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

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. Spirometry was unaffected by ADCR. Levels of serum beta-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-alpha 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.

Figure 1

Asthma subjects lose weight and exhibit improved mood and peak airflow when maintained on and alternate day calorie restriction diet. Body weights (a), mood/energy scores (b), hunger scores (c) and peak expiratory flow (d) were measured at baseline and at the indicated time points during the 2 month ADCR period.

Figure 2

Alternate day calorie restriction results in improved symptoms in subjects with asthma. a. MiniAQLQ scores for four domains (symptoms, activity limitations, emotional function and environmental stimuli) in subjects at baseline and after 8 weeks of ADCR. The differences between the 8 week and baseline values were significantly different for each of the four domains (p<0.004). b. ASUI scores increased rapidly and significantly (p<0.003) within 2 weeks of diet initiation.

Figure 3

Alternate day calorie restriction results in changes in lipid and energy metabolism indicative of improved health in asthma subjects. Levels of total cholesterol (a), 3-hydroxybutyrate (b), leptin (c) and ghrelin (d) were measured in serum samples from asthma subjects on successive ad libitum (AL) and CR days at baseline and at 2, 4 and 8 weeks of ADCR. *p<0.05, **p<0.01 compared to the baseline value; ##p<0.01 compared the corresponding CR value.

Figure 4

Markers of inflammation are reduced in asthma subjects in response to the ADCR diet. Levels of TNF-α (a), BDNF (b) and ceramides (c) were measured in serum samples from asthma subjects on successive ad libitum (AL) and CR days at baseline and at 2, 4 and 8 weeks of ADCR. *p<0.05, **p<0.01, ***p<0.001 compared to the baseline value.

Figure 4

Markers of inflammation are reduced in asthma subjects in response to the ADCR diet. Levels of TNF-α (a), BDNF (b) and ceramides (c) were measured in serum samples from asthma subjects on successive ad libitum (AL) and CR days at baseline and at 2, 4 and 8 weeks of ADCR. *p<0.05, **p<0.01, ***p<0.001 compared to the baseline value.

Figure 5

Markers of oxidative stress are reduced in asthma subjects in response to the ADCR diet. Levels of total protein carbonyls (a), nitrotyrosine (b), 8-isoprostanes (c) and lysine and histidine adducts of 4-hydroxynonenal (d) were measured in serum samples from asthma subjects on successive ad libitum (AL) and CR days at baseline and at 2, 4 and 8 weeks of ADCR. *p<0.05, **p<0.01, ***p<0.001 compared to the baseline value.

Figure 6

Levels of the antioxidant uric acid are increased in asthma subjects in response to the ADCR diet. Levels of uric acid were measured in serum samples from asthma subjects on successive ad libitum (AL) and CR days at baseline and at 2, 4 and 8 weeks of ADCR. *p<0.05 compared to the baseline value.