by Joseph Mercola
Cancer is a
metabolic disease, not a genetic one. The
genetic mutations observed in some cancers are a
downstream effect of defective energy metabolism
in the mitochondria (the energy stations inside
As long as
your mitochondria remain healthy and functional,
your chances of developing cancer are slim
therapy calls for restricting net carbs to 50
grams per day and limiting protein; I recommend
a limit of 1 gram of protein per kilogram of
lean body mass. Fasting glucose needs to be
below 70 mg/dL
If you want to avoid becoming a cancer statistic (and who doesn't?)
you'd do well to familiarize yourself with the metabolic theory of
In August 2016, we presented the Mercola Game Changer Award to
Thomas Seyfried, Ph.D., 1 a professor of biology
at Boston College and a leading expert and researcher in the field
of cancer metabolism and nutritional ketosis.
Following is a rerun of this popular and important article and
interview with Seyfried, in which we discuss his book, "Cancer as a
Metabolic Disease" - an important contribution to the field of how
cancer starts and can be treated.
Each day, some 1,600 people die from cancer in the United States
alone. Worldwide, we're looking at a death toll of about 21,000
people daily. So many of these deaths are unnecessary - they're
preventable and treatable.
Seyfried is one of the pioneers in the application of nutritional
ketosis for cancer; a therapy that stems from the work of Dr.
Otto Warburg, who was undoubtedly one of the most brilliant
biochemists of the 20th century.
Warburg received the
Nobel Prize in Physiology or Medicine in 1931 for the discovery of
metabolism of malignant cells.
Warburg was also an M.D. and a Ph.D., and was personal friends with
Albert Einstein and many of the most prominent scientists of his
time. His life's mission was to find a cure for cancer, and he
Unfortunately, few were able to appreciate the
importance of his findings.
Seyfried has followed in Warburg's scientific footsteps, and is
conducting important research to advance this science. He has in
fact exceeded Warburg's initial supposition, shedding important
light on the metabolic underpinnings of cancer.
Cancer as a
The traditionally held view or dogma is that cancer is a genetic
disease, but what Warburg discovered is that cancer is really caused
by a defect in the cellular energy metabolism of the cell, primarily
related to the function of the mitochondria, which are the little
power stations within each cell.
mitochondria were not well understood in Warburg's time but,
today, we have a much better understanding of how they work.
In my view, this information is the game changer that not only
treats cancer but virtually every single disease known to man,
because at the core of most serious ailments you find mitochondrial
As noted by Seyfried:
"A dogma is
considered irrefutable truth, and that cancer is a genetic
disease is, no question, a dogma.
The problem with
dogma is that sometimes it blinds you to alternative views and
sets up ideologies that are extremely difficult to change.
All of the major college textbooks talk about cancer as a
The National Cancer Institute (NCI) website,
the first thing they say is cancer is a genetic disease caused
by mutations... [and] if cancer is a genetic disease,
everything flows from that concept.
It permeates the pharmaceutical industry, academic industry and
textbook industry - the entire knowledge base. There's very
little discussion of alternative views to the genetic view.
argument now is that, yes, metabolic problems occur in cancer
cells. No one denies that.
But these are all due to the genetic mutations.
Therefore we must
maintain ourselves on the established track that all of this
metabolic stuff could be resolved if we just understood more
about the genetic underpinning of the disease.
Now that would be well and good if it were true. But evidence is
accumulating that the mutations we see that are the prime focus
and the basis for the genetic theory are actually
They're downstream effects of this disturbance in the metabolism
that Warburg originally defined back in the 1920s and '30s."
Metabolic View Alters Cancer Treatment
As Seyfried notes, the problem today is not that scientists and
doctors cannot understand the science; it's that they cannot accept
that this could be the truth behind the nature of the disease,
because it changes how you approach treatment.
If defective mitochondria are responsible for the origin of cancer,
and defective energy metabolism is responsible for the majority of
the phenotypes, i.e., the observable characteristics of the disease
that you see, then how do you treat the disease?
In my view, one of Seyfried's most magnificent contributions to this
science was his compilation of research from independent and
well-respected scientists within various disciplines, who conducted
valuable experiments but had no clue how to interpret the results.
Seyfried put all of their work together, forming a strong scientific
foundation for the theory that cancer is indeed a metabolic disease,
not a genetic one, and that genetic mutations are a downstream
effect of defective energy metabolism in the mitochondria.
transfer experiments were always present in the literature.
They were considered
anomalies. They were not consistent with the view that cancer is
a nuclear genetic disease ... but the observation was not
interpreted in light of [being] the origin of cancer.
I bundled all those observations together in a new light,
looking at the conclusions of those experiments in light of
whether the results would support a nuclear gene-based theory
versus a mitochondrial metabolic theory ...
It was just interpreting a series of experiments in light of the
origin of the disease, and then asking what conclusion would
these experiments support.
Would it support the nuclear genetic
theory of cancer, or would it support the mitochondrial
metabolic theory of cancer?
In each of these cases, the results more strongly supported the
metabolic theory of cancer than the nuclear genetic theory," Seyfried says.
Nuclear Transfer Experiments Showed
The nuclear transfer experiments in question basically involved
transplanting the nuclei of a tumor cell into a healthy and normal
cytoplasm (the material within a cell, excluding the cell nucleus),
which include the mitochondria, the energy-generating organelle of
The hypothesis is that if cancer is nuclear-gene driven and the
phenotype of cancer is dysregulated cell growth, meaning if genetic
mutations are responsible for the observable characteristics of the
disease, then those abnormal genes should be expressed in the new
But that's not what
Again and again, what was observed was that when the nuclei of a
cancer cell were transferred into a healthy cytoplasm, the new
cytoplasm did NOT form cancer. It remained healthy and normal...
"What was interesting
is that in many of these nuclear transfer experiments, the
organisms aborted at certain periods of development.
That abortion seems
to be related to how many mutations were in the nucleus that was
transferred," Seyfried says.
"It was true that these cancer nuclei did contain mutations, but
those mutations were not causing the hallmark feature of the
disease, that is proliferation.
Rather, they were
causing abortion at some developmental point of the organism
that had those nuclei...
On the other hand,
when the normal nucleus was transferred back into a cancer
cytoplasm [which had defective mitochondria], either the cell
died or it formed tumor cells."
Additional evidence has
recently been produced by Benny Kaipparettu, Ph.D., and
colleagues at Baylor University.
When they transplanted
normal mitochondria (with its nuclei intact) into cancer cell
cytoplasm, it caused the cells to stop growing abnormally. It
oncogenes that were alleged to be driving the
tumor and made the cells grow normally again.
On the other hand, when they took the mitochondria from a tumor cell
and moved it into a very slow-growing type of cancer cell, the
cancer cells began growing very rapidly.
As noted by Seyfried,
"When you bundle all
these experiments together, you come to the conclusion that
nuclear mutations cannot be the drivers of the disease."
BRCA1 and Other Inherited Cancer Genes?
A common argument for the genetic theory is that cancer can be
inherited; therefore it must have genetic underpinnings.
2 which raises your risk of developing cancer at a very
young age, and BRCA1, which raises your breast cancer risk, are two
"The answer is, yes,
on the surface, that would appear to be true," Seyfried says.
"But as Warburg said,
there are many secondary causes of cancer but there is only one
primary cause, and that's damage to the respiration. So
inherited mutations through the germ lines that cause cancer to
affect the mitochondria, it is [still] the mitochondria that is
the origin of cancer.
It just so happens that the defect is coming from an inherited
gene rather than a chemical carcinogen, radiation, viral
infection or an infection of some parasite or whatever, all of
which damage respiration; all of which can cause cancer.
Clearly the origin of the disease is a disturbance of the
respiratory capacity of that cell which then, if the cell is to
survive, must up-regulate genes necessary for fermentation.
Many of those genes
are the so-called oncogenes. The oncogenes are simply fulfilling
a rescue event of that cell to function in a fermentation
metabolism rather than an oxidative metabolism.
We can down-regulate
oncogenes simply by putting in new respiration."
If genetic mutations are
not the primary cause of cancer but rather a secondary, downstream
effect of dysfunctional cell respiration, why and how do mutations
As explained by Seyfried,
once the cells' respiration is damaged, that damage then leads to a
compensatory fermentation, which requires the upregulation of
oncogenes (cancer genes).
Damaged respiration also produces large amounts of reactive oxygen
species (ROS) and secondary free radicals that damage DNA proteins
and lipids (fats inside your cellular membranes).
The ROS also cause
mutations in the nuclear genome.
So the mutations are the
result of defective respiration and subsequent exaggerated ROS
Why the War on
Cancer Has Not Yet Been Won
At present, the cancer industry is focusing on the downstream
effects of the problem, which is why the "war on cancer" has been
such a miserable failure.
medicines, checkpoint inhibitors, all of these kinds of
therapies are basically looking at downstream effects of the
disease," Seyfried says.
of the cells in the tumor are all different from each other
genetically. You're not going to be able to target all of the
different cells using these kinds of approaches.
Even though you may
get success for a few months, or even a year in some people, the
majority of people will not respond effectively to these kinds
of therapies for the most part."
Why Being an
Efficient Fat Burner Is so Important
The ROS also target the actual mitochondria themselves, where
respiration occurs, which brings us to a very important point.
ROS are mostly generated
through the co-enzyme Q couple in the electron transport chain. Both
glucose and fatty acids produce FADH2, which can generate ROS.
In contrast, fat-derived
ketone bodies produce only NADH, which
increases the redox span of the co-enzyme Q couple and reduces
production of ROS. Hence, ketone bodies are considered a more
"clean" fuel than is either glucose or fatty acids.
Today, most people are
burning glucose as their primary fuel, thanks to an overabundance of
sugar and processed grains in the diet and a deficiency in healthy
If you have less ROS being generated in the mitochondria, you end up
with less mitochondrial damage and less DNA damage.
So not only is switching
the fuel you're feeding your body the key component of cancer
treatment, but in my view it's the primary way that you prevent
cancer from occurring in the first place.
"I think that's an
important point. One of the things that trigger cancer is
We have inflammation.
Chronic high levels of blood sugar create inflammation. This you
see in a lot of situations. Glucose itself is not carcinogenic,
but elevated dysregulated glucose metabolism can lead to
inflammation, and can cause a number of other disturbances in
the overall metabolism of the body," Seyfried says.
"If you fast, if you
stop eating, your blood sugar goes down. Your insulin levels go
down. The body starts to metabolize fat for energy. But the
fatty acids themselves are only one component. The major
components of course are the ketone bodies...
water-soluble fat products. They readily enter cells and they're
metabolized to acetyl-CoA through a series of steps.
These steps generate nicotinamide adenine dinucleotide (NADH),
which is a reducing equivalent. But they also keep the coenzyme
Q couple in an oxidized state.
This is very
important because it's that coenzyme Q couple where ROS are in
fact generated in the first place...
Ketones are clean fuel only in the sense that they suppress the
formation of ROS, especially when blood sugar levels are low,
because if you have very high ketones AND high blood sugar, you
have ketoacidosis, which is a life-threatening event."
Do Not Confuse
'Nutritional Ketosis' with 'Ketoacidosis'
Nutritional ketosis should NOT be confused with diabetic
ketoacidosis (DKA), which is not a concern unless you have type 1
It's rare for a person
with normal physiology to elevate their ketones above 7 or 8
millimole (mmol). If you have DKA, your ketones will be about 20
mmol. Additionally, your blood sugars will be very high, while in
nutritional ketosis blood sugars are very low. These are clearly two
entirely different states.
And whereas ketoacidosis can be life threatening, nutritional
ketosis is a healthy state that helps you maintain maximum energy
efficiency and reduces ROS production in your body.
As noted by Seyfried,
actually get very healthy when ketones are metabolized as
opposed to some of the other fuels, especially glucose."
For the last few decades,
most natural health enthusiasts would attempt to circumvent the ROS
challenge by taking antioxidants, either through foods high in
polyphenols and other natural antioxidants, or supplements.
I now believe this is a
fatally flawed strategy that has significant drawbacks.
Rather than trying to quell the ROS after they're produced, it's far
more effective to address the ROS generation at its source, which is
the fuel your body is primarily burning for energy.
Change the fuel, from
sugar to fat, and you will generate fewer ROS.
Prevent Dysregulated ROS Production, Thereby Reducing Your Risk for
It's not that ketones don't generate any ROS, they do; just not as
And this brings us to yet
another crucial point.
ROS are not merely agents of destruction;
they're also powerful signaling molecules. If you suppress them
indiscriminately, you'll create biological dysfunction.
So you do not want to eliminate them. You just want to control them
to optimal levels so all the signaling can occur without damage.
That's what happens with
When your body is burning
ketones as its primary fuel, you more or less ensure that you're in
an ideal therapeutic window with regard to ROS generation, so you
have neither too much nor too little ROS.
"There's no question
about that. It's what we call a homeostatic state," Seyfried
dysregulated ROS production... You're allowing your body to
remain healthier for a longer period of time. That's basically
what we're doing here...
Cancer is accelerated
entropy. It's a total disorganization of the homeostatic
parameters within cells and outside the cells in the
morphogenetic field and in the entire body itself.
Cancer patients have all kinds of disturbances in systemic
homeostasis. It's not just in the cells ... When the body has
cancer there are a number of ramifications that take place
throughout the body.
We're producing more acidity. There are a lot of responses in
the part of hormones and signaling cascades throughout the body
as a result of this disease. One has to treat cancer as a
The whole body has to
be treated but in a nontoxic way."
Indeed, toxicity is one
of the biggest failures of current treatment protocols for cancer.
The majority of
treatments for cancer
are extremely toxic, which further exacerbates
the problem. Many cancer recurrences are likely due to the initial
On the other hand, when you view cancer as a metabolic disease, you
can target and manage the disease without creating systemic
As explained by Seyfried,
you do this by targeting the fuels the cancer cells are using,
primarily glucose and glutamine.
"What we have to
recognize... is that if cancer is a mitochondrial metabolic
disease and you get cancer because of mitochondrial failure in
certain populations of cells and certain tissues, if you prevent
your mitochondria from entering into this dysfunctional state...
[then] the probability of getting cancer is going to be
To what percent? I would say a minimum of 80 percent. Cancer is
probably, as I said in my book, one of the most manageable
diseases that we know of...
The problem is that many people don't want [to take the
preventive steps to avoid cancer].
'I have to
therapeutically fast for a week? Oh, I'm not going to. Give
me a break' ...
prevention is to eat less and move more.
A lot of people don't
want to do that... Once you realize what cancer is, that it's a
metabolic disease, you can take charge of those kinds of things.
In other words,
getting cancer is not God's will. It's not bad luck."
Is Rooted in Mitochondrial Dysfunction
Cancer is not the only outcome when mitochondrial respiration goes
This kind of dysfunction
also plays a role in neurodegenerative diseases such as Alzheimer's,
Parkinson's and amyotrophic lateral sclerosis (ALS).
It's also at play in seizure disorders and in diabetes, obesity,
hypertension and hypercholesterolemia. Most of the major diseases
we're currently treating with harsh and toxic drugs can potentially
be solved with proper nutritional intervention that addresses your
choice of cellular fuels.
How exactly do you do that?
According to Seyfried, in
order to achieve
nutritional ketosis, you need to reduce net
carbohydrates (total carbs minus fiber) to less than 100 grams,
probably less than 50 grams.
I have a slightly different view on
this, which I'll expound on in the next section.
You also need to reduce your amino acid content. Glutamine is the
most common amino acid in proteins, and besides glucose, cancer
cells can use glutamine for energy and growth as well.
combination of both glucose and glutamine creates a really
"supercharged system," Seyfried notes.
In order to lower glutamine, you have to eat less protein.
Also, there's a threshold
for amino acids, above which you will simply stimulate the mTOR
pathway, which in conjunction with insulin may wield a more powerful
influence on mitochondrial dysfunction and mitochondrial biogenesis
than insulin alone.
How to Assess
the Health of Your Mitochondria
How can you assess the health of your mitochondria?
There are a couple
of ways of doing this. Seyfried has published a paper on the glucose
ketone index calculator 3 (GKIC) in an open access journal, which can
be accessed by anyone.
You can use that
calculator to assess the health and vitality of your mitochondria.
The GKIC looks at your glucose to ketone ratio. Ketones must be
measured by blood, not urine, and your glucose must be entered in
mmol, not in milligrams per deciliter (mg/dL).
"When you have a
glucose ratio of 1.0 or below, you know your mitochondria are in
a very healthy zone," Seyfried says.
Now, getting down to a
1.0 is quite difficult. I'm typically between 2 and 3, and my diet
is about 80 percent healthy fats with minimal net carbs.
You may need to do a
complete fast in order to get that low. However, you don't need to
remain in that ultralow zone for very long.
On the other hand, if you
have cancer, you'll want to hit that mark as much as possible.
"You do a water fast
for about three to four days, then you can take some exogenous
ketones, and you can get your blood sugars way down," Seyfried
"To prevent cancer,
you don't have to stay there [longer than] four or five days
every six months or something like this. It's just a guide,"
"Some people can get into these zones very quickly and very
easily. Other people really struggle. All of this is a biomarker
We've done some
interesting linear regression analysis on survivability of mice
with cancer using the GKIs, the independent variable, the
There definitely is statistical relationship on how long you can
keep your GKI [and] how long you can survive with a very
Clearly, it's just
one biomarker system that allows individuals to help battle
their own cancer."
Ketosis Made Simpler With a Nutrient Tracker
That strategy will likely be too extreme for most folks, unless
you're faced with death or otherwise highly motivated.
Rather than doing lengthy
water fasting, I believe a more user-friendly strategy would be to
restrict your net carbs below 50 grams per day and your protein to
below 1 gram per kilogram of lean body mass.
Most people eat a lot
more net carbs and protein than that.
To make sure you're actually meeting these targets you need an
analytical tool to do a detailed nutritional analysis of what you're
eating. Otherwise, you really don't know how much fat, carbs and
protein you're getting.
This was my motivation
for working with the developer of
online nutrient tracker, to create a Mercola version of the software
programmed specifically for nutritional ketosis.
You can sign up and use Cronometer for free.
This software will make
all the calculations for you, based on the parameters you enter,
such as your height, weight, body fat percentage and waist
circumference. You can also enter and track various biomarkers, such
as fasting glucose, which is an essential measurement.
You really must keep tabs on your fasting blood sugar. Ideally, you
would measure it twice a day; first thing in the morning and right
before you go to bed. You want to get your blood sugar below 70 mg/dL,
ideally somewhere around 60.
If your fasting blood sugar is significantly higher in the morning
than in the afternoon, it's likely due to glucogenesis, which is a
sign you're not getting enough protein.
You need a certain amount
of amino acids or else your body will start to metabolize lean body
tissue to generate them. In that process, the excess gets shuttled
to your liver, which is what generates the extra glucose (hence the
elevated reading in the absence of food).
If you really want to dig deep into the details of therapeutic
ketosis, read Seyfried's book, "Cancer as a Metabolic Disease
the Origin, Management, and Prevention of Cancer."
If you want to start with
a shorter treatise, you can read through,
Hopefully, we've inspired
you to consider the nutritional roots of cancer and other chronic
I can promise you will
hear a lot more about this in the months and years to come, as I am
convinced addressing mitochondrial dysfunction is the real key to
solving most of our current health problems.
The good news is that
optimizing mitochondrial function can be effectively accomplished
through diet and lifestyle strategies like exercise. No costly drugs
or invasive procedures required.
And, while we still have a long way to go, more doctors are starting
to pay attention.
"This is the tipping
point," Seyfried says. "Many physicians are coming on board. I
think things are going to start changing for the best and for
the success of people."
Too many people have died
and continue to die needlessly. It's time to get back on the right
It's going to require a
lot of education, but the effort is absolutely worth it. The
information about how to prevent cancer and other chronic illness
It's just a matter of