The Origins of the Ketogenic Diet: Epilepsy | MWM 2.38

The Origins of the Ketogenic Diet: Epilepsy | MWM 2.38

August 5, 2019 5 By William Morgan


If you’re interested in the ketogenic
diet keep on watching because this is
where it all got started.
A ketogenic diet has neurological benefits.
Why do we have to eat such an enormous amount of food?
Complex Science.
Clear Explanations.
Class is starting now.
Hi. I’m Dr. Chris Masterjohn of
chrismasterjohnphd.com. And you’re
watching Masterclass with Masterjohn.
We are now in our 38th in a series of
lessons on the system of energy
metabolism and we are now talking for
the first time all about ketogenic diets.
We talked in our ketone unit so far about
ketogenesis in general and we’ve seen
that ketogenesis is an adaptation to fasting.
It allows us to fast, meaning to completely
abstain from food, for a much longer period
of time than we would otherwise be able
to because it rewires our metabolism in a
way that allows the brain to run on
ketones derived from fat instead of
running entirely on glucose, which in the
fasting state is derived mainly from our
muscle protein. By rewiring our
metabolism in that way we can fast for
a very long period of time without
completely destroying our lean
muscle mass. The ketogenic diet was
derived as a way to mimic fasting
metabolism in a way that’s much more
sustainable over time.
The ketogenic diet was first proposed in
1921 by Russell M.Wilder, shown on the right.
Wilder was the head of care for all
diabetic patients at the Mayo Clinic
beginning in 1919. From 1929 to 1931 he was
a professor and department head at the
Department of Medicine at the University
of Chicago, and then in 1931 he returned
to the Mayo Clinic where he was the head
of the Department of Medicine of the Mayo
Foundation. He served briefly as the head
of the National Institute of Arthritis
and Metabolic Diseases from 1950 to 1953,
and then he retired because he became
ill and you can see six years later in
1959 he died. Historical evidence
suggests that fasting has been used to
treat epilepsy at least as far back as
the era of Hippocrates, but in the
turning of the 20th century there were
many modern physicians who were using
fasting to treat epilepsy and documenting
it more clearly. And one of the things that was
discovered in the modern era
was that fasting led to a
decrease in seizures in epileptics and
also led to an increased urinary
excretion of ketone bodies, which was a
much newer discovery that required
modern chemical analysis. Wilder looked
at this and said, if fasting can decrease
seizures in epileptics and it increases
urinary ketones, then maybe the reason
the mechanism by which fasting is
treating epilepsy is by leading to
increased production of ketones,
maybe it’s the ketones that have the
anti-epileptic effect. His hypothesis was
that acetoacetate, one of the two major
ketone bodies, acts on the brain as an
anesthetic. And he proposed the treatment
would be a high-fat, moderate protein, low-
carbohydrate, ketogenic diet. Now the
ketogenic diet was actually born
indirectly out of the research on the anti-
ketogenic diet. Many people at this time
we’re trying to figure out how to treat
diabetes, and one of the most common ideas
was that you should restrict
carbohydrate as much as you can to
reduce the stress on the pancreas of
secreting too much insulin, but you want
to maintain carbohydrate high enough
that it suppresses ketogenesis because
diabetes was seen as in its worst case
scenario leading to ketoacidosis and
coma and possibly death. So researchers
were trying to figure out how to
suppress ketogenesis with diet and at
the time the belief was carbohydrate is
the most suppressive and protein is less
suppressive and fat of course is going
to generate the most ketones out of
everything. So Wilder took this research
on how to suppress ketogenesis and
diabetes and turned it on its head to
say that in epilepsy we want to maximize
ketogenesis. And the way that we do that
is we bring the fat as high as we can, maintaining
protein high enough to mitigate any loss
of lean mass, but no higher than needed,
and to restrict carbohydrates pretty
much as far as possible. At the Mayo Clinic,
Wilder’s idea was put to the test.
Over the course of the decade following
Wilder’s proposal, the Mayo Clinic tested
the effect of the ketogenic diet in
epilepsy and produced several reports.
M. G. Peterman produced the initial reports
and then Henry Helmholz took over and
released reports at 5 years, 8 years,
and 10 years experience with the
ketogenic diet. Peterman described the
protocol in detail in his 1925 report.
The ketogenic diet would be preceded by
three days of gradual carbohydrate
restriction to ease into the diet. Then
the children would be subject to two to
three weeks under close supervision
on a very strict diet.
It had 10 to 15 grams of carbs per
day, one gram of protein per kilogram
body weight, which is a little under a
half a gram per pound body weight
because a kilogram is 2.2 pounds, and the
remainder of the diet is fat. Peterman
acknowledged that you cannot get all
your vitamins and minerals on a diet
like this. Yes certain fats are good sources
of fat-soluble vitamins, but most of the
vitamins are water-soluble and most
minerals are not found in the fatty
portions of foods. You will develop
vitamin and mineral deficiencies on a
diet like this if you don’t use
supplements. So they added supplements
to make sure that the children were
getting everything that they needed, at
least to the degree that this was
understood in 1925 — we didn’t actually
know that much about nutrition then.
And then finally if they needed to they
would restrict the non-fat calories even
further with the goal being two-fold:
number one, make sure that ketones are
spilling into the urine, which is called
ketonuria; and, number two, make sure that
the seizures go away. After they achieved
these goals under close supervision the
children would be released to their
homes and the guidance would be purely
by mail correspondence over distance.
You can imagine that under these conditions
compliance is a lot harder. In any case
the goal was 3 to 4 months of
seizure-free ketosis maintained on the
original diet. After they would stabilize
in this state they would then start
adjusting the non-fat calories upward.
They would do this very slowly.
Each month they would add either 5
grams of carbohydrate or 5 grams of
protein. They would alternate so that one
month they increased carbs,
the next protein, the next carbs, etc.
That’s 5 grams per day
and taking a whole month to let
that change sit in. They would cut back
on the carbohydrate or protein and stop
increasing it if either the seizures
returned or if the ketonuria stopped.
In general those two things tended to
happen together: the seizures would
return if the ketonuria stopped,
reinforcing the idea that the ketones
were an important part of the treatment.
Now what they’re trying to do here is to
start with an extreme diet to make sure
you get the positive effect you’re
looking for and then increase
the non-fat calories to find, what is the
least restriction that we can attain; the
most carb, the most protein; what is the
tolerable maximum that we can put in
without ruining the effects of the diet
on ketonuria and freedom from seizures?
The initial results that Peterman reported in 1925
were stunning.
Keep in mind first of all that Peterman’s
goal here was to treat all of the
patients with idiopathic epilepsy. At the
time — and this dichotomy is still in
use; it’s just more nuanced now — at the
time they divided epilepsy into two categories.
Symptomatic epilepsy was epilepsy where
a particular local part of the brain was
damaged, you could see clearly where that
damage was, what type it was and you
could clearly attribute the seizures to
that local damage. Idiopathic epilepsy
was a more generalized defect where part
of the brain’s energy metabolism or some
unknown aspect of brain metabolism was
damaged all around in a way where you
couldn’t pinpoint it and it was this
general defect that was causing the
seizures. So all of the children with
idiopathic epilepsy were being treated
with the ketogenic diet regardless of
whether the drugs at that time were
useful. In the modern day the ketogenic
diet is said to be used for “refractory”
epilepsy, which means that the
epilepsy does not respond to drugs first.
Peterman was using the diet not for
refractory epilepsy; he was using it as
the first treatment for any idiopathic
epilepsy. Now granted the drug of use at
the time was phenobarbital, which is a
barbiturate and has sedative effects, so
it was obviously undesirable to use
phenobarbital if you didn’t have to and
nowadays it’s thought that other
medications can be used safely with less
side effects and they’re
easier to use and that’s why they go for
them first.
In any case, Peterman reported that in
these children using the ketogenic diet
as a first line of defense, 60% were
seizure-free and 35% improved; that’s 95 %
getting some improvement from
the diet, only 5% not improving at all.
And out of these 37 patients treated
from 3 to 30 months, only two of them had
to be treated with phenobarbital.Thirty-five of
them maintained their benefit with no drugs.
Peterman looked for side effects.
He reported nausea and vomiting as
common early on in the diet and he
relieved them with orange juice. Orange
juice is obviously not ketogenic, but his
goal was to ease them into being
able to tolerate the diet over the long
term. He reported no changes to their
physical development, their basal
metabolic rate, their bone development or
their blood chemistries. In other words,
only the nausea and vomiting were the
side effects. He was enthusiastic about
the effect of the diet on their general
behavior. He wrote that “in all the
children treated with the ketogenic diet
there was a marked change in character
concomitant with the ketosis, a decrease
in irritability and an increased interest
and alertness. The children slept better
and were more easily disciplined. This
action of the diet warrants further study.”
Almost 100 years later and
there’s been very little if any study
into these other effects of the diet.
Just two years later, Henry Helmholz
took over the reporting and his results
were no where near as stunningly positive
as Peterman’s. Listen to what he wrote in
1927: “The results of the first two and a
half years treatment in the Mayo Clinic
were reported in 1925 by Peterman. The
time interval in many cases was of
necessity too short for a determination
of the ultimate outcome and a review at
the present time shows that the results
as published are not quite so successful
as they were pictured. Of the 37 cases in
Peterman’s series, convulsions have not
recurred in ten.”
The proportions benefiting, according to Helmholz’s
report, are shown on the right. Now this
data is taken from 160 patients after
excluding 189 of them; 51 of those
189 were excluded because they had
symptomatic epilepsy, so clearly the vast
majority of their epilepsy cases were
idiopathic. Now Peterman was excluding
the symptomatic epilepsy cases and so in
that way Helmholz and Peterman are
reporting in the same exact way, but
Helmholz was throwing out patients for
additional reasons that Peterman was not.
So 22 of the 189 were tossed out because
there was too short of an observation
period, 89 were tossed out because of
inadequate cooperation with the diet,
which is clearly the largest factor
leading to being tossed out, and 27 for
an assortment of other reasons. So we’re
taking less than half the initial pool
of patients and then we’re saying 21%
improved to some degree, 36% were
seizure free, but 43%
compared to Peterman’s 5% received no
benefit. Unfortunately I don’t know what
happened to Peterman. I couldn’t figure
it out in the time that I had to prepare
this presentation. I don’t know if
Peterman died, I don’t know if Peterman
moved on to something else and Helmholz
took over. In any case it’s unfortunate
to not have Peterman’s perspective on
the five-year experience with
the diet. Was Peterman biased in favor of
the diet? Was Helmholz biased against
the diet? Or is this difference between
Peterman’s 1925 report and Helmholz’s
1927 report simply a matter of an
additional several years needed for
clarity on the true effect of the diet?
One thing we have to keep in mind is
that much of this might be driven by
poor compliance over time. Eighty-nine
subjects that Helmholz was recording
were tossed out of the data because of
inadequate cooperation with the diet, but
what about the ones that were included?
Did they comply perfectly? If you read
both Peterman and Helmholz, it’s clear
that there was a great difficulty
getting perfect compliance with the diet.
Well of course there was because these
are children who are being guided,
their parents are being guided by mail
correspondence, they’re nowhere near the
doctors, and they’re hanging out with a
bunch of other children eating candy, and
according to them quite often when
someone’s seizures would come back it
was because they got their hand into
the candy jar. And so what are you
supposed to do if you don’t have perfect
compliance? So we really don’t know if in
a clinical setting where you could
achieve perfect compliance would the
results look more like what Peterman
described in 1925
than what Helmholz described in 1927?
We don’t know the answer, but no one who
studied the ketogenic diet has ever,
has ever reported results anywhere near
as optimistic as Peterman’s initial
results. So the answer is that probably
compliance has always been an issue for
everyone, but probably in no practical scenario
can you get results that are much better
than Helmholz’s. Indeed the numbers that
he reported at year 8, and at year 10 look
very similar to what he reported in the
5th year shown on the screen. Much has
happened to the ketogenic diet in the
years following the Mayo Clinic’s
experience and several other treatment
centers, especially Johns Hopkins and
Harvard Medical School, have been
incredibly important in the development
of the ketogenic diet. Some of the major
turning points are shown on the screen.
After Wilder proposed the diet in 1921
and Peterman reported the results in
1925 just a little more than a decade
later Merritt and Putnam discovered that the
drug diphenylhydantoin,
also marketed in the modern day as
Dilantin, had the anti-seizure
effects of phenobarbital without the
sedative effects. This was seen as a
goldmine of relatively side-effect free
medications that could be used to treat
epilepsy that were a lot easier than
using the ketogenic diet. So over the
course of the late 1930s through the
1990s interest in the ketogenic diet
waned and very few people were using it.
In fact Wheless, in the citation at the
bottom of the screen, suggests that this
basically had a snowball effect because
as fewer and fewer people were involved
in implementing it the people who did
implement it had fewer dietitians that
knew what they were doing to help them
and in fact even the people implementing
it as doctors may have not fully
understood all the nuances of how to
implement it well. And the cases where it
was not implemented well because not
enough people had the
expertise made it look bad, which
discouraged people from using it even
further. Nevertheless one of the
important milestones was in 1971 in this
period of waning interest when Huttenlocher
developed the MCT oil-based
ketogenic diet. The goal of the MCT oil
diet was to use medium-chain fats
derived from coconut that are much more
easily turned into ketones. You can then
get the same degree of ketogenesis with
less restriction of carbohydrate. That
makes the diet more palatable because
the choices of foods are broader and it
makes it easier to get your vitamins and
minerals and fiber in because you can
eat more vegetables and other
carbohydrate-containing foods that
provide important nutrition. The waning
interest started to reverse when
Dateline featured Charlie. Charlie was an
epileptic child who was treated at Johns
Hopkins with a ketogenic diet after
all the possible medications failed.
His father was a movie director responsible
for a number of famous films that you’ve
probably watched, many of them comedies.
But he also directed a film starring
Meryl Streep called “First do no Harm” in
1997. That was based on Charlie’s case
and featured the usefulness of the
ketogenic diet. This made it wildly
popular in the in the eyes of the public
like it had never been before and that
initiated decades of increased research
and a resurgence of it’s use to treat
epilepsy. In 2003 Kossoff developed the modified
Atkins diet, which is a diet that is less
restrictive, especially of protein. It’s
based on the induction phase of the
Atkins diet and it achieves similar
results in a less restrictive more
palatable way. In 2005 Pfeiffer and Thiele
reported the use of a low-carbohydrate
low-glycemic index diet
to treat epilepsy and innovations have
continued, but these are the major ones.
It was this proliferation of interest in
the ketogenic diet post mid to late 90s
that allowed the ketogenic diet to start
being researched for other things.
For example, it’s use in weight loss, diabetes,
and other things that we’ll discuss in
later lessons, all of that was spawned by
the popularity around the treatment of
epilepsy that mushroomed in the late 90s
and 2000’s. What’s shown on the screen is
a basic comparison of the different
approaches that have been used to
achieve the same thing – a ketogenic diet
that treats epilepsy. The classic
ketogenic diet shown on the left is very
similar to what Peterman was first
reporting. One gram of protein per
kilogram body weight, a four-to-one ratio
of fat to nonfat energy by weight, which
provides about 90% of calories as fat.
You adjust these ratios according to the
need and the tolerance, just like
Peterman reported doing, and so
sometimes it’s a three-to-one diet,
sometimes it’s a higher ratio, but four-
to-one has been the basic classical
starting point. The MCT oil diet does not
actually restrict carbs or protein in
the way that the classic ketogenic diet
does. It’s goal is to get 60% of calories
as MCT. MCTs are made of 8 and 10 carbon fatty
acids. They constitute about 15% of the
natural fat of coconut and in
MCT oil they’re extracted to be
100% of the oil. These fatty
acids are not subject to the anti-
ketogenic effect of carbs and insulin.
Part of the reason is because they
travel directly to the liver where
insulin cannot first promote their
storage in adipose tissue and then also
they get into the mitochondrion without
requiring the carnitine shuttle so
they’re not supressed by the malony CoA
that rises in response to calories and
carbohydrate via all the signals of high
energy status, including but not limited
to insulin, that we’ve discussed in
previous lessons. What that means is that
MCTs are independently ketogenic and you
don’t need to restrict carbs and protein,
but if you’re going to push the MCTs
up to 60% of the calories you obviously
are restricting carbs and protein because
you have to incorporate such an enormous
amount of MCTs into the diet. So when
it’s practically implemented, although
it’s not achieving ketogenesis through
restricting carbohydrate and protein, 70%
of the total calories are coming from
fat, 10% of them are coming from protein
and 20% of them are coming from
carbohydrate. So it’s still a low-
carb, low-protein diet. The modified
Atkins diet is modeled after the
induction phase of the Atkins diet.
It allows 10 grams per day of carb of any
type, except you can exclude
fiber but it does restrict sugar
alcohols. It allows them to gradually
increase to 20 to 30 grams of carb per
day, they get about 65% of calories as
fat, and there’s no restriction of
protein except as with the MCT oil diet
if you’re deliberately trying to push
your fat calories up to 65% you do wind
up eating less protein than you would if
you weren’t trying to push your fat
calories up that far. The low glycemic
index is really the oddball in the group
because this diet is only modestly
ketogenic it only leads to a blood
ketone level of about one millimole per
liter, at least the beta-hydroxybutyrate
level of one millimole per liter so
maybe a total ketone level of somewhere
around 1.5; this is very modestly
ketogenic and yet it seems to work.
It allows 40 to 60 grams per day of
carbohydrates, but only if the
carbohydrates have a low glycemic index,
20 to 30 percent of calories as protein
and about 60% of calories as fat.
Now let’s look at what the evidence says on
the ability of these various diets to
treat epilepsy. There are data on the
screen from two studies that compared
on the top the classical ketogenic diet
to the MCT oil diet; and on the bottom
the classical ketogenic diet to the
modified Atkins diet. And so let’s look
at these one at a time. In the top table
the classic diet is shown on the left
and the MCT diet is shown on the right.
In each case you have the number of
children followed by the percentage of
children in parentheses and we’ll focus
on the percentages. If you want to look
at the degree of treatment between
the two diets you compare the percentage
on the left to the one on the right, but
if you want to see whether there’s a statistically
significant difference, meaning does the
statistical analysis support that
whatever difference is observed is
probably due to a real effect instead of
an effect of chance, then what we want to
see on the right is a p-value of less
than 0.05. We can just look at the
p-values alone to see that all of these
p-values are very, very high;
none of them are anywhere near 0.05,
which suggests that the two diets are
essentially equivalent in their ability
to treat these children or if they are
different you would need a much larger,
much better statistically powered study
to see the difference. Nevertheless if
you look at some of these numbers you
can see 6.8 versus 2.7 for greater than
90% seizure reduction at 3 months. That
makes it look like the classical diet is
better and maybe we just don’t have
enough statistical power. That difference
persists 8.2 to 5.6 at six months, as you
go on to twelve months though
9.6 versus 9.7 have greater
than 90% seizure reduction, 17.8
versus 22.2 greater than
50% seizure reduction, it looks
like over the course of 12 months
these two diets are
substantially equivalent. Now let’s blow
up this second table to see the
tinier numbers on the screen. This is
looking at the classical ketogenic diet
and the modified Atkins diet and the
easiest thing to do is to ignore the
categories on the right that separate
this into children of different ages and
just look at the total pool of children.
If you just look at the p-values what
you’ll see is that they’re all a lot
higher than 0.05, suggesting the modified
Atkins diet is equivalent to the
classical ketogenic diet. Now if you look
at the comparisons on the right you’ll
see one of these p-values has an asterisk
that’s singled out for being less than
0.05 and that means that there was a
statistically significant difference
between the classical ketogenic diet and
the modified Atkins diet for being
seizure free three months after the diet
therapy. And if you look at the numbers
it’s 9 versus 4 children, 53% versus 20%
that actually does look like it
significantly favors the ketogenic diet
because we’re talking about more than
double the number of children
achieving freedom from seizures. On the
other hand, if you look
at this table you can see one, two, three,
four, five comparisons made in this group;
ten made over here, fifteen made over
here. To say a p-value is less than 0.05
means that there’s a less
than 5% chance that you would observe
this difference if it were attributable
simply to random chance. If you make 20
comparisons you are bound to get one
that looks statistically significant, but
it’s still a result of random chance.
They made 15 here and so the chances are
fairly high that they could achieve one
of these having statistical significance
and it’s still being an effect of chance.
So it looks here the general trend in
this study seems to favor under some
circumstances maybe in the youngest
children at the shortest time point you
see the most rigorous effect showing
that seizure freedom is better
maintained on the classical ketogenic
diet than the modified Atkins diet. If we
come back here we saw a similar trend
where when we were looking earlier on
when it was 3 months, 6 months, at the
earlier time points there was a general
tendency for the classical diet to be
better. So maybe if any of these is
superior it is the classical diet, which
is the one that restricts carbohydrate
the most, but the evidence that there’s
anything superior among these diets is
at best equivocal. If we could summarize
the overall results of research in the
modern era we can look no further than
this Cochrane Review, which is a very
prestigious association that conducts
systematic reviews of evidence. They
reviewed all of the randomized
controlled trials that looked at the
ketogenic diet for epilepsy and
according to their results they say they
“identified 7 randomized trials that
recruited 427 children and adolescents
with no adults.” They “could not conduct a
meta-analysis,” meaning pool all the data
together,
“due to the heterogeneity of the studies,”
meaning there were too many differences
in methodology and characteristics
between the studies to pool the results.
“The reported rates of seizure freedom
reached as high as 55% in a four-to-one
ketogenic diet group after three months
and reported rates of seizure reduction
reached as high as 85% in a four-to-one
ketogenic diet after three months.” These
results are actually almost as good as
Peterman’s, but those are the maximum
results. The ones that we just saw on the
screen, for example, didn’t look as good
as these do. They went on to say that “the
most commonly reported adverse effects
were gastrointestinal syndromes. It was
common that adverse effects were the
reason for participants dropping out of
the trials. Other reasons included a lack
of efficacy and non acceptance of the
diet,” the same challenges faced in the
early days by the Mayo Clinic. “Although
there was some evidence for the greater
antiepileptic efficacy of a four-to-one
ketogenic diet over lower ratios the
four-to-one ketogenic diet was
consistently associated with more
adverse effects.” Again, they say “some
evidence,” the evidence for any
comparisons is rather weak. They go on to
say “all of the included studies assess
the efficacy of dietary interventions
in children. However, the evidence for
the use of dietary interventions in
adults with epilepsy appears to be
anecdotal. Therefore, further research is
required to provide high-quality
evidence for the use of dietary
interventions in adults in addition to
expanding on evidence in pediatric
populations.” Although there are no
randomized controlled trials showing the
benefits in adults we have case series
supporting the efficacy in adults. A case
series means just follow a bunch of
people who tried the diet and tell us
what happened. This is what Peterman and
Helmholz were doing in the early days.
And according to this case series: “Twenty-nine
adults and adolescents with a mean age
of 32 years ranging from 11 to 51 years
old were initiated on the ketogenic diet
and followed until it was discontinued.
Fifty-two percent of the patients had a
significant reduction in seizure
frequency on the ketogenic diet
including 45% with more than 50%
reduction. Thirty-one percent had no improvement,
seven percent were unable to
successfully initiate the diet
and 10% had a greater than 50% increase
in seizure free frequency.” Now note about
this increase, this is a case series, it’s
not a randomized controlled trial. If
they had randomly allocated half of the
patients to the ketogenic diet and the
other half of the patients to no
dietary change or some other diet that’s
not effective, probably a much larger
number of those patients would have had
an increase in seizure frequency, so that
doesn’t mean that the ketogenic diet
caused that increase; it might just be
that it didn’t benefit those patients
and they were bound to increase anyway.
Moving on, “The ketogenic diet can be used
safely in the adult and adolescent
population with a response rate similar
to those seen in children.” Case series
also support the benefit of the low
glycemic index diet for the treatment of
epilepsy.
This is the diet that is only moderately
ketogenic. On the screen is data from
one case series and you can see the
description of what they did on the
right. They say “we reviewed the charts of
patients who were initiated on the low
glycemic index diet for intractable
epilepsy over the course of two years.”
There were two categories of patients:
the first category is those who were
placed on the diet while they were
waiting for the traditional classical
ketogenic diet. There were two reasons
for this: one was scheduling constraints
and the other was the parents were not
sure that the kids would be able to
comply with the full-on ketogenic diet.
The second group of patients had
demonstrated improved seizure control in
the ketogenic diet, but they were unable
to tolerate the constraints and they
couldn’t stay on it so they were
transitioned to the low glycemic index
diet. On the left we see the data and the
data is broken up into these two
categories of patients.
The white bars are the ones who got only
the low glycemic index diet and they got
it while they were waiting to get on to
the full keto diet or because their
parents didn’t trust they could tolerate
the full keto diet. And then in grey bars
are the patients who did benefit from
the ketogenic diet, but transitioned away
from it because they couldn’t comply
with it over time. And what you can see
is that, first of all, the number of
patients is small — there’s 19 patients
represented here — the number of patients
is plotted on the vertical axis and it’s
separated into how many patients got
more than 90% benefit, meaning
more than 90% reduction in
seizures, how many patients had 50 to
90% reduction, how many had less than
50% reduction, and how many had no
change or an increase in seizures. And
what you can see is that out of these 19
patients only 2 of them did not
benefit from the diet, and 10 of them,
which is almost half of them, had a
greater than 90% reduction in seizures.
This looks comparable to what you would
get with the other more strong, more
intense ketogenic diets. Now it’s really
important to realize that this isn’t
randomized. The
reason that that’s important is that
there could be a subset of children for
whom the low glycemic index diet would
work well and other subsets for whom it
would not, and the only way to really make
that comparison is to take the same pool
of patients and randomize them to the
full ketogenic diet or the low glycemic
index diet. Nevertheless it’s clear that
for many patients with intractable
epilepsy just using the low glycemic
index diet, which is only
moderately ketogenic
does benefit
epilepsy. So there you have it. The
origins of the ketogenic diet is as a
treatment for epilepsy to mimic the
conditions of fasting.
As it’s gained in popularity we are now
starting to look at the benefits of a
ketogenic diet for other conditions. And
we’ll look at those possible benefits in
future lessons, but for now we’ll say two
things. Number one, it’s clear that the
ketogenic diet
is very effective for at least a large
subset of patients with epilepsy. This is
probably true for adults as well as
children and there are a variety of
different versions of the ketogenic diet
that are all beneficial for at least a
subset of these children. So for
any kind of epilepsy, at least the
ketogenic diet should be considered,
because there is no other diet that has
that kind of effect on epilepsy and in
fact at least the subset of children can
be treated with this without drugs. Now
on the other hand there are some side
effects of the ketogenic diet and we
will talk about those as we progress on
to talking about some of the downsides
and some of the ways that ketogenic
diets need to be troubleshooted.
The second thing that we can say is that
nothing in this presentation clarifies
the mechanism and although we don’t know
why the ketogenic diet is effective
there are hypotheses that we can explore
and exploring those hypotheses about the
mechanism in the next lesson will allow
us to generalize from this. If we better
understand how the ketogenic diet
benefits epilepsy we can then better
understand how it might be useful in
other conditions, obviously neurological
ones, but other conditions where that
same set of mechanisms might be
applicable and understanding the
mechanism will be the bridge between
understanding just the efficacy in
epilepsy and the potential to benefit
many other things. So with that we’ll end
the lesson here and talk about the
mechanism next time.
The audio of this lesson was generously
enhanced and post-processed by
Bob Davodian of Taurean Mixing, giving
you strong sound and dependable quality.
You can find more of his work at
taureanononlinemixing.com.
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All right, I hope you found this useful.
Signing off, this is Chris Masterjohn of
chrismasterjohnphd.com You’ve been
watching Masterclass with Masterjohn.
And I will see you in the next lesson.