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FOR IMMEDIATE RELEASE
Mitochondria Recharged: How the Ketogenic Diet and Fasting Boost Cellular Energy EfficiencyBy Richard Z. Cheng, M.D., Ph.D.Highlights
Mitochondria are the cell's power generators, converting nutrients into usable energy in the form of ATP (adenosine triphosphate). When mitochondrial function falters-due to aging, poor diet, chronic stress, or toxins-the result is a cascade of dysfunctions including fatigue, neurodegeneration, metabolic disease, accelerated aging, and even cancer. Fortunately, two synergistic strategies-the ketogenic diet and intermittent fasting-have been rediscovered as powerful tools to improve mitochondrial health and function. From the perspective of Integrative Orthomolecular Medicine (IOM), these approaches restore metabolic balance and enhance the body's ability to produce energy efficiently, cleanly, and sustainably. A Personal Note: Outlasting the Younger OpponentsFor nearly two decades, I've been a devoted badminton player, often competing in fast-paced, high-intensity matches with players 10 to 30 years younger than myself. In the early years, I found physical endurance to be my biggest challenge. I would often feel exhausted pretty quickly. That struggle led me to explore and apply the principles of ketogenic nutrition, intermittent fasting, and mitochondrial support-not only for my patients but for myself. Today, the difference is striking: I can play intense badminton for 2 to 3 hours-often after a 15-hour fast-and finish the game without feeling excessive fatigue. This personal transformation has confirmed what I've long believed as a physician and scientist: mitochondrial optimization is the key to sustained physical energy and resilience-even as we age. Ketones: Cleaner, More Efficient Mitochondrial FuelWhen the body shifts from a glucose-dependent metabolism to fat-based metabolism, it produces ketone bodies, primarily beta-hydroxybutyrate (BHB). Compared to glucose, ketones are a more efficient fuel, producing more ATP per molecule of oxygen consumed while generating fewer reactive oxygen species (ROS) and oxidative stress byproducts [1,2]. This cleaner energy production reduces mitochondrial damage and supports long-term cellular function-especially in energy-demanding tissues like the brain, heart, and muscles. Fasting and Ketosis Activate Mitochondrial BiogenesisFasting and ketosis both stimulate signaling pathways that upregulate mitochondrial biogenesis-the process of generating new, healthy mitochondria [3,4].
Through these mechanisms, fasting and ketogenic diets not only improve mitochondrial energy output but also enhance their resilience and adaptability. Metabolic Flexibility: A Forgotten Key to HealthMost modern diets-high in carbohydrates and ultra-processed foods-lead to metabolic inflexibility [9], where the body becomes locked into using glucose as its primary fuel. This condition underlies many chronic diseases, including obesity, insulin resistance, and type 2 diabetes [10]. One of the most striking metabolic defects in obesity and type 2 diabetes is the inability to efficiently access and burn stored body fat for energy. Even with large fat reserves, the body remains energy-deprived-dependent on external glucose, trapped in a cycle of fat storage and fatigue. A key manifestation of this dysfunction is the tendency of people with type 2 diabetes to develop hypoglycemic symptoms when a meal is missed. Despite having excessive stored fat, their impaired fat oxidation prevents them from switching to fat as a fuel source during fasting. Their metabolism remains stuck in glucose dependency, making them vulnerable to blood sugar crashes, energy dips, and insulin-driven metabolic chaos. By contrast, nutritional ketosis and intermittent fasting both restore the body's ability to burn its own fat stores for fuel, converting fat into ketones-a cleaner, more efficient energy source [11-13]. This reactivation of the body's fat-burning machinery leads to:
In clinical experience and personal practice, this shift is transformative. Nutritional ketosis and fasting train the body to switch between fuel sources, restoring metabolic flexibility and optimizing energy utilization at the mitochondrial level [14]. This flexibility is critical not just for managing disease, but also for thriving in high-performance physical activities, such as the kind of endurance needed in sustained athletic performance-even beyond midlife. Less Toxins, Less Stress on MitochondriaExcess glucose metabolism generates advanced glycation end products (AGEs), insulin spikes, and mitochondrial stress [15-18]. Both fasting and ketogenic diets:
This reduction in metabolic "noise" allows mitochondria to function with greater clarity and efficiency. Clinical Applications of Fasting + KetosisIn Integrative Orthomolecular Medicine, combining fasting and ketogenic therapy shows promise in:
Patients report enhanced energy, reduced inflammation, improved mental clarity, and better metabolic control. The IOM Protocol for Mitochondrial OptimizationMitochondrial health is central to my approach to disease prevention and reversal, as well as to my pursuit of longevity. Based on my ToolKit approach [45] to health, I include-but am not limited to-the following strategies to support optimal mitochondrial function.:
Conclusion: Ancient Tools for Future EnergyThe ketogenic diet and fasting are not fads-they are time-tested metabolic tools deeply encoded in human physiology. By activating mitochondrial biogenesis, enhancing energy efficiency, and reducing cellular stress, these strategies are foundational in orthomolecular disease reversal and health optimization. Whether you're battling chronic illness or simply striving for more energy, clarity, and physical stamina, supporting your mitochondria may be the most powerful step you can take. I've experienced this firsthand-on the badminton court, on an empty stomach, outlasting younger opponents with energy to spare. The world may revolve around money, but life revolves around energy. This has become my guiding principle-not just for personal performance, but for empowering patients to reclaim their vitality, one mitochondrion at a time. References1. Veech, R. L. 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A ketogenic diet combined with exercise alters mitochondrial function in human skeletal muscle while improving metabolic health. Am J Physiol Endocrinol Metab 319, E995-E1007 (2020). 43. Hasan-Olive, M. M. et al. A Ketogenic Diet Improves Mitochondrial Biogenesis and Bioenergetics via the PGC1α-SIRT3-UCP2 Axis. Neurochem Res 44, 22-37 (2019). 44. Deng, Q., Lv, R. & Zou, T. The effects of the ketogenic diet on cancer treatment: a narrative review. Eur J Cancer Prev (2024) doi:10.1097/CEJ.0000000000000918. 45. Cheng, R. Z. A Paradigm Shift in Epidemic and Chronic Disease Management. https://orthomolecular.org/resources/omns/v20n23.shtml (2024). Orthomolecular MedicineOrthomolecular medicine uses safe, effective nutritional therapy to fight illness. 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Jennifer L. Aliano, M.S., L.Ac., C.C.N. (USA)
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