September 19, 2025 • 17 mins
Glioblastoma multiforme (GBM) remains one of the deadliest brain cancers, with survival measured in months despite surgery, radiation, and chemotherapy. But what if the key isn’t just in attacking tumor cells directly, but in reshaping their fuel supply?
In this episode of The Health Pulse, we uncover the fascinating science showing how GBM cells depend almost exclusively on glucose and glutamine for survival. Unlike healthy brain tissue, these cancer cells struggle to adapt when forced to use ketone bodies as fuel—a weakness that can potentially be exploited.
We explore how ketogenic diets, fasting, caloric restriction, and metabolic-targeted compounds may tilt the terrain against cancer, making tumors more vulnerable to conventional therapies while protecting healthy tissue. With promising results in animal studies and encouraging signs in early human trials, this metabolic strategy represents a paradigm shift in cancer treatment.
While more research is needed, this episode offers hopeful insights into how altering the metabolic environment may open new therapeutic possibilities for GBM patients.
📞 Need lab work done from the comfort of home? QLM offers fast, reliable mobile phlebotomy services—no clinic visit required.
📅 Book your appointment or learn more at:
👉 Quick Lab Mobile
📧 Contact us: info@quicklabmobile.com
💬 Enjoyed the episode? Leave us a review and let us know what topics you'd like us to cover next! Your feedback helps us bring you the content that matters most.
Disclaimer: The information provided in this podcast is for informational purposes only and should not be considered medical advice. The content discussed is based on research, expert insights, and reputable sources, but it does not replace professional medical consultation, diagnosis, or treatment. We strive to present accurate and up-to-date information, medical research is constantly evolving. Listeners should always verify details with trusted health organizations, before making any health-related decisions. If you are experiencing a medical emergency, such as severe pain, difficulty breathing, or other urgent symptoms, call your local emergency services immediately. By listening to this podcast, you acknowledge that The Health Pulse and its creators are not responsible for any actions taken based on the content of this episode. Your health and well-being should always be guided by the advice of qualified medical professionals.
Mark as Played
Transcript
Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Nicolette (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.
Rachel (00:25):
Welcome to the Deep Dive .
We sift through the latestresearch, the newest insights,
really trying to bring you whattruly matters.
Mark (00:33):
And today we're facing a really tough one.
Rachel (00:35):
Yeah, we really are One of the most stubborn and frankly
devastating adversaries inmedicine, glioblastoma or GBM.
Mark (00:45):
It's a form of brain cancer, and the statistics are
just stark.
Rachel (00:53):
They really are.
Our sources state, despitedecades of research, the median
survival for glioblastomaremains just 12, 15 months and
fewer than 7% of patients livebeyond five years.
It's chilling.
Mark (01:02):
And even with the best standard treatments we have now,
you know, surgery, radiation,chemotherapy recurrence is
almost a given.
Rachel (01:09):
It is like hitting a brick wall sometimes.
But what if?
What if our approach has beenmissing something fundamental?
Mark (01:14):
You mean like a different angle.
Rachel (01:15):
Exactly what if, instead of just attacking the cancer
cells, we could actually changethe, the environment, the very
fuel that helps them grow?
Mark (01:24):
Now you're talking about the core idea behind metabolic
therapy.
Rachel (01:27):
That's the premise for this deep dive, isn't it?
Mark (01:29):
It is.
It's a genuinely innovativeperspective.
The idea is shifting the body'swhole energy landscape,
specifically targeting how theseglioblastoma cells use glucose
and glutamine.
Rachel (01:42):
So it's like starving the enemy.
Mark (01:45):
Kind of yeah, but also protecting your own forces.
The goal is making those cancercells really vulnerable while
actually helping the healthybrain tissue around them.
It's like reengineering thebattlefield itself.
Rachel (01:58):
A real paradigm shift, because for so long it's been
seek and destroy direct attack.
Mark (02:03):
Right.
This asks can we cut off thesupply lines without causing
collateral damage to the healthycells?
Rachel (02:09):
That's the crucial insight.
Okay, so let's unpack thisproperly.
In this deep dive, we're goingto explore what makes
glioblastoma so, so difficult.
Mark (02:16):
Why it's remained such a challenge.
Rachel (02:18):
Then we'll get into the really fascinating stuff these
metabolic vulnerabilities thatcancer cells, especially GBMs,
seem to have, their potentialweaknesses, exactly.
We'll look at the promisingtherapeutic strategies coming
out of this thinking and,importantly, we'll look at what
the current research actuallytells us.
Where are we really?
Mark (02:33):
Setting the stage properly .
Rachel (02:34):
Okay, before we jump into those newer strategies,
let's make sure we understandthe enemy.
What is glioblastomafundamentally, and why is it
such a well, such a formidableopponent?
Mark (02:45):
So glioblastoma is classified by the World Health
Organization as a grade fourastrocytoma.
That basically means it's themost malignant, the most
aggressive type of tumor thatcomes from astrocytes, those
star-shaped cells in the brain.
Rachel (02:59):
Grade four sounds serious.
Mark (03:00):
It is.
And just for scale, it accountsfor almost 50 percent of all
malignant primary brain tumorsin adults.
About 13,000 new cases everyyear just in the US.
Rachel (03:11):
Wow, so it's not rare, unfortunately.
Mark (03:13):
No, sadly not.
It's common and devastating.
Now, what makes it soaggressive, so resistant?
It's a combination of things.
Rachel (03:19):
OK.
Mark (03:20):
First it's growth.
It's rapid, but it alsoinfiltrates.
It doesn't just push healthytissue aside, it weaves itself
right into the surrounding brainlike roots in soil.
Rachel (03:29):
Which must make surgery incredibly difficult.
Mark (03:32):
Exactly Complete surgical removal.
It's practically impossible.
You always leave microscopiccells behind, even with the best
surgeons.
Rachel (03:38):
The seeds for recurrence .
Mark (03:39):
Precisely.
Second, it's geneticallydiverse.
We call it heterogeneity.
You see all sorts of mutationsin genes like EGFR, ptn.
Rachel (03:48):
IDH, and that makes it harder to target.
Mark (03:51):
Much harder.
It helps the tumor adapt resisttreatments.
It's like trying to hit amoving target that keeps
changing shape.
Rachel (03:57):
Okay, rapid infiltration genetic diversity.
What else, what else?
Mark (04:00):
And third, angiogenesis.
These tumors are masters atcreating new blood vessels.
They build their own supplylines to get the nutrients they
need for that crazy fast growth.
Rachel (04:10):
So invasive growth, adaptability and their own
dedicated fuel lines it soundslike a perfect storm.
Mark (04:16):
It really is.
And you see why the standard ofcare surgery, then radiation,
then the chemotherapy drugtemozolomide while it does
extend survival, it's just notcurative.
Rachel (04:25):
That 15-month median survival figure really hits home
.
Mark (04:28):
It does.
Recurrence is the norm,unfortunately, and this
aggressive biology, plus thefact that the brain itself has
very limited ability to heal orregenerate it, just highlights
this desperate, urgent need forsomething new.
Rachel (04:41):
Something beyond the conventional, which brings us
back to the metabolism angle.
Mark (04:45):
Right.
If we want to outsmart GBM, weneed to, and how it fuels itself
is well.
It's fundamentally differentfrom our healthy brain cells.
Rachel (04:54):
And maybe that difference, that apparent
strength is actually itsgreatest weakness.
Mark (04:59):
That's the really exciting part.
You know, almost a century ago,Otto Warburg noticed something
peculiar.
It's now called the Warburgeffect.
Rachel (05:05):
Okay, what did he find?
Mark (05:07):
He saw that cancer cells prefer something called aerobic
glycolysis.
Basically, they break downglucose into lactate even when
there's plenty of oxygen around.
Rachel (05:15):
Which is weird, right, because normal cells use oxygen
for much more efficient energyproduction.
Mark (05:20):
Exactly.
It's less efficient, but it'sfast and, crucially, it provides
the building blocks these cellsneed for rapid growth and
division.
Think of it like a quick anddirty production line speed over
efficiency.
Rachel (05:33):
Got it, and GBM cells are particularly reliant on this
.
Mark (05:38):
Especially reliant, yes, on two main fuels First, glucose
metabolism that gives themimmediate energy, ATP, and also
those biosynthetic precursorsfor building new cell parts.
Rachel (05:49):
Okay, glucose is fuel number one.
What's number two?
Mark (05:52):
Glutamine metabolism.
This is really important forfueling the TCA cycle that's the
cell's main power generator,and also for making nucleotides
the building blocks for DNA andRNA.
They need a lot of that fordividing so fast.
Rachel (06:05):
So they're addicted to glucose and glutamine.
Mark (06:08):
Pretty much.
But here's the criticaldifference Unlike our normal
brain cells, our neurons andgluol cells, UBM cells are often
less able to use ketone bodiesfor energy.
Rachel (06:19):
Ketone bodies like beta-hydroxybutyrate.
Mark (06:22):
Exactly Beta-hydroxybutyrate and
acetoacetate.
Healthy brain cells are quiteflexible.
They can easily switch to usingketones if glucose is scarce.
But GBM cells often they'remetabolically inflexible, stuck
on glucose and glutamine.
Rachel (06:35):
Okay.
So wait If GBM cells are thesesort of metabolic specialists
hooked on glucose and glutamine,while our healthy brain cells
are adaptable generalists.
Mark (06:44):
You see it, don't you?
Rachel (06:45):
Does that inflexibility create a real therapeutic window
, a way to target themspecifically?
Mark (06:51):
That's the core insight.
Rachel (06:52):
Yeah.
Mark (06:52):
It potentially creates a profound therapeutic window.
It's not necessarily simple toexecute, but the principle is
quite elegant.
Rachel (06:59):
How does it work?
Mark (06:59):
then, by strategically lowering the availability of
glucose and glutamine in thebody, while at the same time
increasing the levels ofcirculating ketones.
Rachel (07:08):
You stress the tumor cells.
Mark (07:10):
Exactly.
You put metabolic stress on thetumor cells that can't easily
adapt to ketones as fuel.
Meanwhile your normal, healthybrain cells, they adapt readily,
they switch over the ketonesand function just fine.
Rachel (07:23):
So you're selectively starving the cancer while
feeding the brain.
Mark (07:27):
That's the goal, this targeting of energy sources,
this re-engineering of themetabolic battlefield.
That's the foundation ofmetabolic therapy.
Rachel (07:35):
It's a fascinating concept.
So, knowing we might have thismetabolic Achilles heel to aim
for, what's the actual toolkitlook like?
How do we practically exploitthese vulnerabilities?
Mark (07:46):
Well, there are several strategies being actively
investigated.
The first, and probably thebest known, is the ketogenic
diet.
Rachel (07:53):
Right High fat, very low carb.
Mark (07:54):
Precisely.
It's rigorously designed tolower blood glucose and force
the body to produce and useketones for energy.
The rationale comes straightfrom those preclinical models.
Rachel (08:04):
Where the GBM cells couldn't use the ketones
effectively.
Mark (08:07):
Exactly While the normal neurons and glial cells adapted
just fine, potentiallypreserving healthy brain
function even while the tumor isstressed.
Rachel (08:16):
OK, keto diet is one tool.
What else?
Mark (08:18):
Then you have approaches like intermittent fasting and
caloric restriction, bothnaturally lower glucose and
insulin levels.
Rachel (08:25):
Creating a less friendly environment for tumor growth.
Mark (08:28):
Yes, less fuel and lower levels of growth promoting
signals like insulin Fastingmight also boost something
called autophagy.
Rachel (08:36):
Autophagy.
That's like the cell's internalcleanup crew right Recycling
old parts.
Mark (08:40):
Sort of yeah, and for a cancer cell already struggling
for resources, being forced intoautophagy could push it over
the edge, deplete its reserves.
Rachel (08:48):
Interesting.
So diet, fasting, any otherapproaches?
Mark (08:51):
There's also the use of exogenous ketones and
supplements.
These are things like ketoneesters or salts that you can
take to directly raise bloodketone levels.
Rachel (08:59):
So maybe getting some benefits without the extreme
dietary restriction.
Mark (09:03):
Potentially yes.
The research is still ongoing.
And then there are othercompounds being studied, like
dichloracetate, dca andmetformin, the diabetes drug.
Rachel (09:12):
What do they do?
Mark (09:13):
They seem to be able to shift cell metabolism away from
that fast glycolysis that GBMloves, potentially making them
less efficient at producingenergy.
Okay, quite a few differentangles there, but and this is
really crucial none of thesemetabolic strategies are
intended to replace standardtreatments.
Rachel (09:30):
Right, not.
Instead of surgery or radiation?
Absolutely not.
Mark (09:32):
They're designed for combination with standard
treatments.
Right, not instead of surgeryor radiation.
Absolutely not.
They're designed forcombination with standard
therapy.
The idea is synergy.
Rachel (09:38):
Making the standard treatments work better.
Mark (09:40):
Potentially, yes, yeah.
The hope is they mightsensitize glioblastoma cells to
oxidative stress and DNA damage,making them more vulnerable to
radiation and chemo, whilesimultaneously protecting normal
brain tissue.
Rachel (09:53):
So it's not just adding a new weapon.
It's like Making your existingartillery more precise and
powerful by weakening theenemy's defenses.
Mark (10:01):
That's a great way to put it Enhancing the current arsenal
, potentially improving outcomes.
It's a really smart strategy.
Rachel (10:06):
Okay, it sounds incredibly promising in theory,
smart, elegant even.
But you know, theory is onething.
What does the actual researchsay?
Where are we with the evidencefor metabolic therapy and GBM?
Where are we with the evidencefor metabolic therapy?
Mark (10:19):
and GBM.
That's the critical questionalways and there is strong
support from the preclinicalside, from the lab work, the
animal models.
Rachel (10:27):
What did?
Mark (10:28):
those studies show.
In numerous animal models,ketogenic diets have
consistently been shown toreduce tumor growth, enhance
survival times and actuallyimprove the effectiveness of
radiation and chemotherapy.
There's some really solidfoundational work there.
Rachel (10:42):
Okay, promising in animals, what about in humans?
Mark (10:45):
Well, the early human studies are definitely more
limited, but I'd say they areencouraging.
We have things like casereports and pilot trials popping
up.
Rachel (10:52):
Individual stories or small groups.
Mark (10:54):
Exactly Documenting sometimes surprisingly prolonged
survival in certain patientswho managed to stick to really
strict ketogenic regimensalongside their standard care.
Rachel (11:05):
Adherence must be tough.
Mark (11:06):
Incredibly tough.
One phase a clinical trialspecifically looked at
feasibility and safety of theketogenic diet in GBM patients.
It showed it could be donesafely, but it also highlighted
that adherence was challenging.
That's a major hurdle.
Rachel (11:20):
Understandable.
Are there bigger trialshappening now?
Mark (11:22):
Yes, safely, but it also highlighted that adherence was
challenging.
That's a major hurdle,understandable.
Are there bigger trialshappening now?
Yes, critically, there areongoing clinical trials.
These are actively testingwhether adding ketogenic diets
or caloric restrictionstrategies to standard treatment
temozolomide and radiation canactually improve outcomes in a
larger group of patients.
Rachel (11:39):
So we're waiting on those results, which brings up,
you know, the limitations.
It sounds exciting, but whatare the caveats we need to keep
in mind right now?
Mark (11:47):
Absolutely crucial to be realistic, the limitations are
significant at this stage.
First, as we mentioned, moststudies so far have small sample
sizes.
We just don't have those largescale randomized controlled
trials completed yet.
Rachel (12:00):
The gold standard for evidence.
Mark (12:01):
Right.
Second, that issue of dietaryadherence is a huge barrier.
Rachel (12:05):
Yeah.
Mark (12:06):
Especially for patients who are already very thick
dealing with treatment sideeffects.
It's a massive commitment.
Rachel (12:10):
Yeah, it's not just a lifestyle choice at that point.
Mark (12:13):
Not at all.
And finally, it really remainsunclear which patients might
benefit the most.
Is it everyone, specificgenetic subtypes?
We don't know yet.
And we also don't know for sureif long-term metabolic therapy
impacts survival independentlyof standard care or if its main
power is purely synergistic.
Rachel (12:32):
Lots of unanswered questions still.
Mark (12:34):
Definitely, these are the key questions the current
research is trying to tacklequestions the current research
is trying to tackle.
Rachel (12:41):
So, summing that section up promising preclinical data,
encouraging but limited humandata.
Significant challenges likeadherence and the need for
bigger trials, but still viewedas a promising adjunctive
strategy.
Mark (12:51):
I think that's fair.
It absolutely warrants moreinvestigation, more research.
The field is moving forward,but cautiously, aware of the
hurdles.
Rachel (12:59):
Okay, let's say someone was going down this path working
with their medical team.
It sounds like it requires alot of careful management.
You mentioned adherencechallenges, but what about
monitoring?
It can't be a set it and forgetit thing, right?
Mark (13:09):
Oh, absolutely not.
It's a highly dynamic andpersonalized approach.
Implementing metabolic therapysafely and effectively for
glioblastoma demands reallycareful ongoing monitoring, and
lab tests are key here.
Glioblastoma demands reallycareful ongoing monitoring.
Rachel (13:20):
And lab tests are key here.
Mark (13:22):
Laboratory testing plays a central role.
Definitely.
It guides the therapy, allowsthe clinical team to make
adjustments, ensure safety.
Rachel (13:30):
What kinds of things are being tracked?
Mark (13:33):
Well, first and foremost, glucose and ketones.
You need regular monitoring,usually blood tests for glucose
and beta-hydroxybutyrate, toconfirm the patient is actually
in the target state ofnutritional ketosis and staying
there.
Rachel (13:43):
Makes sense Checking the fuel mix.
Mark (13:44):
Exactly.
Then you look at markers likeinsulin and HbA1c.
These give you insights intolonger term glucose control and
insulin sensitivity.
Is this strategy having asustained impact?
Rachel (13:54):
Okay, what about potential side effects,
especially with high fat diets?
Mark (13:58):
Good point.
A comprehensive lipid profileis crucial, Checking cholesterol
, triglycerides, LDL, maybe evenApoB.
You need to monitorcardiovascular risk.
Make sure the diet isn'tcausing other problems.
Rachel (14:09):
Right, anything else.
Mark (14:11):
We'd also often look at inflammatory markers like
high-sensitivity C-reactiveprotein, hscrp or IL-6.
Inflammation plays a role intumor biology, so tracking that
can be informative.
Rachel (14:24):
And nutrients if the diet is restrictive.
Mark (14:26):
Absolutely critical.
Ensuring adequate nutrientstatus is paramount.
You might test for things likevitamin D, magnesium, selenium,
other micronutrients, just tomake sure the restrictive diet
isn't leading to deficiencies.
Rachel (14:38):
Wow.
So it's a constant feedbackloop, monitoring, adjusting.
Mark (14:42):
It really is.
It's this ongoing adjustmentbased on the lab data and how
the patient is doing.
It's vital for both safety andmaximizing the potential
effectiveness.
Rachel (14:51):
It really underscores that this is a complex, highly
managed therapy, not a simpledietary switch, far from set it
and forget it.
Mark (14:58):
Precisely.
It requires a dedicated patientand a knowledgeable clinical
team working closely together.
Rachel (15:04):
Okay, so let's try and bring this all home for you
listening.
Glioblastoma, it remains thisincredibly tough, devastating
cancer.
Standard treatments are vital,absolutely, but recurrence is
still far too common.
Mark (15:16):
A heartbreaking reality for many.
Rachel (15:18):
But this deep dive into metabolic therapy offers well,
maybe, a glimmer of real hope.
Not as a replacement forstandard care, let's be clear on
that.
Mark (15:28):
No, as a sophisticated complementary approach.
Rachel (15:30):
Right One that could potentially change the game by
targeting how the cancer fuelsitself.
Mark (15:36):
Exactly by focusing on those fundamental metabolic
vulnerabilities the reliance onglucose and glutamine, the
inability to use ketoneseffectively, strategies like
ketogenic diets maybe fasting.
Rachel (15:53):
all carefully supported by that detailed lab monitoring.
They aim to create anenvironment where the cancer
struggles right yeah, whilehealthy brain cells are
supported, even strengthened.
Mark (15:59):
It's about trying to outsmart the tumor on a
completely different front.
It's energy supply.
Rachel (16:03):
And look, we absolutely need more research.
Those large scale randomizedtrials are crucial and we're
eagerly waiting for thoseresults.
Mark (16:10):
We are, the limitations are real.
Rachel (16:12):
But the early findings, the preclinical work, the pilot
studies, they're undeniablyintriguing.
They represent a reallysignificant shift in how we
think about treating cancer.
Mark (16:22):
Moving beyond just directly killing cells to
influencing their survivalmechanisms, their environment.
Rachel (16:28):
It's a fundamental change and it makes you wonder,
if we consider just how deeplyour metabolic health influences
literally every cell, everydisease process in our bodies.
What other doors could thisopen?
Mark (16:41):
Right Understanding and maybe leveraging these
fundamental metabolic processes.
What could that mean for healthcare in the future?
Rachel (16:47):
Way beyond just glioblastoma.
It's a really provocativethought to leave you with
something worth mulling over andperhaps a future worth working
towards.
Nicolette (17:00):
Thanks for tuning into the Health 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.
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.
Rachel (00:25):
Welcome to the Deep Dive .
We sift through the latestresearch, the newest insights,
really trying to bring you whattruly matters.
Mark (00:33):
And today we're facing a really tough one.
Rachel (00:35):
Yeah, we really are One of the most stubborn and frankly
devastating adversaries inmedicine, glioblastoma or GBM.
Mark (00:45):
It's a form of brain cancer, and the statistics are
just stark.
Rachel (00:53):
They really are.
Our sources state, despitedecades of research, the median
survival for glioblastomaremains just 12, 15 months and
fewer than 7% of patients livebeyond five years.
It's chilling.
Mark (01:02):
And even with the best standard treatments we have now,
you know, surgery, radiation,chemotherapy recurrence is
almost a given.
Rachel (01:09):
It is like hitting a brick wall sometimes.
But what if?
What if our approach has beenmissing something fundamental?
Mark (01:14):
You mean like a different angle.
Rachel (01:15):
Exactly what if, instead of just attacking the cancer
cells, we could actually changethe, the environment, the very
fuel that helps them grow?
Mark (01:24):
Now you're talking about the core idea behind metabolic
therapy.
Rachel (01:27):
That's the premise for this deep dive, isn't it?
Mark (01:29):
It is.
It's a genuinely innovativeperspective.
The idea is shifting the body'swhole energy landscape,
specifically targeting how theseglioblastoma cells use glucose
and glutamine.
Rachel (01:42):
So it's like starving the enemy.
Mark (01:45):
Kind of yeah, but also protecting your own forces.
The goal is making those cancercells really vulnerable while
actually helping the healthybrain tissue around them.
It's like reengineering thebattlefield itself.
Rachel (01:58):
A real paradigm shift, because for so long it's been
seek and destroy direct attack.
Mark (02:03):
Right.
This asks can we cut off thesupply lines without causing
collateral damage to the healthycells?
Rachel (02:09):
That's the crucial insight.
Okay, so let's unpack thisproperly.
In this deep dive, we're goingto explore what makes
glioblastoma so, so difficult.
Mark (02:16):
Why it's remained such a challenge.
Rachel (02:18):
Then we'll get into the really fascinating stuff these
metabolic vulnerabilities thatcancer cells, especially GBMs,
seem to have, their potentialweaknesses, exactly.
We'll look at the promisingtherapeutic strategies coming
out of this thinking and,importantly, we'll look at what
the current research actuallytells us.
Where are we really?
Mark (02:33):
Setting the stage properly .
Rachel (02:34):
Okay, before we jump into those newer strategies,
let's make sure we understandthe enemy.
What is glioblastomafundamentally, and why is it
such a well, such a formidableopponent?
Mark (02:45):
So glioblastoma is classified by the World Health
Organization as a grade fourastrocytoma.
That basically means it's themost malignant, the most
aggressive type of tumor thatcomes from astrocytes, those
star-shaped cells in the brain.
Rachel (02:59):
Grade four sounds serious.
Mark (03:00):
It is.
And just for scale, it accountsfor almost 50 percent of all
malignant primary brain tumorsin adults.
About 13,000 new cases everyyear just in the US.
Rachel (03:11):
Wow, so it's not rare, unfortunately.
Mark (03:13):
No, sadly not.
It's common and devastating.
Now, what makes it soaggressive, so resistant?
It's a combination of things.
Rachel (03:19):
OK.
Mark (03:20):
First it's growth.
It's rapid, but it alsoinfiltrates.
It doesn't just push healthytissue aside, it weaves itself
right into the surrounding brainlike roots in soil.
Rachel (03:29):
Which must make surgery incredibly difficult.
Mark (03:32):
Exactly Complete surgical removal.
It's practically impossible.
You always leave microscopiccells behind, even with the best
surgeons.
Rachel (03:38):
The seeds for recurrence .
Mark (03:39):
Precisely.
Second, it's geneticallydiverse.
We call it heterogeneity.
You see all sorts of mutationsin genes like EGFR, ptn.
Rachel (03:48):
IDH, and that makes it harder to target.
Mark (03:51):
Much harder.
It helps the tumor adapt resisttreatments.
It's like trying to hit amoving target that keeps
changing shape.
Rachel (03:57):
Okay, rapid infiltration genetic diversity.
What else, what else?
Mark (04:00):
And third, angiogenesis.
These tumors are masters atcreating new blood vessels.
They build their own supplylines to get the nutrients they
need for that crazy fast growth.
Rachel (04:10):
So invasive growth, adaptability and their own
dedicated fuel lines it soundslike a perfect storm.
Mark (04:16):
It really is.
And you see why the standard ofcare surgery, then radiation,
then the chemotherapy drugtemozolomide while it does
extend survival, it's just notcurative.
Rachel (04:25):
That 15-month median survival figure really hits home
.
Mark (04:28):
It does.
Recurrence is the norm,unfortunately, and this
aggressive biology, plus thefact that the brain itself has
very limited ability to heal orregenerate it, just highlights
this desperate, urgent need forsomething new.
Rachel (04:41):
Something beyond the conventional, which brings us
back to the metabolism angle.
Mark (04:45):
Right.
If we want to outsmart GBM, weneed to, and how it fuels itself
is well.
It's fundamentally differentfrom our healthy brain cells.
Rachel (04:54):
And maybe that difference, that apparent
strength is actually itsgreatest weakness.
Mark (04:59):
That's the really exciting part.
You know, almost a century ago,Otto Warburg noticed something
peculiar.
It's now called the Warburgeffect.
Rachel (05:05):
Okay, what did he find?
Mark (05:07):
He saw that cancer cells prefer something called aerobic
glycolysis.
Basically, they break downglucose into lactate even when
there's plenty of oxygen around.
Rachel (05:15):
Which is weird, right, because normal cells use oxygen
for much more efficient energyproduction.
Mark (05:20):
Exactly.
It's less efficient, but it'sfast and, crucially, it provides
the building blocks these cellsneed for rapid growth and
division.
Think of it like a quick anddirty production line speed over
efficiency.
Rachel (05:33):
Got it, and GBM cells are particularly reliant on this
.
Mark (05:38):
Especially reliant, yes, on two main fuels First, glucose
metabolism that gives themimmediate energy, ATP, and also
those biosynthetic precursorsfor building new cell parts.
Rachel (05:49):
Okay, glucose is fuel number one.
What's number two?
Mark (05:52):
Glutamine metabolism.
This is really important forfueling the TCA cycle that's the
cell's main power generator,and also for making nucleotides
the building blocks for DNA andRNA.
They need a lot of that fordividing so fast.
Rachel (06:05):
So they're addicted to glucose and glutamine.
Mark (06:08):
Pretty much.
But here's the criticaldifference Unlike our normal
brain cells, our neurons andgluol cells, UBM cells are often
less able to use ketone bodiesfor energy.
Rachel (06:19):
Ketone bodies like beta-hydroxybutyrate.
Mark (06:22):
Exactly Beta-hydroxybutyrate and
acetoacetate.
Healthy brain cells are quiteflexible.
They can easily switch to usingketones if glucose is scarce.
But GBM cells often they'remetabolically inflexible, stuck
on glucose and glutamine.
Rachel (06:35):
Okay.
So wait If GBM cells are thesesort of metabolic specialists
hooked on glucose and glutamine,while our healthy brain cells
are adaptable generalists.
Mark (06:44):
You see it, don't you?
Rachel (06:45):
Does that inflexibility create a real therapeutic window
, a way to target themspecifically?
Mark (06:51):
That's the core insight.
Rachel (06:52):
Yeah.
Mark (06:52):
It potentially creates a profound therapeutic window.
It's not necessarily simple toexecute, but the principle is
quite elegant.
Rachel (06:59):
How does it work?
Mark (06:59):
then, by strategically lowering the availability of
glucose and glutamine in thebody, while at the same time
increasing the levels ofcirculating ketones.
Rachel (07:08):
You stress the tumor cells.
Mark (07:10):
Exactly.
You put metabolic stress on thetumor cells that can't easily
adapt to ketones as fuel.
Meanwhile your normal, healthybrain cells, they adapt readily,
they switch over the ketonesand function just fine.
Rachel (07:23):
So you're selectively starving the cancer while
feeding the brain.
Mark (07:27):
That's the goal, this targeting of energy sources,
this re-engineering of themetabolic battlefield.
That's the foundation ofmetabolic therapy.
Rachel (07:35):
It's a fascinating concept.
So, knowing we might have thismetabolic Achilles heel to aim
for, what's the actual toolkitlook like?
How do we practically exploitthese vulnerabilities?
Mark (07:46):
Well, there are several strategies being actively
investigated.
The first, and probably thebest known, is the ketogenic
diet.
Rachel (07:53):
Right High fat, very low carb.
Mark (07:54):
Precisely.
It's rigorously designed tolower blood glucose and force
the body to produce and useketones for energy.
The rationale comes straightfrom those preclinical models.
Rachel (08:04):
Where the GBM cells couldn't use the ketones
effectively.
Mark (08:07):
Exactly While the normal neurons and glial cells adapted
just fine, potentiallypreserving healthy brain
function even while the tumor isstressed.
Rachel (08:16):
OK, keto diet is one tool.
What else?
Mark (08:18):
Then you have approaches like intermittent fasting and
caloric restriction, bothnaturally lower glucose and
insulin levels.
Rachel (08:25):
Creating a less friendly environment for tumor growth.
Mark (08:28):
Yes, less fuel and lower levels of growth promoting
signals like insulin Fastingmight also boost something
called autophagy.
Rachel (08:36):
Autophagy.
That's like the cell's internalcleanup crew right Recycling
old parts.
Mark (08:40):
Sort of yeah, and for a cancer cell already struggling
for resources, being forced intoautophagy could push it over
the edge, deplete its reserves.
Rachel (08:48):
Interesting.
So diet, fasting, any otherapproaches?
Mark (08:51):
There's also the use of exogenous ketones and
supplements.
These are things like ketoneesters or salts that you can
take to directly raise bloodketone levels.
Rachel (08:59):
So maybe getting some benefits without the extreme
dietary restriction.
Mark (09:03):
Potentially yes.
The research is still ongoing.
And then there are othercompounds being studied, like
dichloracetate, dca andmetformin, the diabetes drug.
Rachel (09:12):
What do they do?
Mark (09:13):
They seem to be able to shift cell metabolism away from
that fast glycolysis that GBMloves, potentially making them
less efficient at producingenergy.
Okay, quite a few differentangles there, but and this is
really crucial none of thesemetabolic strategies are
intended to replace standardtreatments.
Rachel (09:30):
Right, not.
Instead of surgery or radiation?
Absolutely not.
Mark (09:32):
They're designed for combination with standard
treatments.
Right, not instead of surgeryor radiation.
Absolutely not.
They're designed forcombination with standard
therapy.
The idea is synergy.
Rachel (09:38):
Making the standard treatments work better.
Mark (09:40):
Potentially, yes, yeah.
The hope is they mightsensitize glioblastoma cells to
oxidative stress and DNA damage,making them more vulnerable to
radiation and chemo, whilesimultaneously protecting normal
brain tissue.
Rachel (09:53):
So it's not just adding a new weapon.
It's like Making your existingartillery more precise and
powerful by weakening theenemy's defenses.
Mark (10:01):
That's a great way to put it Enhancing the current arsenal
, potentially improving outcomes.
It's a really smart strategy.
Rachel (10:06):
Okay, it sounds incredibly promising in theory,
smart, elegant even.
But you know, theory is onething.
What does the actual researchsay?
Where are we with the evidencefor metabolic therapy and GBM?
Where are we with the evidencefor metabolic therapy?
Mark (10:19):
and GBM.
That's the critical questionalways and there is strong
support from the preclinicalside, from the lab work, the
animal models.
Rachel (10:27):
What did?
Mark (10:28):
those studies show.
In numerous animal models,ketogenic diets have
consistently been shown toreduce tumor growth, enhance
survival times and actuallyimprove the effectiveness of
radiation and chemotherapy.
There's some really solidfoundational work there.
Rachel (10:42):
Okay, promising in animals, what about in humans?
Mark (10:45):
Well, the early human studies are definitely more
limited, but I'd say they areencouraging.
We have things like casereports and pilot trials popping
up.
Rachel (10:52):
Individual stories or small groups.
Mark (10:54):
Exactly Documenting sometimes surprisingly prolonged
survival in certain patientswho managed to stick to really
strict ketogenic regimensalongside their standard care.
Rachel (11:05):
Adherence must be tough.
Mark (11:06):
Incredibly tough.
One phase a clinical trialspecifically looked at
feasibility and safety of theketogenic diet in GBM patients.
It showed it could be donesafely, but it also highlighted
that adherence was challenging.
That's a major hurdle.
Rachel (11:20):
Understandable.
Are there bigger trialshappening now?
Mark (11:22):
Yes, safely, but it also highlighted that adherence was
challenging.
That's a major hurdle,understandable.
Are there bigger trialshappening now?
Yes, critically, there areongoing clinical trials.
These are actively testingwhether adding ketogenic diets
or caloric restrictionstrategies to standard treatment
temozolomide and radiation canactually improve outcomes in a
larger group of patients.
Rachel (11:39):
So we're waiting on those results, which brings up,
you know, the limitations.
It sounds exciting, but whatare the caveats we need to keep
in mind right now?
Mark (11:47):
Absolutely crucial to be realistic, the limitations are
significant at this stage.
First, as we mentioned, moststudies so far have small sample
sizes.
We just don't have those largescale randomized controlled
trials completed yet.
Rachel (12:00):
The gold standard for evidence.
Mark (12:01):
Right.
Second, that issue of dietaryadherence is a huge barrier.
Rachel (12:05):
Yeah.
Mark (12:06):
Especially for patients who are already very thick
dealing with treatment sideeffects.
It's a massive commitment.
Rachel (12:10):
Yeah, it's not just a lifestyle choice at that point.
Mark (12:13):
Not at all.
And finally, it really remainsunclear which patients might
benefit the most.
Is it everyone, specificgenetic subtypes?
We don't know yet.
And we also don't know for sureif long-term metabolic therapy
impacts survival independentlyof standard care or if its main
power is purely synergistic.
Rachel (12:32):
Lots of unanswered questions still.
Mark (12:34):
Definitely, these are the key questions the current
research is trying to tacklequestions the current research
is trying to tackle.
Rachel (12:41):
So, summing that section up promising preclinical data,
encouraging but limited humandata.
Significant challenges likeadherence and the need for
bigger trials, but still viewedas a promising adjunctive
strategy.
Mark (12:51):
I think that's fair.
It absolutely warrants moreinvestigation, more research.
The field is moving forward,but cautiously, aware of the
hurdles.
Rachel (12:59):
Okay, let's say someone was going down this path working
with their medical team.
It sounds like it requires alot of careful management.
You mentioned adherencechallenges, but what about
monitoring?
It can't be a set it and forgetit thing, right?
Mark (13:09):
Oh, absolutely not.
It's a highly dynamic andpersonalized approach.
Implementing metabolic therapysafely and effectively for
glioblastoma demands reallycareful ongoing monitoring, and
lab tests are key here.
Glioblastoma demands reallycareful ongoing monitoring.
Rachel (13:20):
And lab tests are key here.
Mark (13:22):
Laboratory testing plays a central role.
Definitely.
It guides the therapy, allowsthe clinical team to make
adjustments, ensure safety.
Rachel (13:30):
What kinds of things are being tracked?
Mark (13:33):
Well, first and foremost, glucose and ketones.
You need regular monitoring,usually blood tests for glucose
and beta-hydroxybutyrate, toconfirm the patient is actually
in the target state ofnutritional ketosis and staying
there.
Rachel (13:43):
Makes sense Checking the fuel mix.
Mark (13:44):
Exactly.
Then you look at markers likeinsulin and HbA1c.
These give you insights intolonger term glucose control and
insulin sensitivity.
Is this strategy having asustained impact?
Rachel (13:54):
Okay, what about potential side effects,
especially with high fat diets?
Mark (13:58):
Good point.
A comprehensive lipid profileis crucial, Checking cholesterol
, triglycerides, LDL, maybe evenApoB.
You need to monitorcardiovascular risk.
Make sure the diet isn'tcausing other problems.
Rachel (14:09):
Right, anything else.
Mark (14:11):
We'd also often look at inflammatory markers like
high-sensitivity C-reactiveprotein, hscrp or IL-6.
Inflammation plays a role intumor biology, so tracking that
can be informative.
Rachel (14:24):
And nutrients if the diet is restrictive.
Mark (14:26):
Absolutely critical.
Ensuring adequate nutrientstatus is paramount.
You might test for things likevitamin D, magnesium, selenium,
other micronutrients, just tomake sure the restrictive diet
isn't leading to deficiencies.
Rachel (14:38):
Wow.
So it's a constant feedbackloop, monitoring, adjusting.
Mark (14:42):
It really is.
It's this ongoing adjustmentbased on the lab data and how
the patient is doing.
It's vital for both safety andmaximizing the potential
effectiveness.
Rachel (14:51):
It really underscores that this is a complex, highly
managed therapy, not a simpledietary switch, far from set it
and forget it.
Mark (14:58):
Precisely.
It requires a dedicated patientand a knowledgeable clinical
team working closely together.
Rachel (15:04):
Okay, so let's try and bring this all home for you
listening.
Glioblastoma, it remains thisincredibly tough, devastating
cancer.
Standard treatments are vital,absolutely, but recurrence is
still far too common.
Mark (15:16):
A heartbreaking reality for many.
Rachel (15:18):
But this deep dive into metabolic therapy offers well,
maybe, a glimmer of real hope.
Not as a replacement forstandard care, let's be clear on
that.
Mark (15:28):
No, as a sophisticated complementary approach.
Rachel (15:30):
Right One that could potentially change the game by
targeting how the cancer fuelsitself.
Mark (15:36):
Exactly by focusing on those fundamental metabolic
vulnerabilities the reliance onglucose and glutamine, the
inability to use ketoneseffectively, strategies like
ketogenic diets maybe fasting.
Rachel (15:53):
all carefully supported by that detailed lab monitoring.
They aim to create anenvironment where the cancer
struggles right yeah, whilehealthy brain cells are
supported, even strengthened.
Mark (15:59):
It's about trying to outsmart the tumor on a
completely different front.
It's energy supply.
Rachel (16:03):
And look, we absolutely need more research.
Those large scale randomizedtrials are crucial and we're
eagerly waiting for thoseresults.
Mark (16:10):
We are, the limitations are real.
Rachel (16:12):
But the early findings, the preclinical work, the pilot
studies, they're undeniablyintriguing.
They represent a reallysignificant shift in how we
think about treating cancer.
Mark (16:22):
Moving beyond just directly killing cells to
influencing their survivalmechanisms, their environment.
Rachel (16:28):
It's a fundamental change and it makes you wonder,
if we consider just how deeplyour metabolic health influences
literally every cell, everydisease process in our bodies.
What other doors could thisopen?
Mark (16:41):
Right Understanding and maybe leveraging these
fundamental metabolic processes.
What could that mean for healthcare in the future?
Rachel (16:47):
Way beyond just glioblastoma.
It's a really provocativethought to leave you with
something worth mulling over andperhaps a future worth working
towards.
Nicolette (17:00):
Thanks for tuning into the Health 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.
Popular Podcasts
Stuff You Should Know
If you've ever wanted to know about champagne, satanism, the Stonewall Uprising, chaos theory, LSD, El Nino, true crime and Rosa Parks, then look no further. Josh and Chuck have you covered.
Las Culturistas with Matt Rogers and Bowen Yang
Ding dong! Join your culture consultants, Matt Rogers and Bowen Yang, on an unforgettable journey into the beating heart of CULTURE. Alongside sizzling special guests, they GET INTO the hottest pop-culture moments of the day and the formative cultural experiences that turned them into Culturistas. Produced by the Big Money Players Network and iHeartRadio.
Crime Junkie
Does hearing about a true crime case always leave you scouring the internet for the truth behind the story? Dive into your next mystery with Crime Junkie. Every Monday, join your host Ashley Flowers as she unravels all the details of infamous and underreported true crime cases with her best friend Brit Prawat. From cold cases to missing persons and heroes in our community who seek justice, Crime Junkie is your destination for theories and stories you won’t hear anywhere else. Whether you're a seasoned true crime enthusiast or new to the genre, you'll find yourself on the edge of your seat awaiting a new episode every Monday. If you can never get enough true crime... Congratulations, you’ve found your people. Follow to join a community of Crime Junkies! Crime Junkie is presented by audiochuck Media Company.