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Cancer

Rethinking Cancer as a Metabolic Disease: The Potential of Targeting Cellular Metabolism

Dr. Thomas Seyfried contends we should view cancer as a metabolic rather than genetic disease. He advocates therapies targeting the abnormal tumor metabolism through diet and metabolic inhibitors. Early evidence demonstrates potential, though more research is required.

Rethinking Cancer as a Metabolic Disease: The Potential of Targeting Cellular Metabolism
Photo by Renaldo Matamoro / Unsplash

Cancer remains one of the most devastating diseases worldwide, with over 600,000 deaths annually in the United States alone. Despite decades of research and billions spent on new therapies, survival rates for many advanced cancers have not substantially improved. Dr. Thomas Seyfried, a pioneering researcher who argues we need to fundamentally rethink our model of cancer, from a genetic disease to a metabolic disease.

The Metabolic Difference in Cancer Cells

What is known is that the metabolism and respiration of cancer cells differs markedly from healthy cells. Whereas most cells generate energy using oxygen through a process called oxidative phosphorylation in their mitochondria, cancer cells rely on fermentation of glucose for energy production even in the presence of ample oxygen. This is known as the Warburg Effect, named after Nobel laureate Otto Warburg who made this discovery in 1924.

Cancer cells essentially hijack the ancient process of fermentation that human cells can utilize in the absence of oxygen. And just as yeast derive energy from sugar fermentation to make alcohol, tumor cells ferment glucose and glutamine. By targeting these two essential fermentable fuels, Seyfried argues we could effectively starve cancer cells of their energy sources.

Pivoting from Genetic Damage to Metabolic Dysfunction

But what causes a cell to switch to this aberrant metabolic process in the first place? The current model views cancer as originating from genetic mutations that accumulate over time, which then promote uncontrolled growth and proliferation. However, Seyfried contends that the numerous mutations observed are actually a downstream effect, not the cause, of the fundamental problem.

Seyfried proposes that chronic damage and dysfunction at the mitochondrial and cellular respiration level diminishes a cell's ability to produce energy using oxygen. Factors like chronic inflammation from obesity, smoking, poor diet, and lack of exercise create an environment that can gradually damage mitochondria and normal respiration over years and decades. This dysfunction impairs oxidative phosphorylation, forcing the cell to shift to the ancient process of fermentation for its energy needs to survive.

According to Seyfried's model, the initial trigger that sets off this metabolic cascade begins with chronic damage to cellular respiration and oxidative phosphorylation. What causes this prolonged mitochondrial injury over time? Seyfried points to modern lifestyle factors like consuming highly processed foods high in sugar, lack of exercise, chronic stress, and obesity. These factors create sustained inflammation and damage at the cellular level that impairs normal mitochondrial function. This then necessitates the shift to abnormal fermentation metabolism for a cell’s basic energy needs. Just as cardiovascular disease progresses over decades from diet and lifestyle factors, Seyfried views cancer as likewise emerging slowly from accumulated dysfunction in cellular energetics.

In this model, the proliferation of mutations is actually the end result of malfunctioning cellular energetics. The mutations themselves are not the prime cause, but rather a downstream effect from damaged respiration. Just as a heart attack is the end result from years of cardiovascular dysfunction and damage, the uncontrolled growth is the consequence of prolonged mitochondrial and metabolic dysfunction at the cellular level.

Insights from History and Indigenous Cultures

Several lines of evidence support looking at cancer as a metabolic rather than genetic disorder. Cancer is extremely rare in indigenous cultures and ancestral hunter-gatherers. The Inuit of Alaska, hunter-gatherer cultures in Africa, and Australian aborigines traditionally had almost no cancer. Yet when exposed to a modern Western diet, their cancer rates rose precipitously. Seyfried argues their low cancer rates stemmed from low carbohydrate intake and constant low level ketosis, where the body derives energy from fat breakdown rather than glucose.

In the early 20th century, the famed physician Albert Schweitzer observed over several decades that the African natives he worked with had negligible cancer rates. Yet cancer rapidly emerged once sugar and refined flour was introduced into the diet. Thomas Seyfried contends when our cells exist in sustained ketosis from low carb intake, the mitochondria and respiration remain healthy. This makes it exceedingly difficult for cells to become cancerous.

Targeting Cellular Metabolism and Energetics

Rather than targeting signaling pathways involved in cell proliferation, which has seen limited success, Thomas Seyfried advocates going upstream to the root metabolic origins of cancer. Animal models and over a dozen human case reports have shown major responses from metabolic therapies that lower glucose and use drugs to inhibit glutamine, another key fuel for tumors.

This so-called “press-pulse strategy” transitions the body into ketosis through diet to lower glucose levels. Then it uses low dose drugs briefly to target glutamine and deprive cancer cells of their two major fermentable fuels. This approach aims to effectively starve and kill tumor cells from the inside with minimal side effects. Press-Pulse staggers the use of drugs and diet while supporting body’s natural immune defenses, in contrast to continuous chemo. Combined with standard care, this strategy aims to manage cancer as a chronic disease that can potentially extend survival for years rather than months.

While decades of research have improved our understanding of the genetic landscape and signaling pathways within cancer, this has failed to move outcomes for many advanced cancers. As Seyfried concludes, with over 1600 cancer deaths daily in the U.S., it is clear our existing models are missing something fundamental. Reconsidering cancer as originating from metabolic dysfunction rather than genetic mutations may provide the fresh conceptual leap needed to finally make progress against such a devastating disease. The theory must still be rigorously tested, but the hope is that targeting the aberrant energetics of cancer cells could offer an elegant strategy for managing cancer in the future.

Buy Dr Seyfried's book published 23 April 2023

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