TMR 302 : Prof. Thomas N. Seyfried : Cancer as a Metabolic Disease

Episode Transcript
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(00:10):
Hello everybody. Julian Charles here oftheMIND Renewed dot com. Coming to you
as usual from the depths of theLancashire countryside here in the UK and today
I am delighted and indeed honored towelcome to the program Professor Thomas Seafried,
who is Professor of Biology at BostonCollege, Massachusetts in the US. In
twenty twelve, Professor Sefred published thegroundbreaking work entitled Cancer as a Metabolic Disease.

(00:35):
After a PhD from the University ofIllinois and a postdoc fellowship at Yale
University in neurology, he has enjoyeda long and distinguished career researching in areas
such as gene environmental interactions, lipidbiochemistry, neurodegeneration, epilepsy, cancer,
metabolism, brain tumors, autism,ketogenic diets, amongst many many other things,

(00:58):
and in addition to numerous lifetime Achievementawards for his work, he's also
on the board of several academic journals. Professor Sefred, thank you very much
indeed for joining us on the MindRenewed. Thank you, Julian, It's
a real pleasure to be here.It's fantastic to have you on, as
I say, a privilege to bespeaking with you now. Before we do
get onto the conversation, I alwayslike to make an important note. Always

(01:19):
do this with the sort of medicaltype conversation, So please, anybody listening,
please do note nothing in this conversationshould be understood as personal medical advice,
because everybody's different. All of thisis for information purposes only. Please
do consult your doctor first before makingany changes to your diet or your lifestyle
or medications, or indeed any changesas a consequence of what you've heard here

(01:42):
today on this program. So,Professor Seefred, you have been working in
this area of cancer research for somedecades now only recently come across your work.
It's absolutely fascinating. And over thattime, we've gone from a situation,
say back in the nineteen nineties,where it was said that something like
one in three of us will maybedevelop cancer or probably develop cancer at some

(02:04):
point in our lives, to asituation now where I'm hearing people saying things
like, well, it's more likeone in two of us. So obviously
something is going drastically wrong, andit seems to me that we're not fundamentally
changing So what's going wrong in yourview? Yeah, well, thank you.
Well, I think a number ofthings are going wrong. Whenever you

(02:25):
have a situation like you've just mentioned, something is increasing. When hundreds of
millions of dollars are being spent inan attempt to manage cancer and yet we're
getting more cancer, it clearly speaksto something, as you said, that
we're doing or not or not doing. And it comes down to the continuous

(02:49):
Western diet and lifestyle. But Ilook at it as both dietary lifestyle issues
in our environments are becoming more insome ways polluted. We are not getting
as much exercise as we did inthe past, We're eating more highly processed
foods than we had in the past, and as you can see, the

(03:10):
obesity epidemic, at least in ourcountry, is really an epidemic. And
all of these are signs that linkto chronic diseases, cancer being a primary
one, but we also have increasesin type two diabetes, cardiovascular disease,
macular degeneration, hypertension, high bloodpressure. All of these kinds of disorders

(03:34):
are linked in one way or anotherto rather sharp changes in diets and lifestyles,
not to any genetic or predisposition riskfactor. That's very interesting you should
say that because I think a lotof people would think, oh, well,
isn't cancer entirely a genetic matter?No doubt. We'll talk about that
in due course. It's very interestingyou should say that because a lot of

(03:57):
what you said there connects with whatdoctor Paul Marik said on this program to
do with metabolic diseases and how thoseseem to be going up all the time.
There's something that we're doing wrong,very definitely. Now, is it
true that people from let's say,non Western ancestral populations, let's say,
if they change their lifestyles and theyadopt a typical Western diet and lifestyle,

(04:18):
that they often start to get thesekinds of diseases. Is that true?
Yes, there's a lot of stronginformation to support that. I had the
opportunity a couple of years ago tovisit the medical school at thunder Bay,
Canada. It's on Lake Superior,and that medical school services the Inuit group

(04:39):
in the Arctic circle. Apparently it'snot appropriate to use the term Eskimo,
but in it is the more correctterm. I guess you could say,
but those folks are really riddled withtype two diabetes, cancer, heart disease.
They were an extremely resilient and healthypopulation. Those individuals that do maintain

(05:02):
their traditional diet and lifestyles do remaina relative fit. But as soon as
they hit the you know, thefried chicken, hamburgers, every other kind
of processed food, their physiology isextremely susceptible to rapid change. So within
a generation or two, you gofrom a healthy population into one where you

(05:25):
know, every other person has typetwo diabetes or as obese and has afflicted
with all these other chronic diseases,including cancer. As a matter of factually,
I have a paper that came outof England in the eighteen eighties and
what was the predominant I think itwas in Wales, I guess not England,
Wales where they looked at the afflictionsof people and a lot of it

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was infections and influenza and things likethis. Cancer was very minor. And
then they looked at the same populationtoday within the last couple of years,
and cancer and heart disseis and allthese kinds of things are skyrocketing. So
clearly, any population, whether ancestralpopulations or people transitioning more and more to

(06:10):
a Western diet lifestyle seems to carrythe baggage of type two diabetes, cancer,
hypertension, and all these other thingsto go along with it. Right,
And so this puts to a certainextent the lie to the idea this
is just because people are living longernow. I often hear this, whatever
it is, deventia or heart disease, we're all living longer now, So
you know that's the cause of it. There'd be some truth to that,

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of course, but that's not acomplete explanation, isn't it. No.
A lot of people, for certain, are living longer, but are they
living healthier. So we have alongevity, but we also have a healthy
life. And a lot of folksare in nursing homes. Yeah, they're
living five or ten years longer,but I wouldn't consider them very healthy.
Because we've eliminated a lot of thingsthat would kill us in the past,

(06:53):
like infections. That was generally away to die was bacterial infections and these
kinds of things. And with theadvent of more and more solutions and therapies
for infection and bacterial infection, viralinfection, people survive, but they now
are afflicted with all kinds of chronicdiseases. You're substituting one problem with another,
but you are living longer. ButI'm not necessarily sure that that's also

(07:16):
linked to healthy longevity. Right,So there's life span, but there's also
a health span A lot of peopleare talking about today because it is crucially
important. Yes. Indeed, nowyou've said in a number of presentations that
our bodies are actually quite resistant tocancer. At least they should be,
you know, if it wasn't forall the toxes, the poor diet,
the lack of exercise, et cetera, too many medications, et cetera.

(07:38):
That actually we're quite resistant. Ithink that's an astonishing thing to hear,
because, as I said before,you know, people tend to think before
hearing you. We tend to thinkit's already a down to your genes and
it's all predetermined, you know.But no, we're actually quite tough cookies
to crack in some ways. Ohyeah, we're we evolved over the ice
ages, deserts, starvation. Thehuman being is an incredibly resistant animal because

(08:03):
we had to survive on the harshestkinds of conditions. We are supremely designed
to live without food. Because inour paleolistic lithic past, processed carbs were
not part of our diet. Itwas primarily a hunter gatherer hunter. What
does that mean? Hunting you hadto run after something and kill it and

(08:24):
then eat it. Takes a lotof energy to do that. And you're
not going to get too fat eatingyou know, the liver from an elk
or a bear or whatever you're goingto kill. You're going to be lean
and mean and and you're going tobe very buff. The only thing that's
going to a major thing that's goingto kill you is is an infection from
an attack or a fall or abroken bone or something like that. And

(08:46):
arthritis too. We've seen older folkscan in Paleolithic periods. If the diet
wasn't completely balanced, arthritis would bewould be a contraquence of that. But
you're right, I mean, weare pretty healthy folks if we're not beaten
down from years and years of alack of exercise and consumption of highly processed

(09:07):
foods with minimal nutritional value. Yeah, and I suppose fasting will come into
that as well, because go backto doctor Mark, who's talking a lot
about fasting. But presumably we'd befeasting when we found the animal, and
that's yeah, we'd all gather aroundthat and we'd have a good old time
and then it might be some timebefore we find food again. So again,
that's part of the way we're supposedto be. Really, and we
crumb our faces full of food allthe time. Three times a day is

(09:28):
remarkable. Yeah, yeah, wenever you're right, we put up with
it. Yeah, yeah, Andyou're right about the feast. I mean,
to catch a big animal and killit takes a tremendous amount of energy.
And you don't do that like threetimes a day. No, you
know, you have to track downsome poor animal. The wife tells you
that because I'm hungry. Now whatyou're out killing another deer for us?

(09:52):
Well, you know, this isnot a this is not something that we
take up readily. You know,let's enjoy it while we have it,
and they will. Well, we'rehungry enough, we'll go out do it
again. So obviously, yes,we should learn from the way we were
adapted or designed, or however youwant to look at that. Indeed,
Okay, so your work is challengingthe idea to some extent that this is
all genetically predetermined, etc. I'mwondering how to go about this. One

(10:16):
of the things that you do inone of your lectures is to critique something,
and perhaps you'll tell us exactly whatthis is. In a moment,
you critique something called the somatic mutationtheory and you say that it's not up
to snuff to try and explain everything, and you show that there are some
problems with that theory, and fromthat then you have your own approach to
this. Could you tell us somethingabout that and why you critique that.

(10:39):
Yeah, Well, you know,theories in science have led to major changes
and advancements and how we think aboutthings. And I always introduce the heliocentric
theory versus the geocentric theory. Theheliocentric theory of Copernicus, Galileo, and
Kepler pretty much solidified that it wasthe Sun that was the center of the

(11:01):
Solar system, with the Earth revolvingaround that. Now, of course that
was a major intellectual conceptual advancement,but it wasn't associated with nearly seventeen hundred
people a day dying as the resultof not embracing that concept. Lewis Pasteur's
germ theory replaced Galen's bad air theoryfor the understanding of germs linked to disease.

(11:28):
So the current view now is thatcancer is a genetic disease caused by
somatic mutations. These are mutations inthe genome that are acquired during the course
of one's life. And if yougo to the National Cancer Institute of the
United States and you go to theirwebsite and it says you know what is
cancer? Cancer is the definition ofcancer is cell division, out of control,

(11:52):
disregulated cell growth. And according tothe National Cancer Institute and also the
NHS in England, they say disregulatedgrowth is the result of these a collection
of somatic mutations that lead to thedisregulated the growth. So the competing theories
is that no, the disregulated growthin the mitochondrial metabolic theory says that it's

(12:16):
the organelle the mitochondria that generates energyand when that organelle becomes defective, it
leads to reactive oxygen species. Theseare like a carcinogenetic and mutagenic. So
according to the real accurate definition isthat cancer dysregulation comes from the inability to
regulate energy metabolism in the cell andthe mutations, the somatic mutations are downstream

(12:41):
effects rather than the causes of disregulatedgrowth. All right, So if we
have genetic mutations, whether they happenwithin our lifetime or perhaps even if they're
inherited, they wouldn't necessarily determine thatway are going to develop accounts, so
they would predispose us. Would thatbe right? Well, I think for
inherited mutation would be what we calla risk factor. It's a secondary risk

(13:03):
factor, not a primary risk factor. The only way that cancer can occur
is when the organelle that generates energywithin the cell becomes chronically disrupted and replaced
by energy through fermentation, which isenergy without oxygen. So every cancer cell

(13:24):
that we have ever studied can growin the absence of oxygen, in other
words, in hypoxia. One ofthe great clear indications of this is that
you know as well as everyone thatif you drink cyanide, it will kill
you very very quickly, because weblock the ability of our body to get
energy from oxygen, so we diefast with cyanide. Cyanide has no effect

(13:48):
on the growth of a tumor cell, so tumor cells can live in the
presence of cyanide. As we Warburgand others have tested and clearly this distinguishes
the cancer cell very strikingly from anormal cell. Because we can't live in
the presence of cyani We die veryquickly because all the energy in our body
would be shut off immediately. Thecancer cell does not use energy from oxygen.

(14:13):
It uses ancient fermentation pathways. Wow, energy without oxygen, and this
makes us a clear and striking differencebetween cancer and normal cells. Wow.
This is fascinating because this goes tothe heart of your work. And I'm
wondering whether we could sort of collectthese ideas around an historic character I believe
was very very important for you,which is Otto Warburg, who was a
medical doctor physiologist from the earlier partof the twentieth century. Could you pinpoint

(14:37):
what it is that he discovered whythat is so key for your work.
Yeah. He showed in no uncertainterms, in slices of normal tissue and
tumor tissue, he used oxygen consumption, which we now know there's a problem
with that, but at face value, we're going to look at it as
a marker. He found that ifyou take a slice of a liver or

(15:01):
a kidney and look at the consumptionof oxygen over time, you find it
to be quite steady and high.And if you take a slice of a
tumor from a human or rat ora mouse, and you compare it exactly
to the consumption of a similar human, mouse or rat tissue, you find
that the oxygen consumption of the tumoris always lower in the cancer cell.

(15:26):
And not only that, the cancertissues always excreted large amounts of lactic acid
lactate, and that's a marker forglucose fermentation. So rather than being metabolized
for energy completely, the cancer celltakes in the sugar, the glucose,
but then wastes a lot of itby dumping out lactic acid where the normal

(15:48):
cells would burn the end product lackof glycolic, which is pyruvate, and
get a lot of energy from this. So normal cells. The waste product
in our normal cells is CO twoand water. So every breath that we
exhale has moisture and CO two thatwe blow back into the atmosphere. The

(16:08):
cancer cell produces largely lactic acid.Okay, it will produce some CO two,
but it's mostly lactic acid the wasteproduct. So clearly Warburg showed in
no uncertain terms, that all cancersthat he studied had lower oxygen consumption and
a much greater production of lactic acidin the presence of one hundred percent oxygen.

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So in one hundred percent oxygen,normal cells should produce no lactic acid,
but cancer cells continue to produce highamounts of lactic acid. And he
attributed that to a failure of somesort in the respiratory capacity of the cell.
And he pinpointed that to the organellecalled the mitochondria. He called them

(16:51):
granite in those days, but nowthey're called mitochondria. So he was able
to say that all cancers arose froma chronic disruption of their ability to generate
energy by the consumption of oxygen,thereby falling back on a fermentation pathway.
And I and others have shown thatall cells on our planet did the same

(17:12):
kind of metabolism before oxygen came intothe atmosphere two point five billion years ago,
produced by cianobacteria that produced oxygen forthe first time. So cancer cells
are doing nothing more than falling backon ancient, prehistoric metabolic pathways driven by
fermentation. And Albert seen Georghi saidthat was the alpha period of life on

(17:36):
Earth where cells were constantly in adisregulated growth of disregulated proliferation, and they
would only stop proliferating when the fermentablefuels in the environment were used up and
disappeared, and then these cells woulddie. So cancer cells are essentially doing
the very similar thing. They liveon fermentable fuels, the sugar glucose and

(17:59):
the aminio asi a glutamine, andas long as the cancer cells have access
to these two fermentable fuels, theywill continue to grow, right, right,
So it's not a mystery. Yeah, yeah, So most of these
cells then have potentially two main waysof generating energy, and if the mitochondria
are dysfunctional, then they will sortof say to themselves, okay, well

(18:21):
we can't generate energy that way anymore, will shift back to an ancient way
of doing this that doesn't involve oxygen. We'll do it that way. And
this is the fermentation process. Andyou say that that is that is kind
of out of control, and ituses I understand, it uses a lot
of glucose and it's not regulated,and can I just check these things through

(18:42):
with you? Then? So mostnormal cells, I believe it doesn't include
red blood cells. So most normalcells, they use this process that you've
described called oxidative phosphorylation. So isthat the that's oxygen plus glucose making energy,
making ATP come out energy, andthat's in the mitochondria. But then

(19:02):
if the mitochondria are dysfunctional, itstarts to go wrong, so that the
cells say to themselves, you know, I'm being poetic here. Of course,
they say to themselves, woops,we can't do it that way anymore.
We're going to do it in adifferent way. We're going to ferment,
we're going to we need even moreglucose. We're going to make ourselves
even more able to use glucose,and we're not going to involve oxygen.
So we'll produce a lot of lacticacid. And this won't be happening in

(19:25):
the mitochondria as will be happening outsidethe mitochondria in the cell, and there
may be a lot of oxygen outthere available, but well, we're not
going to do this. We can'tdo it because our mitochondria are just not
working properly. Will We'll produce energythis way and that then becomes dysregulated,
that becomes out of control, andthat's the cancer cell. Have I got
that? Is that the basic picture. Yeah, and Julie and you have

(19:45):
it pretty well defined. The issuehere, of course, is that if
that disruption to the energy metabolism ofthe mitochondria is acute, it will kill
the cell dies. Just like Isaid with cyanide, you disrupt that process
acutely and the cell dies. Andas Warburg said, you can never get
a cancer cell from a dead cell. So the disruption of the oxidata phosphorylation,

(20:08):
as you're absolutely correct, production ofATP, which is the energy chemical
currency in the cell from the consumptionof oxygen and full oxidation of the glucose
molecule producing the waste products of COtwo and water, as opposed to the
cancer cell that can't fully metabolize theglucose and dumps a lot of it out

(20:33):
in the form of lactic acid,even in the presence of oxygen. But
the important issue to remember is thatthis transition from respiration to fermentation is a
chronic one rather than an acute one, and the cell will do everything possible
to attempt to maintain oxidata phosphorylation.But here's the interesting thing. What would

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cause this to happen in the firstplace, where a cell would undergo chronic
disruption of oxidata phosphorylation, and there'sso many like exposure to carcinogens. Carcinogens
will enter the cell and right enterinto the mitochondria itself and chronically disrupt the
ability of the cell to get energyfrom oxygen. So over time that cell

(21:17):
gradually starts to ferment. Now,the interesting thing is the mitochondria controls the
regulation of the cell cycle, sothe regulation of the differentiated state, the
quiescent state, is under the controlof that energy deriving organelle, the mitochondria.
It controls the cell cycle, soit allows cells like normal cells will
grow in our body, but theyhave regulated growth, they don't have disregulated

(21:40):
growth. So the transition from oxidataphosphorylation to fermentation has to be a gradual,
chronic one. And interestingly enough,that mitochondria is so sensitive for the
presence of oxygen. As soon assomething starts to disrupt the ability to generate
energy from oxygen, the mitochondria thenucleus, it's an epigenetic signaling system,

(22:03):
and then the cell all of asudden starts to produce transporters on the surface
of the cell, like you said, to bring in far more glucose because
you're not fully metabolizing the glucose.So the mitochondria signals the nucleus to turn
on genes that upregulate the transporters toget more glucose into the cello and also
glutamate. So the mitochondria signaled thatthe cell is suffocating slowly, and this

(22:30):
transition from using energy with oxygen tousing energy without oxygen is a chronic one.
But at the same time, asthe mitochondria struggle to maintain energy balance,
they are throwing out these radical biomoleculescalled a reactive oxygen species, the
radical oxygen molecule, the oh anidradical. These are carcinogenic and mutagenic.

(22:52):
So the damage to the nucleus iscoming as a secondary downstream effect of the
disturbed metabolism in the in the mitochondria, leading to what we call the somatic
mutations. But at the same time, the cell is opening up these transporters
to allow it to use a fermentationmetabolism, and this happens over time until
the cell has lost all of itscontrol. The mitochondria controlled the apototic the

(23:18):
cell death, signaling it controls thequiescent state, It controls the cell cycle.
So when that the controlling mechanism ofthe cell becomes corrupted, the cell
falls back on these ancient pathways,no growth control any longer growing out of
control. And as long as thosefermentable fuels and the transporters are upregulated,
these cells are going to survive andthey're going to grow. And so it's

(23:41):
just a metabolic transition from one energeticstate to the other. But these so
called oncogenes that people say cause cancer, no, oncogenes are simply facilitators of
the fermentation condition driven by the abnormalmitochondria. So they're not the drivers of
this whole thing. And the reasonwe know this because if we take cancer
cells and replace bad mitochondria with newmitochondria, the entire fermentation pathways that are

(24:07):
down regulated and turn off and thecell enters back into a growth regulated state.
So clearly those are not they're notthe drivers. There's just facilitators of
a fermentation metabolism. And if youtake away put new mitochondria, everything turns
off and the cell comes back toa normal state, normal growth regulated state.
Okay, so what you're describing hereis actually experimental evidence, is it?
Yes, experimental evidence. So thenuclear transfer experiments and mitochondria transfer experiments

(24:34):
have all documented this. So andthe nucleus persists with all the damaged chromosomes
and mutations, but the cell isnow in a growth regulated way. So
clearly the nuclear mutations are not thecause of this. They're the effects.
They're secondary downstream effects. So acell can still maintain growth regulation despite having
a range of chromosomal and gene mutations. Does this go back then to I

(24:57):
think in one talk you talk aboutresearch that was done back and I think
in the late nineteen sixties with atadpole cloned from the nucleus of a frog's
kidney tumaicile or something. But yeah, yeah, but he no, that
was the work of mckennal. Yeah, mckennel. I had to before he
passed away. I had a greatopportunity. He was the curator of the
Medical Library at the University of Minnesotain Minneapolis, and I had the chance

(25:22):
to sit in his office for hourstalking about his tadpole nuclear transfer experiments where
he transferred the nucleus of a ragingkidney tumor highly malignant kidney tumor and put
it into an innucleated egg. Infrogs, you can do these kinds of
experiments, but they were also donein mice much later by doctor Rudy Yanish

(25:42):
down here at MIT. But whatmckinnal did was he took a fertilized egg
of the frog and replaced that.It's like we cloned Dolly the sheep today
and do these things, but theearly work was done on amphibians and frogs.
So McKinnel then removed the new cliusthe fertilized nucleus of an egg frog

(26:03):
egg, and then replaced that withthe nucleus of the tumor cell. So
everything was the same. The cytoplasmwas normal, but now the nucleus of
the tumor was placed into the cytoplasmof the fertilized egg to see what would
happen. And what he found wasthat this nucleus of the tumor cell formed
a perfectly normal tadpole. Tadpoles canregenerate their tail, so he cut the

(26:29):
tail off the tadpole and it regenerateda perfectly normal tail. And this is
all together with the nucleus from theraging kidney tumor. Interestingly enough, the
tadpole could never develop into a matureadult frog. So there was some genetic
abnormality in the nucleus of the tumorcell that aborted development but did not cause

(26:53):
this regulated cell growth. So therewas DNA damage was there actually in that
material in see the nucleus, butit wasn't causing that dysregulation of growth?
Is that right? That's right,that's exactly right. Wow. And then
Rudy Yanish went on and he didthe same thing in mice. He transplanted
nuclei from melanoma, skin cancer cellsand pancreatic cancer's nuclei into the stem cells

(27:18):
of the mouse. And of coursethe procedures are a lot more sophisticated than
with the frog, but he wasable to show in no uncertain terms that
mouse embryos could be developed to acertain stage of development with no dysregulated growth,
but then they liked the frog,would abort. And he found out
that how many how much DNA damagein the nucleus was the determining factor as

(27:44):
to how far in development the frogor the mouse would grow or would would
develop. So nuclei that had fewchromosomal abnormalities were allowed from a cancer.
A cancer nucleus with fewer chromosomal abnormalitiescould persist longer in development than mice clone
from the nuclei of cancer cells.With massive rearrangements of the genetic material,

(28:07):
those guys would abort earlier in development. And Jim Morgan's group at Saint Jude's
in Memphis, Tennessee, showed thesame thing. He was cloning mice from
the nuclei of brain tumors, andagain they would go no dysregulator, everything
was quite in order, but thenthey would reach some bottleneck and the whole
system would implode or aboard. Soclearly there was the genetic abnormalities in the

(28:30):
nucleus were not leading to dysregulated growth, but disruption of development. So clearly
these findings show that it's not themutations in the nucleus that are leading to
disregulated growth, it's something in thecytoplasm. And then that was clearly shown
with the transplantation of mitochondria from onecell to the other, and you could

(28:52):
completely shut down the oncogenic profile thedisregulated growth by putting new mitochondria in there.
So these groups of experiments in totalyou can't look at any one by
itself, right, You have tolook at it right. So you could
do it the other right, soyou could take could you take the nucleus
from healthy cell and s to getinside a cancer cell and see what happens
with that? To me, yeah, yeah, Israeli Shaeffer did those beautiful

(29:15):
experiments up at the University of verMonth. So they took cancer cells in
vitro. These cells, when youput them into the flank of a rat,
they formed big tumors. So whathe did is he took the nucleus
from cells in culture that didn't formtumors when you put them into the rat,
so they were considered non tumorogenic.And he put that normal nucleus into

(29:37):
the cytoplasm of the aggressive tumor andput them into the rat and got big
tumors despite the normal nucleus present.And he did the reversed experiments again.
You know, when you put thecancer nucleus into the normal cytoplasm, you
got regulated growth, and when youput the normal cell into the cancer side
and get disregulated growth. So itwas clearly related to the mitochondria and the
cytoplasm, not the condition of thenucleus. So you do all of those

(30:00):
experiments over and over again, repeatthem by different investigators in different laboratories,
using different tumor systems, and youcome to the same general conclusion. The
origin of dysregulated growth comes from thecytoplasm and not from the nucleus. And
when we look at the cytoplasm ingreater detail, we find abnormalities in the

(30:21):
number, structure, and function ofthe mitochondria. So what I did is
I went back and I looked atevery major human cancer. And you have
to go and look under electron microscopy, because unlike the nucleus, the mitochondri
is very tiny network and you can'treally see them clearly under light microscopy.
So I had to go back inthe nineteen sixties and seventies and eighties and

(30:45):
look at those studies on cancer thatwere done by electron microscopy, and then
you look at the mitochondria, andin every major cancer you can clearly see
the organelle is all abnormal in structureand function. And in biology, primary
tenet of the field is that structuredetermines function, and when the structure of
the organelle that it's necessary for energygeneration through oxidative phosphorylation is dysfunction. When

(31:11):
the structure of that organ LLE isabnormal, the function and getting energy is
going to be abnormal, and inorder for the cell to survive, it's
going to have to ferment because itcannot use respiration. So the evidence is
so strikingly clear that no cancer cellthat we have found has a normal content
or composition of the mitochondria. Andknowing that, we then interrogated these cancer

(31:33):
cells more intensely to see if therewas any fuel that could substitute for glucose
and glutamine, and that's when wecame to the glutamine realization that cancer cells
are fermenting an amino acid called glutaminemore than any other amino acid. So
it's a sugar and an amino acidthat are driving all major cancers. And
as long as the cancer cell,regardless of it's a lung, colon,

(31:56):
bladder, breast, as long asit has access to glucose and glutamine,
it can survive under all kinds oftoxic treatments. But as soon as you
pull the plug or interrupt the twopathways using glucose and glutamin, these tumor
cells can't survive and they can't switchto fatty acids and keytne bodies because you
need a good mitochondary to burn fattyacids and keytone bodies. This is so

(32:16):
the solution to me. Yeah,the solution to the cancer problem is not
that complicated. You bring people intoa state of nutritional ketosis where you lower
blood sugar as much as possible andtransition the entire body over to ketones which
the tumor cells can't use. Andthen you use drugs to target the glutamine
and you can take away the glucoseand the glutamat and you will see these

(32:38):
tumors melt away. They can't survive, and you don't have the toxicity to
the rest of the body. Theproblem is what I just told you cannot
be accepted or understood by the vastmajority of people working in the oncology field.
Yeah, we'll come to that.That blindness is incredible, and I've
heard you talk about that before.Absolutely astonishing and tragic. Indeed, that

(33:00):
you know this seems to be anunwillingness even to consider this and look into
this. I'm going to go backto this glutamine So the glutamine was an
addition that you have made to aWarburg's theory, which I'm presumably was just
to do with glucose, wasn't it. He wasn't talking about glutamine. Is
that right? That's correct, thepathway that was not known at the time
of Warburg. There were several issuesby which Warburg was displaced in his ideas.

(33:22):
One was the fact that he usedoxygen consumption as a marker for the
fidelity of oxidative phosphorylation, and wenow know that's not true in the cancer
cell. It's true in the normalcell, but not the cancer cell.
Cancer cells will consume oxygen, butthe problem is it's not linked to efficient
ATP synthesis through oxidative phosphorylation, unlikethe normal cell. He knew nothing about

(33:44):
the glutaminolysis pathway as the second fermentationpathway. So we showed cancer cells can
live in the absence of oxygen inglutamine, so they can survive for some
time in the glutamine. It's beingfermented, it's not being respired. That's
another major miss understanding of the cancerfield. They think glutaminus is respired,
not fermented. No, glutamine isfermented through the glutaminolysis pathway. That's our

(34:07):
major new contribution to the cancer field. We have a second fuel, an
amino acid that can be fermented,and it is glutamine. And we interrogated
every other amino acid. Nothing comesclose to what glutamine can do to drive
the metabolism of the cancer cell.And then the other thing is that Warburg
was counting the production of lactic acidas a marker for energy in the cytoplasmic

(34:29):
glycolysis pathway, and we now knowthat that's also not an accurate marker because
there's another cancer cells have the secondform of enzyme called pyruve kinase M two,
which makes lactic acid without producing ATP. So Warburg was driven by quantification
to try to prove his point thatcancer was a mitochondrial metabolic disease. But

(34:51):
the readouts, his quantitative readouts werein era not complete era. But he
knew nothing about glutamine fermentation. Hethought ox consumption was linked to ATP synthesis
through oxfoss. That's incorrect because hedidn't have some of the evidence we have
today, and he was using lacticacid as a readout for ATP synthesis through
the cytoplasm, and we know thatthat can happen for sure, but not

(35:14):
as quantitative as what Warburg had thought. So we're putting together the whole field
why he was attacked, the misunderstandingfrom those who thought he was wrong,
and we're going to clean the wholemess up and bring Warburg's idea back on
track, but also move it forwardbecause he was always considered they called it
the Warburg hypothesis because many other folkssaid, oh, cancer cells can consume

(35:37):
oxygen just as readily as normal cells. The problem is they grouped all kinds
of miles human and rat tissues together. They didn't separate them based on species,
so you get a lot of misunderstandmisinformation from that. So we can
clear up most of the misunderstanding andmistakes made and bring the entire cancer feel
back on its rightful track, whichis that it's a mitochondrial metabolic disorder driven

(36:00):
by fermentation metabolism, and you canmanage the disease quite readily by simultaneously targeting
fermentation while the body is in astate of nutritional or therapeutic ketosis. We
have seen this happen over and overagain for humans and dogs, and this
will be the future. This isthe way you manage the disease. And
we don't like to call it cure. We like to call it a management.

(36:22):
How long can you keep someone alive? Does that mean the tumor goes
way? No? Pablo Kelly inEngland from Devon, England is alive today
after nine years with a glioblastoma.His tumor is still there, but it's
indolent, it's not growing wildly,so he's learned to live with it.
Is he cured? No? Didhe live far, far longer than he

(36:42):
would have if he had standard ofcare radiation? And oh he's nine years
out And I mean, what's theprognosis for that? Is really bad?
Isn't it as very aggressive as Yeah, people don't live very long at all
with oh yeah, no, no, you can see people die usually under
two years, eight to fifteen months, and the older you are dead sometimes
before a year nine to ten,you know, twelve months? Did he

(37:04):
contact you? Was it through yoursuggestion? Yeah? He contacted Yeah,
he contacted me. And I didn'twrite the paper up for a long time
because I thought he was going tobe dead. He contacted me. He
said, I heard about this metabolicstuff, and then he said, I
didn't want He has a very interestingstory. You should interview him on your
program. You get a real kickout of it. He can give you
the nitty gritty details of what theygrabbed them. They packed off his beard,

(37:28):
they put a big cage on hishead, ready to radiate the guy
and he said, I don't wantany of this. He just came in
for a consultation. But any event, he rejected all radiation and chemo.
And yeah, just say that.I'm sure I heard you say that the
radiotherapy itself can actually give rise toa preponderance of glucose, which which is
even more problematic. Is that right, Yeah, that's right, that's absolutely

(37:50):
correct. Good And yeah, Iknow, and you know that the tragic
loss of people with leo blastoma iscreated in a large part by how we
treat the patient one hundred percent correct. You know, as soon as they
finish the debulking surgery, they goin with radiation. And you can take
a normal person and just to radiateany part of their body and blood sugar
goes flying up really high because ofthe stress and not only that when you

(38:15):
irradiate somebody's brain, the head getshot, the tissue gets hot and starts
to swell. So they give thesefour patients high dose of dexamethone. It's
a steroid which causes the blood sugarto go up into the range of a
diabetic. And not only that,when you irradiate, you break apart these
very tightly controlled glutamine glutamate cycle.And the brain is part of our the
way our nerves communicate with each other. So you free up massive amounts of

(38:38):
glutamine in the micro environment, andthen you give all the steroids, and
you give massive doses of glucose.So the two fuels that drive the dysregulated
growth are made in a great abundanceby the very treatments that we're giving to
these patients. And if you lookat the survival statistics across all major medical

(38:59):
schools out the world, you knowalmost everybody is dead within two years.
You really get long term survivors.And we've made no major progress in brain
cancer management for one hundred years.Can you believe this? Wow? It's
like and they keep and even thoughI publish the details, I publish the
details, I publish open access papersshowing exactly why all these patients are dying

(39:22):
so fast. The field ignores it. They say, glutose has nothing to
do with the dysregulated growth. Theynever heard of glue to meat. And
so you say to yourself, Ifeel so bad seeing these people slaughtered by
the system. I mean, it'sjust terrible. So you have a reservations
about radiotherapy that does that just applyto brain cancers or that's generally in cancer?

(39:42):
Well, I would certainly limit itright now to brain cancer. But
you have to realize any time youradiate your body, you're going to raise
blood sugar, which isn't good.I think we've seen some level of success
when patients are in nutritional ketosis wherethe body is now burning keytnes. And
then if you have a localized lesionwhere a radiation bolt could cure it or

(40:05):
eliminate it completely, you know,there's certainly that has to be taken under
consideration. If you can be assuredthat the radiotherapy for a localized mass and
that's where it is, you cancertainly improve the outcome by radiating that person
when they're in a state of nutritionalkeytosis. For sure, for metastatic cancer

(40:27):
where the cells have spread and you'reusing radiation as kind of a whack a
mole. I would not recommend itin those cases, especially if we pull
the plug on the glucose and glued. I mean, we can get rid
of most of this anyway, Sowhy are we using radiation in the first
place? Right? So let's callit your pro I think you call it
a press pulse protocol or approach.So you're not suggesting that as an alternative
to all these other ways of dealingwith cancer, but it's another tool in

(40:51):
the toolbox. You've got, yougot your your chemotherapy, you've got your
radiotherapy. You are using the presspulse, and that was sort of clearing
the way for a more targeted useof these other therapies. Is that right?
Yeah? I think that's true.In other words, a hybrid system,
and we've seen some really good success. If you can reduce half or
by three quarters the amount of chemotherapyif the patient is in a state of

(41:13):
nutritional keytosis, that chemotherapy can actuallybe very effective and actually works a little
bit better and reduces a lot ofthe side adverse effects. From that,
we published a paper on breast cana woman with breast cancer who was given
one month to live, and sheflew from Ohio Cleveland, Ohio to Istanbul,
Turkey, where some of our colleaguesare working over there. She almost

(41:37):
died on the trip and she wasin the emergency room for two and a
half weeks, and they gradually loweredher blood sugar. They gave her a
very low dose of chemo while shewas in a kind of a ketotic state,
and gradually she started to turn around. And she had cancer in her
brain bones, you know, stagefour. You know, that's why they

(41:57):
gave her so little time to live. And then within a year and a
half she was well. We couldn'tthey couldn't find any lesions. And we
got a picture of her in Hawaiiwith a husband enjoying honeymoon or something,
you know, and people say,oh, that's a fluke Well, Pablo
Kelly, you know, and wehave another Greek guy who had metastatic lung
cancer to the brain ethanou So he'sout nine and a half years. We

(42:22):
published that case report and people sayto us, oh, well, you're
only public one at a time,you know, one of this Are you
kidding me? I mean, canyou imagine if we were able to do
this at a larger scale, theoutcome you'd get. I mean, but
there's so much resistance because they thinkcancer is a genetic disease. And as
long as your brain is infistated withwith the wrong idea, you're going to

(42:44):
continue to do stupid things. SoI've got a little questions to ask about
that sort of institutional approach to things. Could you describe to us a little
bit more about this press pulse protocolor approach. I mean, I can
understand, great idea to reduce glucose, reduced sugar intake. You know,
ketogenic diets, et cetera. Okay, so the concer cell requires the glucose,

(43:06):
but our normal cells can survive withketones, et cetera. So it
seems like a good strategy to dothat. But of course the glutamine is
something that we cannot do without,so you can't just cut that out it,
So you've got to do it inthis sort of pulsed way. So
how does that all work? Yeah? Well, I took that idea,
the press pulse concept from Aarons andWest. They were paleobiologists studying the history
of life on Earth, and theyhad in the past, they had these

(43:30):
extreme exterminations of organisms on the planet. It never happened with one event,
it always happened together with another event. So you had a stress, maybe
a climate or a nutritional stress ona large number of organisms and populations.
But there were survivors. But it'sonly happened when you have a calamitous volcanic

(43:52):
or meteor strike. When you havea climate stress, that you get complete
extermination of species. So there's alwayssome survivors under one or the other,
but there's no survivors under both.So I use that concept and said that,
well, if we know that cancercells cannot survive without glucose and glutamine,
is it a way we can takethat paleobiological concept and move it into

(44:15):
the cancer field. So we realizethat you can lower blood sugars in a
patient to almost very very low conditions. From physiological studies and humans, we
know we can get them down reallyreally low. So we said, well,
we can press glucose down through fasting, isn't it is that right?
Well? Through fasting and also keytone supplementation as well, So there you

(44:38):
can do water only fasting, keytone supplementation, and you'll push blood sugars
down really low. And then whathappens. The brain is the greatest demand
for glucose, so it starts consumingmore glucose even though but it can transition
to keytone bodies as well. Butthe tumor cells are absolutely dependent on this
glucose. So now for the firsttime, the tumor cells are under a

(45:00):
direct competition for a valuable metabolite withtheir own normal cells. When you have
so much glucose in the blood thatthe brain has everything it needs, All
the other organs has everything they need, and there's no pressure on the tumor
cell. So the tumor cell hasall the fuel that it needs. It's
only when you lower that blood sugarthe brain now can transition. All organs

(45:20):
can transition over to ketones, butthe tumor cells are marginalized. They must
have the sugar. They're now ina direct competition with the normal cells of
the body, and the tumor cellsstart to lose. But you're right about
the glutamine. So the glutamine isthe most abundant amino acid in our body.
It's absolutely essential for the gut,the health of our gut our immune
system, the ureacycle. So youcan't go in like a bull in a

(45:42):
china shop and go after the glutamine. That's why we decided to use the
pulse strategy where we can target glutaminefor a short period of time which selectively
will kill tumor cells, and thenpull it off and let our immune cells
recover and they can come in andpick up the dead tumor cells the corpses,
because once you slaughter a whole bunchof cells, you're left with a

(46:04):
bunch of dead cells in the microenvironment, and our immune cells, macrofages
and such go into the micro environmentand fabricatize the dead cells and clean up
the mess. They need lutamine too, so you can't prot press. Yeah,
you can't press the you got.This is the key, Julian.
You must know biology, you mustknow systems, physiology. You must understand

(46:25):
these processes. Otherwise what I'm sayingmakes absolutely no sense to anybody. You
really have to understand biology, andyou know how to play one cell,
a group of cells off of anothergroup of cells. You know how evolution
works, so you can exploit thatin knowing how cells evolved in what they
need to do. So once youput all that together, you know,
killing tumor cells is not for us. It's quite logical, and the problem

(46:49):
is you can't get the medical communityto no one tell them talking about it.
Yeah. Yeah, So when youpulse in this way, you use
substances in order to actually suppress theglutamine getting in to the concer cells.
Is that right? I think youyou mentioned something called down. I don't
know whether you still use that becauselooking at Jane McClellan's book, she I
think she says something like, youused to have that approach, but it

(47:09):
was just it was a little bittoo vigorous. Is that right to you
know when you're in something different,don't know. DON works beautifully, especially
when you're in keytosis. The reasonwhy it was toxic is people weren't targeting
glucose and you were dumping large amountsof DON on the cancer patient. Damaging
is got damaging the immune system?Yeah, killing some cancer cells. But

(47:29):
again you have to know the biologyof what you're dealing with, so you
don't pressed on your pulse it andthe toxicity goes way way down. This
is the amazing thing, and weshowed that the ketogenic diet facilitates delivery of
DON to the target right through theblood brain barrier and other places as well.
Wow, again, you must understandbiology if you want to successfully manage

(47:51):
cancer. And unfortunately the cancer fieldhas no clue about most of what I
just said. I have come througha musical background. I have the picture
of the conductor at the front ofthe orchestra and it has to know exactly
which instrument is about to play.And if you don't know, it's going
to be a cacophony. So ifthis one called don here, just so

(48:12):
people know what it is, isthis variety here we go six diazo five
oxo l nor lucine. Is thatit? Yes, it, that's it.
I'm surprised. Yeah, they dida very good job. Excellent to
put you in the Candler clinic.I think you'd have more success than most
of the folks working there. ButI looked it up and I thought,
I've got to say what it isare These people will wonder what DON means?
Do you put somebody working at auniversity into your body? But they

(48:34):
were, yeah, yeah, that'strue. The you know it is,
it's a it's a it's a moleculethat looks very very similar to glue to
me, and the body, thebody looks at it as their cells look
at it as if it were gluedto me. So the cancer cells suck
it up. But the key enzymethat metabolizes glutamine to glutamate, which is
a glutaminase, gets paralyzed. Sothe DON paralyzes one of the key pairs

(49:00):
ways in the glutaminolysis pathway, deprivingdepriving the cell of energy through glutamine fermentation.
So essentially you've shut down the gluetaminolysis pathway with DON, and you're
shutting down the glycolysis pathway with veryrestricted glucose. So you're taking the two
pathways that are essential, what wecall necessary and essential for the disregulated growth

(49:22):
of the tumor cell, and you'resimultaneously shutting those two pathways down using DON
to shut down glutamine. And peoplealways say, oh, what can I
eat to reduce nothing? Julian,You must tell people there is no diet
that will restrict the glue to me. The only way you can get a
little glutamine down. We found GeorgeCahill down at Joslyn diabetes when he was

(49:44):
alive back in the sixties and seventies. He fasted people for at least twenty
one days and that brought glutamine down, but it didn't eliminate glutamine. So
you can do that with glucose goesdown, glutamine goes down. But if
you really want to get rid ofall the glutamine, you got to use
a little bit of a drug andyou have to pulse it so people stay
healthy and you pull it off oryour pulse, you press your pulse and

(50:06):
you can gradually. We're trying toand most of these folks that have cancer,
they have high blood pressure, typetwo diabetes, hypertension, they got
a whole slug of things, andyou manage all of these things together.
Like Guy Tanenbaum, he had advancedprostate cancer to the bone. He went
on several eighteen day water only fastingsand he lost a lot of weight.
He got rid of his type twodiabetes. Prostate cancer is managed, can't

(50:30):
find it anywhere. Hypertension, highblood pressure, and all of those things
went away along with the prostate cancer. So that's why some people say this
procedure metabolic therapy is it's what wecall the disruptive technology. Right. Yeah,
it's incredible stuff, it really is. And you brought up the prostate
cancer. So can this general approachbe used for all cancers or any particular

(50:52):
ones? You know? As Isaid, when I went through the entire
literature looking for any kind of acancer that would have a normal iidochondria that
would not respond then to metabolic therapy, we couldn't find any. And this
is what Warburg said. Warburg saidthat cancer is a disease of the mitochond
disorder of the mitochondria. Every cancerthat he looked at, every cancer that

(51:12):
I've looked at, have abnormal mitochondrasstructure and function. That means they must
ferment. So the strategy should workvery well against all cancers. And as
I said, we haven't found anythat doesn't respond, that doesn't respond at
all. And we have lung cancer, call and cancer, bladder cancer,
breast cancer, brain cancer, allorectalcancer, they're all the same. They
all have the same problem. Theycan't live without fermentation. This is another

(51:37):
disruptive technology. But I just arethere any danger? People can't believe it.
They can't believe it. I mean, it's all very exciting, but
I just wonder, you know,some people might be thinking, well,
maybe there are some dangers to thiskind of approach. I mean, people
associate drastic weight loss sometimes with havinga cancer. You know, if you're
going through some process where you're noteating normal foods, you know, and
you're dieting excessively and fasting, you'regoing to get great weight loss. Put

(51:59):
that could that be really dangerous.Well, there's two times of weight loss.
We have pathological weight loss and wehave therapeutic weight loss, totally different
kinds of things. So when youhave pathological weight loss, if you are
a healthy guy and someone gives youpoison, you get diarrhea, vomiting,
fatigue, you lose weight because you'repoisoned. But most people who are poisoned

(52:20):
don't go out and need a lot, so they lose weight because they've been
poisoned. Right, That's called pathologicalweight loss. And then you can have
cockexia, which is a factor wherethe cancer cells themselves will send signals to
the muscle and the muscle starts tobreak down. Feeding amino acids, either
converted to glucose or glutamine itself goesright to the cancer cell, so the

(52:42):
tumor cells are eliciting a wasting syndromecalled kockxia. Those are called pathological states,
both the cockectic state and the poisonstate. People will lose body weight
because of the pathology associated with thosephenomena, a therapeutic weight loss as you
stop eating, but your mitochondria getssuper healthy and they become much more energy

(53:05):
efficient. At first, a cancerpatient may lose weight, but you have
a combination of pathological and therapeutic weightloss overlapped on top of each other.
As the cancer cells gradually get destroyedand reabsorbed into the body, the patient
begins to eat again and puts onnormal weight as the cancer cells are eliminated.
So again it's understanding the physiology andbiology of the entire body and system

(53:30):
to separate pathological weight loss from cancer. And you go to the oncology center's
the physicians say eat as much sugarand cake as you possibly tend to gain
weight weight on. I mean,this is not this is like throwing gasoline
on the fire. I mean,when you have folks that I know,
it's tragic. I don't want toeven laugh about it. It's the irony

(53:50):
of it. It's the irony.It's so ironic that the very folks that
you would trust your dear soul inexistence to are clueless on the biology of
the disease they're treating. And it'sclear why cancer is now ready to replace
cardiovascular disease as the number one killerin Western societies. It becomes entirely clear

(54:12):
why all the see because the folksthat are supposed to know don't know.
It's amazing. After there's the ironyjust walking into the hospital and you want
to have something to eat and youfind was not that easy to get a
slid as much easier to get abag of chips or something. Oh yeah,
it's supposed to be Yeah, it'ssupposed to be a hospital. What's
going on here? I know it'sof course, it's all to do the
business side of things, of course, but it's it is tragic. Well,
I think it's lack of knowledge.I think once the oncologists are trained

(54:37):
and learned in medical school about howto use diet nutrition as a weapon to
manage cancer, and know how towork certain drugs and procedures off of each
other, then this whole cancer thingwill be under control. We can worry
about other things, maybe dementia,because there's no therapy on the horizon like
we have on cancer. Cancer hasa very bright end of the time.

(55:00):
We're very hopeful. The only thingimpeding what I'm saying is they're resistant to
change and the lack of knowledge,and maybe also a revenue generation because you
can't come into a system where they'regenerating millions and millions of dollars in the
academic and the pharmaceutical industries and thenyou know, have them completely change shop
overnight. So that's why I thinkwe have a hybrid system that will keep

(55:22):
everybody employed for a while doing whatthey do in a different kind of a
context, seeing rather remarkable and spectacularresults on some folks, and then they'll
gradually slowly drift to the point wheremetabolic therapy becomes the primary treatment modality for
these patients, but it will taketime. So is it right that a
lot of councer research is focused onfinding that this gene and that gene that's

(55:46):
supposedly is it responsible for using whateveraccounts there it is, and that's where
a lot of the funding is going. Is that right? Oh? Yeah,
that's exactly right. Immunotherapy is thehot thing though aminotherapy. You know,
that's where you give patients these onecart t imunotherapy. You're trying to
use your immune system to kill thetumor cells. You've got to realize the

(56:07):
metastatic cell is already part of ourimmune system. It's a hybrid macrofage of
this regulated growing macrofage, and itfires out and kills some of these immune
cells. But what you're trying todo, they're trying to look for markers
on the surface of the tumor cell, so then you can train an immune
cell to go after that tumor cellmarker and kill the tumor cell at a

(56:27):
high cost. The problem with someof those immune therapies. Yes, there
are some folks that do really,really well, there's a lot of folks
who don't get any better. Andthen there's about fifteen to eighteen percent of
them that have hyper progressive disease wherethe immunotherapy will accelerate the growth of the
tumor cell, and not only that, it'll attack liver and kidneys, and
you get off target effects from atargeted therapy with off target effects, so

(56:52):
some folks die twice as fast withthe immunotherapy because it's based on the also
based on the somatic mutation theory.I you know, therapy is based on
the somatic mutation theory of cancer.If the somatic mutation theory of cancer,
the outcome will never be optimal.You're never going to have an optimal outcome
when you're treating a disease based onan incorrect theory. Period It is tragic,

(57:14):
isn't it? Because that fits withthe whole individualized medicine, which in
many ways sounds like a great idea. But if that's sort of twisted by
this wrong way, the wrong paradigm, then you know, a great idea
can actually become a barrier to thebest idea. No, you're one hundred
percent correct. I mean this isyou're running into. These are the kinds
of extenuating circumstances that prevent change inthe right direction. I don't know the

(57:37):
English UK government, but the Americangovernment spent billions of dollars on the cancer
genomatlists, looking at every kind ofa mutation in every kind of a cell
from billions of dollars, and wehave all of this stuff and it drives
an entire feel looking for mutations andall this, and it's all downstream effects,
and it's like you've invested so muchand you expect an outcome to be

(58:00):
comparable to the investment and you're notgetting it at all, mainly because the
original theory was incorrect. It wasn'tthe correct theory, you know, And
that's the tragedy. Yeah, itis. It's like a massive machine that
self perpetuates. How do you turnthat around? You know, mixed metaphors
there. I'm thinking of the youknow, the massive liner on the ocean,
and it's got a massive momentum.How do you turn that round?

(58:22):
When you can talk about it likethis, And it's great to hear what
you say, etc. Oncologists takingon board what you say is their sort
of grassroots support that can change thisover time. Well, you know,
you know what I find is themost interesting thing. Many of the people
who read my work and think aboutit carefully email me and they say,
you know, I know you're onehundred percent correct. I've been thinking about

(58:44):
that for a long time. Butmost of these guys are now retired,
they're no longer in this system,and now for the first time, they're
thinking about things and putting it intothe context of their life experiences and know
all along that I'm running the coldconcept of answer is a metabolic disease.
But when they're when they're in thetrenches, working day to day to handle
mobs of cancer people and never beingtrained to understand what I'm saying, you

(59:09):
know, it's just a continuation ofa tragic situation until the medical schools can
start training on cologists to understand thatcancer is not a genetic disease. It's
a mitochondrial metabolic disease, and dietand drug combinations are very, very powerful
in managing cancer without toxicity. Then, and we keep publishing papers like Pablo

(59:32):
Kelly. Like I told you,I didn't want to publish Pablo because you
know, if he died at threeor four years, people say, well,
that's a normal course of action.The guy's out nine years now,
and I said to him, andI said, well, we're going to
write him up. And we wroteup a couple of other people that are
out far, far longer than youwould ever expect it. So we keep
doing that, and believe me,people are smart. They look around and

(59:52):
they say, geez, I wantthat, and you give me. When
they start stampeding in to the oncologies. I want metabolic. Then they're going
to change, they have to change. Well, I'm going to go to
the next question here by saying exactlythat. Well that I mean I don't
actually have a diagnosis of cancer,you know, thankfully, but if somebody

(01:00:12):
like me, I'm thinking to myself, well, okay, I'm going to
reduce sugar. I'm going to reducethe highly processed carbohydrates. Would that be
a good thing to do? Notfor prevention, et cetera, because you
can you're not necessarily going to beable to prevent something from happening necessarily,
but perhaps we're reducing your risk ofdeveloping such a thing. Would that be
a good idea? Does that makesense? Oh, it makes perfect sense

(01:00:34):
because you can't get cancer if yourmitochondria remain healthy, because cancer starts with
chronic damage to the oxidator phosphorylation systemin the mitochondria. So as long as
that ox farst system is working,it's very difficult to get cancer. So
the question is how do you keepyour ox fast healthy? Well, you,
as you just said, we tryto avoid risk factors. You know,
no exercise, big risk factor,lack of exercise, regular exercise.

(01:01:00):
Smoking which is now being replaced byobesity, is replacing smoking as a risk
factor. Don't just eat highly processedfoods, restrict calories, walk so you
can keep your mitochondria healthy without droppingout of society completely. You know,
we just reduce the provocative agents thatwould damage oxidata phosphorulation. And as I

(01:01:22):
said, the body is if giventhe opportunity, it will heal. So,
even though we have damaged our mitochondrithrough various risk factors, if we
can avoid them for a while,give our mitochondria a chance to regain.
Because the process of autophogy is selfdigestion of mitochondria, so water only fasting

(01:01:44):
allows ineffective mitochondria, partially effective mitochondriabeing digested inside the cell, and what
you're left with is highly functioning mitochondria. So intermittent fasting, like skipping meals
periodically or going eighteen to twenty hourswithout eating, these kinds of things give
the body a chance to heal andmitochondriac can remain functional for a longer period

(01:02:07):
of time. Thereby you reduce risk. You don't eliminate, absolutely eliminate the
probability of getting cancer, but yousignificantly reduce risk, so prevention can be
done. Most people discount prevention.Obviously, we have an obesity epidemic.
If people were really concerned about cancer, there would not be an obesity epidemic,
because it's what everyplace is smoking asa risk factor. So clearly,

(01:02:31):
as long as people know, thenthey can make a choice as to what
to do. But even if theychoose not to do any preventative measures and
they do get dysregulated neoplastic growth,we have a solution, a non toxic
strategy. They're going to eventually haveto go into the water only fasting anyway,
because it makes the whole system workbetter. The pulse therapies work better

(01:02:52):
when you're in a state of nutritionalketosis. But you know, people are
more willing to do the restrictions andthe approaches when the angel of death is
looking over your shoulder. You'd besurprised how motivated some people become. Indeed,
indeed, yes I do. Ido find this notion of the therapeutic

(01:03:12):
ketos is very attractive and exciting.But I do wonder, you know,
how easy is it to get intothat state. I mean, I assume
that most people walking around in ukUS places like that don't generally have a
great glucose ketne balance. So Imean, how easy is it to get
a great balance so that you actuallyhave a therapeutic condition going on. Yeah,

(01:03:32):
well it's not easy, but we'vetried to take No. I mean,
the Japanese and the Chinese don't wantany part of it either, nor
to the Koreans. So it's notjust English in the United States. No,
No, the Germans don't want anypart of it. Italians. I
mean, you go around the world. Is he what the guys are eating?
They nobody wants to give up therice, the pasta, the potatoes,
and the bread. Oh I gota lot of bread, you know.

(01:03:53):
But the issue here is for cancerpatients because you know, we're not
out trying to tell folks down atthe pub to, you know, stop
eating the chips. But the guywho has the cancer is the guy that
would be more motivated to do this. It's easy to tell somebody to stop
eating, but it's hard to doit, and I've tried it. It's

(01:04:14):
brutal. It's a bitch. AsI said, you know, I went
three days without eating anything. Thiscompany made these ketogenetic muffins. I tasted
one before I went on the fast. I said, you wouldn't give this
muffin to the dog, it's sobad. So I sounded like contradictions in
terms, Yes, yeah, Butthen I went on three days of water
fasting and I broke my fast eatingthis. It was the best damn muffin

(01:04:36):
I rate my life. I gotclumbs all over the place that was shaken
while I was eating the muffins.Yeah. It's all about perspective, isn't
it? Absolutely, God absolutely allabout perspective. Yeah. But it's interesting
is that if you do actually cutdown the you know, the number of
carbohydrates that you eat, and youeat more good fats, et cetera.
And it's actually easier than to transitiononto fasting, isn't it after that rather

(01:04:58):
than going straight? Oh? Absolutely? Oh, absolutely yes, And that's
what we decided. We work withsome clinicians and nutritionists. So what we
do is the patient is told toeat whatever they want as long as they
can bring their glucose ketone index downto two point zero or below. So
if they are a plant eater orcarnivore or vegetarian or whatever you want to

(01:05:19):
pescatarian Mediterranean, and people say,can I eat this? Can I eat
that? I said, I don'tknow what is it doing to your GKOI?
And when they look at the GKIthey said, oh, I can't
barely eat anything. I said,now you've come to know what were the
glucose ketone index and what is thisbalance? Then? Yeah, one relate

(01:05:39):
to the other. What's the ratio? The ratio is about two points,
So it's the ratio of glucose andmilli molar. It's a ketone basically beta
hydroxy butery and milli molar in theblood. And most folks eating a Western
diet will be up and around fiftyor sixty. And you want to bring
that number down to two point zeroor preferably below one. So is that
a ratio of fifty to one doyou mean? Yeah? Yeah, that

(01:06:00):
means you have much more glucose thanketone in your blood if you're eating carbohydrates
and things. Yeah, it's amazing. So you can bring it down,
like, for example, if youeat carnivore, just meat, forget about
the potatoes, the bread and whatever, you can bring that GKI down.
Really good plants are a little harderbecause there's a little bit more carbohydrate in
some of the plants than there isin meat. But you know, vegans

(01:06:23):
can bring vegetarians can bring it downas long but they realize they have to
eat a lot less. But it'sthe shock of you don't have to go
cold turkey on food. You cangradually transition away, and then once the
patient hits the GKI lower levels,that's when we start the drugs, the
Dawn and some of the other drugs, and then they can jump to water

(01:06:44):
only fasting. The jump is notso dramatic anymore like you went with cold
turkey. It's like jumping off theside of a building rather than taking the
stairs, you know, So yougradually bring your body into a new state,
and it's not so traumatic when youdo that list. Oh, my
body has already transitioned over the keytones, so now I can just drink water.
And then when the drugs come in, man, they just hammer the

(01:07:06):
hell out of those tumor cells.These tumor cells don't know what hit them,
put it that way, struggling fortheir own existence. They say,
what the hell's going on? Jellydonu or that pork pie. It wasn't
anymore. Oh dear, this isvery very exciting stuff. Indeed it did
is you say, this is sotragic that this is not taken seriously by

(01:07:28):
the establishment. So how easy isit to monitor your own GKI? Is
there some sort of device to that? Yeah? Well there you can buy
these on Amazon. Uh okay.Dorian Greenow built the Keto Mojo. I
wanted to patent the glucose keytone index, but we can't pat in a formula,
so I said, oh wow.So the Keto Mojo group picked it

(01:07:49):
up and they put it into akeytone meter, so you can from the
same drop of blood, you measureyour blood sugar on one strip and your
keytones on a keytone strip, andyou put it into the meter and then
you push the button and it givesyou the ratio of glucose to ketones.
And that allows the cancer patients toknow at what point they're in therapeutic ketosis,

(01:08:11):
so it allows them to either takehyperbaric oxygen or glutamine inhibitors or further
glucose inhibitors and low doses, verylow doses, so there's no toxicity associated
with any of these kinds of therapies. You don't need to have hair loss
and nausea and vomiting and all thiskind of crazy stuff. None of that
stuff. Very very rarely do youhave anybody that experiences that unless they didn't
do the procedure in the right order, in the correct way. And then

(01:08:35):
you find people that come back andthey say, oh, my doctor,
I went there and the tumor thatwas spotted all over the place and I
had this big thing is gone orit's shrunk down by three quarters. And
the doctors don't understand what happened.I said, they should know exactly what
happens with these guys. They shouldknow exactly what happened and the logic behind

(01:08:57):
it. The cancer cell is dyingbecause it can't get the ruel that it
needs for fermentation. The tablets justthat simple. Well, on the surface,
obviously there's a huge amount of biomedicalinformation under the surface. But on
the surface, yes, it doesseems incredibly straightforward. You know, certain
types of cell need it and certaintypes of cells can do without it,
et cetera. Yeah, but Imean talking about oncologists in their retirement showing

(01:09:19):
interests et cetera. What about doctorswho are actually dealing with patients and they
find that this is an amazing remissionthat takes place and they can't understand it.
Do they actually serving GPS and practicingoncologists, et cetera. Do they
get in touch with you to say, can you explain what's going on here?
Is it really that straightforward? Giveus the loadown on this? Do
you get that? Very rarely?A lot of the physicians say, I

(01:09:43):
don't really care what you're doing,but it seems to be working. Just
keep doing what you're doing, AndI say, aren't you interested in knowing
why you're seeing what you see?They always call it a miracle or some
unexploit I've never seen anything like this. Well, for crying out loud,
don't you want to know the mechanism? Or no, no, just keep
doing what you're doing. Yeah,it's unbelievable. It's like their brain is
not allowed to open up to thinkanything different than what they were trained to

(01:10:05):
do. That's amazing. Yes,it's amazing. It's almost like an instant.
Some of those neuropsychiatric guys must beable to figure this out. Something
happens to the brain where it makesit incapable of knowing anything more than it
was trained to know and whatever theywant to know about it. So it's
not all. I don't want tosay everything on collegist is like this course,

(01:10:26):
but I would say that nine outof ten are or paradigms are very
very powerful. I don't think peoplerealize quite how easily we can get caught
up in that and be you know, we can mean very well, I
think we're doing the right thing,but we just cannot think outside the box.
As the expression and applies to lotsof things, and it's quite incredible,
you know. Yeah, when Iwas surprised about it, it's the
same in all the major countries.I thought from India they would be a

(01:10:48):
little bit more flexible. No,they just irradiate people. I put them
in China, Germans, the English, the Americans, Japanese, they will
do the same thing. It's like, kid, you guys think that this
is not working. We have anepidemic. It's a worldwide paralysis of thinking.
All the oncology centers do the samething. Are you freely are you

(01:11:10):
freely able to research involving patients?It in any country or the more restrictions
in some places than others. Well, if there any countries are more enlightened
than others. No, I haven'tfound one yet. So they're always telling
me we can have this clinic somewherein Africa or something like this. But
we try to get this in majorhospitals. Okay, which is this metabolic

(01:11:31):
therapy. And what they say is, okay, we'll do standard of care
and then we'll do standard of carewith metabolic therapy, but we won't do
metabolic therapy in the absence of standardof care. So what you have is
a gaping missing control group, theexperimental group. I should say, because
God forbid, if metabolic therapy ismuch better than standard of care and even

(01:11:55):
better than standard of care with metabolictherapy, and standard of care as a
hybrid and metabolic therapy by itself isso much superior. Oh that would be
and you did a clinical trial onthat, the whole field would overturn.
I mean, you wouldn't be ableto and the cancer patients would stampede for
metabolic therapy. They don't want radiation. EMO. I don't know anybody who
really got upset by saying, youknow, oh, I'm really upset he

(01:12:18):
told me I didn't need radiation.You know. It's like they say,
thank god, I don't need radiationabsolutely so yeah. So it's a really
it's a worldwide phenomenon. And PeytonRouse said the semantic mutation theory acts like
a tranquilizer on the brain. AndI absolutely believe that. I just can't.
I don't know what's going on.So it's just a matter of time

(01:12:39):
because more and more people are comingon the web, like Pablo Kelly.
I mean, Pablo is dead.He should have been dead years ago.
He's had two kids, he gotmarried. You know, he's just one.
But I said, we have manyothers. I just don't have time
to write them all up. Youknow, it's hard writing up case reports.
And I do the basic research onthe pre clinical systems. I show
it works. I mean, wehaven't covered on every different way, you

(01:13:01):
know, and yet people don't wantto know about it. Julian, tell
me what's wrong with this picture?You seem so amazingly positive though, I
mean, you've talked about all thesebarriers there are to these sort of ideas
being accepted, and yet you seemincredibly you know, you're you're laughing on
your check and you're talking about thiswill be the future, et such,
about how on earth. Is itgoing to be the future if there's such

(01:13:23):
resistance. No, I'm not tryingto bore cold water on this. I
just wonder because people want to live. That's the motive. People want to
live, and that's the motivation.And once they realize this and it spreads
like a grass fire, they're theconsumers. Those are the folks that are
going to go into the oncology clinicsand say I want metabolic therapy. And

(01:13:44):
if they say you can't, Ican't do that, well, I'm going
somewhere where I can get it.You know, all of a sudden it
will change. This is why ourtarget audience is predominantly cancer patients because I
can talk to my academic colleagues untilI'm blue in the face, and you
might as well be talking to aplug socket. They can't get away from
the paradigm. But the people withcan't. And that's another thing too.
I can't tell you how many physicianshave called me for their wives, of

(01:14:08):
their loved one or themselves wanting metabolictherapy. Yeah you know, yeah,
yeah. You can't keep a goodidea down forever, can you, especially
when it is desperately needed. Whenpeople are calling out for it. So,
yeah, that does make sense.Yeah, I mean it took how
long it took the Catholic Church torealize that the Earth was no longer the

(01:14:29):
center of the solace, That wasa paradise. The poor brutown of Bruto
stripped naked and burnt to death forsaying that there might be life on another
planet. I'm so glad that's nottrue anymore, because I've said many times
on this show, I think theirlife another planet there, Yeah, was
unacceptable. You can think like that. But that's amazing how and it's not

(01:14:53):
not the Catholic Church now, butit's amazing how that's kind of approach,
although not burning people at the stake, But nevertheless, there are modern equivalents
of that. Oh yes, absolutely, you know, absolutely, and we
just have to work through the resistance. But I think you know the target
audience here. I publish all mypapers open access. You know, I
don't have time to discuss the intricaciesof what I'm saying at the molecular and

(01:15:14):
biochemical level, because I think mostof the folks would be turned off from
that. But if they want thatdetail, all of our papers are published
open access. All I have todo is put my name into Google and
say Sea Freed Publications and you'll getthe details of the press, pulse,
glucos ketone index papers, the strategiesPablo Kelly's published there. Several other breast

(01:15:36):
cancer and lung cancer patients are publishedthere. So you can read the case
reports, see what those folks did, why they're doing so well, and
you can read those who really wantto get into the metabolic mud and the
details of the pathways that's there too. Oh he didn't tell us about how
to do this, and well,go read the papers. You get all
the information, and then if youstill have questions on a real depth level,

(01:15:59):
I'll be happy to address something ata deeper level if people want to
go that way. Excellent. WellI'm glad you didn't go into as much
detail as you could have done onthis show, because I'd have had trouble
catching up with it. It's verydifficult to follow all of it, of
course, but of course it's reallyinteresting to get this kind of surface view
which you have to get initially inorder to get the idea of it.
So I'm hugely grateful to you forcoming on to share this and your enthusiasm

(01:16:23):
and your your vision and your experienceof this. It really is fascinating.
And so you talk about how easyit is, in fact to get hold
of the information that you have published. Is there one particular repository for that
or is it just a case ofusing a search engine to find these materials?
Just my name and publication, right, Yeah, just go onto Google
Thomas NC Freed Publications and you'll getmost of what I've done. I make

(01:16:45):
it a point to publish open access, so it's not behind a journal a
wall publication wall where people have tohave a subscription, so they can get
it free, it doesn't cost anything, and then they can bring the paper
down to their oncologists and say Andwe're also working on a really comprehensive treatment
protocol with my associate doctor Thomas Adourier, who is an mdphd. And we're

(01:17:08):
putting together with a number of otherco authors, physicians and scientists, a
comprehensive treatment protocol for glioblastoma how tomanuals so to speak. So anybody with
a medical degree should be able toapply this to their patients, and then
with a few tweaks, it willbe applicable to almost all of the major
cancers. So once we have thatpublishment and we hope to put that on

(01:17:30):
open access as well, so thenany physician anywhere can The only problem is
is that the system prevents them fromdoing it. It's not part of the
standard of care. And right nowin the United States, physicians could lose
their license to practice if they wereto choose something that wasn't sanctioned by the
system. So essentially it's the systemitself that's preventing. And then they say,

(01:17:55):
you know there's no clinical trials,Well, who's going to run a
clinical trial when you have nobody thatknows how to do it? And who's
going to pay for a clinical trialutelybecause usually pharmaceutical companies pay for this.
There's millions of dollars, and becausethey've got to potentially profit from a drug
that might keep someone alive for threeextra weeks, you know, so let's
let's take a metabolic therapy keep yourlife for three or four extra years.

(01:18:17):
But you can't make any it's nota revenue generating process. Yeah. Indeed,
it's amazing how that story is croppedup in recent years so much.
It's tragic on a number of levels. Anyway, Yeah, again, Professor
say thank you ever so much forcoming on the show to discuss this,
and thank you also for all yourwork over the years in such great depth.

(01:18:40):
And it's very exciting to find thatyou're having great success with this,
and thanks for continuing to draw attentionon podcasts like this and speak to people
like me. As I said atthe beginning of the show, you know
I don't have that biological background,so thank you ever so much. And
just before we go, I willsay, as I always say, none
of this is personal medical advice.Everybody is different. This is all for
information purposes only. By all meanshare it with your your doctor, of

(01:19:00):
course, but please do first consultyour doctor before making any changes to your
diet, lifestyle or medication. Soonce again, Professor Safred, thank you
ever so much for coming on.It's been a delight to speak to you
and enjoyed it very much and I'msure people will find it very exciting and
interesting. Thank you, Thank youvery much, Julian, it was nice
to be here. Show notes forthis program can be found at the Mind

(01:19:21):
Renewed theMIND Renewed dot com podcast.Music by the brilliant Anthony Rajakoff attribution on
commercial sharer like four point zero International. You have been listening to me,
Julian Charles and my guest professor ThomasSeefried, and I very much look forward
to speaking to you again in thenear future.

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TMR 302 : Prof. Thomas N. Seyfried : Cancer as a Metabolic Disease

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