Metabolic Switching and Different Forms of Fasting

Explore the recent NEJM review on intermittent fasting and its effects on metabolic switching. Gain insights into the distinct forms of fasting, their physiological effects, and the need for further research to understand their impact on health and disease.

Intermittent fasting (IF) has received considerable attention in recent years for its potential health benefits. However, a recent review published in The New England Journal of Medicine (NEJM) highlights the need for a more nuanced understanding of different forms of fasting and their effects on health and disease.

The review article, titled "Effects of Intermittent Fasting on Health, Aging, and Disease," explores the mechanisms underlying the beneficial effects of IF, such as metabolic switching and stress resistance. Metabolic switching refers to the body's ability to shift from using glucose as a fuel source to utilizing fatty acids and ketone bodies. This ability is considered an indicator of metabolic flexibility.

The authors note that IF encompasses three distinct forms of fasting: alternate-day fasting (ADF), 5:2 intermittent fasting (5:2), and daily time-restricted feeding (TRF). However, the conflation of these forms in the definition of IF can be confusing and inaccurate. Each form of fasting may have different physiological effects, and lumping them together may dilute our understanding of their individual insights.

One of the key questions raised in the review is the level of ketosis required to elicit the benefits associated with fasting. Ketone bodies, which are produced during fasting, not only serve as an alternative fuel source but also act as signaling molecules that influence metabolism, health, and aging. Studies in mice suggest that a minimum threshold of around 1 mM of ketones is necessary to achieve these benefits.

However, the review highlights a lack of studies in humans that measure plasma ketones during IF, TRF, or ADF. While some studies have reported an increase in plasma ketones to 0.2-0.5 mM within the first 24 hours of fasting, it remains unclear whether different types of fasting can reach the threshold of 1 mM. This raises the possibility that certain forms of fasting may not induce the desired metabolic switch.

Furthermore, the review emphasizes the need for more in-depth and longer-term studies to evaluate the impact of different forms of fasting on metabolic flexibility. Questions regarding the increase in ketone levels over time, the comparative efficacy of various fasting regimens, and the relationship between TRF and ketogenic diets remain unanswered.

In conclusion, the NEJM review highlights the need for further research to elucidate the effects of different forms of fasting on metabolic switching and overall health. By conducting more comprehensive studies that measure plasma ketones and explore various forms of fasting, we can gain a better understanding of the physiological effects and potential benefits of these dietary approaches.

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