageal acid contact times on 24h esophageal pH tests which were found in 82% of asthmatics examined consecutively.103 An interesting study was made by
Ekström and Tibbling. They studied 37 patients with nocturnal asthma and found
significantly lower morning PEF values in those patients who had pathologic nocturnal GER
compared to patients with no GER at night, suggesting a relationship between GER and
nocturnal asthma. Previously published placebo-controlled studies with H2 blockers have
been able to show an amelioration in nighttime asthma symptoms.169 S Chakrabarti, et al. noted that an increased incidence of gastroesophageal reflux has been reported in patients with bronchial asthma. They studied the pulmonary effects of acid instillation in the esophagus on fifteen patients with bronchial asthma and 15 healthy adults in the age group 15-50 years. The control subjects were first screened for bronchial hyperreactivity by a methacholine challenge test. Patients and controls were both subjected to modified Bernstein test. Spirometry was done at baseline and after each instillation of either acid or saline. Respiratory and reflux symptoms were noted after each infusion and antacid administration. They found that five patients and one control subject had history of reflux symptoms (p < 0.05) and six patients had nocturnal asthma. There was a significant fall in FEV1/FVC after acid infusion patients; this improved significantly after antacid administration. All six patients with nocturnal asthma had respiratory signs or symptoms and had more than 20% fall in FEV1 on acid instillation in the esophagus, while none in the control group developed the same. They concluded that gastroesophageal reflux occurs more frequently in patients with bronchial asthma and acid instillation in the esophagus triggers bronchoconstriction.104 Flavonoids and H2-Receptor
Blocking Drugs It has been shown that H2-receptor
blocking drugs can reduce histamine levels. Similar reductions of histamine levels by
flavonoids have been related to reduction in gastric secretions. The following studies
indicate the wide variety of flavonoids which have been shown to have an antihistaminic
effect. In 1984, research showed that proanthocyanidins (found in grape seed extract) have an antihistamine effect. Eleven naturally occurring flavonoids representing five different chemical classes were studied for their effects on human basophil histamine release triggered by six different stimuli. The flavonoids included flavone, quercetin, taxifolin, chalcone, apigenin, fisetin, rutin, phloretin, tangeretin, hesperetin, and naringin. The stimuli were antigen, anti-IgE, concanavalin A, ionophore A23187, formylmethionylleucylphenylalanine, and tetradecanoyl phorbol acetate. Concentration-effect relationships were established for each flavonoid (5-50 microM) at concentrations of stimuli which produced near optimal histamine release. Variable degrees of inhibition were
noted depending on the nature of the stimulus and flavonoid structure. The flavonols, quercetin
and fisetin, and the flavone, apigenin, exhibited a predilection to inhibit histamine
release stimulated by IgE-dependent ligands (antigen, anti-IgE, and con A).105 In a previous study, Middleton and
Drzewiecki had noted that structure-activity relationship studies have been performed on
the inhibition of antigen-induced histamine release from human basophils by various
naturally occurring flavonoids. Quercetin was the most active compound. They also found that of the transitional metal ions, Cu2+ most effectively blocked the inhibitory activity of quercetin, possibly through a chelation mechanism. This is of interest in the synergy of nutritional supplementation, in that zinc deficiencies can lead to excess copper levels, since zinc and copper compete for absorption. Also, a high intake of vitamin C, zinc
and other minerals may decrease the absorption of copper. It is therefore hypothesised
that proper nutritional intake may reduce the inhibition of the antihistamine activity of
quercitin and other flavonoids.106 In a consequent study, Middleton and G
Drzewiecki noted that naturally occurring plant flavonoids affect a variety of cell
activation phenomena including the secretion of histamine from human basophils.107 Dr. H. Kakegawa and colleagues reported
that catechine and the dimeric proanthocyanidine inhibit the degranulation of mast cells.
Degranulation of mast cells would release not only histamine, but all the mediators of the
allergy response.108 SM Vela and colleagues noted that the main substances in the active extract of Stachytarpheta cayennensis schauer (verbenaceae) are flavonoids and amines. A purified extract from this plant presented a specific activity 5-10 times higher than that detected in the original extract. Data from pharmacological studies have indicated that S. cayennensis inhibits gastric action. Both cholinergic and histaminergic stimulation of acid secretion were similarly reduced by the extracts suggesting inhibition of common steps in both pathways, possibly at the level of histamine release/H2 receptor interaction, or at the proton pump.109 W Beil, et al., report similar effects
from the flavonoids flavone, flavonone and quercitin. All flavonoids inhibited acid
production in parietal cells in response to histamine. Flavone and flanonone also
stimulated prostaglandin E2 production.110 B Friesenecker and colleagues, of the
Department of Anesthesiology and Intensive Care Medicine, University of Innsbruck,
Austria, report that a compound of the flavonoids diosmin and hesperidin lowered
the release of histamine and decreased leukocyte-dependent enothelial damage.111 JA Emim and associates, reported that hesperidin
may present a potential therapeutic use as a mild anti-inflammatory agent, being also
useful as a precursor of new flavonoids endowed with such activity.112 P Borrissova, et al., also noted
anthocyane flavonoids and rutin have anti-inflammatory properties.113 JH Jaffar and FL Pearce, of the
Department of Chemistry, University College London, UK, noted that secretion of histamine
induced by ATP was largely unaffected by the anti-asthmatic drugs disodium chromoglycate
and nedocromic sodium, but was inhibited by structurally related flavonoids.114 JB Wu, and colleagues, reported three
flavonoids inhibited induced histamine release from mast cells. They also exhibited
significant anti-allergy activity in PCA test with p.o. administraion.115 CM Simoes et al. report that quercitin
exhibited anti-spasmodic and anit-inflammatory properties induced by acetylcholine,
histamine, noadrenaline and barium chloride in four different smooth muscle tests.116 MJ Fanning and colleagues, reported
that quercitin inhibits antigen-induced release of histamine from mast cells and
basophils and also inhibits contractions induced by histamine, acetylcholine and PGE2.
It was noted that the effect was concentration-dependent.117 FL Pearce, et al. reported similar
findings. The found that quercitin, a naturally occurring flavonol structurally
related to the antiallergic drug disodium cromoglycate, inhibits anaphylactic histamine
release.118 M Sasajima, and associates, reported
that the isoprenyl flavonoids sophoradin and sophoranone significantly reduced the volume
of gastric juice.119 I Lambev, et al., reported rutin prevents the release of mastcytic histamine.120 Enzymes, Flavonoids and
Vitamin C Compared to NSAIDS JP Tarayre and H Lauressergues reported that a synergistic combination of enzymes, flavonoids and vitamin C (ascorbic acid) reduces capillary permeability induced by histamine. They concluded that the synergistic combination showed a more complete spectrum of action than 7 non-steroid antiinflammatory substances against initial symptoms of inflammation.121
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