A Pilot Study To Investigate the Immune-Modulatory Effects of Fasting in Steroid-Naive Mild Asthmatics

Abstract

A fasting mimetic diet blunts inflammation, and intermittent fasting has shown ameliorative effects in obese asthmatics. To examine whether canonical inflammatory pathways linked with asthma are modulated by fasting, we designed a pilot study in mild asthmatic subjects to assess the effect of fasting on the NLRP3 inflammasome, Th2 cell activation, and airway epithelial cell cytokine production. Subjects with documented reversible airway obstruction and stable mild asthma were recruited into this study in which pulmonary function testing (PFT) and PBMCextraction was performed 24 h after fasting, with repeated PFT testing and blood draw 2.5 h after refeeding. PFTs were not changed by a prolonged fast. However, steroid-naive mild asthmatics showed fasting-dependent blunting of the NLRP3 inflammasome. Furthermore, PBMCs from these fasted asthmatics cocultured with human epithelial cells resulted in blunting of house dust mite-induced epithelial cell cytokine production and reduced CD4 T cell Th2 activation compared with refed samples. This pilot study shows that prolonged fasting blunts the NLRP3 inflammasome and Th2 cell activation in steroid-naive asthmatics as well as diminishes airway epithelial cell cytokine production. This identifies a potential role for nutrient level-dependent regulation of inflammation in asthma. Our findings support the evaluation of this concept in a larger study as well as the potential development of caloric restriction interventions for the treatment of asthma.

Effects of short-term fasting on cancer treatment

“…The weight loss during STF is approximately 0.9 kg per day and decreases during prolonged fasting to 0.3 kg per day by the third week [26, 121]. Various studies examined the potential of fasting in the treatment of mood disorders, rheumatic diseases, asthma, chronic pain syndromes, hypertension, and metabolic syndrome [122, 123]. For example, a large cohort study of more than 2000 subjects with chronic illness and pain syndromes, who used a very low-calorie diet of 350 kcal per day for 7 days, showed an increase in quality of life without any serious side effect [122].…”

Enemy or ally? Fasting as an essential regulator of immune responses

“…In a pilot observational human study (NCT02471300) i , the effect of 24-h fasting on immune responses was tested in mild asthmatics. In this cohort of 18 patients, fasting resulted in inhibition of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome, and reduced the production of disease-mediating cytokines, such as thymic stromal lymphopoietin in airway epithelial cells, and IL-4 from Type 2 T helper (Th2) cells [57]. Thus, although pending further studies, it is possible that CR or transient fasting might counterbalance certain mechanisms promoting chronic inflammation, without impairing protective immunity to infection.…”

“…From another angle, chronic inflammatory conditions, such as asthma caused by exposure to allergens, have been blunted by dietary intervention in mice and humans, mainly by modulating type 2 immune responses [54][55][56][57]. In a pilot observational human study (NCT02471300) i , the effect of 24-h fasting on immune responses was tested in mild asthmatics.…”

Fasting Ramadan During COVID-19 Pandemic: Immunomodulatory Effect

“…On the other hand, Ramadan diurnal intermittent fasting has a positive effect on the overall inflammatory status of the human body ( 24 – 27 ) and tends to decrease such pro-inflammatory cytokines, particularly IL-6, IL-1β ( 6 , 7 ), and proinflammatory chemokines CXCL1, CXCL10, and CXCL12 ( 24 – 27 ), which might alleviate lung tissue damage. Ramadan intermittent fasting has a modulatory effect on macrophages and render them to produce low amounts of cytokines ( 32 ), previously proven to positively affect asthma patients ( 33 ). Of note is that fasting restored the balance of renin–angiotensin system ( 34 , 35 ), which is crucial to reduce the effect of angiotensin II, pro-inflammatory cytokines, and fibrosis in the lung tissue ( 30 ).…”