On July 24, 2025, the BSI Medical Society Journal Club, hosted by Bob Kaplan with contributions from Pete Shaw, discussed the paper High-Fat Diet Improves Metabolic Flexibility During Progressive Exercise to Exhaustion (VO2max Testing) and During 5 km Running Time Trials. The group reviewed how metabolic flexibility—the ability to switch between fat and carbohydrate as fuel—relates to performance and health. While traditional views place carbohydrates as the dominant fuel for high-intensity exercise, newer evidence shows that fat oxidation can be sustained at surprisingly high rates under low-carbohydrate, high-fat (LCHF) dietary conditions. The discussion drew connections to earlier research, particularly the “crossover” concept, and examined how measurement tools like respiratory quotient (RQ) and substrate oxidation calculations shape interpretations of fuel use.
The meeting emphasized that athletes on an LCHF diet demonstrated higher fat oxidation during both progressive exercise and 5K trials, though overall performance (VO2max and average pace) was not consistently superior to a high-carbohydrate, low-fat diet. This suggests that metabolic flexibility itself—rather than reliance on a single fuel—may be key for endurance and health. They also noted the practical implications for training and fueling strategies, including “train-low, compete-high” approaches that aim to optimize fat oxidation capacity while still leveraging carbohydrates for peak performance. Ultimately, they concluded that individualized nutrition strategies, grounded in metabolic flexibility, may offer the best path forward for both athletic output and long-term health.
A 10-minute summary of the webinar is available here free, for anyone, while the full video is available for Medical Society Members and MetFix affiliates in their dashboard.
Bob Kaplan is an independent research analyst. Bob previously served as director of research at Early Medical, contributing to The Drive podcast with Peter Attia and its other properties. Kaplan was a researcher at the Nutrition Science Initiative (NuSI), and an exercise physiologist at the University of Nevada, Las Vegas. His current and previous research interests include meta-research, chronic diseases, bioenergetics, exercise physiology, and nutrition.
Support the Broken Science Initiative.
Subscribe today →
recent posts
Metabolic health, medical education, and the case for bringing clinicians and coaches together
At the 2026 Unbreakable Health Retreat in Miami, Emily Kaplan hosted a panel with Bob Kaplan, Professor Thomas Seyfried, and Dr. Derek Lee on what it means to treat cancer as a metabolic disease. They discussed the glucose-ketone index (GKI), nutritional ketosis, and strategies aimed at restricting the fuels cancer cells depend on while considering how metabolic therapy can fit alongside standard cancer treatment.
The conversation also addressed the practical realities patients face when trying to pursue a metabolic approach within the conventional oncology system, including questions about nutrition, repurposed drugs, inherited cancer risk, and how to evaluate different treatment options. Seyfried and Lee connected these clinical questions back to mitochondrial dysfunction, fermentation, and the metabolic vulnerabilities that may offer additional targets for cancer treatment.
An abbreviated version of this discussion is available here, for free.
At the 2026 Unbreakable Health Retreat in Miami, Professor Thomas Seyfried presented the case that cancer is fundamentally a mitochondrial metabolic disease rather than primarily a genetic one. He contrasts the dominant somatic mutation theory with a metabolic model in which impaired mitochondrial respiration drives a shift toward fermentation, dysregulated cell growth, and the mutations commonly associated with cancer.
Citing the work of Otto Warburg and research from his lab at Boston College, Seyfried explains how cancer cells rely heavily on fermentable fuels—particularly glucose and glutamine—and why mitochondrial dysfunction sits upstream of many of the genetic abnormalities seen in tumors. He also discusses reactive oxygen species, altered cellular signaling, and the role of mitochondria in regulating cell growth and behavior.
The presentation then turns to the therapeutic implications of this model. Seyfried explains strategies aimed at placing tumor cells under metabolic stress by restricting the fuels they depend on, including ketogenic metabolic therapy and approaches targeting glucose and glutamine. For Seyfried, the therapeutic target follows directly from the biology: restrict the fuels cancer cells depend on, exploit their metabolic weaknesses, and treat mitochondrial dysfunction as the central feature of the disease.
An abbreviated version of this discussion is available here, for free.
MetFix and BSI Members can view the full 54-minute video.
