By Dr. Mercola
Each year during the anniversary week of Mercola.com, we recognize a
Game Changer; someone whose work stands as a great service to humanity
by making a significant contribution to improving people's health.
This year, we present the 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.
His book, "Cancer as a Metabolic Disease"
is an important contribution to the field of how cancer starts and can
be treated. Seyfried's work is also heavily featured in Travis
Christofferson's excellent book, "Tripping Over the Truth: The Metabolic
Theory of Cancer."
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. He received the Nobel Prize in Physiology or Medicine
in 1931 for the discovery of metabolism of malignant cells.
Warburg also held a doctorate in chemistry 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 actually
did. 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 Metabolic Disease
The traditionally held view or dogma is that cancer is agenetic
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.
The 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 dysfunction.
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 genetic disease. 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. The 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 epiphenomenal.
They're downstream effects of this disturbance in the metabolism that Warburg originally defined back in the 1920s and '30s."
How the 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.
"Those nuclear 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.
What the 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
cell.
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
cytoplasm. But that's not what happened.
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 downregulated the
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."
What About 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. Li-Fraumeni
syndrome,2 which raises your risk of developing cancer at a very young age, and BRCA1, which raises your breast cancer risk are two examples.
"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 upregulate 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 downregulate 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 occur? 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 production.
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.
"Personalized medicines, checkpoint inhibitors, all
of these kinds of therapies are basically looking at downstream effects
of the disease," Seyfried says.
"Unfortunately, most 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 fats.
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 inflammation. 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 ... They are
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 diabetes. 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,
"Mitochondria 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.
Ketones Prevent Dysregulated ROS Production, Thereby Reducing Your Risk for Cancer
It's not that ketones don't generate any ROS, they do; just not as
much. 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 ketones. When your body is burning ketones as its
primary fuel, you more or less ensure that you're in an ideal
therapeutic window with regards 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 notes."Ketones
prevent 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 systemic [disease].
The whole body has to be treated but in a non-toxic 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 treatment. On the other hand,
when you view cancer as a metabolic disease, you can target and manage
the disease without creating systemic toxicity. 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 significantly reduced. 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]. They're like, 'I have to
therapeutically fast for a week? Oh, I'm not going to. Give me a break'
... An effective 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."
Most Disease Is Rooted in Mitochondrial Dysfunction
Cancer is not the only outcome when mitochondrial respiration goes
awry. 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. The 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 calculator3
(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 ultra-low 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 says. "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," Seyfried says.
"Some people can get into these zones very quickly
and very easily. Other people really struggle. All of this is a
biomarker gauge. We've done some interesting linear regression analysis
on survivability of mice with cancer using the GKIs, the independent
variable, the glucose-ketone index.
There definitely is statistical relationship on how
long you can keep your GKI [and] how long you can survive with a very
aggressive cancer. Clearly, it's just one biomarker system that allows
individuals to help battle their own cancer."
Therapeutic 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 www.Cronometer.com/mercola, an online nutrient tracker, to create a
Mercola version of the software programmed specifically for nutritional
ketosis.
You can sign up and use Cronometer.com/Mercola
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).
More Information
If you really want to dig deep into the details of therapeutic ketosis, read Seyfried's book, "Cancer as a Metabolic Disease." If you want to start with a shorter treatise, you can read through his paper, "Cancer as a Metabolic Disease: Implications for Novel Therapeutics," published in the journal Carcinogenesis in 2014, or his 2015 paper in the journal Frontiers, titled "Cancer as a Mitochondrial Metabolic Disease.".4
Hopefully, we've inspired you to consider the nutritional roots of
cancer and other chronic disease. 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 track. 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 already exists. It's
just a matter of applying it.
You or Your Doctor Can See Dr Seyfried Live Next Month
Last but not least, if you want to learn more about cancer, be sure to attend the ACIM Conquering Cancer Conference
in Orlando, September 22 through 24. Seyfried and I will both be there,
along with a long list of other excellent speakers. There, you'll learn
more about how to implement a ketogenic diet and much more. I will also
be speaking and attending the event and will share my absolute latest
on how to use nutritional ketosis, many of which have never been
previously presented.
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