Ketogenic Diet in Combination with Calorie Restriction and
Hyperbaric Treatment Offer New Hope in Quest for Non-Toxic Cancer
Treatment
June 30, 2013
Story at-a-glance
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A mounting body of research suggests most cancers are highly
responsive to therapeutic ketosis—a natural physiologic
state induced during prolonged states of decreased
glucose—in combination with calorie restriction
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One way to achieve this is to use a ketogenic diet that
retains non-starchy vegetable carbohydrates, replacing them
with high amounts of healthy fats and adequate amounts of
high-quality protein
-
Healthy cells have the metabolic flexibility to adapt from
using glucose to using ketone bodies. Cancer cells lack this
metabolic flexibility, so when you eliminate carbs, which
are metabolized to glucose, you effectively starve cancer of
its primary fuel source.
-
Intermittent fasting, where you gradually restrict the
window of time during which you eat food down to about six
to eight hours per day aids in the transition from burning
carbs to burning fat
-
The ketogenic diet by itself can extend survival in animal
models of metastatic cancer, but recent research shows that
when it’s combined with hyperbaric oxygen therapy three
times per week, there is a significant additive effect
By Dr. Mercola
Cancer is now so common it affects about one of two of us and
most will face it at some point in their lives, either
personally or through a friend or relative. Compelling research
indicates that the answer to our burgeoning cancer epidemic
could be far closer than previously imagined, in the form of a
ketogenic diet.
Personally, I believe this is an absolutely crucial facet of
cancer prevention and treatment, for whatever type of cancer
you’re trying to address, and hopefully, some day it will be
adopted as a first line of treatment by mainstream medicine.
A ketogenic diet calls for eliminating all but non-starchy
vegetable carbohydrates, and replacing them with high amounts of
healthy fats and low to moderate amounts of high-quality
protein.
The premise is that since
cancer cells need
glucose to thrive, and carbohydrates turn into glucose in your
body, then lowering the glucose level in your blood through carb
and protein restriction literally starves the cancer cells to
death. Additionally, low protein intake tends to minimize the
mTOR pathway that accelerates cell proliferation and lowers the
amount of one particular amino acid, glutamine, which is also
known to drive certain cancers.
This type of diet is what I recommend for everyone, whether
you have cancer or not, because it will help you convert from
carb burning mode to fat burning, which will help you optimize
your weight and prevent virtually all chronic degenerative
disease.
The Ketogenic Diet—An Excellent Approach to Cancer Prevention
and Treatment
Dr. Dominic D’Agostino, PhD is an assistant professor at the
University of South Florida College of Medicine.
He teaches courses in molecular pharmacology and physiology,
and maintains involvement in several studies researching
metabolic treatments for neurological disorders such as
seizures, Alzheimer’s, ALS, and cancer—all of which are
metabolically linked.
His entry in to this field began when, in 2007, the Office of
Naval Research funded his study into seizures related to oxygen
toxicity experienced by Navy SEAL divers using closed-circuit
breathing apparatus. At this juncture, he came across the
ketogenic diet, which has already been confirmed as an effective
treatment for epilepsy and a variety of seizure disorders.
“I came across the work of
Thomas Seyfried,” he says. “I found a large
amount of evidence that suggested that cancer was
metabolically unique. Genetically, it was very
heterogeneous. There are a host of different genetic
anomalies in the cancer cells, but one characteristic is
that it had this ubiquitous metabolic phenotype, which was
aerobic glycolysis.
Even in the presence of oxygen, it was shown that
cancer cells continue to pump out lactate, suggesting that
they’re fuelling their metabolism from excess glucose
consumption.
From my perspective, the only reason cancer cells
would be pumping out lactate and deriving energy from
glucose at such a high rate would be because they are
metabolically compromised with mitochondrial deficiency.”
A mounting body of evidence suggests cancer is responsive to
therapeutic ketosis—a natural physiologic state induced during
prolonged states of decreased glucose. Nutritional ketosis
involves restricting carbohydrates in order to decrease the
availability of glucose. Restricting carbs also increases
production of ketone bodies from your liver. Nearly all of your
normal cells have the flexibility to readily adapt to using
ketone bodies for fuel in lieu of glucose, but cancer cells
do not have this metabolic flexibility. Hence, they
effectively starve to death while all your normal cells actually
operate more efficiently than before.
Another Key Component for Cancer Prevention and Treatment:
Calorie Restriction
When you restrict carbohydrates, you prevent spikes in blood
sugar, insulin and IGF-1 from occurring. These spikes are
actually very pro-inflammatory, and can activate oncogenes
(genes that contribute to the conversion of a normal cell into a
cancerous cell), and enhance both cancer cell proliferation and
the metastatic process.
But here’s a key point: While carb restriction will reduce
these spikes, it will not have a major impact on baseline levels
of blood glucose, unless you also restrict your calorie and
protein intake. So for cancer prevention and treatment,
carb restriction must be combined with calorie restriction and
moderate protein restriction in order to effectively “starve”
cancer cells of their preferred fuel (glucose and glutamine).
“The ketogenic diet is, I think, a very good strategy
to make calorie restriction tolerable,” Dr. D’Agostino
says. “Because when your brain in particular is craving
glucose, and, say, for example, you go on a
calorie-restricted diet, but it’s a high-carbohydrate diet,
you’re still getting fluctuations in blood glucose. Your
brain goes through these intermittent periods of glucose
deprivation and you get very hungry. It’s not a very
comfortable feeling.
Nutritional ketosis, which occurs with carbohydrate
restriction and is further enhanced with calorie
restriction, forces the physiological shift from a
glucose-based metabolism to a fatty acid and ketone
metabolism. When your body is, shall we say, keto-adapted,
your brain energy metabolism is more stable and your mood is
more stable. It may take a few weeks to adapt
physiologically to this. But nutritional ketosis can be
maintained and sustained with carbohydrate restriction and
is further enhanced with calorie restriction.
The total calories really need to be restricted, and
also protein. Protein is gluconeogenic. There are
gluconeogenic amino acids in protein. If protein is at, say,
for example, two or three grams per kilogram per day that is
probably going to feed in through the gluconeogenic pathway
and contribute to glutaminolysis. It will be hard to deplete
your glycogen stores, which is necessary to drive the
ketogenesis in your liver.”
How Much Protein Is Advisable?
So to summarize, in order to maintain and sustain nutritional
ketosis, you need to decrease both carbohydrates and
protein. But how much protein is enough, or too much?
As Dr. D’Agostino mentions above, eating two to three grams
of protein per kilogram of bodyweight—which translates to
100-300 grams of protein per day for some people—is an enormous
overload. Many bodybuilders will consume this much though, and
many non-athletes as well. The bodybuilding industry has
fostered the idea that you need tons of protein to build muscle,
but as Dr. D’Agostino explains, if you restrict protein, and
replace both the lost protein and carbs with healthful fats, the
elevation in your blood ketones will have a protein-sparing, or
anti-catabolic, effect.
“It will help you preserve lean body mass and a
physical performance during a calorie deficit. This is why
the ketogenic diet is an effective strategy for losing
weight and retaining muscle, especially if it’s complemented
with resistance exercise or some kind of physical activity,”
he says.
Your end goal needs to be taken into consideration here
though. A bodybuilder’s purpose for embarking on a ketogenic
diet will be different from someone with cancer or a seizure
disorder. In the latter case, you’d need to be far more strict
with reducing protein in order to achieve and maintain ketosis.
Personally, I’m intrigued with the concept promoted by one of
my mentors, Dr. Ron Rosedale, who advocates restricting protein
to one gram per kilogram of lean body mass. Typically, for
someone like myself, that amounts to about 50-70 grams of
protein per day. The reason he promotes this so much is because
of the stimulatory effect protein (branch-chained amino acids
specifically) has on mammalian target of rapamycin (mTOR)—a
pathway that seems to be largely responsible for the pathology
seen in cancer growth.
When you reduce protein to just what your body needs, mTOR
remains inhibited, which helps lessen your chances of cancer
growth.
“I agree that mTOR is an important signal once you
have cancer,” Dr. D’Agostino says. “The amino acid
leucine is a powerful activator of the mTOR pathway, and
stimulates skeletal muscle protein synthesis. Now, if a
normal healthy person consumes boluses of leucine [a
branch-chained amino acid], say five grams a couple of times
a day, which a lot of bodybuilders and athletes do, can this
enhance cancer growth?
This is an interesting question, and one that I’ve
been researching. We’re about to set up a study where we
give large doses of branch-chained amino acids in a
metastatic model of cancer. My opinion is that
branch-chained amino acids, which activate mTOR, in a normal
healthy person are not counterproductive. They do not
increase one’s susceptibility to cancer and may even prevent
muscle wasting (e.g. cachexia) associated with cancer.”
The 'Meat' of the Ketogenic Diet—FATS
Most people who follow a ketogenic diet inadvertently
restrict their calories without actually reaping the metabolic
benefits of a calorie deficit, which include reductions in blood
glucose, insulin, and triglycerides. The reason for this is that
they don’t replace the carbs (and protein) they’ve eliminated
with high enough amounts of healthy fats.
“Paradoxically, when you’re eating more fat, your
blood fats will go down, due to a calorie deficit, and HDL
[so-called ‘good’ cholesterol] goes up. Almost everyone that
I see on these high-fat ketogenic diets has improved HDL
levels,” Dr. D’Agostino says.
Now, when we say increase the fat, we’re not talking about
the most common fat that people eat, which are primarily highly
processed vegetable oils that are full of omega-6 fats, or trans
fats found in French fries and doughnuts. We’re
talking about high-quality fats like avocados, butter, coconut
oil, macadamia nuts, and olives. These types of fats, which Dr.
Rosedale believes are metabolically neutral because they don’t
tend to trigger hormonal signaling events like leptin, insulin,
and the mTOR pathway.
“I think a lot of the fats can be used in place of
protein. And fats are very protein sparing, decreasing your
need for protein,” Dr. D’Agostino says.
Bear in mind that while a traditional ketogenic diet calls
for quite a bit of dairy products, dairy can actually be
problematic and may prevent many of the health benefits that you
can get from the ketogenic diet described by D’Agostino and
Seyfried. Lactose is a sugar
made from galactose and glucose that is found in milk, making up
anywhere from two to eight percent of milk by weight. These
extra sugars can be problematic when seeking to lose weight or
treat cancer, even if from raw organic sources. Dairy fat is
acceptable (e.g. sour cream, butter, etc.), but foods
high in dairy protein or lactose should be minimized or avoided.
Why You’d Want to Become a Fat-Burner
Your body can burn two types of fuel: fat and carbs. In my
estimation, I suspect about 99 percent of Americans are adapted
to burning carbs as their primary fuel. It’s important to
realize that when your body is adapted to burning carbs, you’re
quite inflexible, metabolically speaking. Without fail, your
body will be screaming for food about every two to three hours.
These kinds of hunger pangs vanish once you become fat adapted,
however. Then you can go all day and not be hungry, because you
have far more fat in your body to burn than glucose.
So how do you achieve this metabolic switch-over?
In my experience,
intermittent fasting, where you gradually restrict the
window of time during which you eat food down to about six to
eight hours, is one of the most effective ways to make this
transition.
“I think from a practical standpoint, the important
question is what’s a person going to follow? From my
perspective, the biggest hurdle here is compliance;
compliance to a dietary strategy that makes calorie
restriction feasible and possible. And you know,
carbohydrate restriction, high-fat diet, and intermittent
fasting is one way to achieve that,” Dr. D’Agostino
says.
“There are a lot of advantages to this pattern of
intermittent fasting. I think that it is a good strategy to
promote metabolic health and to maintain nutritional
ketosis, if you can adapt to it. In some lifestyles, people
cannot readily adapt to it. But I’ve found that most people
can if they give it a try for at least several weeks. Most
people are resistant. Even with people that are resistant-
once they try it, they’re amazed at how much better they
feel.”
It’s not an ideal course for everyone, however. As a general
rule, intermittent fasting is contraindicated if you’re:
- An elite athlete
- Pregnant
- Suffer with adrenal stress
- Already at a low BMI (< 19)
Hyperbaric Treatment Works Synergistically with Ketogenic Diet
Against Cancer
Dr. D’Agostino recently published a paper in the journal
PLoS One, titled “The Ketogenic Diet and Hyperbaric Oxygen
Therapy Prolong Survival in Mice with Systemic Metastatic Cancer1.”
Most people who die of cancer die from the metastatic process,
rather than from the tumor itself. There’s really no treatment
or cure for metastatic cancer. Dr. D’Agostino’s team has
demonstrated that the ketogenic diet by itself can extend
survival in animal models of metastatic cancer, but when it’s
combined with hyperbaric oxygen therapy three times per week,
there is an additive effect2.
“You get a significant reduction in tumor growth,
decrease in tumor size, and significant extension of life
when the therapeutic ketosis achieved through the ketogenic
diet is combined with hyperbaric oxygen,” he says.
“Tumors thrive in a low-oxygen environment. As a
tumor grows, it exceeds its ability to supply oxygen to the
center of the tumor. That low level of oxygen, called
hypoxia, further activates the oncogenes; cancer promoting
genes. It activates things like HIF-1-alpha and VEGF. IGF-1
signaling goes up. Hyperbaric oxygen can reverse tumor
hypoxia intermittently. In doing that, it can actually turn
off the oncogenes. There are published reports on this.
... [T]he tumor thrives in a low-oxygen environment,
and it’s adapted to that low-oxygen environment. When you
saturate a tumor with oxygen, because the mitochondria are
damaged, it overproduces oxygen free radicals in the form of
superoxide anion. This oxygen-induced increase in free
radicals can actually cause the tumor to kill itself.”
How to Determine if You’re in Ketosis
To help you determine if you’re in ketosis, you can purchase
a blood ketone and glucose meter, both of which are available in
most drug stores. Amazon.com also sells them. Dr. D’Agostino
recommends the Precision Xtra by Abbott Labs. Their ketone test
strips are called Precision Xtra. Glucose meter strips typically
sell for about 50 cents per strip, while ketone strips can range
from $3-6 each.
“Another option is the CardioChek meter. This is an
interesting meter, because it can measure glucose, ketones,
HDL, LDL, triglycerides, and a number of things.”
By testing your glucose and ketones, you can monitor your
response to a nutritional intervention, and then adjust your
calories and the macronutrient ratios to optimize your body to
be in what Dr. D’Agostino calls the “metabolic zone.” The
metabolic zone is defined as sustained hypoglycemia (55-75
mg/dl) with elevated blood ketones (>2 mM).
“If you can produce sustained hypoglycemia with
carbohydrate and calorie restriction and simultaneously
elevate blood ketones, it actually makes the hypoglycemia
tolerable,” he explains. “The ketones replace the
glucose as the primary energy fuel for your brain. It
basically keeps your brain metabolism optimized and prevents
fluctuations in your mood and your energy levels, if you can
sustain therapeutic ketosis with a properly balanced
ketogenic diet.”
As you implement the ketogenic diet, you can just check your
glucose and ketones once a week if you find the cost of the
strips to be prohibitively expensive for more frequent testing.
Typically, if your blood glucose stays at 75 or below with
carbohydrate restriction, there’s a good chance that you’ll be
in nutritional ketosis, which is where you want to be.
If you’re in ketosis by evidence of ketones in your urine,
you’re in a situation where you likely have depleted glycogen
stores in your liver. This means you’re maintaining a low blood
glucose, which is good. The driver for hepatic ketogenesis is
low blood glucose and low glycogen levels in the liver, as this
means your body is depleted of glycogen. Your body will not
really make adequate ketones (>2 mM), and they won’t spill over
in your urine, unless you’ve achieved that level of glycogen
depletion. So remember, when your levels of blood ketones
are 1-3 millimolar (mM) that’s a good biomarker of nutritional
ketosis.
More Information
While Dr. D’Agostino does not treat patients, he has plenty
of resources to offer for anyone interested in learning more. If
you have cancer, you could bring these resources to your
oncologist for discussion. For everyone else, a ketogenic diet
is an excellent way to optimize your health and prevent chronic
diseases of all kinds. Helpful books and websites where you can
learn more include:
- KetogenicDietResource.com3.
This site is maintained by a friend of Dr. D’Agostino. Here
you can also find a ketogenic diet handbook for cancer
patients called Fight Cancer with a Ketogenic Diet
- Dr. D’Agostino’s website KetoNutrition.org4
contains a wide variety of therapy resources for patients
- Miriam Kalamian, EdM, MS, CNS offers ketogenic diet
consulting services for cancer patients. For information,
see dietarytherapies.com5
- The book, Cancer as a Metabolic Disease: On the
Origin, Management, and Prevention of Cancer, by Thomas
Seyfried
- The book, The Cantin Ketogenic Diet: For Cancer,
Type I Diabetes & Other Ailments, by Elaine Cantin,
which specifically outlines a dairy-free ketogenic diet
Last but not least, ketoresearchchem.com6
is a resource for scientists interested in ketone research.
Please note that the ketone supplements offered there are
strictly for research only, and are NOT available for sale to
cancer patients.
The Ketogenic Diet for Optimal Health and Disease Prevention
I firmly believe the ketogenic diet can be a tremendously
beneficial strategy for optimizing your health and disease
prevention and treatment plan, including cancer. It’s already a
well-established first line of treatment against many seizure
disorders. While most of your body’s cells have the metabolic
flexibility to use either fat or sugar for fuel, cancer cells
differ in that they cannot use fat (ketones) to
survive—they need glucose, and a low-oxygen environment.
Back in the 1930’s, Dr. Otto Warburg actually received a
Nobel Prize for his discovery that sugar is the primary fuel
substrate for cancer cells. The “Warburg effect” in cancer cells
is the basis of
positron emission tomography (18-FDG PET), a
medical imaging technique to visualize cancer. Oncologists
have ignored this vital information for over 80 years and don’t
use it therapeutically, which in my view is just reprehensible
malpractice... So many people suffer needlessly because they
don’t have access to this simple nutritional therapeutic
strategy, which, in a nutshell, takes advantage of this
intrinsic metabolic differential between healthy and cancerous
cells.
Your body has a limited storage of sugar, stored in the form
of glycogen, typically in your muscles and liver. These glycogen
stores are depleted in about 12 hours or so, at which point your
body has to switch to burning fat. This is part of what makes
intermittent fasting so beneficial, because by not eating for
12-18 hours or longer each day, your body shifts into this
fat-burning mode. While frequent hunger is a major issue for
most people who are reliant on burning carbs for energy,
fat-burners can go all day, or a number of days if necessary,
without food, since most of us have plenty of fat to be used for
fuel.
While most people can still eat some carbs, along with
moderate amounts of high-quality protein, those with cancer need
to be far more strict. Cancer patients also need to combine a
ketogenic diet with calorie restriction to achieve glucose
depletion that will effectively starve the cancer cells. Recent
research also shows that adding hyperbaric oxygen treatment will
dramatically reduce cancer growth and shrink tumors. All in all,
I can find no drawbacks to eating this way, which is why I
highly recommend it for everyone.
© Copyright 1997-2013 Dr. Joseph Mercola. All Rights Reserved.
http://articles.mercola.com/sites/articles/archive/2013/06/30/dagostino-cancer-research.aspx
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