The metabolic
theory of cancer postulates that cancer is primarily the result of
defective energy metabolism in and damage to the cells’ mitochondria
Genetic
mutations are not the primary cause of cancer but are rather a
downstream effect of the defective energy metabolism; as long as your
mitochondria remain healthy and functional, your chances of developing
cancer are very slim
Normal
mitochondria suppress cancer growth, and in order for cancer cells to
proliferate, you must have dysfunctional mitochondria
Cancer growth
and progression can be managed following a whole-body transition from
fermentable metabolites, such as glucose and glutamine, to respiratory
metabolites, primarily ketone bodies that are formed when you follow a
ketogenic diet
Ketogenic diets
promote healthy mitochondrial function and respiration, reduce tumor
vascularity and inflammation, and enhance tumor cell death
In the featured podcast, Dr. Peter Attia
interviews professor Thomas Seyfried, Ph.D., recipient of our Game
Changer Award in 2016 for his work on cancer as a metabolic disease, which is also the title of Seyfried's book1 on this topic. His work is also heavily featured in Travis Christofferson's excellent book, "Tripping Over the Truth: The Metabolic Theory of Cancer."
The actual podcast can be heard on Dr. Attia's site
Seyfried, in my view, is simply the best cancer biologist in the world. The featured interview2
goes into great technical detail that can be challenging for some, but
if you're interested in understanding the mechanics of cancer, I highly
recommend taking the time to listen to it in its entirety, especially
toward the end.
Without a doubt, it is one of the finest detailed discussions about
why cancer cells grow and how conventional medicine has it mostly wrong
when it comes to treatment, especially radiation and chemo. Without a
doubt, it is one of the best interviews Seyfried has ever done. Although
Attia is a Harvard trained physician with oncology training, he
frequently disagrees with Seyfried, who schools him in the basics.
I have listened to the entire interview twice and learned even more
the second time. Now I have a fairly good background on this topic so if
you are new to it and have a loved one who needs this information you
may need to listen a few times. Toward the end of the interview Seyfried
gets into some very important principles in cancer treatment, such as:
Being careful to avoid biopsies if at all possible as they are strongly related to allowing the cancer to metastasize.
Surgical therapy can be a useful intervention but it should be
delayed as long as possible while the patient is on metabolic therapy so
the tumor will shrink and allow the margins to be more well defined so
it can be removed more easily.
Avoid radiation and chemotherapy at all costs as they typically
impair the immune system that is ultimately responsible for resolving
the tumor.
More than 1,600 people die from cancer every DAY in the U.S., but
8,100 die from cancer every day in China, where the problem is far
worse. Remember these are deaths per day, not cancer diagnosis.
It is vital to understand that more people die from cancer treatment than the cancer itself.
Introduction to Cancer as a Metabolic Disease
The established dogma that cancer is a genetic disease currently
rules everything, from the research that receives funding to the
treatment you can expect from an oncologist. Indeed, this dogma is what
fuels the entire cancer industry. Unfortunately, it's not leading to any
significant breakthroughs in treatment, let alone prevention.
Seyfried and others have been able to advance the theory that cancer
is primarily the result of defective energy metabolism in and damage to
the cells' mitochondria. Simply put, genetic mutations are not the
primary cause of cancer but are rather a downstream effect of the
defective energy metabolism. As long as your mitochondria remain healthy
and functional, your chances of developing cancer are actually slim.
According to Seyfried, while it's still poorly understood how a ketogenic diet works to subdue epileptic seizures,
the mechanism of action on cancer cells is really clear, and is based
on the pioneering findings of Dr. Otto Warburg, a classically trained
biochemist who in 1931 received the Nobel Prize in Physiology or
Medicine for his discovery of the nature and mode of action of the
respiratory enzyme cytochrome C oxidase.3
Warburg's work shows how cells obtain energy from respiration, and
how cancer cells have a fundamentally different energy metabolism
compared to healthy cells (see section on Warburg Effect below).
Following in Warburg's footsteps, research by Seyfried and others
show that cancer is primarily a metabolic disease involving disturbances
in energy production through respiration and fermentation in the cells.
Studies have actually shown that cancer is suppressed when the nucleus
from a tumor cell is transferred to cytoplasm of normal cells with
normal mitochondria.
What this tells us is that normal mitochondria suppress cancer
growth, and in order for cancer cells to proliferate, you must have
dysfunctional mitochondria.
Seyfried's research has shown that cancer growth and progression can
be managed following a whole-body transition from fermentable
metabolites, such as glucose and glutamine, to respiratory metabolites,
primarily ketone bodies that are formed when you follow a ketogenic diet. This transition reduces tumor vascularity and inflammation while enhancing tumor cell death.
Source: peterattiamd.com. Image credit: Thomas Seyfried
The Warburg Effect
Warburg discovered that even in the presence of oxygen, cancer cells
derive energy from the ancient process of anaerobic fermentation
(sometimes called glycolysis), which causes an overproduction of lactic
acid. This is known as the Warburg Effect:
Aerobically, in the mitochondria
Anaerobically, in the cytoplasm, which generates lactic acid, a toxic byproduct in high concentrations
Aerobic respiration is far more efficient, capable of generating more than 30 times more adenosine triphosphate (ATP)
than anaerobic energy generation. As explained in the featured
interview, normal, healthy cells will produce very minimal amounts of
lactic acid in the presence of oxygen. Cancer cells, on the other hand,
behave very differently.
Cancer cells continue to produce massive amounts of lactic acid, even
in a 100-percent oxygen environment, which caused Warburg to conclude
that the primary cause of cancer is that the respiratory system of
cancer cells is defective, causing the cells to revert from healthy
aerobic energy generation to unhealthy anaerobic fermentation. You can
read Warburg's 1956 paper4 "On the Origin of Cancer Cells" here.
Please note that respiratory system in this context does not refer to
the lungs but rather to the processing of oxygen from the lungs in the
electron transport chain of the mitochondria that ultimately passes the
electrons from your food to oxygen to create water and ATP.
So, in a nutshell, what Warburg discovered is that cancer cells have
dysfunctional mitochondria — hence the claim that cancer is a metabolic
disease rooted in mitochondrial dysfunction.
Different Types of Mitochondrial Abnormalities Are Found in Cancer Cells
One of the primary reasons why modern researchers have failed to
realize that all cancer cells have impaired respiration is because they
started researching cancer using cell cultures, and when you separate
the cells from the tissue and grow it in a medium, it causes them to
behave in ways they normally wouldn't when in the animal or human.
Hence many researchers have claimed that cancer cell respiration is
normal, when in fact it is not. According to Seyfried, during in vitro
or culture research, it looks like cancer cells consume a lot of oxygen,
even when producing lactic acid, which creates confusion.
He does point out that while all cancer cells have defective
mitochondria, how that defect came about will vary from one cancer to
another. In some cancers, there's simply a lack of mitochondria, meaning
the cell does not have enough organelles to generate energy through
respiration and therefore falls back on fermentation as a source of
energy production.
In other cancers, the cells appear to have plenty of mitochondria,
but the organelles are structurally abnormal. As noted by Seyfried,
"structure dictates function," so if the structure of the mitochondria
is abnormal, its function will also be abnormal. However, all cancer
cells use fermentation for energy production. Seyfried has not found a
single cancer with normal respiration.
In order to grow and spread, cancer cells also need ample building
blocks, which Seyfried says they get from the pentose phosphate pathway,
the glycolytic pathway and from glutamine. "Between glucose and
glutamine, you're getting all the building blocks you need for rapid
cell division," he says.
Cancer Is Not a Gene-Driven Disease
Seyfried also stresses that in his research, no genetic abnormalities
were found in cancer cells at all, which firmly disputes the genetic
theory which postulates that cancer is driven by genetic mutations.
Sadly, Attia is still convinced that the gene theory of cancer is true.
It's quite sad that such a brilliant and innovative physician fails to
appreciate the depth of beauty of Seyfried's work.
Overall, an estimated 5 percent of cancers are caused by germline
mutations, such as BRCA1, an inherited genetic risk factor known to
raise your risk for breast cancer, or BRCA2, which raises your risk for
ovarian cancer.
But as noted by Seyfried, "They're not deterministic." A certain gene
mutation may raise your risk, but it's no guarantee you will actually
develop the cancer in question, and it is ultimately not the true cause
if you do get cancer. An exception is if the mutation damages the
mitochondria's respiratory system; then cancer is a very real
possibility.
Warburg's Missing Link
The featured interview also delves into the details of mitochondrial
substrate level phosphorylation (mSLP) — the missing link in Warburg's
cancer theory. When mitochondria are damaged, causing them to revert to
such an inefficient form of energy production, how is it that they have
enough energy to massively reproduce and grow?
For years, Seyfried suspected glucose fermentation wasn't the whole
story, and his research shows cancer cells can in fact ferment not only
glucose but also glutamine, and the majority of the energy for cancer
formation actually comes from the glutamine.
Glutamine is fermented via mSLP in the tricarboxylic acid (TCA) cycle
— also known as the Krebs cycle — of the mitochondria. The TCA or Krebs
cycle is a series of chemical reactions catalyzed by enzymes that form a
key part of aerobic respiration. Seyfried explains:
"mSLP is the production of ATP when you move a phosphate group
from an organic substrate onto an ADP molecule, so it's an ancient way
of generating energy. In other words, it's an organic molecule that is
an electron acceptor rather than oxygen …
You're moving phosphate groups from an organic substrate onto the
ADP as the acceptor, and you can generate massive amounts of energy
from this process which can replace the level of lost energy from the
damaged mitochondria …
In the normal cell, you're making most of your ATP from oxidative
phosphorylation, but in the cancer cell you're making most of it from
mSLP inside the same organelle [i.e., the mitochondria]."
Source: peterattiamd.com. Image credit: Thomas Seyfried
Source: peterattiamd.com. Image credit: Thomas Seyfried
Why Cancer Cells Don't Self-Destruct
Another question of import is "Why don't cancer cells die through the
apoptotic mechanisms?" meaning the mechanism that triggers cellular
suicide when the cell is damaged or malfunctioning. In short, because
the mitochondria that actually controls that self-destruct "switch" is
dysfunctional.
"The cell bypasses the normal control of life and death — apoptosis
of the cell — because the very organelle that dictates that is [the
mitochondria], is now defective," Seyfried says. As a consequence, the
cell reverts back "to the way it existed before oxygen came into the
atmosphere on the planet."
Healthy Mitochondrial Respiration Prevents Cancer Formation
The take-home message here is that as long as your mitochondrial
respiration remains healthy, cancer will not develop. "That goes back to
prevention," Seyfried says. "How do you prevent cancer? You prevent it
by keeping your mitochondria healthy."
And how do you keep your mitochondria healthy? Primarily by avoiding
toxic environmental factors and implementing healthy lifestyle
strategies. This is in fact the sole focus of the metabolic mitochondrial therapy program detailed in my book "Fat for Fuel." Topping my list of strategies to optimize mitochondrial health — which you can learn more about in my book — are:
Cyclical nutritional ketosis — The
divergence from our ancestral diet — this massive prevalence of
processed, unnatural foods and excessive amounts of added sugars, net
carbs and industrial fats — is responsible for a majority of the damage
to your mitochondria.
High-carb, processed food diets prevent your body from efficiently
burning fat as its primary fuel, and burning fats and ketones is far
more efficient, inducing far less oxidative stress, than burning carbs.
So, a foundational dietary strategy to optimize your mitochondrial
health is to eat the right fuel. Once you become an efficient fat
burner, you minimize the oxidative stress placed on your mitochondria,
which is key.
Calorie restriction — Another
extremely effective strategy for reducing mitochondrial free radical
production is to limit the amount of fuel you feed your body. This is a
noncontroversial position as calorie restriction has consistently shown many therapeutic benefits.
Meal timing
— Meal timing is also important. Specifically, eating too late in the
evening, when your body doesn't need the energy, is one of the worst
things you can do to your mitochondria, as it creates a buildup of ATP
that is not being used.
As a result, it's not being broken down into ADP, causing ATP
synthase to shut down. At that point, the entire electron transport
chain backs up, causing excessive amounts of free radicals to spill out
and damage the mitochondrial DNA.5
Normalizing your iron level — Iron
also plays an important role in mitochondrial function, and contrary to
popular belief, excessive iron levels are far more prevalent than iron
deficiency. Virtually all men over the age of 16 and post-menopausal
women are at risk of high iron.
Menstruating women are protected since they lose blood, and hence
iron, each month. While most people damage their mitochondria by eating a
high-carb, low-fat diet and/or excessive protein, elevated iron levels
can cause profound mitochondrial damage as well.
When you have high iron levels in your mitochondria, it enhances
oxidation, creating high levels of damaging reactive oxygen species and
free radicals. Fortunately, high iron is easy to address. Simply check
your iron level with a serum ferritin test, and if your level is high,
donate blood two or three times a year to maintain a healthy level.
An ideal iron ferritin level is between 40 to 60 nanograms per
milliliter (ng/mL). Below 20 ng/mL is a deficiency state, and you
definitely do not want to be above 60 or 80 ng/mL.
An important side note to this is that excess carbohydrates in
particular, when eaten late at night, result in a backup of electrons,
causing the production of superoxide. While not a pernicious free
radical in and of itself, if you have high iron levels combined with
high superoxide, it produces hydroxyl free radicals, which is one of the
most harmful.
The chemical reaction that creates these hydroxyl free radicals is
known as the Fenton reaction. While you certainly need enough iron,
having too high an iron level can cause severe damage, and this is one
way in which it does that.
Exercise — Exercise upregulates
PGC-1 alpha and Nrf2 — genes that promote mitochondrial efficiency,
helping them grow and divide so that you actually have more
mitochondria.
In simple terms, by placing an increased energy demand on your cells
through physical activity, free radicals signal that you need more
mitochondria to meet the energy demand. As a result, your body adapts to
your level of activity by creating more mitochondria and making them
work more efficiently.
Interestingly, in his book "Mitochondria and the Future of Medicine,"
Dr. Lee Know, a naturopathic physician, explains how some people need
more exercise to maintain mitochondrial health.6
When hydrogen ions flow back through ATP synthase, energy is created.
But in some cases, and in certain tissues, such as in brown adipose
tissue, this process can become uncoupled.
Instead of the hydrogen ions flowing back through ATP synthase, they
flow through a different channel, creating heat rather than energy. A
benefit of this is that it allows the electron transport chain to
continue to operate even though you're not using up energy. The hydrogen
gradient is being dissipated through the generation of heat instead.
If your genetic heritage stems from equatorial regions and/or if you
have very dark skin, you will tend to have less brown fat, and hence
less mitochondrial uncoupling, which raises your risk of chronic
disease. To counteract this, you will need to exercise regularly. Also,
be mindful of your vitamin D level, and consider cold thermogenesis (cryotherapy) to build brown and beige adipose tissue.
Nutritional supplements — The following nutrients and cofactors are also needed for mitochondrial enzymes to function properly:
How Metabolic Therapy Can Improve Cancer Treatment
Seyfried is not alone in his strong belief in the metabolic origins of cancer. Dr. Abdul Slocum,
a physician from Turkey, is already using this information in his
clinical practice, where he treats many end-stage cancer patients. A
significant number of his patients have pancreatic cancer, which has one
of the worst prognoses of any cancer.
Over 90 percent of pancreatic cancer patients die within five years.
When they enter his clinic, patients are immediately placed on a
ketogenic diet and remain on it throughout their treatment.
Remarkably, Slocum is able to save many of these "hopeless" patients.
What's more, his treatment protocols are nontoxic. By harnessing your
body's ability to fight the tumor naturally, through the implementation
of nutritional ketosis and other strategies, any chemotherapy agents
used can be applied in the lowest possible dose. Slocum's practice
reveals the very real benefits of treating cancer as a metabolic
disease.
Support Cutting Edge Metabolic Therapies That Address the True Cause of Cancer: Defective Mitochondria
Seyfried is conducting preclinical research at Boston College,
exploring a cocktail of metabolic therapies in a metastatic mouse model,
including the combination of:
Ketogenic diet
Glycolytic inhibitors
Oxygen therapy
Glutamine inhibitors
Exogenous ketones
Other metabolic targeting therapies
The goal of this advanced research is to develop a nontoxic diet/drug
therapeutic cocktail that can resolve both primary tumor growth and
secondary tumor metastatic lesions in a range of preclinical models of
cancer. For more information, you can read through his team's paper,7
"Press-Pulse: A Novel Therapeutic Strategy for the Metabolic Management
of Cancer," published in 2017 in the journal Nutrition &
Metabolism.
To further this project, Travis Christofferson founded the nonprofit
Foundation for Metabolic Cancer Therapies (formerly Single Cause Single
Cure Foundation8).
I encourage you to make a donation to this incredible research project,
as the possibilities of it actually saving lives are far greater than
most other cancer organizations, which exist solely to support the
slash, poison and burn paradigm.
I am working with Christofferson to have Seyfried's metabolic
therapies available for use as a primary intervention in a few cancer
clinics and will have that information posted when they are available.
Importantly, while other organizations will take a large percentage
of your donations for administrative expenses, 100 percent of donations
to Foundation for Metabolic Cancer Therapies will go to fund Seyfried's
research. You can make a tax-deductible donation online or by mailing in
a check:
Send a check of any amount made out to and mailed
to The Foundation for Metabolic Cancer Therapies, 3213 West Main Street
#256, Rapid City, SD 57702
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