August 11, 2025 • 17 mins
Could the deadliest form of brain cancer have a metabolic Achilles’ heel? In this episode of The Health Pulse, we explore Dr. Thomas Seyfried’s groundbreaking theory that glioblastoma multiforme (GBM) is not just a genetic disease, but fundamentally a metabolic disorder—one that can be targeted by cutting off its preferred fuel sources.
Building on Otto Warburg’s historic observation that cancer cells rely heavily on fermentation even in the presence of oxygen, Seyfried’s work reveals GBM’s metabolic inflexibility: while healthy cells can adapt to burning different fuels, GBM cells with damaged mitochondria remain dependent on glucose and glutamine. This opens the door to the PRESS-pulse strategy—a therapeutic ketogenic diet combined with fasting, glutamine restriction, and hyperbaric oxygen therapy.
We discuss compelling case studies showing extended survival and improved quality of life, why these therapies remain underutilized, and how patient advocacy is driving change. If you’ve ever wondered how nutrition and metabolism could play a role in cancer care, this conversation will challenge everything you thought you knew.
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Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:01):
Welcome to the Health Pulse, your go-to source for
quick, actionable insights onhealth, wellness and diagnostics
.
Whether you're looking tooptimize your well-being or stay
informed about the latest inmedical testing, we've got you
covered.
Join us as we break down keyhealth topics in just minutes.
Let's dive in.
Speaker 2 (00:25):
Welcome to the Deep Dive where we cut through the
noise and get straight to theinsights you need.
Today we're plunging into oneof medicine's most formidable
challenges glioblastomamultiforme, or GBM.
This is arguably the deadliestbrain cancer out there and
despite aggressive standardtreatments, the median survival
time remains a grim 12 to 15months.
(00:46):
It's a truly heartbreakingreality.
Speaker 3 (00:48):
It is, and the sheer resistance of GBM is what makes
it so formidable.
It's not just fast growing,it's incredibly invasive these
almost microscopic,tentacle-like projections that
spread deep into the brain.
That makes complete surgicalremoval virtually impossible
without damaging vital healthytissue.
It also constantly adapts,finding ways to bypass
(01:09):
traditional therapies.
Speaker 2 (01:11):
That's the challenge.
But what if our fundamentalunderstanding of this disease
needs a radical rethink?
This deep dive is going toexplore a bold, scientifically
grounded idea.
That's flipping the script.
What if cancer, especially GBM,isn't primarily a genetic
disease, something driven byrogue genes, but rather a
metabolic disorder?
It's a massive shift inperspective.
Speaker 3 (01:30):
That's the core argument from Dr Thomas N
Seyfried, a professor of biologyat Boston College.
He's really at the forefront ofthis paradigm shift, suggesting
that the root cause of cancerlies not in mutated genes as the
primary driver, but indysfunctional cellular energy
production.
Speaker 2 (01:46):
And that's our mission today.
We're going to unpack DrSeyfried's revolutionary
approach, diving into itshistorical roots, how it
identifies cancer's uniquemetabolic weaknesses and the
specific strategies he proposesto literally starve these
aggressive tumors.
What if the key to fighting oneof the toughest cancers lies
not in its DNA but in its dailyfuel?
Ok, let's unpack this.
(02:07):
So, for those of us who mightnot be completely familiar, can
you help us paint a clearerpicture?
What exactly is glioblastomaand what makes it so incredibly
lethal?
Speaker 3 (02:16):
Sure.
Glioblastoma multiforme is themost aggressive and common
malignant brain tumor in adults.
It originates from glial cells,specifically a type called
astrocytes, which are thebrain's support cells.
Its lethality stems fromseveral key characteristics.
First, as we touched on, it'sfast-growing and incredibly
invasive.
Imagine trying to completelyclear a root system that's
(02:38):
already intertwined deep intothe soil without disturbing the
surrounding earth.
That's essentially what thosetentacle-like projections do.
They make surgical removalalmost impossible without
causing significant damage tohealthy brain tissue.
Speaker 2 (02:51):
Wow, that imagery really helps put it into
perspective.
And it's not just the invasion,is it?
I understand these tumors areincredibly heterogeneous.
Speaker 3 (02:59):
They are absolutely.
They contain a mix of celltypes and mutations, making them
highly adaptable and verydifficult to target with just a
single drug or therapy.
And then there's the brain'sown protective mechanism, the
blood-brain barrier.
While essential for keepingharmful substances out, it also,
unfortunately, prevents manychemotherapy agents from
effectively reaching the tumorcells, reducing their impact.
Speaker 2 (03:20):
Right.
So even when we try to fight itwith traditional methods like
chemotherapy, the very design ofour brain kind of works against
us.
What's the standard course ofaction right now when someone is
diagnosed with GBM?
Speaker 3 (03:33):
Well, the conventional approach typically
involves surgical resection, ifthat's even feasible, followed
by radiation therapy and thentemozolomide chemotherapy.
Yet even with this aggressivemultimodal treatment, the median
survival remains a sobering 12to 15 months, and the five-year
survival rate is less than 10%.
Yeah, it's grim.
Speaker 2 (03:53):
That's a truly grim prognosis.
And it's clear the problemisn't just its physical location
or the blood-brain barrier.
There's a deeper biologicalresistance at play here, right.
Speaker 3 (04:02):
Absolutely.
Gbm's resilience goes waybeyond its physical infiltration
.
It thrives in inflammatoryenvironments, in low oxygen or
hypoxic conditions, andespecially on high glucose
environments.
It also has this uncannyability to recruit its own blood
supply through a process calledangiogenesis, essentially
building its own lifeline, andit's adept at evading the body's
(04:22):
natural cell death mechanismsand even the immune system.
All these factors contribute toits formidable nature.
Speaker 2 (04:29):
So it's a master of survival, constantly building
its own infrastructure, escapingdetection, resisting being
killed off.
But you mentioned its relianceon the metabolic environment.
Does that point to a potentialweakness?
Speaker 3 (04:40):
It does.
That's the key insight.
Speaker 2 (04:42):
Its dependence on its metabolic environment is
actually a criticalvulnerability that Dr Seyfried
and others are activelyinvestigating.
Where it gets reallyinteresting Back in the 1920s,
(05:02):
Warburg made this incrediblediscovery Cancer cells generate
energy through fermentation,even when oxygen is readily
available.
This phenomenon became known asthe Warburg effect.
Speaker 3 (05:13):
It's a fascinating and counterintuitive discovery
that puzzled scientists fordecades.
To understand why, let'scompare.
Healthy cells have a superefficient power plant their
mitochondria.
They start with glucose, breakit down and then burn it cleanly
through oxidativephosphorylation in the
mitochondria to get a massiveenergy yield, A lot of APP.
It's like a highly efficient,clean burning engine.
Speaker 2 (05:34):
Right, very efficient .
But cancer cells, especiallyglioblastoma, are completely
different.
They seem to prefer a much lessefficient but incredibly fast
method.
Speaker 3 (05:43):
Exactly.
They rely heavily on what'scalled aerobic glycolysis.
This means they take that sugarand ferment it to lactate, and
they do this even when there'splenty of oxygen around.
It's a bit like a car that'sstuck in first gear, revving its
engine and burning fuelinefficiently, but moving
incredibly fast to support theirrapid growth and proliferation.
Speaker 2 (06:03):
And this difference, this inefficient energy
production, is the key tounderstanding GBM's
vulnerability.
Speaker 3 (06:08):
It is Glioblastoma.
Cells consume massive amountsof glucose, they thrive in those
low-oxygen environments we justmentioned and, crucially, their
mitochondria are often damagedor dysfunctional.
This impairs their ability toefficiently use alternative
fuels like fat or ketones forenergy.
The big idea, the corevulnerability, is precisely this
Take away glucose and youstarve the tumor.
Speaker 2 (06:32):
It makes so much sense when you put it like that.
It's a direct, almost brutalsimplicity to the approach.
Speaker 3 (06:36):
It is, and this is where Dr Seyfried's argument
truly expands beyond thetraditional genetic focus.
He posits that many of thegenetic mutations we see in
cancer cells are actuallysecondary to the primary issue,
this mitochondrial dysfunction.
From his perspective, cancer isfundamentally a metabolic
disease, and the Warburg effectisn't just a quirky behavior or
(06:57):
a defect.
It's both a symptom of thiscore metabolic problem and a
survival strategy for a cellthat has lost its normal energy
production capacity.
Speaker 2 (07:06):
So if a cell's mitochondria are broken, it's
forced to rely on this lessefficient but faster
fermentation process to survive,and it seems glioblastoma has
specific preferred fuels it'sdependent on.
Speaker 3 (07:17):
Yes, exactly.
Glioblastoma's heavy relianceon both glucose and glutamine
for its survival makes ituniquely vulnerable to therapies
designed to restrict thesespecific fuels.
This metabolic dependency isthe central pillar of Seyfried's
entire approach.
Speaker 2 (07:30):
That's truly fascinating.
So Dr Seyfried is essentiallyflipping the script on how we
understand cancer, proposingthat the problem begins with
damaged mitochondria anddisordered energy metabolism,
with genetic mutationsaccumulating as a downstream
effect.
He lays this out in hisinfluential book Cancer as a
Metabolic Disease.
It's a direct challenge to themainstream view.
Speaker 3 (07:52):
It is In his model.
The mitochondrial damage comesfirst, disrupting normal cell
signaling and energy production.
This forces the cell tocompensate by relying on
fermentation.
Only then do genetic mutationsaccumulate, not as the primary
drivers but as consequences ofthat initial metabolic breakdown
.
It's a profound reframe askingus to look deeper than just the
(08:14):
genetic blueprint.
Speaker 2 (08:15):
So cancer cells, according to Seyfried, are
metabolically inflexible.
They're kind of stuck on justtwo main fuels.
Speaker 3 (08:20):
That's right.
They thrive predominantly onglucose, which they process
through glycolysis into lactateand glutamine, which they can
also use for a quick energyboost, even with their damaged
mitochondria, usingsubstrate-level phosphorylation.
Speaker 2 (08:33):
And this metabolic inflexibility is the therapeutic
target.
The goal is to induce ametabolic crisis in these tumor
cells by cutting off both theseprimary fuels, and the beauty of
this approach in theory is thatit aims to lead to tumor cell
death apoptosis without harmingnormal, healthy cells.
Speaker 3 (08:50):
Precisely.
Our healthy cells aremetabolically flexible.
They can switch to using fatand ketones for energy, unlike
the cancer cells.
This is the differentialadvantage we exploit.
Speaker 2 (09:01):
OK, that brings us to his innovative PRESS pulse
strategy.
It sounds like a sophisticatedtwo-pronged attack designed to
exploit this difference.
Yeah, what does PRESS refer to?
Speaker 3 (09:11):
PRESS refers to applying chronic pressure on the
cancer cells.
This is primarily achievedthrough a therapeutic ketogenic
diet which creates a low-glucose, high-ketone environment in the
body.
It's a continuous metabolicsqueeze on the tumor.
Speaker 2 (09:24):
A constant pressure, and then there's the pulse.
I imagine that's a moretargeted blow.
Speaker 3 (09:27):
Exactly.
The pulse involves acuteinterventions designed to
deliver metabolic shocks to thecancer cells.
Think of things like strategicfasting, hyperbaric oxygen
therapy or even specificglutamine inhibitors.
Together, the PRESS and PULSEstrategies exploit the metabolic
inflexibility of cancer cells,pushing them towards programmed
(09:48):
cell death, while sparinghealthy cells that can readily
adapt to different fuel sources.
Speaker 2 (09:53):
Okay.
So if the idea is to starve thetumor, let's dive into the
specifics of how Dr Seyfriedproposes we do that.
First up is the therapeuticketogenic diet.
Most people might associateketo with weight loss, but this
sounds far more precise.
Speaker 3 (10:06):
It is quite different in its application and
strictness for a therapeuticcontext.
A ketogenic diet for cancer isvery high in fat, moderate in
protein and extremely low incarbohydrates.
The goal is to drasticallylower blood glucose while
simultaneously elevating ketonebodies like beta-hydroxybutyrate
or BHB, which our healthy cellscan happily use for fuel.
Speaker 2 (10:26):
But glioblastoma cells cannot.
That's the crucial differentialimpact.
Speaker 3 (10:30):
That's right.
Glioblastoma cells with theirdefective mitochondria simply
cannot efficiently use ketones.
Studies have shown thattherapeutic ketosis can slow
tumor growth, reduceinflammation and even sensitize
tumors to other treatments,making them more vulnerable to
attack.
Speaker 2 (10:46):
So glucose restriction is a big part of the
press, but you mentionedglutamine as the other major
fuel.
How do you restrict that?
It sounds a lot harder tocontrol than diet.
Speaker 3 (10:55):
You're right, it is.
Glutamine is synthesized andcirculates throughout the body,
making direct restriction morechallenging.
Glutamine is synthesized andcirculates throughout the body,
making direct restriction morechallenging.
However, protocols proposedinclude specific fasting
regimens to lower overallglutamine availability, and
investigational inhibitors likeDON, that's,
6-diazo-5-oxo-l-norelacine, toblock its metabolism.
Time-restricted eating andcaloric restriction are also
(11:16):
considered to lower systemicgrowth signals that cancer cells
might hijack.
The research strongly suggeststhat some combination of both
glucose and glutaminerestriction is necessary for
full suppression of glioblastoma.
Speaker 2 (11:28):
That makes sense.
It's not just about cutting offone supply line if the tumor
has another.
Okay.
And what about hyperbaricoxygen therapy, hbot?
That seems like an interestingaddition to the arsenal.
Speaker 3 (11:38):
It is.
Remember, tumor cells thrive inthose low-oxygen hypoxic
environments where they relyheavily on glycolysis.
Hbot works by significantlyincreasing oxygen saturation in
the blood and tissues.
This disrupts that preferredhypoxic environment for the
tumor and enhances oxidativestress in cancer cells,
especially when combined withketosis.
(11:59):
Early animal studies suggestthat HBOT synergizes powerfully
with ketogenic therapy to slowtumor progression, essentially
making the environment hostilefor the cancer.
Speaker 2 (12:08):
So it's not just about what you take away from
the tumor, but also creating anenvironment it simply can't
tolerate.
Are there other supportivemeasures or ways to track
progress for patientsundertaking this?
Speaker 3 (12:19):
Yes, absolutely.
To support the body'smitochondrial health during
these therapies, supplementslike CoQ10, magnesium, B
vitamins and L-carnitine areoften considered and, crucially,
progress is carefully monitoredby tracking the glucose ketone
index, or GKI, which gives ameasure of the patient's
metabolic status.
Other markers like CRP, lactate, insulin and
(12:41):
beta-hydroxybutyrate are alsotracked to ensure the patient is
in the desired metabolic state.
Speaker 2 (12:46):
So it's a finely tuned, monitored approach.
It sounds like a trulyintegrated protocol combining
diet, fasting, oxygen andtargeted supplements.
Speaker 3 (12:55):
It is.
Saferoot's protocol is acoherent strategy that combines
ketosis, glutamine restriction,oxygen therapy and fasting.
The aim is to metabolicallyweaken glioblastoma without the
severe toxicity often associatedwith traditional chemotherapy,
thereby offering a gentler, yetpotentially powerful alternative
or adjunct.
Speaker 2 (13:13):
This sounds incredibly promising, rooted in
fundamental biology.
So why isn't every oncologistrecommending this for GBM
patients right now?
What are the challenges and youknow, controversies preventing
metabolic therapy from beingmainstream?
Speaker 3 (13:24):
That's a vital question.
There are significant practicaland institutional hurdles.
One of the biggest is the lackof large-scale clinical trials.
While preclinical animal modelsand individual case reports
show real promise, robustrandomized controlled trials,
which are, you know, the goldstandard for mainstream medical
adoption, are still quitelimited for these metabolic
(13:45):
approaches.
Speaker 2 (13:46):
Right.
So without those big trialsit's tough to integrate with
standard care which relies ondecades of trial backing for
surgery, radiation andchemotherapy.
Speaker 3 (13:54):
Precisely.
Most oncologists prioritizeapproaches with extensive trial
backing.
There are also valid concernsabout potential nutrient
deficiencies with veryrestrictive diets, the fear of
delaying standard establishedtreatments and practical issues
like lack of insurancereimbursement or established
institutional protocols forthese metabolic approaches.
It's a complex landscape tonavigate.
Speaker 2 (14:17):
And even with metabolic restriction.
Gbm is known for its incrediblecomplexity and adaptability,
isn't it?
Speaker 3 (14:22):
It absolutely is.
Glialblastomas are highlyadaptable.
Even if you cut off theirprimary fuel sources, there's
always the concern they couldshift fuel sources or even
hijack surrounding healthysupport cells, like astrocytes,
to survive.
This means metabolic therapy isnot a silver bullet.
It's more accurately viewed asa potentially powerful adjunct
(14:42):
to standard care, not areplacement.
Speaker 2 (14:45):
Despite those limitations, there's growing
hope right.
We're seeing compellingclinical case reports and
emerging data that suggest thisisn't just theory.
Speaker 3 (14:52):
That's correct.
There are compelling casestudies of GBM patients who have
experienced extended survival,tumor shrinkage or a
significantly improved qualityof life using metabolic
approaches, often alongsidestandard treatments.
For instance, a 2010 case studypublished in Nutrition and
Metabolism reported stabledisease in a GBM patient who
(15:12):
used a calorie-restrictedketogenic diet.
This kind of real-world data iscrucial.
Speaker 2 (15:17):
And it sounds like the future is moving in this
direction, with new pilot trialsexploring these combinations.
Speaker 3 (15:22):
That's right.
New pilot trials are activelyexploring combinations of
ketogenic therapy, hyperbaricoxygen and even immunotherapy.
As interest grows amongpatients, more clinicians and
researchers are beginning toexplore these interventions,
especially for cases wherestandard options are limited.
Speaker 2 (15:40):
It's interesting how much of this demand seems to be
patient-led.
Speaker 3 (15:43):
It really is.
Many patients and caregiversare driving this demand through
online communities, integrativeoncologists and platforms like
the Metabolic Health Summit.
While it's still consideredexperimental by some, these
approaches often give patients asense of control over their
treatment.
Plus, many report reducedtreatment-related side effects
and often see improved overallmetabolic health and immune
(16:05):
support.
Speaker 2 (16:06):
So what's the outlook for metabolic therapy for
glioblastoma?
Where do we stand?
Speaker 3 (16:11):
Well, the bottom line is that while it's not yet
mainstream, it's definitely nolonger fringe With growing
scientific interest in patientadvocacy.
It's very much pushing towardsbecoming a vital part of
personalized integrative cancercare.
It's an exciting area to watch.
Speaker 2 (16:26):
So let's bring it all back to the central idea here.
The paradigm shift is fromfocusing solely on genetic
mutations to really targetingcancer's core survival
mechanisms, its fundamentaldependence on glucose and
glutamine and its starkinability to adapt to
ketone-based energy.
Speaker 3 (16:44):
Exactly, and the strategies to exploit that
vulnerability are multifacetedTherapeutic ketogenic diets,
glutamine inhibition, strategicfasting and calorie restriction,
and even hyperbaric oxygentherapy.
Speaker 2 (16:56):
It's powerful to think that such an aggressive
cancer could have such afoundational metabolic weakness.
This isn't about offering falsehope or a magic bullet.
It's about giving patientsanother tool, one rooted in
rigorous science and metaboliccommon sense, especially when
used alongside standard care.
So what does this all mean foryou listening?
Speaker 3 (17:15):
Well, it raises an important question for us to
consider.
If an aggressive cancer likeglioblastoma has such a
fundamental metabolicvulnerability that can be
exploited, what does thissuggest about the potential for
metabolic therapies in tacklingother complex, seemingly
intractable diseases?
Speaker 1 (17:37):
It definitely leaves you with something to mull over.
Thanks for tuning into theHealth Pulse.
If you found this episodehelpful, don't forget to
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For more health insights anddiagnostics, visit us online at
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Stay informed, stay healthy andwe'll catch you in the next
episode.
Welcome to the Health Pulse, your go-to source for
quick, actionable insights onhealth, wellness and diagnostics
.
Whether you're looking tooptimize your well-being or stay
informed about the latest inmedical testing, we've got you
covered.
Join us as we break down keyhealth topics in just minutes.
Let's dive in.
Speaker 2 (00:25):
Welcome to the Deep Dive where we cut through the
noise and get straight to theinsights you need.
Today we're plunging into oneof medicine's most formidable
challenges glioblastomamultiforme, or GBM.
This is arguably the deadliestbrain cancer out there and
despite aggressive standardtreatments, the median survival
time remains a grim 12 to 15months.
(00:46):
It's a truly heartbreakingreality.
Speaker 3 (00:48):
It is, and the sheer resistance of GBM is what makes
it so formidable.
It's not just fast growing,it's incredibly invasive these
almost microscopic,tentacle-like projections that
spread deep into the brain.
That makes complete surgicalremoval virtually impossible
without damaging vital healthytissue.
It also constantly adapts,finding ways to bypass
(01:09):
traditional therapies.
Speaker 2 (01:11):
That's the challenge.
But what if our fundamentalunderstanding of this disease
needs a radical rethink?
This deep dive is going toexplore a bold, scientifically
grounded idea.
That's flipping the script.
What if cancer, especially GBM,isn't primarily a genetic
disease, something driven byrogue genes, but rather a
metabolic disorder?
It's a massive shift inperspective.
Speaker 3 (01:30):
That's the core argument from Dr Thomas N
Seyfried, a professor of biologyat Boston College.
He's really at the forefront ofthis paradigm shift, suggesting
that the root cause of cancerlies not in mutated genes as the
primary driver, but indysfunctional cellular energy
production.
Speaker 2 (01:46):
And that's our mission today.
We're going to unpack DrSeyfried's revolutionary
approach, diving into itshistorical roots, how it
identifies cancer's uniquemetabolic weaknesses and the
specific strategies he proposesto literally starve these
aggressive tumors.
What if the key to fighting oneof the toughest cancers lies
not in its DNA but in its dailyfuel?
Ok, let's unpack this.
(02:07):
So, for those of us who mightnot be completely familiar, can
you help us paint a clearerpicture?
What exactly is glioblastomaand what makes it so incredibly
lethal?
Speaker 3 (02:16):
Sure.
Glioblastoma multiforme is themost aggressive and common
malignant brain tumor in adults.
It originates from glial cells,specifically a type called
astrocytes, which are thebrain's support cells.
Its lethality stems fromseveral key characteristics.
First, as we touched on, it'sfast-growing and incredibly
invasive.
Imagine trying to completelyclear a root system that's
(02:38):
already intertwined deep intothe soil without disturbing the
surrounding earth.
That's essentially what thosetentacle-like projections do.
They make surgical removalalmost impossible without
causing significant damage tohealthy brain tissue.
Speaker 2 (02:51):
Wow, that imagery really helps put it into
perspective.
And it's not just the invasion,is it?
I understand these tumors areincredibly heterogeneous.
Speaker 3 (02:59):
They are absolutely.
They contain a mix of celltypes and mutations, making them
highly adaptable and verydifficult to target with just a
single drug or therapy.
And then there's the brain'sown protective mechanism, the
blood-brain barrier.
While essential for keepingharmful substances out, it also,
unfortunately, prevents manychemotherapy agents from
effectively reaching the tumorcells, reducing their impact.
Speaker 2 (03:20):
Right.
So even when we try to fight itwith traditional methods like
chemotherapy, the very design ofour brain kind of works against
us.
What's the standard course ofaction right now when someone is
diagnosed with GBM?
Speaker 3 (03:33):
Well, the conventional approach typically
involves surgical resection, ifthat's even feasible, followed
by radiation therapy and thentemozolomide chemotherapy.
Yet even with this aggressivemultimodal treatment, the median
survival remains a sobering 12to 15 months, and the five-year
survival rate is less than 10%.
Yeah, it's grim.
Speaker 2 (03:53):
That's a truly grim prognosis.
And it's clear the problemisn't just its physical location
or the blood-brain barrier.
There's a deeper biologicalresistance at play here, right.
Speaker 3 (04:02):
Absolutely.
Gbm's resilience goes waybeyond its physical infiltration
.
It thrives in inflammatoryenvironments, in low oxygen or
hypoxic conditions, andespecially on high glucose
environments.
It also has this uncannyability to recruit its own blood
supply through a process calledangiogenesis, essentially
building its own lifeline, andit's adept at evading the body's
(04:22):
natural cell death mechanismsand even the immune system.
All these factors contribute toits formidable nature.
Speaker 2 (04:29):
So it's a master of survival, constantly building
its own infrastructure, escapingdetection, resisting being
killed off.
But you mentioned its relianceon the metabolic environment.
Does that point to a potentialweakness?
Speaker 3 (04:40):
It does.
That's the key insight.
Speaker 2 (04:42):
Its dependence on its metabolic environment is
actually a criticalvulnerability that Dr Seyfried
and others are activelyinvestigating.
Where it gets reallyinteresting Back in the 1920s,
(05:02):
Warburg made this incrediblediscovery Cancer cells generate
energy through fermentation,even when oxygen is readily
available.
This phenomenon became known asthe Warburg effect.
Speaker 3 (05:13):
It's a fascinating and counterintuitive discovery
that puzzled scientists fordecades.
To understand why, let'scompare.
Healthy cells have a superefficient power plant their
mitochondria.
They start with glucose, breakit down and then burn it cleanly
through oxidativephosphorylation in the
mitochondria to get a massiveenergy yield, A lot of APP.
It's like a highly efficient,clean burning engine.
Speaker 2 (05:34):
Right, very efficient .
But cancer cells, especiallyglioblastoma, are completely
different.
They seem to prefer a much lessefficient but incredibly fast
method.
Speaker 3 (05:43):
Exactly.
They rely heavily on what'scalled aerobic glycolysis.
This means they take that sugarand ferment it to lactate, and
they do this even when there'splenty of oxygen around.
It's a bit like a car that'sstuck in first gear, revving its
engine and burning fuelinefficiently, but moving
incredibly fast to support theirrapid growth and proliferation.
Speaker 2 (06:03):
And this difference, this inefficient energy
production, is the key tounderstanding GBM's
vulnerability.
Speaker 3 (06:08):
It is Glioblastoma.
Cells consume massive amountsof glucose, they thrive in those
low-oxygen environments we justmentioned and, crucially, their
mitochondria are often damagedor dysfunctional.
This impairs their ability toefficiently use alternative
fuels like fat or ketones forenergy.
The big idea, the corevulnerability, is precisely this
Take away glucose and youstarve the tumor.
Speaker 2 (06:32):
It makes so much sense when you put it like that.
It's a direct, almost brutalsimplicity to the approach.
Speaker 3 (06:36):
It is, and this is where Dr Seyfried's argument
truly expands beyond thetraditional genetic focus.
He posits that many of thegenetic mutations we see in
cancer cells are actuallysecondary to the primary issue,
this mitochondrial dysfunction.
From his perspective, cancer isfundamentally a metabolic
disease, and the Warburg effectisn't just a quirky behavior or
(06:57):
a defect.
It's both a symptom of thiscore metabolic problem and a
survival strategy for a cellthat has lost its normal energy
production capacity.
Speaker 2 (07:06):
So if a cell's mitochondria are broken, it's
forced to rely on this lessefficient but faster
fermentation process to survive,and it seems glioblastoma has
specific preferred fuels it'sdependent on.
Speaker 3 (07:17):
Yes, exactly.
Glioblastoma's heavy relianceon both glucose and glutamine
for its survival makes ituniquely vulnerable to therapies
designed to restrict thesespecific fuels.
This metabolic dependency isthe central pillar of Seyfried's
entire approach.
Speaker 2 (07:30):
That's truly fascinating.
So Dr Seyfried is essentiallyflipping the script on how we
understand cancer, proposingthat the problem begins with
damaged mitochondria anddisordered energy metabolism,
with genetic mutationsaccumulating as a downstream
effect.
He lays this out in hisinfluential book Cancer as a
Metabolic Disease.
It's a direct challenge to themainstream view.
Speaker 3 (07:52):
It is In his model.
The mitochondrial damage comesfirst, disrupting normal cell
signaling and energy production.
This forces the cell tocompensate by relying on
fermentation.
Only then do genetic mutationsaccumulate, not as the primary
drivers but as consequences ofthat initial metabolic breakdown
.
It's a profound reframe askingus to look deeper than just the
(08:14):
genetic blueprint.
Speaker 2 (08:15):
So cancer cells, according to Seyfried, are
metabolically inflexible.
They're kind of stuck on justtwo main fuels.
Speaker 3 (08:20):
That's right.
They thrive predominantly onglucose, which they process
through glycolysis into lactateand glutamine, which they can
also use for a quick energyboost, even with their damaged
mitochondria, usingsubstrate-level phosphorylation.
Speaker 2 (08:33):
And this metabolic inflexibility is the therapeutic
target.
The goal is to induce ametabolic crisis in these tumor
cells by cutting off both theseprimary fuels, and the beauty of
this approach in theory is thatit aims to lead to tumor cell
death apoptosis without harmingnormal, healthy cells.
Speaker 3 (08:50):
Precisely.
Our healthy cells aremetabolically flexible.
They can switch to using fatand ketones for energy, unlike
the cancer cells.
This is the differentialadvantage we exploit.
Speaker 2 (09:01):
OK, that brings us to his innovative PRESS pulse
strategy.
It sounds like a sophisticatedtwo-pronged attack designed to
exploit this difference.
Yeah, what does PRESS refer to?
Speaker 3 (09:11):
PRESS refers to applying chronic pressure on the
cancer cells.
This is primarily achievedthrough a therapeutic ketogenic
diet which creates a low-glucose, high-ketone environment in the
body.
It's a continuous metabolicsqueeze on the tumor.
Speaker 2 (09:24):
A constant pressure, and then there's the pulse.
I imagine that's a moretargeted blow.
Speaker 3 (09:27):
Exactly.
The pulse involves acuteinterventions designed to
deliver metabolic shocks to thecancer cells.
Think of things like strategicfasting, hyperbaric oxygen
therapy or even specificglutamine inhibitors.
Together, the PRESS and PULSEstrategies exploit the metabolic
inflexibility of cancer cells,pushing them towards programmed
(09:48):
cell death, while sparinghealthy cells that can readily
adapt to different fuel sources.
Speaker 2 (09:53):
Okay.
So if the idea is to starve thetumor, let's dive into the
specifics of how Dr Seyfriedproposes we do that.
First up is the therapeuticketogenic diet.
Most people might associateketo with weight loss, but this
sounds far more precise.
Speaker 3 (10:06):
It is quite different in its application and
strictness for a therapeuticcontext.
A ketogenic diet for cancer isvery high in fat, moderate in
protein and extremely low incarbohydrates.
The goal is to drasticallylower blood glucose while
simultaneously elevating ketonebodies like beta-hydroxybutyrate
or BHB, which our healthy cellscan happily use for fuel.
Speaker 2 (10:26):
But glioblastoma cells cannot.
That's the crucial differentialimpact.
Speaker 3 (10:30):
That's right.
Glioblastoma cells with theirdefective mitochondria simply
cannot efficiently use ketones.
Studies have shown thattherapeutic ketosis can slow
tumor growth, reduceinflammation and even sensitize
tumors to other treatments,making them more vulnerable to
attack.
Speaker 2 (10:46):
So glucose restriction is a big part of the
press, but you mentionedglutamine as the other major
fuel.
How do you restrict that?
It sounds a lot harder tocontrol than diet.
Speaker 3 (10:55):
You're right, it is.
Glutamine is synthesized andcirculates throughout the body,
making direct restriction morechallenging.
Glutamine is synthesized andcirculates throughout the body,
making direct restriction morechallenging.
However, protocols proposedinclude specific fasting
regimens to lower overallglutamine availability, and
investigational inhibitors likeDON, that's,
6-diazo-5-oxo-l-norelacine, toblock its metabolism.
Time-restricted eating andcaloric restriction are also
(11:16):
considered to lower systemicgrowth signals that cancer cells
might hijack.
The research strongly suggeststhat some combination of both
glucose and glutaminerestriction is necessary for
full suppression of glioblastoma.
Speaker 2 (11:28):
That makes sense.
It's not just about cutting offone supply line if the tumor
has another.
Okay.
And what about hyperbaricoxygen therapy, hbot?
That seems like an interestingaddition to the arsenal.
Speaker 3 (11:38):
It is.
Remember, tumor cells thrive inthose low-oxygen hypoxic
environments where they relyheavily on glycolysis.
Hbot works by significantlyincreasing oxygen saturation in
the blood and tissues.
This disrupts that preferredhypoxic environment for the
tumor and enhances oxidativestress in cancer cells,
especially when combined withketosis.
(11:59):
Early animal studies suggestthat HBOT synergizes powerfully
with ketogenic therapy to slowtumor progression, essentially
making the environment hostilefor the cancer.
Speaker 2 (12:08):
So it's not just about what you take away from
the tumor, but also creating anenvironment it simply can't
tolerate.
Are there other supportivemeasures or ways to track
progress for patientsundertaking this?
Speaker 3 (12:19):
Yes, absolutely.
To support the body'smitochondrial health during
these therapies, supplementslike CoQ10, magnesium, B
vitamins and L-carnitine areoften considered and, crucially,
progress is carefully monitoredby tracking the glucose ketone
index, or GKI, which gives ameasure of the patient's
metabolic status.
Other markers like CRP, lactate, insulin and
(12:41):
beta-hydroxybutyrate are alsotracked to ensure the patient is
in the desired metabolic state.
Speaker 2 (12:46):
So it's a finely tuned, monitored approach.
It sounds like a trulyintegrated protocol combining
diet, fasting, oxygen andtargeted supplements.
Speaker 3 (12:55):
It is.
Saferoot's protocol is acoherent strategy that combines
ketosis, glutamine restriction,oxygen therapy and fasting.
The aim is to metabolicallyweaken glioblastoma without the
severe toxicity often associatedwith traditional chemotherapy,
thereby offering a gentler, yetpotentially powerful alternative
or adjunct.
Speaker 2 (13:13):
This sounds incredibly promising, rooted in
fundamental biology.
So why isn't every oncologistrecommending this for GBM
patients right now?
What are the challenges and youknow, controversies preventing
metabolic therapy from beingmainstream?
Speaker 3 (13:24):
That's a vital question.
There are significant practicaland institutional hurdles.
One of the biggest is the lackof large-scale clinical trials.
While preclinical animal modelsand individual case reports
show real promise, robustrandomized controlled trials,
which are, you know, the goldstandard for mainstream medical
adoption, are still quitelimited for these metabolic
(13:45):
approaches.
Speaker 2 (13:46):
Right.
So without those big trialsit's tough to integrate with
standard care which relies ondecades of trial backing for
surgery, radiation andchemotherapy.
Speaker 3 (13:54):
Precisely.
Most oncologists prioritizeapproaches with extensive trial
backing.
There are also valid concernsabout potential nutrient
deficiencies with veryrestrictive diets, the fear of
delaying standard establishedtreatments and practical issues
like lack of insurancereimbursement or established
institutional protocols forthese metabolic approaches.
It's a complex landscape tonavigate.
Speaker 2 (14:17):
And even with metabolic restriction.
Gbm is known for its incrediblecomplexity and adaptability,
isn't it?
Speaker 3 (14:22):
It absolutely is.
Glialblastomas are highlyadaptable.
Even if you cut off theirprimary fuel sources, there's
always the concern they couldshift fuel sources or even
hijack surrounding healthysupport cells, like astrocytes,
to survive.
This means metabolic therapy isnot a silver bullet.
It's more accurately viewed asa potentially powerful adjunct
(14:42):
to standard care, not areplacement.
Speaker 2 (14:45):
Despite those limitations, there's growing
hope right.
We're seeing compellingclinical case reports and
emerging data that suggest thisisn't just theory.
Speaker 3 (14:52):
That's correct.
There are compelling casestudies of GBM patients who have
experienced extended survival,tumor shrinkage or a
significantly improved qualityof life using metabolic
approaches, often alongsidestandard treatments.
For instance, a 2010 case studypublished in Nutrition and
Metabolism reported stabledisease in a GBM patient who
(15:12):
used a calorie-restrictedketogenic diet.
This kind of real-world data iscrucial.
Speaker 2 (15:17):
And it sounds like the future is moving in this
direction, with new pilot trialsexploring these combinations.
Speaker 3 (15:22):
That's right.
New pilot trials are activelyexploring combinations of
ketogenic therapy, hyperbaricoxygen and even immunotherapy.
As interest grows amongpatients, more clinicians and
researchers are beginning toexplore these interventions,
especially for cases wherestandard options are limited.
Speaker 2 (15:40):
It's interesting how much of this demand seems to be
patient-led.
Speaker 3 (15:43):
It really is.
Many patients and caregiversare driving this demand through
online communities, integrativeoncologists and platforms like
the Metabolic Health Summit.
While it's still consideredexperimental by some, these
approaches often give patients asense of control over their
treatment.
Plus, many report reducedtreatment-related side effects
and often see improved overallmetabolic health and immune
(16:05):
support.
Speaker 2 (16:06):
So what's the outlook for metabolic therapy for
glioblastoma?
Where do we stand?
Speaker 3 (16:11):
Well, the bottom line is that while it's not yet
mainstream, it's definitely nolonger fringe With growing
scientific interest in patientadvocacy.
It's very much pushing towardsbecoming a vital part of
personalized integrative cancercare.
It's an exciting area to watch.
Speaker 2 (16:26):
So let's bring it all back to the central idea here.
The paradigm shift is fromfocusing solely on genetic
mutations to really targetingcancer's core survival
mechanisms, its fundamentaldependence on glucose and
glutamine and its starkinability to adapt to
ketone-based energy.
Speaker 3 (16:44):
Exactly, and the strategies to exploit that
vulnerability are multifacetedTherapeutic ketogenic diets,
glutamine inhibition, strategicfasting and calorie restriction,
and even hyperbaric oxygentherapy.
Speaker 2 (16:56):
It's powerful to think that such an aggressive
cancer could have such afoundational metabolic weakness.
This isn't about offering falsehope or a magic bullet.
It's about giving patientsanother tool, one rooted in
rigorous science and metaboliccommon sense, especially when
used alongside standard care.
So what does this all mean foryou listening?
Speaker 3 (17:15):
Well, it raises an important question for us to
consider.
If an aggressive cancer likeglioblastoma has such a
fundamental metabolicvulnerability that can be
exploited, what does thissuggest about the potential for
metabolic therapies in tacklingother complex, seemingly
intractable diseases?
Speaker 1 (17:37):
It definitely leaves you with something to mull over.
Thanks for tuning into theHealth Pulse.
If you found this episodehelpful, don't forget to
subscribe and share it withsomeone who might benefit.
For more health insights anddiagnostics, visit us online at
wwwquicklabmobilecom.
Stay informed, stay healthy andwe'll catch you in the next
episode.
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