FOCUS ON:

FASTING
DAVID PERLMUTTER, MD
TABLE OF CONTENTS

From The Desk of Dr. Perlmutter 3

Articles
 enefits of Intermittent Fasting
B
for Your Brain and Body 4
Why Fast? 7
How To Fast 8
New to a Low-Carb Keto Diet?
Avoid These Common Mistakes 9
High BDNF Tied to Lower Alzheimer’s Risk 14
The Empowering Neurologist 16
David Perlmutter, MD & Dr. Valter Longo
Science and Studies 17
About The Grain Brain Whole Life Plan 19

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FROM THE DESK OF
DR. PERLMUTTER
A Note Before Reading
What’s the longest you’ve gone without putting some food
into your body?

The six-to-eight hours you’re sleeping every night?

Perhaps the length of a long plane ride you took?

What if I asked you to go 24, or even 48, hours without

putting anything into your body except water?
It may sound uncomfortable and unenjoyable, but science is
giving us mountains of evidence that putting your body into a
state of short-term caloric restriction, or fasting, can now only
reduce the size of your waist, but improve the health of your
brain and fight off brain disease!

24 hours of fasting in exchange for 24+ years of better brain

health? Sounds like a good deal.

In the pages that follow I’ll explain the science behind

intermittent fasting, why it’s good for your brain, how to get
started, and explore some of the associated lifestyle choices
that can further amplify the beneficial impacts of intermittent
fasting (a ketogenic diet, BDNF-producing activities)

When you’ve finished reading, do visit my website to learn

and discover even more. I’ll continue to scour medical journals
for the latest research, and help you understand what this all
means for your health.

In good health,

3
 Benefits of Intermittent Fasting
for Your Brain and Body
With all of the hype around fasting, you may
believe it to be just another modern dietary
fad, but the truth is that fasting is as old
as our species. Until very recently, humans
have always had periods of going without
food. Fasting is baked into our physiology
and it can yield benefits to our brains and
bodies, at a biochemical level, that we’re
only just beginning to understand.
Many of us are blessed to live in a world
with abundant food, but that wasn’t always
the case. Throughout our evolutionary
history, sometimes days, weeks, and months
would pass during which food resources
were scarce. These periods without food
provided small hormetic stresses on our
genome — meaning stresses that turn out to
be beneficial to our bodies. In the absence
of calories, life-sustaining, protective genes
responsible for cellular repair and protection
are activated, inflammation is reduced, and
anti-oxidative defenses are increased.
This means that simply going without
food for a while may have anti-aging, anti-
inflammatory, and anti-tumor benefits that
are available to anyone, at any
time.
4
Fasting Basics
Readers of my book Grain Brain know that
the first step I recommend in the Grain
Brain diet is a 24- to 48-hour water fast
(with the important caveat that you should
check with your physician first). This can be
as simple as eating normally on a Sunday,
finishing dinner by 6 PM, and drinking only
water until 6 PM on Monday, when you can
again enjoy a nice meal. I recommend doing
a 24- to 48-hour fast at least four times a
year, though some enjoy doing a 24-hour
fast as often as twice each week.
One of the most obvious and immediate
benefits of fasting is psychological — the
opportunity to conquer a fear of hunger.
We’ve been indoctrinated to avoid hunger
at all costs, fearing a blood-sugar crash
or the feeling of being “hangry.” Fasting
gives you the chance to push through the
discomfort of mild hunger to discover the
clarity and freedom on the other side. It
can reinvigorate your whole relationship
with food and give you a greater sense of
balance, control, and enjoyment.
Fasting’s Effect on the Body
When our bodies fast, we begin to mobilize
glycogen from the liver and the muscles.
When our glycogen stores are depleted, our
metabolism shifts and we start to mobilize
fat and use it to create ketones, a source of
energy that powers the brain in a different
way, helping it to function
more efficiently. Beta-
HBA, the principal
ketone, has been
shown to be a
super-fuel that
produces ATP
energy more
efficiently than
glucose.
Not only does
Beta-HBA protect
neuronal cells from toxins
associated with Alzheimer’s
and Parkinson’s, it also improves
antioxidant function, increases the
number of mitochondria, and stimulates
the growth of new brain cells.
Daily Caloric Restriction
vs. Fasting
Caloric restriction is one way to spur
production of this valuable ketone, but
many people find reducing daily caloric
intake too tough to adhere to long-term.
The good news is that intermittent fasting
— restricting food intake for anywhere from
24- to 72-hours — is another effective way
5
of increasing production of beta-HBA, and
many people find it much more manageable
and sustainable than daily caloric restriction.
Fasting can help us reap many of the
benefits of caloric restriction in a way that
allows us to eat normally for a majority of
the time. In addition to increasing beta-
HBA, fasting also activates the Nrf2 gene
pathway that aids detoxification, decreases
inflammation, and stimulates mitochondrial
growth. When the body is in a fasted
state, even the process of apoptosis
(or programmed cell death) is refined,
eliminating damaged cells that can
lead to the development of
cancer.
Does Fasting
Slow Metabo-
lism?
Even with all
these important
benefits, some
may be reluctant
to try fasting due
to the outdated
belief that it lowers
metabolism and forces
the body into starvation
mode, causing it to hang on
to fat. But in fact, the opposite is
true. A regular schedule of
intermittent fasting can actually accelerate
and enhance weight loss. According to a
recent review of 40 independent studies,
intermittent fasters lost an average of 7-11
pounds over the course of ten weeks.
Supercharge your Brain
Another benefit of fasting is the stimulation
of BDNF, a protein that plays an integral role
in stimulating the growth of new brain cells
and the performance of existing neurons.
BDNF is best described as the brain’s
“growth hormone,” and stimulating its
production is easily one of the best things
you can do for your body and your brain.
To recap, some of the many benefits of
fasting include:
• Enhancing the same beneficial genetic
pathways that are activated by caloric
restriction, with a fraction of the
difficulty
• Stimulating the production of BDNF,
the brain’s growth hormone, which also
supports the function of existing neurons
• Stimulating mitochondrial replication
• Accelerating weight loss (when done on
a regular schedule)
• Decreasing inflammation
• Enhancing protection from diseases
including Alzheimer’s, Parkinson’s, and
cancer
• Improving antioxidant function
• Increasing production of beta-HBA, a
super-fuel for the brain and body
But again, it’s important that you consult
your physician before integrating fasting
into your life. It may be contraindicated for
those who are insulin-dependent diabetic,
have a history of eating disorders, or suffer
from ulcers.

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 Why Fast?
As we’re all accustomed to, food nowadays
is plentiful. We have our three meals each
day, 365 days each year. But it wasn’t
always like that.
In our hunter-gatherer days, obviously,
there were times when we didn’t have food
accessible at all. This would create a type
of stress in the body that would affect our
genome.
When we didn’t have food, when we
didn’t have calories, life-sustaining,
protective genes would be activated,
increasing antioxidant coverage, reducing
inflammation, and ultimately positively
impacting the health of the brain.
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When our bodies fast we begin to mobilize,
initially, sugar, cleated from the gylcogen in
our bodies. Once that has been expended,
we start to mobilize fat — and that’s a good
thing!
Mobilizing fat creates ketones that power
the brain in unlimited ways. When the brain
is powered by ketones, in functions in a
more efficient and effective way.
Fasting has been a part of the human
experience for as long as we’ve been,
but we are only just now beginning to
understand the profound biochemistry of
fasting, and why it’s really a really good
thing for your health.
 How
To Fast
Ready to get started? First, give it a go
with a 24-hour fast. As you get more
comfortable with it, and your body becomes
more efficient at using fat for fuel, you can
experiment with occasional fasts of 48- or
even 72-hours. But for now, choose one day
that you want to spend fasting. Some prefer
a Sunday, others like to fast on a workday
when they can stay busy and distracted.

If you opt to fast on a Monday, finish your

dinner on Sunday by around 6 PM, then
stop consuming all calories. Nothing should
pass your lips except water or some herbal
tea.

Stay well-hydrated throughout the day, and

notice how you feel. Hunger may start to
roll in waves by late morning, but notice
how it always eventually subsides. Do you
notice more mental clarity than usual?
Rest assured, your body will use its ample
reserves of glycogen and fat to provide you
with the fuel and energy you need.

By 6 PM on Monday, you’re all done! Treat

yourself to a healthy and nutritious meal.
Take the opportunity to savor each bite and
notice how delicious it tastes.

Your body and brain will thank you.

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 New to a Low-Carb Keto Diet?
Avoid These Common Mistakes
The ketogenic diet is one of the most talked
about and debated diet trends today.
And I bring it up here because it goes
hand-in-hand with a dietary program that
incorporates intermittent fasting.
You’ve probably heard celebrities, athletes,
and neighbors raving about the benefits
of this dietary approach. Interestingly,
the science backs up its rapid growth in
popularity, as a ketogenic diet has been
shown to have numerous health benefits for
its adherents. The diet can reduce the risk
of heart disease, improve glycemic control
in both Type 1 and Type 2 diabetes, help
individuals struggling with obesity lower
their BMI, and even improve or control
symptoms of debilitating neurodegenerative
conditions like Parkinson’s and epilepsy.
There is even some evidence to suggest
that a ketogenic diet can play a role in the
treatment of cancer! If it is implemented
properly, adopting a ketogenic diet can be
a very powerful tool in the fight against a
variety of chronic diseases.
If you’ve recently made the decision
to transition to a ketogenic diet or are
exploring the possibility of a change,
chances are you might currently find
yourself in a world of confusion. What is
ketosis? What are ketones? Can I really eat
all the fatty foods I want? How can this
possibly be good for me?
Allow me to address some of these
questions.
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While the ketogenic diet may sound
“new,” it actually parallels the way many
of our ancestors ate, before the advent of
agriculture allowed for the domestication
of staple crops like wheat and corn. Before
the widespread emergence of these crops
into the modern diet, which are high in
carbohydrates and sugar (particularly in
their most processed forms), our ancestors
ate a wide variety of wild plants and animals
and much less carbohydrate or sugar. This
diet, naturally lower in carbohydrate, forced
our ancestors’ bodies to burn fat for fuel as
opposed to carbohydrates — the core goal
of the ketogenic diet.
As a clinician, I have recommended the
ketogenic diet both as a clinical intervention
for patients suffering from a wide variety of
ailments as well as a general suggestion for
people looking to optimize their cognitive
health. And while the diet is relatively easy
to follow, there are a number of common
misconceptions and lots of outright
misinformation that one must be aware of.
If you’re looking to incorporate a ketogenic
diet into your lifestyle or just wanting to
learn more, I’ve compiled a few tips for you
here.
Ketosis Basics
The central aim of the ketogenic diet is
to push the body into a state of ketosis,
where metabolism shifts from burning
carbohydrates as the primary energy
source to fat, or “ketone bodies.” These
ketones are a special type of fat that serve
as cellular “superfuel.” In order to achieve
ketosis, one must consume a diet high
in healthy fats and dramatically lower in
sugar and carbohydrates. This allows blood
sugar to drop to the point that glucose is
significantly less available to the body to
burn as a source of fuel. In the absence of
glucose, the body shifts its focus to ketones
for energy production. Ketosis not only
burns fat—which supports weight loss and
BMI reduction if in a calorie deficit—it also
transitions the body’s energy source to
what clearly turns out to be a better fuel.
In fact, energy derived from burning fat is
associated with a remarkable reduction in
the amount of damaging free radicals in the
body, in comparison to burning sugar.
Focus on Net Carbs
Maintaining a state of ketosis is as
simple as following the same dietary
parameters that got the body into
that state in the first place. If you limit
carbohydrates and sugars in your diet,
your body will opt to burn the healthy
fats you consume for energy. However,
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when cutting carbs
from your diet it is
very important to
focus on limiting net
carbs, which is simply
the number of grams of
total carbohydrates in a
portion of food minus the
grams of fiber. Constipation
is a very common issue for new
adherents to the ketogenic diet, and it is
caused by foregoing fiber in an attempt
to limit total carbohydrates. So to prevent
constipation from derailing your ketogenic
diet, simply make sure you consume
adequate levels of fiber!
What About Fasting?
One of the most powerful tools available to
individuals on the ketogenic diet is fasting.
Caloric restriction forces the body to burn
through all of its available carbohydrates.
Therefore fasting serves as an excellent
kick start for getting the body into ketosis.
Furthermore, periodic fasting while the
body is in ketosis helps maintain that state
because it keeps carbohydrate levels in the
body negligible. Not to mention, fasting
has been practiced by many cultures for
thousands of years, and has numerous
health benefits, generally, and is an
incredibly powerful tool for improving brain
health, specifically.
Before you fast, consult your health care
provider to ensure it is a safe exercise for
you. After confirming you can safely fast,
I recommend kicking off a ketogenic diet
with a 24-48 hour fast, during which time
you consume nothing but water—but make
sure you drink plenty of it. Once your body
is in ketosis and you shift to maintenance
 mode, I suggest
fasting once or
twice a year for
the same period
of time and with
the same, water-
only restrictions.
While fasting can be
challenging, especially
in the beginning, if you
stick with it you can reap huge
benefits.
Which Fats are Healthy?
One of the easiest traps to fall into when
starting a ketogenic diet is the assumption
that all fats are healthy. It is not uncommon
to see new adherents loading up their
plates with industrially harvested bacon,
exclaiming, “I’m keto, so it’s healthy!” In
reality, because ketosis repositions ketones
as your primary fuel source, ensuring you
consume healthy fats becomes even more
important on the ketogenic diet.
Similar to the recommendations I make in
Grain Brain, a ketogenic diet should derive
a majority of its calories from fat. However,
the optimal macronutrient ratio will vary
from person to person. Some will thrive on
roughly 80% of calories from healthy fats
and 20% from carbohydrates and protein.
Others may do better in the range of 60 –
75% of calories from fat and slightly more
protein. I encourage you to experiment to
find what works best for you. To meet this
goal, you must consume plentiful amounts
of healthy plant and animal fats. Some good
examples of healthy fats include:
• Plant-based: Organic avocado, organic
11
extra virgin olive and organic coconut
oil, nuts—excluding peanuts, which are a
legume, and seeds from chia, flax, hemp
and pumpkin plants.
• Animal-based: Organic grass-fed and
finished beef, pasture-raised chicken,
wild-caught fish, organic grass-fed
butter, and full-fat live culture yogurt.
• Supplements: MCT oil and fish oil,
ensuring they are USDA-organic, hexane-
free, and non-GMO. One important
thing to note: MCT oil delivers beta-
hydroxybutyric acid (BHB), which is the
most important ketone body, and its
benefits can be gained without fasting or
even carbohydrate restriction.
Ensuring that you consume adequate levels
of healthy fats is vital to the success of
any ketogenic diet. Avoiding bad fats, like
industrially-farmed meat, hydrogenated
oils, and processed vegetable oils, is just as
important to ensure that you provide your
body with a suitable source of energy in lieu
of carbohydrates.
To Meat or Not to Meat?
One of the central questions new adherents
to the ketogenic diet must answer is
whether or not they want to incorporate
meat into their new diet. It is entirely
possible to consume adequate levels of
healthy fats whether you approach the
diet as an omnivore or a vegetarian, so this
decision is largely a personal one. However,
if you choose to incorporate meat into your
version of the ketogenic diet, it is crucial
to ensure it is grass-fed, organic, and free
of antibiotics. Furthermore, it is important
to focus primarily on above-ground leafy
vegetables, with meat serving as a side
dish. An example of the perfect plate for a
keto omnivore would be a sizeable portion
of colorful, above-ground leafy vegetables
covered with a healthy fat like olive oil,
paired with a 3-5 oz serving of high-quality
meat.
Avoiding the “Low-Carb Flu”
Arguably the most challenging period
of transitioning to a ketogenic diet is the
first few days as your body adjusts to the
dramatic decrease in carbohydrate intake
and your metabolism begins its shift to
fat as its primary fuel source. It is not
uncommon during this period to experience
a lack of energy, irritability, ravenous
hunger, and brain fog, symptoms commonly
referred to as the “low-carb flu.” These
uncomfortable symptoms arise because a
ketogenic diet eliminates the spikes in blood
sugar that follow carb-heavy meals, keeping
insulin levels low (because it is no longer
needed in response to said blood sugar
spikes) and triggering the kidneys to excrete
high levels of electrolytes—think sodium,
potassium, and magnesium. Additionally,
many people transition to a ketogenic diet
from a standard, modern diet, which was
likely rich in processed foods packed with
sodium, so electrolyte levels drop simply
because you aren’t getting enough sodium
to replace that which you previously took in
from processed foods. In the end, if you do
not replace these excreted and/or missing
electrolytes in your new ketogenic diet,
it can ultimately lead to a drop in blood
pressure and bring about the symptoms of
“low-carb flu.”
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Rest assured, not everyone experiences this
side effect of the ketogenic diet and, if you
do, it will abate on its own; furthermore,
there are some simple preventative steps
you can take to lower your likelihood of
“catching” this flu. As you adopt a ketogenic
diet, make sure you replace electrolytes,
eat enough fat to meet your total caloric
needs, drink plenty of water, and exercise as
you are able. It’s very important, however,
to ensure that you aren’t relying on sugary
sports drinks to replace electrolytes,
as all that added sugar will prevent
your metabolism from entering ketosis.
Ultimately, electrolytes play a crucial role
in our health and many Americans do not
consume them at adequate levels, so it is
very important to monitor your intake of
these nutrients regardless of whether or not
you are an adherent of the ketogenic diet.
In the end, the “low-carb flu” should be
viewed as a testament to the power of the
ketogenic diet. After all, eliminating the
pressure on your body to regulate the blood
sugar spikes that follow “normal” meals is
ultimately what leads to these symptoms!
The ketogenic diet is an incredibly powerful
tool that can be wonderfully effective in
treating a variety of health issues facing
modern society. By allowing the body to
burn fat for fuel, the ketogenic diet can
not only lead to sustainable weight loss,
but it actually pushes the body to use an
alternative and potentially superior fuel
source. If you are just starting a ketogenic
diet, use the tips outlined above and stick
with it; it can be a challenging transition, but
there are many, many benefits of long-term
adherence to this diet.
13
 High BDNF Tied to
Lower Alzheimer’s Risk
Growth hormone for the brain. What a
concept. Truth is, science has indeed
identified a protein that does exactly that,
and it’s called brain-derived neurotrophic
hormone (BDNF). Knowing about BDNF
is even more important now, as a new
report clearly links higher levels of BDNF
to remarkably reduced risk for Alzheimer’s
disease.
In a recent issue of the Journal of the
American Medical Association, researchers
from Boston University measured baseline
BDNF levels in a group of adults and
followed them for up to ten years. They
found that those individuals with the highest
baseline BDNF levels developed dementia
50% less often compared to those with the
lowest levels.
BDNF is a protein that plays a pivotal role
in neuronal health. Your brain contains as
many as 100 billion neurons and the health,
14
vitality, and, perhaps most importantly,
functionality of each one of your brain cells
is intimately influenced by BDNF.
Early in life, BDNF regulates not only the
growth of brain cells, but also their ability
to make connections to other brain cells,
a process fundamental to our ability to
create a more powerful brain. But keep in
mind that the process of growing new brain
cells, neurogenesis, continues throughout
your entire life! Think of it. As you are
reading this report, your brain is actively
producing new brain cells, and brain cells
are always busy creating new connections
with their neighbors in a process called
neuroplasticity.
Both of these events, neurogenesis and
neuroplasticity, are directly enhanced
by BDNF, and who wouldn’t want more
brain cells that are more connected? No
doubt you are now wondering what you
can do to get hold of this magic elixir that
builds a better brain. But while BDNF isn’t
something you can buy at the pharmacy,
the good news is that you can absolutely
increase your body’s ability to create this
powerful protein and pave the way for a
healthier, more resilient brain.
I’ve discussed how the omega-3 oil DHA
can enhance BDNF as well as how it can be
enhanced with aerobic exercise in previous
posts. You can get a lot more information
beginning on page 126 in Grain Brain.
I’ve also written about how sunlight can turn
on BDNF production. In this report from Dr.
Marc Molendijk and colleagues at Leiden
University in the Netherlands, a profound
seasonal variation in blood level of BDNF
was observed with increasing amounts of
BDNF found in the blood during months
with the most sunshine. Interestingly, they
were able to correlate levels of BDNF with
the diagnosis of depression as well with
15
low BDNF levels highly related to this
diagnosis. This information has important
implications. Not only does it offer up yet
another lifestyle modification to provide our
bodies with more BDNF (sunlight exposure),
it might well explain why individuals may
become depressed during winter months
and when living in places with little
sunshine.
And, you may have guessed, there’s one
more way to increase the levels of BDNF in
your body: regularly practicing intermittent
fasting!
Getting sunshine, exercising, intermittent
fasting, and taking DHA are proven
methods to raise BDNF, and now we see
the science that clearly correlates elevated
levels of this powerfully important factor
with reduced Alzheimer’s risk. As this is a
disease for which we have no cure, this is
empowering information to learn.
THE EMPOWERING NEUROLOGIST
David Perlmutter, MD
& Dr. Valter Longo
VL Why do you want to mimic fasting? The main reason, I think, is the
clearance of damaged cells and components of cells. White blood cells
can be destroyed with a fasting-mimicking diet, which can be effective
in clearing out immune cells that are attacking the myelin in the spinal
cord. So for multiple sclerosis, for example, you can kill those rogue
immune cells and turn on hematopoietic stem cells, so the stem cells
of the body can give rise to the new, young, functional white blood
cells. So that’s one reason, at the cellular level, we want our bodies to
experience what happens during a weeklong fast. But for most people,
it’s very difficult to do that kind of fast safely. But research is pointing
us to the idea that there can still be positive effects on stem cell
activation when engaging in an intermittent fast.

VL One remarkable effect of fasting is its effect on visceral fat. Visceral

fat is one of the only components that gets broken down specifically
during fasting and fasting-mimicking diets. It doesn’t get rebuilt during
the feeding period. You can lose visible fat, specifically, without losing
muscle mass.

DP With fasting, we are emulating our ancestors’ appropriation of

caloric resources. We experienced times of caloric scarcity, in which
these pathways would have been activated — survival pathways if you
will. To put it in that context, I think it validates the underlying principle
of the so-called paleo movement. We’re just trying to emulate
what our genome and what our physiology evolved to
respond to.

Click here
to watch
full interview

16
SCIENCE AND STUDIES
> Early Time-Restricted Feeding Improves Insulin Sensitivity, Blood Pressure, and Oxidative
Stress Even without Weight Loss in Men with Prediabetes. Cell Metabolism, 2018 [LINK]

> Effects of eight weeks of time-restricted feeding on basal metabolism, maximal strength,
body composition, inflammation, and cardiovascular risk factors in resistance-trained
males. Journal of Translational Medicine, 2016 [LINK]

> Effect of intermittent fasting and refeeding on insulin action in healthy men. Journal of
Applied Physiology, 2005 [LINK]

> Fasting-mimicking diet and markers/risk factors for aging, diabetes, cancer, and
cardiovascular disease. Science Translational Medicine, 2017 [LINK]

> Fasting-Mimicking Diet Promotes Ngn3-Driven Beta-Cell Regeneration to Reverse

Diabetes. Cell, 2017 [LINK]

> Fasting and cancer: molecular mechanisms and clinical application. Perspectives, 2018
[LINK]

> Fasting Serum Glucose Level and Cancer Risk in Korean Men and Women. Journal of the
American Medical Association, 2005 [LINK]

> Higher normal fasting plasma glucose is associated with hippocampal atrophy.
Neurology, 2012 [LINK]

> Intermittent Fasting Promotes White Adipose Browning and Decreases Obesity by
Shaping the Gut Microbiota. Cell Metabolism, 2017 [LINK]

> Rapid Improvement in Diabetes After Gastric Bypass Surgery. Diabetes Care, 2013
[LINK]

> Short-term modified alternate-day fasting: a novel dietary strategy for weight loss and
cardioprotection in obese adults. American Journal of Clinical Nutrition, 2009 [LINK]

17
 About Grain Brain
Revised Edition
Dr. Perlmutter’s #1 New York Times bestseller about the devastating effects of
gluten, sugar, and carbs on the brain and body is back — updated with the latest
nutritional and neurological science.

in this fully revised, five-year-anniversary edition, Dr. Perlmutter builds on his mission.
Drawing on the latest developments in scientific research, which have further
validated his recommendations, he explains how the Grain Brain program boosts
the brain, shows the benefits of using fat as a main fuel source, and puts forth the
most compelling evidence to date that a non-GMO, gluten-free, and low-carb diet is
crucial for cognitive function, weight loss and long-term health.

Facebook.com/DavidPerlmutterMD Instagram.com/DavidPerlmutter

Twitter.com/DavidPerlmutter https://DrPerlmutter.com

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