Original Contribution
Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma

https://doi.org/10.1016/j.freeradbiomed.2006.12.005Get rights and content

Abstract

Asthma is an increasingly common disorder responsible for considerable morbidity and mortality. Although obesity is a risk factor for asthma and weight loss can improve symptoms, many patients do not adhere to low calorie diets and the impact of dietary restriction on the disease process is unknown. A study was designed to determine if overweight asthma patients would adhere to an alternate day calorie restriction (ADCR) dietary regimen, and to establish the effects of the diet on their symptoms, pulmonary function and markers of oxidative stress, and inflammation. Ten subjects with BMI > 30 were maintained for 8 weeks on a dietary regimen in which they ate ad libitum every other day, while consuming less than 20% of their normal calorie intake on the intervening days. At baseline, and at designated time points during the 8-week study, asthma control, symptoms, and Quality of Life questionnaires (ACQ, ASUI, mini-AQLQ) were assessed and blood was collected for analyses of markers of general health, oxidative stress, and inflammation. Peak expiratory flow (PEF) was measured daily on awakening. Pre-and postbronchodilator spirometry was obtained at baseline and 8 weeks. Nine of the subjects adhered to the diet and lost an average of 8% of their initial weight during the study. Their asthma-related symptoms, control, and QOL improved significantly, and PEF increased significantly, within 2 weeks of diet initiation; these changes persisted for the duration of the study. Spirometery was unaffected by ADCR. Levels of serum β-hydroxybutyrate were increased and levels of leptin were decreased on CR days, indicating a shift in energy metabolism toward utilization of fatty acids and confirming compliance with the diet. The improved clinical findings were associated with decreased levels of serum cholesterol and triglycerides, striking reductions in markers of oxidative stress (8-isoprostane, nitrotyrosine, protein carbonyls, and 4-hydroxynonenal adducts), and increased levels of the antioxidant uric acid. Indicators of inflammation, including serum tumor necrosis factor-α and brain-derived neurotrophic factor, were also significantly decreased by ADCR. Compliance with the ADCR diet was high, symptoms and pulmonary function improved, and oxidative stress and inflammation declined in response to the dietary intervention. These findings demonstrate rapid and sustained beneficial effects of ADCR on the underlying disease process in subjects with asthma, suggesting a novel approach for therapeutic intervention in this disorder.

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.

References (51)

  • S.A. Summers

    Ceramides in insulin resistance and lipotoxicity

    Prog. Lipid Res.

    (2006)
  • A. Nadeem et al.

    Increased oxidative stress and altered levels of antioxidants in asthma

    J. Allergy Clin. Immunol.

    (2003)
  • C.P. Fenster et al.

    Weight loss and race modulate nitric oxide metabolism in overweight women

    Free Radic. Biol. Med.

    (2004)
  • J.B. Johnson et al.

    The effect on health of alternate day calorie restriction: eating less and more than needed on alternate days prolongs life

    Med. Hypotheses

    (2006)
  • E.H. Bel

    Clinical phenotypes of asthma

    Curr. Opin. Pulm. Med.

    (2004)
  • S.A. Shore et al.

    Obesity and asthma

    Pharmacol. Ther.

    (2005)
  • B. Stenius-Aamiala et al.

    Immediate and long term effects of weight reduction in obese people with asthma: randomized controlled study

    BMJ

    (2000)
  • L.M. Schachter et al.

    Obesity is a risk for asthma and wheeze but not airway hyperresponsiveness

    Thorax

    (2001)
  • L.G. Wood et al.

    Biomarkers of lipid peroxidation, airway inflammation and asthma

    Eur. Respir. J.

    (2003)
  • N.L. Reynaert et al.

    Nitric oxide and redox signaling in allergic airway inflammation

    Antioxid. Redox Signal.

    (2005)
  • B. Shakoory et al.

    The role of human mast cell-derived cytokines in eosinophil biology

    J. Interferon Cytokine Res.

    (2004)
  • A. Yokoyama et al.

    Circulating interleukin-6 levels in patients with bronchial asthma

    Am. J. Respir. Crit. Care Med.

    (1995)
  • A. Sharma et al.

    Lipid peroxidation in bronchial asthma

    Indian J. Pediatr.

    (2003)
  • J.C. Virchow et al.

    Neurotrophins are increased in bronchoalveolar lavage fluid after segmental allergen provocation

    Am. J. Respir. Crit. Care Med.

    (1998)
  • O. Noga et al.

    The influence of inhalative corticosteroids on circulating nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in allergic asthmatics

    Clin. Exp. Allergy

    (2001)
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