Fuel, Glucose and the Regulation of Exercise
Understanding how diet, blood glucose and the brain influence physical performance.
Overview
For decades, the prevailing explanation for fatigue in endurance sport has centred on the working muscles: as exercise continues, muscle glycogen falls and performance declines. Prof Tim Noakes’ research has long questioned whether this explanation tells the whole story.
His earlier work on the Central Governor Model proposed that exercise is regulated through a complex interaction between the brain and the body. An athlete’s pace, effort and eventual decision to stop cannot necessarily be explained by a single fuel store reaching empty. That question, what actually regulates performance? continues to shape much of this current research focus.
More recent work has brought blood glucose into sharper focus. The body holds a relatively large amount of glucose as glycogen in the muscles, but the glucose circulating in the blood, supported by the liver, forms a much smaller and more tightly regulated supply. Research into these large and small glucose pools asks whether the ability to maintain blood glucose during prolonged exercise may be more important to fatigue than muscle glycogen depletion alone.
This changes the questions asked about carbohydrate. Rather than treating an athlete’s habitual diet and their fuelling during exercise as the same issue, the research examines them separately. How does the body adapt to eating less carbohydrate? Can an athlete continue to perform while using more fat as fuel? Why might a small amount of carbohydrate consumed during exercise improve performance after adaptation to either a low- or high-carbohydrate diet?
These questions have implications beyond choosing a diet. They challenge established models of how the body supplies fuel, protects blood glucose and regulates effort. The aim is to test those models against what happens in athletes during exercise, and to refine them as new evidence emerges.
Why is this important?
Sports nutrition advice has often assumed that maximizing carbohydrate availability is the key to sustaining endurance performance. Muscle glycogen clearly has a role, but research comparing different diets and fuelling strategies suggests that the relationship between carbohydrate intake and performance is more complex.
An athlete can adapt to using more fat during exercise without necessarily losing the ability to perform. At the same time, carbohydrate consumed during prolonged exercise can help prevent a fall in blood glucose and improve performance. Understanding why both findings can be true may lead to a more useful account of fatigue and more precise questions about when, how much and for whom carbohydrate intake is beneficial.
This remains an area of scientific debate. The value of the research lies in testing explanations that have often been taken for granted, including the assumption that the amount of glycogen in the working muscles is the principal factor determining when exercise must end.
Building on Prof Tim Noakes’ work
Lore of Running brought together Prof Noakes’ research on the physiology, training and practice of endurance running.
Its fourth edition explored ideas about fatigue and the brain’s role in regulating exercise that challenged conventional thinking at the time.
Prof Noakes has now completed a full rewrite of the fourth edition, which is currently being edited. The new book incorporates the latest research on glucose pools, carbohydrate regulation and exercise performance. It will allow readers to follow how his thinking has developed, from questions about the brain’s regulation of effort to newer evidence about blood glucose, fuel use and fatigue.
The publications below show that progression. Earlier work established a broader model of exercise regulation; subsequent studies tested how athletes respond to different diets; and recent research has examined the distinction between muscle glycogen and the smaller glucose supply that must be maintained during exercise.
Salient research outputs
This paper proposed that exercise performance is regulated through interactions between the brain and the body, rather than being determined solely by a physical limit in the working muscles. It provides an important foundation for the continuing investigation into what causes an athlete to change pace or stop. bjsm.bmj.com
This study found that cyclists accustomed to a low-carbohydrate diet responded differently to a glucose tolerance test than cyclists eating a mixed diet. It raised an important question about how to interpret glucose measurements in people whose bodies have adapted to a different habitual fuel supply. pubmed.ncbi.nlm.nih.gov
By comparing diets with the same energy content, this study examined what changed when carbohydrate intake changed. It measured exercise performance alongside fat use, glucose patterns and metabolic health markers, connecting questions about athletic fuel use with questions about glucose regulation. www.frontiersin.org
Low carbohydrate high fat ketogenic diets on the exercise crossover point and glucose homeostasis
This review questions whether the conventional model of a shift towards carbohydrate use at higher exercise intensities applies in the same way after adaptation to a low-carbohydrate diet. It also considers how the body maintains blood glucose under different dietary conditions. www.frontiersin.org
Carbohydrate ingestion eliminates hypoglycemia and improves endurance exercise performance in triathletes adapted to very low- and high-carbohydrate isocaloric diets
Winner of the American Journal of Physiology–Cell Physiology Best Impact Paper Award, presented at APS 2026.
After adapting to either a very low- or high-carbohydrate diet, trained triathletes performed similarly during strenuous exercise when they consumed no carbohydrate during the test. Just 10 g of carbohydrate per hour during exercise prevented low blood glucose and improved time to exhaustion following both diets. The result brings the research question into focus: carbohydrate consumed during prolonged exercise may help by maintaining blood glucose, even when the athlete’s habitual diet and use of fuel differ substantially. American Physiological Society
Carbohydrate Ingestion on Exercise Metabolism and Physical Performance
This extensive review re-examines evidence spanning more than a century of exercise research. It asks whether the benefits of carbohydrate consumed during exercise are best explained by replacing muscle fuel, maintaining blood glucose, or other regulatory effects. It develops the distinction between the large muscle glycogen pool and the smaller glucose supply available to the rest of the body. pubmed.ncbi.nlm.nih.gov
Does a low-carbohydrate diet impede endurance sports performance? No
This contribution to a scientific debate sets out Prof Noakes’ interpretation of the evidence on low-carbohydrate adaptation and endurance performance. It argues for closer attention to blood glucose regulation during prolonged exercise, while acknowledging that carbohydrate consumed during exercise can be useful. ajcn.nutrition.org
Where this research is going next
The next challenge is to test more precisely how the brain, blood glucose and the body’s fuel stores interact during exercise. Why do athletes respond differently to the same dietary approach? When does blood glucose begin to affect performance? And does the carbohydrate needed during an event depend on its duration, intensity and the athlete’s prior adaptation?
The complete rewrite of Lore of Running brings the history of these questions together with the latest research. This page provides a window into that continuing work: revisiting accepted explanations, testing alternatives and building a more complete understanding of human performance.
