How Metabolic Therapies Prevent and Treat Chronic Diseases from Dr. Mercola
How Metabolic Therapies Prevent and Treat Chronic Diseases
December 02, 2017 • 119,112views
Story at-a-glance
Mounting
evidence shows conditions such as Alzheimer’s and cancer are metabolic
diseases, which means you can prevent, treat and recover from them like
other metabolic conditions, such as Type 2 diabetes and heart disease
A
number of experts and researchers are now convinced the answer to our
burgeoning cancer and Alzheimer’s epidemics is a ketogenic diet and
other metabolic support, such as fasting, hyperbaric oxygen treatment
and dietary supplementation
During
fasting or ketosis, your brain switches to using ketone bodies derived
from dietary fats as its primary fuel, and ketones have potent
neuroprotective effects and enhance brain function
Healthy
cells have the metabolic flexibility to use either glucose or ketones
(obtained through your diet from carbohydrates and healthy fats
respectively), whereas cancer cells cannot use ketones for fuel due to
having damaged mitochondria
Nutritional
ketosis prevents and combats cancer by optimizing mitochondrial
function, decreasing blood glucose and insulin, increasing tissue
oxygenation, decreasing free radical generation, downregulating
oncogenes and upregulating tumor suppressor genes
By Dr. Mercola
Cancer has become Americans' No. 1 health concern. According to the
American Cancer Society, more than 1,600 people die every day from
cancer in the U.S. That's over 600,000 people each year. When you
include the entire world population that number climbs tenfold to over
7.6 million. Statistics suggest half of all men and 4 out of 10 women
will develop cancer during their lifetimes. Alzheimer’s disease
is another major health threat that has dramatically increased in
recent years. Between 1999 and 2014, the death rate from Alzheimer’s
increased by 55 percent. According to the latest statistics, Alzheimer’s
claims the lives of more than half a million Americans each year, and
unless there are radical changes, many experts project half of the
population will eventually develop it.
These are grim statistics, but there is hope. Mounting evidence shows
both of these conditions — as well as many other top killers — are metabolic diseases.
This is actually good news, because that means you can prevent, treat
and recover from them like other metabolic conditions, such as Type 2 diabetes and heart disease.
Ketogenic Diet Shows Tremendous Promise as Tool Against Chronic Disease
A number of experts and researchers are now convinced the answer to
our burgeoning cancer and Alzheimer’s epidemics is a ketogenic diet and
other metabolic support. Nutritional ketosis is the metabolic state
associated with an increased production of ketones in your liver; i.e.,
the biological reflection of being able to burn fat, and is defined as
having blood ketones in the range of 0.5 to 3.0 millimoles per liter.
Personally, I believe metabolic therapy — starting with a ketogenic diet
— is an absolutely crucial facet of dementia and cancer prevention and
treatment, and hopefully some day it will be adopted as a first line of
treatment by mainstream medicine. The two videos included in this
article feature Dominic D’Agostino, Ph.D., 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.
What Is Metabolic Therapy?
Metabolic therapy is an umbrella term that includes nutrition
(primarily in the form of a ketogenic diet), dietary supplements, drugs
that have a therapeutic influence on energy metabolism, fasting,
hyperthermia, hyperbaric oxygen therapy and more. The focus of
D’Agostino’s talk is the biological effects of nutritional ketosis and
ketone supplements. The first 15 minutes or so are spent explaining the
background of how he got into looking at fasting as a therapeutic aid to
improve brain metabolism.
The second half of the video goes into practical applications of
nutritional ketosis, and its anticancer effects. In my latest book, “Fat for Fuel,” I present a program called metabolic mitochondrial therapy (MMT), which is a form of metabolic therapy.
MMT includes not only cyclical ketosis, but also a variety of other
strategies to improve your mitochondria other than diet, such as cold
thermogenesis, photobiology, detox, exercise and electromagnetic field
(EMF) avoidance. As noted by D’Agostino, metabolic therapies have the
ability to treat a broad range of pathologies, not just cancer, making
it all the more valuable from a clinical standpoint.
“In one way or another, most diseases, especially diseases of the
brain — neurodegenerative diseases — are linked pathophysiologically to
energy dysregulation,” D’Agostino says. “So, a metabolic therapy can
often enhance brain energy metabolism in the face of these metabolic
deficits.” What this means is that while you may be addressing a
specific problem such as cancer, the therapy will enhance other aspects
of your health as well, including your brain function. So, it’s a
multiple-win situation.
Ketones Fuel Your Body and Brain During Starvation
As explained by D’Agostino, it had long been thought that the brain
could only function on glucose, but studies looking at the effects of
starvation showed otherwise. In fact, during starvation, such as a bout
of fasting, your brain switches to using ketones derived from dietary
fats, as its primary fuel, and ketones actually enhance brain function.
If you eat a regular diet, which tends to be higher in net carbs than
fats, your brain will almost exclusively use glucose as its primary
fuel.
D’Agostino cites a study in which overweight participants fasted for
40 days. After the first week, their ketones skyrocketed, overtaking
glucose as the primary fuel source for the body (and brain). Studies
have also shown that during fasting, at least two-thirds or more of the
energy your body produces is derived from ketone bodies. “So, ketones
function as an alternative fuel for the brain [when] glucose is not
available,” D’Agostino explains.
Now, putting your body into starvation mode through longer water fasts
is not an attractive option for most people. The good news is a
ketogenic diet mimics the effects of fasting in that it elevates ketones
and lowers blood glucose. The key to nutritional ketosis is twofold:
You need to dramatically reduce the amount of net carbohydrates you eat
(total carbs minus fiber), and you need to eat a significant amount of
healthy dietary fats.
This combination is what elevates your ketone level and lowers your
glucose and insulin. It also mobilizes stored energy in your fat cells,
which is why a ketogenic diet typically results in significant weight
loss.
The Benefits of Ketone Supplementation
Ketones made by your body are called endogenous. But you can also
supply your body with exogenous ketone salts or esters or from ketone
precursors such as medium chain triglyceride (MCT) oil, Coconut oil
contains some MCTs, but straight MCT oil is a more concentrated source
of the shorter chain fats that more easily convert to ketones.
Most commercial brands of MCT oil contain just two of the fatty acids
found in coconut oil: eight-carbon (C8) and 10-carbon (C10) fats. They
usually contain close to a 50/50 combination of both chain lengths.
I prefer taking straight C8 (also known as caprylic acid), as it
converts to ketones far more rapidly than do C10 fats, and may be easier
on your digestion. Coconut oil provides a mixture of all the
medium-chain fats, including C6, C8, C10 and C12 fats, the latter of
which is also known as lauric acid, which makes up over half of the fat
in coconut oil. There are benefits to all of these fatty acids. However,
MCT oil is more efficient at increasing ketone levels.
MCTs are processed differently from the long-chain fats in your diet.
Normally, a fat taken into your body must be mixed with bile released
from your gallbladder and acted on by pancreatic enzymes to break it
down in your digestive system. MCTs don’t need bile or pancreatic
enzymes. Once they reach your intestine, they diffuse through your
intestinal membrane into your bloodstream and are transported directly
to your liver, which naturally converts the oil into ketones.
Your liver then releases the ketones back into your bloodstream,
where they are transported throughout your body. They can even pass your
blood-brain barrier to supply your brain with energy. As noted by
D’Agostino, research shows MCT oil can improve cognitive function in
people with mild cognitive impairment. MCT oil will raise your ketone
level even if you’re not on a ketogenic diet or fasting. The effect is
not going to be as dramatic as when you’re fasting or eating a ketogenic
diet, but it can mimic a mild ketogenic state.
D’Agostino also reviews the use of ketone salts and synthetic ketone esters,
which he uses in his own research. Tests reveal the administration of a
single dose of the synthetic ketone acetoacetate causes a rapid
elevation of ketone esters within 30 minutes and is sustained for over
four hours. Some of D’Agostino’s research shows nutritional ketosis can
be sustained for up to 12 hours using supplemental ketones.
According to D’Agostino, “Therapeutic ketosis, up to 2.5 millimolar
[per liter], is difficult to sustain, but with dietary ketone
supplementation we found that it’s possible. So, we can deliver ketones
within 15 to 30 minutes with administration of these synthetic ketogenic
agents.” Ketone supplementation also causes a significant decrease in
glucose within 30 to 60 minutes of administration. In fact, glucose is
reduced to a greater degree than what can be achieved with anti-glycemic
drugs like metformin.
Ketogenic Diet Often Better Than Drugs for the Treatment of Epilepsy
Epilepsy is a neurological disorder
marked by abnormal electrical discharges in the brain that trigger
seizures. The Epilepsy Foundation suggests epilepsy is the fourth most
common neurological condition, with an estimated 65 million people
worldwide affected by it.1
Some 150,000 Americans are diagnosed with epilepsy annually, with
children and older adults experiencing the highest incidence rates.2
Nutritional ketosis has been shown to be a very effective treatment for
many epileptics, especially children who do not respond well to the
medications used.
Research shows administration of synthetic ketone ester raises
seizure resistance in rats by a whopping 575 percent, “which is above
and beyond any anti-seizure medication that has been tried in this
model,” D’Agostino notes. He then goes on to describe and explain the
anticonvulsant and neuroprotective mechanism of ketones. In summary,
both a ketogenic diet and synthetic ketone supplementation alters the
ratio of gamma-aminobutyric acid (GABA) and glutamate in your brain.
Glutamate is an excitatory neurotransmitter used to produce GABA,
which has an inhibiting effect. The ratio between glutamate (excitatory)
and GABA (inhibitory) determines the net excitability of the neurons in
your brain. When you are in ketosis, the ratio of GABA to glutamate is
higher than when you’re not in ketosis, which has a stabilizing and
neuroprotective effect on your brain.
As explained by D’Agostino, “Not only does it deliver more energy to
your brain, it prevents the brain from being in a hyperexcitable state
that could trigger a seizure.”
Conditions and Diseases That Can Benefit From Ketones
D’Agostino’s research also shows that ketones suppress the generation
of reactive oxygen species (ROS), damaging free radicals, by enhancing
mitochondrial function. He explains, “Mitochondria are the energy
organelles within the cell. They’re also the site of free radical
production.
By enhancing mitochondrial efficiency — as oxygen goes through the
mitochondria to produce energy — less of that oxygen becomes an oxygen
free radical.” In other words, one of the neuroprotective mechanisms of
ketones is their ability to reduce ROS.
This also has direct implications for cancer development. ROS are
mostly generated through the coenzyme 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 coenzyme Q couple and reduces production
of ROS. Hence, ketone bodies are considered a “cleaner” fuel than
glucose.
Now, 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.
Ketones — whether from nutritional ketosis or use of a ketone
supplement — also enhance brain energy metabolism and increase the
energy reserves in your brain. These therapeutic effects can be
exploited for the benefit of many different conditions and diseases,
including:
Hypoxia (which can result from a stroke, space flight or even just exposure to high altitude)
Glucose transporter deficiency syndrome (a genetic seizure disorder)
Angelman’s syndrome (a seizure and motor dysfunction disorder)
Lou Gehrig’s disease (ALS)
Alzheimer’s disease
Parkinson’s disease
Epilepsy
Traumatic brain injury
Impaired wound healing
Cancer
Some of these syndromes, glucose transporter deficiency syndrome and
Angleman’s syndrome specifically, require patients to remain on a very
strict ketogenic diet to avoid seizures. D’Agostino’s research suggests
supplemental ketones may be used, allowing these patients to be less
strict with their diet, without forgoing the benefits of strict
nutritional ketosis. In terms of wound healing, ketones have been shown
to increase profusion of blood into the wounded area, thereby
facilitating healing.
How Ketones Affect Cancer Cells
D’Agostino has shown that oxygen, at levels that are nontoxic to
healthy cells, are toxic to cancer cells. In essence, cancer cells are
more vulnerable to oxygen toxicity. His team has also demonstrated that
ketones are toxic to cancer cells. When cancer cells are placed in a
petri dish and fed only ketones, they simply die. Healthy cells, on the
other hand, will thrive in the presence of ketones without glucose.
What this and other research tells us is that healthy cells,
including brain cells, have a very high degree of metabolic flexibility
and are able to thrive on either glucose or ketones (obtained through
your diet from carbohydrates and healthy fats respectively). Not so with
cancer cells. Defects in their metabolism due to having damaged
mitochondria prevent them from metabolizing ketones. For this reason,
glucose is the predominant fuel that allow cancer cells to thrive.
Research by Thomas Seyfried, Ph.D., professor of biology at Boston College and a leading expert and researcher in the field of cancer metabolism and nutritional ketosis, shows that tumor growth is tightly correlated with blood glucose levels.
When glucose and glutamine levels are low, and ketone levels are
high, very little tumor growth occurs, and as glucose levels rise, tumor
growth increases right along with it. In fact, the fluorodeoxyglucose
PET scan is a technology that shows glucose consumption in tissue,
allowing you to identify and track the aggressiveness of cancer tumors.
All Cancers Arise From Mitochondrial Dysfunction
Regardless of the cancer, cancer cells have the same metabolic
phenotype — they all suffer from glucose overconsumption, which is the
result of mitochondrial dysfunction. Ketones are metabolized entirely
within the mitochondrial membrane, so the mitochondria must be fully
functional in order to make energy from the ketones, and this is the
functionality that all cancer cells lack.
Now, aside from a poor diet, your mitochondria can also be damaged
from a number of chemical and environmental triggers, which is why it’s
so important to eat organic whole food (to avoid pesticides and
synthetic food additives) and avoid chemical exposures from household
and personal care items used on a daily basis.
Also, as explained by D’Agostino, your mitochondria become
increasingly damaged and dysfunctional with advancing age, and, since
the mitochondria produce at least 90 percent of the energy in your
cells, as your mitochondrial function starts to decline, glucose
metabolism is upregulated to make up for the decline in energy
production. As mitochondrial function declines, you also get
destabilization of the nuclear genome, which triggers the activation of
oncogenes — genes that cause cancer.
It can also inhibit tumor suppressor genes. With the activation of
oncogenes, enzymatic activity of glycolysis is also increased, allowing
increased generation of energy from sugar.
As noted by D’Agostino, “If all cancer arises from mitochondrial
dysfunction, then replacement of damaged mitochondria with normal
mitochondria should prevent cancer. In other words, mitochondrial
producing sufficient respiration, i.e., energy, should suppress tumor
growth regardless of the numbers and types of mutations … present in the
nucleus of cancer cells.”
This, in a nutshell, is what metabolic therapies are all about, as
healthy mitochondria act as an ultimate tumor suppressor. Research even
shows healthy mitochondria suppress tumor growth even in the presence of
an oncogene in the nucleus of a cell. As mentioned, mitochondrial
function can be improved in a number of different ways, but when it
comes to diet, a low-carb, high healthy-fat diet and/or fasting are the
keys that unlock mitochondrial health.
According to D’Agostino, in rats, the best results were obtained from
a combination of ketogenic diet, ketone supplementation and hyperbaric
oxygen therapy. In summary, the rationale for using a ketogenic diet and
other metabolic therapies is to address and repair the mitochondrial
defects causing the condition or disease in the first place. Again,
nutritional ketosis prevents and combats cancer by:
Optimizing mitochondrial function, mitochondrial biogenesis and energy production
Decreasing blood glucose, glycolysis and glucogenesis
Decreasing your insulin level
Increasing tissue oxygenation
Decreasing ROS generation and secondary free radicals
Downregulating oncogenes and upregulating tumor suppressor genes
How to Assess the Health of Your Mitochondria
So, 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 (GKI) calculator3
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 GKI calculator looks at your glucose to ketone ratio. Ketones must
be measured by blood, not urine, and your glucose must be entered in
millimoles, not in milligrams per deciliter (mg/dL).
If you have a glucose-to-ketone ratio of 1.0 or below, you know you
have healthy mitochondria. Now, getting down to a 1.0 can be difficult.
The last time I did a four-day fast, on the last day my glucose was 40
(2.2 mmol/l) and ketones were 8, giving me a ratio of 0.27, well below
the 1.0 threshold.
You will likely need to do a complete water fast like I did 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.
As explained by Seyfried in a previous interview,4
you can drive your blood sugar way down by doing a water fast for three
to four days and then taking some exogenous ketones, such as MCT oil.
Also, to prevent cancer, you don’t have to remain at this low level for
longer than about five days every six months, as a general guide. If you
already have cancer, you’ll want to remain at a low level longer. As
explained by Seyfried:
“We’ve done some interesting linear regression analysis on
survivability of mice with cancer using the GKI … 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.”
Helpful Resources for Implementing Metabolic Therapy
If you end up being as convinced of the merits of this theory as I
am, there are several really good resources out there that you can
peruse to learn more about the practical implementation of various
metabolic therapies. As mentioned, “Fat for Fuel” details my complete
program aimed at optimizing mitochondrial function. I also offer an online course on MMT to go along with the book.
The course consists of seven comprehensive lessons to teach you the
keys to fighting chronic disease and optimizing your health and
longevity. If you or someone you love has cancer, it will also augment
any oncological treatment you might be undergoing. A key component that
differentiates MMT from most other ketogenic eating plans is its
emphasis on CYCLICAL ketosis.
Once your body starts to burn fat for fuel, you need to switch to a
cyclical ketogenic diet, as long-term continuous ketosis has some
serious drawbacks that may actually undermine your health and longevity.
The “metabolic magic” in the mitochondria actually occurs during the
refeeding phase, not during the starvation phase. Alas, you cannot get
to that magic unless you first go through the starvation phase. Other
helpful resources include the following:
DietaryTherapies.com: A
resource provided by Miriam Kalamian, a nutritionist who has worked
with Seyfried since the very beginning, and has counseled many cancer
patients about the ketogenic diet he recommends. She also collaborated
with me on the creation of my MMT course
MetabolicOptimization.com:6
A blog created by D’Agostino and Travis Christofferson, author of
"Tripping Over the Truth: The Return of the Metabolic Theory of Cancer
Illuminates a New and Hopeful Path to a Cure.” Here you can find
interviews with scientists involved in ketogenic research and much more
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