Thomas Seyfried’s Metabolic Theory of Cancer and How The Paleo Diet Could Help Curtail the Disease

Despite billions of dollars and countless research hours, cancer still takes over 1,670 lives each day. [1] Ultra-modern “genetic” therapies and theories, along with debilitating radiation, chemotherapy, and surgical interventions have done little to reduce casualties in this protracted war.

Cancer has always existed as part of the human condition; it became widespread with the rise of Western civilization, [2] [3] along with diabetes and cardiovascular disease. Many carcinogens are well known—pollution, chemicals, tobacco, among others—but our complete understanding of the mechanism by which they destabilize healthy cells has remained elusive.

In his groundbreaking book,“Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer,” Dr. Thomas Seyfried offers a comprehensive and penetrating examination of why current research (especially in genetics) misses the mark—and how basic cellular biology offers direct insight into both cause and treatment. [4]

His theory of impaired cellular respiration (which revisits the “Warburg Theory”) offers both an elegant explanation and reveals a surprising dietary connection. The theory postulates that cancer cells lose their ability to produce energy using oxygen and instead rely on fermentation. In other words, cancer cells have to rely almost exclusively on glucose for their energy, and dietary changes that severally reduce carbohydrate intake can effectively “starve” cancer cells.

Treat the cause, not the symptoms

In a recent presentation, Seyfried asked a question that alluded to his position that genetic cancer markers offer more insight into effect than cause [5]:

“Is it more logical to focus on the common problem that exists in all of the cells of the tumor, or does it make more sense to focus on the individual unique differences in every cell in that tumor?”

In other words, he ponders whether we should be fighting cancer cells on a specific cell-by-cell level, or on a more global, whole-system level, looking for the commonalities in the cancer cells?

Seyfried takes the latter approach, preferring to analyze what it is about the cancer cells that is causing the mutations.

By contract, the current “somatic mutation theory” takes the former approach. It is based on the idea that cancer starts with a single somatic cell that accumulates mutations. The approach catalogues genetic anomalies in an attempt to customize treatment based on a host of mutations.

While Seyfried’s approach may seem like common sense, it should be noted that for decades the medical profession, academia, institutional review boards, and regulators have all strongly favored the somatic mutation theory. Lack of treatment success has not prevented this theory from becoming an entrenched dogma—making genuine alternatives (like Seyfried’s update of the Warburg Theory) difficult to research or promote.

Multiple researchers including Seyfried’s team [6] have observed repeatedly (and reproducibly) that cancer cells appear to share a common characteristic: they no longer metabolize oxygen correctly for energy production. In other words, they are no longer able to produce energy aerobically. Instead, cellular mitochondria (unable to “breathe” using their normal process of oxidative phosphorylation) begin to produce energy by fermenting glucose and glutamine.

This dysfunction in the cancer cells also appears to help the cell evade programmed cell death (apoptosis)—the normal fate of unhealthy cells. Instead, fermentation produces reactive oxygen species, which promote uninhibited further mutation and cancer cell growth.

Experimental support

In a 2015 review, Seyfried details several experiments showing how this mitochondrial dysfunction may be at the center of cancer development. These novel experiments transferred nuclei (where the bulk of our DNA resides) between healthy and cancerous cells. [6]

The findings suggested that when the nucleus of a cancerous tumor cell is transplanted into a healthy cell with properly functioning mitochondria, the cell continues to divide and produce new healthy cells. That is, the genes within the cancerous nucleus do not produce new cancer cells.

However, when healthy nuclei are transplanted into a cancerous cell where mitochondria are already fermenting glucose/glutamine for energy, the new cell either dies or produces cancerous offspring. As Seyfried explains, “the mitochondria are calling the shots, not the nucleus.”
 

How cancer is transferred by mitochondria and rogue macrophages

Like zombies from a horror film, the death-proof, substrate-fermenting mitochondria in cancerous cells corrupt adjoining cells and tissue. In the worst-case scenarios, the mitochondrial dysfunction is transferred to different body locations—a process known as metastasis (or how cancer spreads). [7]

According to Seyfried, white blood cells called macrophages drive metastasis. Macrophages, workhorses of the immune system, travel throughout the body, freely entering and exiting the circulatory system. Under healthy conditions, they attack incipient cancer cells as they would any other microbial threat or infectious agent. Macrophages normally assimilate these invaders, digesting them to neutralize their harmful effects. However, in metastasis, the assimilating cancerous cytoplasm appears to “infect” the macrophage instead, converting its own energy production from oxidative to fermentation.

These infected, or “rogue” macrophages then travel to other parts of the body and, in their attempt to heal and stimulate growth, instead propagate dysregulated cell growth in other parts of the body.

Arresting fermentation is the key

The fermentation process underlying dysregulated cell growth relies on glucose—or in the absence of glucose, primarily on glutamine, the most abundant amino acid in the human body. Tumors thrive on glucose and glutamine. Cancer cells derive up to 95 percent of their energy by breaking down these two fuels through glycolysis and the Krebs cycle. [8] [9]

So, one way to “starve” a cancer cell is to inhibit these primitive (literally, pre-oxygen) metabolic pathways by removing their preferred fermentable fuels.

Seyfried points out that cancer cells cannot ferment ketone bodies, which are readily used for energy by healthy cells. Where ketone bodies are present, in the absence of glucose and glutamine, cancer cells literally starve, while healthy cells, which can survive on ketone bodies and fatty acids, continue to function normally. Tumors may shrink or even disappear.

Elevated ketone bodies are a hallmark of the “ketogenic diet.” A clinical version of this diet is integral to a multifaceted metabolic treatment that Seyfried calls “press-pulse” therapy. It should be noted that just “going keto” is not a cancer treatment. Medical supervision is required, and press-pulse also includes tailored administration of glucose- and glutamine suppressing drugs, hyperbaric oxygen treatment, and intensive stress management. [10]

Seyfried’s recommended ketogenic diet is “calorie restricted,” ideally preceded by three to five days of water fasting. Calories should be reduced to 30-40 percent of normal intake. The diet should consist mostly of fat (up to 80 percent of calories), along with protein. [10] The idea is to aggressively trigger and maintain therapeutic ketosis. It is not a lifestyle or dietary change one should make casually.

The inflammation connection: diet vs. disease 

A common thread in Seyfried’s book, [11] papers, and many online presentations is that chronic systemic inflammation is recognized as a “carcinogen” along with many other more widely recognized culprits (chemicals, pollution, pesticides, tobacco smoke, etc.) Many have observed that cancer and other chronic diseases are relatively unknown in non-Western, pre-industrial, or Ancestral populations—and increase when these populations adopt the Western diet. [12-15] The Western diet, which is heavy on sugars, carbohydrates, and industrial seed oils is widely recognized as pro-inflammatory and linked to many diseases besides cancer. [16-17] Chronically elevated blood glucose may actually contribute to cancer (inflammation damaging mitochondrial respiration) and encourage its growth (glucose-feeding tumor cells.) Ancestral dietary approaches, which are naturally lower in carbohydrates—especially simple sugars—and based on nutrient-dense whole foods, can be just as anti-inflammatory as ketogenic dieting. While draconian calorie-restricted keto may be warranted as part of late-stage intervention and therapy, concerned dieters may find ancestral practices more sustainable over time.

Seyfried on the “standard of care”

While describing advantages and early successes [18] of “press-pulse” cancer therapy, Seyfried notes that practitioners must still also use conventional treatments like chemotherapy and radiation—despite their systemic toxicity and the possibility that they encourage new tumors even as old ones die off. If these modalities (i.e. the current “standard of care”) aren’t included in a treatment plan, the physician may lose his or her license to practice medicine. So, while radiation and chemo may be counter-productive, not to mention debilitating to the patient, they will continue to be used in Western societies for some time. The hope is that this will not obscure the true effectiveness of “press-pulse” and other metabolic therapies, or even delay their implementation. 


Press Pulse Therapy: Adjust Cancer Cell Metabolism to Improve Condition

Seyfried believes the existing cancer treatment system is “broken.” He said once people understand the metabolic theory of cancer, treatments like chemotherapy and radiotherapy will be replaced by new treatments.

Based on the theory, Seyfried and his team developed the “press pulse therapy” [9][10][11], which is a cocktail treatment consisting of the ketogenic diet, glutaminase inhibitor medicine, and stress management.

The ketogenic diet is adopted because cancer cells have defective mitochondria and impaired metabolism, so they can only rely on fermented sugars and glutamine for energy. Cancer cells cannot obtain energy as ketone bodies cannot be fermented. As for cells with normal metabolic function, they can obtain energy by metabolizing ketone bodies [12].

The purpose of a ketogenic diet combined with basic drugs is to control the ratio of glucose and ketone bodies in the blood to an ideal range while inhibiting the ability of cancer cells to acquire glutamine. In this way, we can “starve” cancer cells from a metabolic perspective, thereby achieving the same effect as cancer treatments.

An important aspect of “stress pulse therapy” is stress control and emotional management. Seyfried emphasized in the interview that people’s mental stress has a direct relationship with the development of cancer. When patients are diagnosed with cancer, they experience extreme panic and cannot rest or eat in peace. Excessive stress can raise blood sugar levels, which can feed cancer cells into rapid growth. As a result, cancer cannot be controlled. Easing the emotional and stress levels of the patient and his or her family can further stabilize the patient’s psychological and physical condition.

There have been many successful cases of cancer control by managing metabolism. Moreover, many patients use this method when traditional cancer treatments, such as chemotherapy and radiotherapy, are ineffective, or when cancer has spread.

A 38-year-old man developed symptoms in February 2016 and was subsequently diagnosed with glioblastoma multiforme (the most common and malignant form of primary adult brain cancer). After 20 months of ketogenic diet therapy and completion of chemotherapy and radiotherapy, the patient’s tumor decreased by approximately 1.5 cm in diameter. He seemed in good health with no apparent clinical or neurological deficits [13].

Another 54-year-old man was diagnosed with lung cancer; the cancer cells had metastasized and tumors were found in his brain. Radiotherapy and chemotherapy had no effect, so the patient opted for a ketogenic diet. Two years later, the tumors in his brain and lungs shrank; after nine years of treatment, the brain and lung cancer tumors remained stable in size [14].

A 45-year-old woman in Ohio was diagnosed with breast cancer in late 2016. In August 2018, the cancer had spread and she developed tumors in her brain, lungs, mediastinum, liver, abdomen, and bones. Her doctor expected her to have less than a month to live. The patient began receiving stress pulse therapy in November 2018. In April 2019, the scan report indicated that the treatment was effective. According to the published study, her last check-up was in March 2021 and the results showed a stable condition, no recurrence, and improved quality of life [15].

In a study published in the Clinical Nutrition journal (2020), 80 patients with locally advanced and metastatic breast cancer were randomly assigned to a ketogenic diet or a control group for a 12-week treatment test. Patients in the ketogenic diet group had lower serum insulin levels, and their tumors shrank [16].

Two papers published in Nature: Prostate Cancer and Prostatic Disease describe the therapeutic benefits of a low-carb diet and a fasting-mimicking diet for patients with prostate cancer [Chi 2022][Watt 2022]. A ketogenic diet, which requires fasting and has low carbohydrates, can lower blood sugar levels and control tumor growth. These findings support the hypothesis that elevated ketone bodies are associated with reduced tumor growth [19].

Exercising, Fasting, and Avoiding High-Carb Diets May Keep Cancer Away

As for how an average person can maintain a healthy metabolism and prevent cancer, Seyfried said that by keeping the mitochondria in cells healthy, people are less likely to get cancer. He said this can be achieved through a certain period of fasting (drinking only water), a low-carb diet, and exercise.

He also emphasized that high carbs and un-nutritious foods such as junk food can cause cancer, and advised to stay away from such foods. It’s not just cancer, diseases like Alzheimer’s, Type 2 diabetes, and obesity, among others are all related to the Western diet.

“As soon as the Western diet comes into the population, you get cancer … and diabetes and things like this.”

According to an umbrella review (review of meta-analyses) published in BMJ (2023):

A dose-response meta-analysis showed that the risk of hepatocellular carcinoma increased by 100% for the highest sugar sweetened beverage consumption compared with the lowest. Additionally, a meta-analysis conducted by Aune and colleagues found that 25 g/day of fructose intake was linearly associated with a 22% higher risk of pancreatic cancer.

That said, an August 2023 study, published in The Journal of Nutrition, indicates that extreme eating patterns related to fats and carbohydrates could impact longevity. The research, led by Dr. Takashi Tamura from Nagoya University Graduate School of Medicine in Japan, reveals that men with low carbohydrate consumption and women with high carbohydrate consumption face increased risks of overall and cancer-related death. 

Their findings suggest that people should pursue a balanced diet rather than heavily restricting their carbohydrate or fat intake.

REFERENCES: 

  1. “Cancer Statistics.” National Cancer Institute, 2 Apr. 2015, https://www.cancer.gov/about-c… Suggest That Cancer Is Purely Man-Made. https://medicalxpress.com/news/2010-10-scientists-cancer-purely-man-made.html. Accessed 18 Nov. 2019.
  2. “Earliest Human Cancer Found in 1.7-Million-Year-Old Bone.” National Geographic News, 28 July 2016, https://www.nationalgeographic.com/news/2016/07/oldest-human-cancer-disease-origins-tumor-fossil-science/.
  3. Seyfried, M.D., Thomas. Cancer as a Metabolic Disease: On the Origin, Management and Prevention of Cancer. 2012. First Edition, John Wiley and Sons Inc., Hoboken, New Jersey.
  4. Dr. Thomas Seyfried: Cancer as a Mitochondrial Metabolic Disease. https://www.crossfit.com/essentials/seyfried-2018-health-conference-video. See 16:35 mark
  5. Seyfried, Thomas N. “Cancer as a Mitochondrial Metabolic Disease.” Frontiers in Cell and Developmental Biology, vol. 3, July 2015. PubMed Central, doi:10.3389/fcell.2015.00043.
  6. Seyfried, pp. 215-241
  7. Seyfried/Crossfit video, see 17:05 mark
  8. Setfried, p. 50
  9. Seyfried, Thomas N., et al. “Press-Pulse: A Novel Therapeutic Strategy for the Metabolic Management of Cancer.” Nutrition & Metabolism, vol. 14, no. 1, Feb. 2017, p. 19. BioMed Central, doi:10.1186/s12986-017-0178-2.
  10. Seyfried, p. 181
  11. Mozaffarian, Dariush, et al. “Role of Government Policy in Nutrition—Barriers to and Opportunities for Healthier Eating.” BMJ, vol. 361, June 2018. www.bmj.com, doi:10.1136/bmj.k2426.
  12. Cummings, John H., and Sheila A. Bingham. “Diet and the Prevention of Cancer.” BMJ, vol. 317, no. 7173, Dec. 1998, pp. 1636–40. www.bmj.com, doi:10.1136/bmj.317.7173.1636.
  13. CLATICI, Victor Gabriel, et al. “Diseases of Civilization – Cancer, Diabetes, Obesity and Acne – the Implication of Milk, IGF-1 and MTORC1.” Mædica, vol. 13, no. 4, Dec. 2018, pp. 273–81. PubMed Central, doi:10.26574/maedica.2018.13.4.273
  14. “Global Cancer Hotspots: Burden of Disease Is Shifting to Developing World.” The Independent, 18 Dec. 2015, http://www.independent.co.uk/life-style/health-and-families/health-news/western-lifestyle-to-blame-for-growth-of-cancer-worldwide-new-data-suggests-a6777881.html.
  15. AG, BIOCOM. Western Diet Triggers Inflammatory Diseases. https://european-biotechnology.com/up-to-date/latest-news/news/western-diet-triggers-inflammatory-diseases.html. Accessed 18 Nov. 2019.
  16. Manzel, Arndt, et al. “Role of ‘Western Diet’ in Inflammatory Autoimmune Diseases.” Current Allergy and Asthma Reports, vol. 14, no. 1, Jan. 2014, p. 404. PubMed Central, doi:10.1007/s11882-013-0404-6.
  17. Seyfried/Crossfit, see 48:05 mark


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