Flipping the Metabolic Switch: Understanding and Applying Health Benefits of Fasting

Intermittent fasting may have potential in the treatment of obesity and related metabolic conditions.

FEB, 2018

Written by Stephen D. Anton, Keelin Moehl, William T. Donahoo, Krisztina Marosi, Stephanie Lee, Arch G. Mainous III, Christiaan Leeuwenburgh,Mark P. Mattson

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Intermittent fasting (IF) is a term used to describe a variety of eating patterns in which no or few calories are consumed for time periods that can range from 12 hours to several days, on a recurring basis. Here we focus on the physiological responses of major organ systems, including the musculoskeletal system, to the onset of the metabolic switch – the point of negative energy balance at which liver glycogen stores are depleted and fatty acids are mobilized (typically beyond 12 hours after cessation of food intake). Emerging findings suggest the metabolic switch from glucose to fatty acid-derived ketones represents an evolutionarily conserved trigger point that shifts metabolism from lipid/cholesterol synthesis and fat storage to mobilization of fat through fatty acid oxidation and fatty-acid derived ketones, which serve to preserve muscle mass and function. Thus, IF regimens that induce the metabolic switch have the potential to improve body composition in overweight individuals. Moreover, IF regimens also induce the coordinated

activation of signaling pathways that optimize physiological function, enhance performance, and slow aging and disease processes. Future randomized controlled IF trials should use biomarkers of the metabolic switch (e.g., plasma ketone levels) as a measure of compliance and the magnitude of negative energy balance during the fasting period.



There are many reasons some individuals experience difficulties adhering to IF regimens, but most notably is the fact that very few studies ensured that “the switch” was truly flipped ketosis was achieved. Although some individuals have difficulties in adherence, the of studies show similar dropout or non-adherence rates in the treatment and control groups. Finally, despite the many longer-term studies with very few adverse events, safety remains a potential concern. If findings of the research outlined above provide additional support for the metabolic benefits of IF, however, it is foreseeable in the near future that healthcare professionals may recommend IF regimens to patients who are overweight, insulin resistant, and/or hypertensive.