Fasting has surged to the forefront of popular health trends, embraced by millions seeking weight loss and metabolic benefits. Yet, emerging research from the University of British Columbia Okanagan (UBCO) reveals that the metabolic and immunological responses to fasting are far from uniform across different body types. In particular, individuals living with obesity demonstrate a markedly distinct physiological reaction compared to their leaner counterparts, shedding new light on the complex interplay between nutrition, metabolism, and immune function.
At the heart of this investigation lies the ketogenic diet, characterized by a severe reduction in carbohydrate intake, which promotes the body’s shift from glucose to fat utilization through the production of ketone bodies. Fasting exacerbates this metabolic state by further depleting glucose reserves, thus intensifying ketone generation—a process believed to enhance fat burning and improve various health parameters. However, Dr. Hashim Islam, Assistant Professor at UBCO’s School of Health and Exercise Sciences and the Centre for Chronic Disease Prevention and Management, emphasizes that this metabolic switch may not equally benefit all individuals, particularly those affected by obesity.
The UBCO research team, including lead author Dr. Helena Neudorf, conducted a controlled clinical trial to dissect how fasting influences both metabolism and immune responses in people with obesity relative to lean individuals. Participants were subjected to a 48-hour fast, during which multiple blood samples were collected to quantify changes in hormones, metabolites, metabolic rate, inflammatory markers, and crucially, the activity of T cells—white blood cells implicated in immune defense and chronic inflammation.
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Their findings, published in the journal iScience, reveal a pronounced divergence: individuals with obesity exhibited persistently elevated pro-inflammatory T cells even after the fasting period, coupled with a blunted increase in circulating ketones when compared to lean participants. This suggests a diminished capacity to transition metabolically in response to nutrient deprivation, highlighting an impaired immunometabolic flexibility that may underlie chronic inflammatory states often associated with obesity.
The inability of immune cells in obese individuals to adapt metabolically to fasting was further underscored by Dr. Neudorf, who noted that T cells in lean participants successfully shifted their fuel utilization toward increased fat metabolism during fasting. This metabolic flexibility is critical, as it not only fuels immune cells under nutrient stress but also supports an anti-inflammatory immune environment. In contrast, this adaptive metabolic response was weaker or absent in obese participants, possibly perpetuating a pro-inflammatory milieu.
Ketone bodies, traditionally regarded as alternative energy substrates during fasting or ketogenic diets, also play a pivotal regulatory role in immune function through chemical modifications such as ketone conjugation to amino acids or proteins. The study revealed that these ketone-related immunoregulatory pathways were less active in people with obesity, further implicating a disrupted biochemical network that could influence immune dysfunction.
These revelations challenge the simplistic view that fasting is universally beneficial and caution against a one-size-fits-all approach. While fasting remains a promising intervention for metabolic health, Dr. Islam notes the nuanced response in people with obesity calls for a deeper understanding of how adiposity and chronic inflammation impact fasting physiology and its long-term health effects.
Importantly, the research does not conclude whether the altered response in obese individuals is inherently detrimental or potentially advantageous under certain circumstances. Instead, it underscores the enormous complexity underlying human nutritional physiology, particularly the interdependence between metabolism and immune regulation. This intricate balance dictates not only energy homeostasis but also susceptibility to inflammation-driven diseases, many of which disproportionately affect those with obesity.
The study’s randomized controlled design strengthens the validity of these findings by directly comparing immunometabolic changes within and between groups under a standardized fasting regimen. By integrating blood-based biochemical and immunological assessments, the research provides a comprehensive snapshot of fasting’s multifaceted impact on human physiology.
These insights also open avenues for personalized nutritional therapies tailored to individual metabolic and immunological profiles, especially in the context of obesity-related chronic diseases. Therapeutic fasting protocols may require adjustment in duration, frequency, or nutritional composition to maximize benefits and minimize potential adverse effects in distinct populations.
The UBCO research team highlights the urgent need for further investigations to elucidate the molecular mechanisms driving these differential responses, including the role of adipose tissue inflammation, mitochondrial function, and ketone metabolism pathways. Such knowledge could revolutionize dietary interventions and fasting-based therapies, transforming them from generic trends into scientifically grounded medical treatments.
In summary, this groundbreaking study advances our understanding of how fasting intersects with obesity, metabolism, and immune function, revealing that the metabolic and immunological benefits of fasting are not uniformly experienced. People living with obesity exhibit a distinct immunometabolic profile that modulates their response to fasting, especially in terms of inflammatory activity and ketone metabolism. These findings challenge current dietary paradigms and affirm the need for personalized approaches in applying fasting as a therapeutic modality.
Subject of Research: People
Article Title: Altered immunometabolic response to fasting in humans living with obesity
News Publication Date: 18-Jul-2025
Web References:
https://pubmed.ncbi.nlm.nih.gov/40662191/
References:
iScience, DOI: 10.1016/j.isci.2025.112872.
Keywords: Human health, Clinical medicine, Diseases and disorders, Health care
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