A new study published in *Nature Communications* sheds light on the physiological and metabolic impacts of seven days of water-only fasting on human physical performance and skeletal muscle adaptation. This research, conducted by a team of renowned scientists, delves into the evolutionary and physiological mechanisms that enable humans to endure prolonged periods without food. The findings, which detail the complex interplay between muscle strength, endurance, and metabolic adaptations, provide a comprehensive understanding of how the human body maintains physical capability during severe caloric deprivation.
The study involved 13 participants, seven males and six females, who underwent a week-long fasting protocol. Over this period, participants lost an average of 5.8 kilograms in body weight, with significant reductions in lean mass (4.6 kilograms) and fat mass (1.4 kilograms). Despite this substantial loss, maximal isometric and isokinetic strength in the leg muscles remained remarkably intact. These results suggest that humans have evolved mechanisms to preserve critical physical capabilities necessary for survival during periods of starvation.
The participants’ metabolic profiles underwent dramatic shifts during the fasting period. Continuous glucose monitoring revealed a steady decline in blood glucose levels during the first three days, followed by stabilization. Resting metabolic rate (RMR) remained consistent throughout the fasting period, yet the body’s energy substrate utilization shifted markedly. Fat oxidation increased from 37% to 73% of total energy turnover, accompanied by a decline in carbohydrate contribution from 53% to 19%. This metabolic shift underscores the body’s reliance on fat reserves to sustain energy needs in the absence of dietary intake.
Interestingly, muscle glycogen stores, a key substrate for high-intensity exercise, were halved during the fasting period. This reduction aligns with the observed decline in peak oxygen consumption (VO2peak), which dropped by 13% in absolute terms and 7% relative to body weight. Participants’ peak power output during aerobic exercise decreased by 16%, reflecting diminished endurance capacity. The preservation of muscle glycogen and oxidative enzyme expression in skeletal muscle, despite these changes, highlights the body’s ability to conserve essential energy reserves while prioritizing survival.
One of the most striking findings of the study was the 13-fold increase in pyruvate dehydrogenase kinase 4 (PDK4) expression in skeletal muscle. PDK4 plays a crucial role in regulating carbohydrate metabolism by inhibiting pyruvate dehydrogenase (PDH) activity, effectively reducing carbohydrate oxidation during exercise. This adaptive mechanism likely prevents hypoglycemia during prolonged fasting but comes at the cost of reduced aerobic capacity. Elevated phosphorylation of PDH at inhibitory sites further corroborated this metabolic shift, illustrating the body’s prioritization of glucose conservation.
The study also explored the effects of fasting on other metabolic markers. Plasma free fatty acids (FFA) quadrupled, and the maximal rate of fat oxidation nearly doubled during exercise. Ketone bodies, particularly β-hydroxybutyrate, rose significantly, serving as a key energy substrate for skeletal muscle and the brain. Notably, ketone levels decreased during exercise in the fasting state, suggesting their utilization as a critical energy source during physical activity.
While muscle strength was preserved, the study revealed a decline in high-intensity endurance capacity. Respiratory exchange ratio (RER) values, indicative of substrate utilization during exercise, fell from 1.12 pre-fasting to 0.93 post-fasting. This shift reflects a reduced reliance on carbohydrate oxidation and an increased dependency on fat metabolism. The decrease in lactate production during exercise further supports the notion of diminished anaerobic capacity, a trade-off for enhanced fat utilization.
From an evolutionary perspective, these findings underscore the human body’s remarkable ability to adapt to periods of caloric deprivation. The preservation of muscle strength, particularly in the legs, would have been essential for mobility and survival during times of food scarcity. The observed decline in endurance capacity, while notable, may have been less critical in the context of intermittent physical exertion typical of early human foraging and hunting activities.
The study’s comprehensive methodology, including advanced metabolic analyses and muscle biopsies, provides valuable insights into the molecular mechanisms underlying fasting-induced adaptations. The authors highlight the role of PDK4 as a key regulator of carbohydrate metabolism during prolonged fasting. By inhibiting PDH activity, PDK4 ensures glucose conservation while promoting reliance on fat and ketone bodies as alternative energy sources.
Despite the significant metabolic shifts observed, participants reported minimal adverse effects, and no serious complications were recorded. This finding demonstrates the feasibility of prolonged fasting in healthy individuals under controlled conditions. However, the authors caution against generalizing these results to broader populations, particularly those with underlying health conditions or limited fat reserves.
This study paves the way for future research exploring the therapeutic potential of fasting in various contexts, including weight management, metabolic disorders, and physical performance optimization. The authors emphasize the need for further investigations into the long-term effects of fasting, particularly its impact on muscle protein turnover and mitochondrial function. Additionally, the integration of fasting protocols with exercise interventions may offer novel strategies for enhancing metabolic health and physical performance.
In conclusion, this landmark study reveals the human body’s extraordinary resilience and adaptability during periods of prolonged caloric deprivation. By preserving muscle strength and oxidative capacity while prioritizing fat and ketone metabolism, the body demonstrates a finely tuned balance between survival and physical performance. These findings not only deepen our understanding of human physiology but also offer intriguing possibilities for harnessing fasting-induced adaptations in health and performance contexts.
Subject of Research: Human physiology and metabolic adaptation during prolonged fasting
Article Title: Effects of seven days’ fasting on physical performance and metabolic adaptation during exercise in humans
News Publication Date: 02 January 2025
Article Doi References: 10.1038/s41467-025-00122-0
Image Credits: Scienmag
Keywords: fasting, physical performance, metabolic adaptation, muscle strength, endurance capacity, fat oxidation, PDK4, skeletal muscle, human physiology, ketone metabolism
