Original ContributionAlternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma
Introduction
The cause(s) and pathogenic mechanisms of asthma are poorly understood, and available treatments can alleviate symptoms but do not reverse the disease process [1]. The prevalence of asthma in industrialized countries throughout the world has increased significantly during the past 30 years, particularly in children where rates have nearly doubled [2]. This recent surge of asthma prevalence does not appear to be the result of increases in specific allergens. Instead, increasing evidence points to a link between overeating/obesity and asthma. Weight loss often improves asthma symptoms in obese subjects [3], and low calorie diets and exercise programs result in weight loss and can reduce asthma symptoms in overweight children and adults [4], [5]. However, while obesity is a risk factor for asthma-related symptoms such as wheezing, it may not be a cause of airway hyperresponsiveness [5], [6]. It is therefore unclear whether weight loss modifies the asthma disease process.
The molecular and cellular mechanisms underlying airway hyperresponsiveness and asthma symptoms are complex and poorly understood. Two general alterations in the lungs are increased oxidative stress and inflammation [7], [8], [9], [10], [11]. The local changes in the lungs are associated with increases in markers of inflammation and oxidative stress in the blood including TNF [12], interleukin-6 [13] and lipid peroxidation products [14]. In addition, circulating levels of brain-derived neurotrophic factor (BDNF) are increased in patients with asthma and other allergic disorders [15], [16]. Although capable of transiently relieving asthma symptoms, agents such as corticosteroids and β-adrenoreceptor agonists do not block or reverse the underlying disease process and their long-term use poses a considerable risk of morbidity and mortality [17], [18].
Caloric restriction (CR) improves numerous health indicators in rodents, monkeys, and humans, including those associated with risk of cardiovascular disease, type 2 diabetes, and cancers [19], [20], [21]. Similar to daily CR (on a long-term basis), intermittent CR can extend lifespan and protect multiple organ systems against disease in rodents [22], [23], [24]. However, despite considerable evidence that intermittent CR is beneficial in rodent disease models, the potential application of intermittent CR to human diseases is largely untested [25]. In light of the poor adherence of subjects to continuous CR diets and adverse consequences associated with gastric bypass surgery and pharmacological interventions [26], we designed a pilot study aimed at determining the feasibility and efficacy of an intermittent CR diet in treating overweight patients with moderate asthma.
Section snippets
Subjects
This study was approved by an independent Review Board (Cresent City IRB) and analyses of serum samples were approved by the IRB of the National Institute on Aging Intramural Research Program. Participants were recruited through newspaper advertisements in the New Orleans metropolitan area. Inclusion and exclusion criteria were assessed by telephone, an in person interview, and a physician-conducted examination. Participants meeting the following criteria were included in the study: stable body
Alternate day calorie restriction improves asthma symptoms and pulmonary function
Of 40 responders to the newspaper advertisement, 23 met inclusion and exclusion criteria and 14 agreed to enroll in the study. Of these, one died of unknown causes during the baseline, one dropped out due to a change in vacation plans during baseline, one decided not to continue during the first study week, and one dropped out the second study week due to work-related travel. Of the remaining 10, 9 completed the study; one subject did not complete the study because she volunteered that she was
Discussion
Nine of the 10 asthma subjects who began the ADCR regimen complied with the diet, as indicated by progressive weight loss, and completed the study. All 9 subjects exhibited improved asthma symptoms, control, and quality of life, demonstrating a clinical benefit of the ADCR diet. An improvement of ACQ or mini AQLQ score of 0.5 is considered clinically important and has been repeatedly shown to be useful in research and management of individual asthma patients. In a recent clinical study of 1414
Acknowledgment
This research was supported, in part, by the National Institute on Aging Intramural Research Program, NIH.
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