May 21, 2025 • 17 mins
In this episode of The Health Pulse Podcast, we dive into the powerful and controversial theory that cancer may be driven more by metabolic dysfunction than by genetic mutations. Drawing on the research of Dr. Thomas Seyfried and the foundational work of Otto Warburg, we explore how damaged mitochondria and altered energy metabolism could be the true origin of cancer.
Learn how cancer cells rely on glucose and glutamine fermentation for survival, why ketogenic diets and metabolic therapies show early promise, and how healthy mitochondria can reverse malignant behavior even in cells with genetic damage. We also discuss why integrating both genetic and metabolic approaches may offer a more effective, less toxic path forward in cancer care.
🎧 Tap play to learn how rethinking cancer as a metabolic disease could change how we understand, prevent, and treat it.
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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 (00:24):
So what if the way we've thought about cancer for well,
for decades, really this ideathat it's all about genetics?
What if that's not the fullpicture?
Mark (00:33):
Right, it's a huge question and it's really being
pushed forward by people like DrThomas Seyfried over at Boston
College.
Seyfried, yeah, His book Canceras a Metabolic Disease at
Boston College, Seyfried, yeah,His book Cancer as a Metabolic
Disease, Exactly.
He makes this well prettycompelling case that cancer is
fundamentally a metabolicproblem about energy.
Rachel (00:52):
Okay, metabolic, so how cells make and use energy.
That's the core idea.
Mark (00:57):
That's it and you know it's not entirely out of the
blue.
It actually connects back tosome really early observations
in science.
Rachel (01:04):
You mean Otto Warburg, way back.
Mark (01:06):
Precisely Warburg won a Nobel Prize and way back in the
1920s he noticed somethingreally odd about how cancer
cells produce energy.
Seyfried's work really buildsright on top of that foundation.
Rachel (01:17):
Interesting.
So okay, for this deep dive.
Our mission is really to unpackthis metabolic theory.
What is it saying?
What's the science?
Mark (01:27):
And crucially yeah, what could it actually mean for
treatment?
Could it lead to maybe lesstoxic approaches?
That's a big part of theinterest.
Rachel (01:30):
And just to be clear for you listening, this isn't
necessarily about throwing outeverything we know about cancer
genetics.
Mark (01:36):
Not at all.
It's more about reframing it,looking at the origin
differently.
Where does the problem start?
And that shift?
Well, it can lead to some realaha moments.
Rachel (01:45):
So, before we dive into Seyfried's view, let's quickly
touch on the standard model, theone that's dominated for the
last 50 years the somaticmutation theory, SMT.
Mark (01:54):
Right, the SMT.
It's been the bedrock.
The basic idea is that cancerkicks off when a normal cell
racks up enough damage to itsDNA, enough mutations.
Rachel (02:04):
Like flipping the wrong switches.
Mark (02:05):
Pretty much.
These mutations might turn ongenes that push growth, on
haggadgenes, or they mightswitch off the brakes, the tumor
suppressor genes.
And if the DNA repair systemsare also hit, things can really
spiral.
Rachel (02:18):
And this model has driven so much right Screening,
like for BRCA.
Mark (02:22):
Yeah, brca, tp53 markers, all that.
And drug development too, thosetargeted therapies aiming at
specific mutations, even how weclassify cancers, you know,
based on their genetic subtypesit's all flowed from the SMT.
Rachel (02:34):
But there must be cracks in that foundation, or we
wouldn't be having thisconversation.
What are the issues?
What doesn't the SMT quiteexplain?
Mark (02:43):
Well, that's the thing.
It's powerful, but it faceschallenges like heterogeneity.
You see two patients with thesame type of cancer, but their
tumors have totally differentmutation sets.
Rachel (02:56):
And even within one tumor.
Mark (02:57):
Yeah, Massive variation sometimes.
Then there's treatmentresistance.
You target one mutation.
The tumor just seems to evolve.
New mutations pop up.
The drug stops working.
Rachel (03:08):
It's frustrating, and I guess the big one is finding
cancers that don't even havethose common mutations you'd
expect.
Mark (03:13):
Exactly.
Sometimes aggressive cancerslack the usual suspects, which
leads to that big question Arethe mutations really the cause,
or are they maybe a symptom, adownstream effect of something
else going wrong?
Rachel (03:24):
first, Okay, so that's the perfect lead-in to Seyfried
and the metabolic hypothesis.
Mark (03:32):
He's taking Warburg's old observations and running with
them.
He really is.
Rachel (03:34):
He's building on that Warburg effect, the aerobic
glycolysis thing Right, thatweird thing where cancer cells
ferment glucose like yeast doeswithout oxygen, but they do it
even when oxygen is available.
Mark (03:45):
Seems backwards inefficient.
It does seem inefficient from apure ATP perspective.
Yeah, and Seyfried's bigargument is this isn't just some
weird side effect, he thinksthis metabolic shift is causal,
it's the driver.
Rachel (03:56):
And the root cause, he says, isn't the DNA in the
nucleus, it's the mitochondria,the cell's power plants.
Mark (04:03):
That's the core hypothesis .
It starts with mitochondrialdysfunction, damage to their
ability to do their main jobrespiration.
Rachel (04:10):
Okay, so break down Seyfried's theory for us.
What are the key steps orprinciples?
Mark (04:14):
All right.
So first, something damages themitochondria, impairs their
respiration.
Second, because they can't makeenergy properly that way, the
cells switch strategy.
They ramp up fermentation usingglucose and also another fuel,
glutamine.
Rachel (04:28):
Glucose and glutamine OK .
Mark (04:29):
Third, this messed up energy system is what fuels the
crazy growth, the genomicinstability, the resistance to
cell death, all that cancerstuff.
Rachel (04:37):
And the mutations?
Where do they fit in?
Mark (04:39):
He sees them as secondary.
They happen, sure, but they'rea consequence of this underlying
metabolic chaos and theoxidative stress it generates,
not the primary cause.
Rachel (04:50):
He really hammers this point in his book right that the
altered metabolism is universalin cancer but specific
mutations aren't always there.
Mark (04:57):
Exactly that.
Universality is a key piece ofhis evidence.
And then there are thosefascinating nuclear cytoplasmic
transfer experiments.
Rachel (05:06):
Oh yeah, Tell us about those.
They sound crucial.
Swapping bits between cells.
Mark (05:10):
Pretty much.
You take the nucleus from acancer cell with all its mutated
genes and pop it into a healthycell cytoplasm, one with
healthy mitochondria.
Rachel (05:18):
And what happens?
Does it become cancerous?
Mark (05:20):
Yep?
Generally it doesn't.
The mutations alone, in thecontext of healthy mitochondria,
were enough to drive cancer.
Rachel (05:27):
Wow, ok, and the reverse Healthy nucleus, but damaged
mitochondria.
Mark (05:31):
That's where it gets really telling.
Put a healthy nucleus intocytoplasm with dysfunctional
mitochondria and the cell startsacting cancerous even with
normal genes.
Rachel (05:41):
So the state of the mitochondria seems to dictate
the cell's behavior more thanthe nuclear DNA itself.
Mark (05:47):
That's the conclusion Seyfried draws.
It's like the mitochondria arethe operating system and they're
corrupted.
Doesn't matter as much whatsoftware the nuclear genes
you're running.
Rachel (05:55):
That's a really different way of looking at it.
It suggests we should befocusing on fixing mitochondria
or maybe cutting off those fuelsthey're forced to use.
Mark (06:03):
Precisely.
It opens up a whole avenue fortherapies that could be, you
know, less toxic, targeting theenergy supply, restoring
function.
Rachel (06:10):
Let's go back to that Warburg effect again.
It seems so central.
Remind us exactly what it isand why Seyfried thinks it
points to mitochondrial failure.
Mark (06:19):
Sure.
So the Warburg effect.
Cancer cells prefer glycolysis.
They ferment glucose intolactate even with oxygen around
Normal cells.
With oxygen would fully oxidizeglucose in the mitochondria for
way more energy.
Rachel (06:35):
Much more ATP that way.
Mark (06:36):
Loads more.
Warburg spotted this nearly 100years ago.
It's a hallmark of most cancers.
Rachel (06:41):
And Seyfried's take is this isn't a choice, it's a
necessity because themitochondria are broken.
Mark (06:46):
That's his interpretation.
Yes, damaged mitochondria justcan't handle the normal
oxidative process efficiently,so the cell compensates.
It ramps up glucose intake,ramps up glutamine intake and
pushes them through fermentationpathways instead.
Rachel (07:01):
But why fermentation If it's less efficient for ATP?
What's the upside for thecancer cell?
Mark (07:06):
Well, several things.
One if your mitochondria arebusted, you don't have much
choice for getting energyquickly.
Glycolysis and glutaminemetabolism give you some ATP.
Two these pathways aren't justabout ATP.
They spin off building blocks.
Rachel (07:19):
Building blocks.
Mark (07:20):
Yeah, the raw materials, nucleotides for dna, lipids for
membranes, amino acids needed tobuild new cells rapidly.
Rachel (07:26):
fermentation is good for that ah, okay, so fuels growth
directly, not just energy right.
Mark (07:32):
And third, it seems to help them survive in low oxygen
areas within a tumor, thehypoxic zones and the
inefficiency in at they justmake up for it by grabbing way
more glucose.
Rachel (07:42):
That's why PE scans light up tumors.
Mark (07:44):
Exactly they become glucose augs.
But there are other potentialperks too.
This metabolic state mightprotect them from oxidative
stress, resist programmed celldeath.
Basically helps them surviveunder tough conditions.
Rachel (07:57):
So Seyfried sees cancer cells as metabolically
inflexible, stuck in thisfermentation mode.
Mark (08:03):
Very much so that inflexibility is key.
Healthy cells can usuallyswitch fuels pretty easily.
Cancer cells, according to thistheory, get locked into,
relying heavily on glucose andglutamine.
Rachel (08:14):
And that inflexibility, that's the weakness, that's the
target.
Mark (08:18):
That's the potential Achilles heel.
Yes, If they're so dependent onthese specific fuels, maybe we
can cut off the supply.
Rachel (08:24):
Which brings us neatly to the therapeutic side.
If cancer is metabolic, maybetreatment should target
metabolism.
Mark (08:30):
Logically yes.
Instead of just focusing on DNAmutations, focus on how the
cancer cell fuels itself, andthis leads directly to metabolic
therapies.
The best known example isprobably ketogenic metabolic
therapy, or KMT.
Rachel (08:43):
The keto diet high fat, super low carb.
How does that target cancermetabolism?
Mark (08:48):
Well, the keto diet forces your body into ketosis.
You start burning fat andproducing ketone bodies for
energy, instead of relying onglucose from carbs.
Rachel (08:58):
Okay.
Mark (08:58):
The theory is, most cancer cells are poorly equipped to
use ketones efficiently for fuel.
They're geared up for glucose,so by drastically cutting carbs
you limit their primary foodsource.
Rachel (09:10):
You essentially starve them of glucose.
Mark (09:12):
That's the goal.
But importantly, your healthycells, especially your brain and
muscles.
They can adapt.
They switch over to usingketones quite well.
Rachel (09:20):
So it's potentially selective hits the cancer cells
harder than the normal cells.
Mark (09:24):
That's the principle Create a metabolic environment
that favors healthy cells andstresses the cancer cells.
Plus, keto might have otherbenefits, like what it could
lower insulin and IGF-1 growthfactors that can push cancer
growth.
It might reduce inflammation,oxidative stress, maybe even
hinder angiogenesis, the growthof new blood vessels tumors need
.
Rachel (09:44):
Has this been tested in people with cancer?
Are there studies?
Mark (09:47):
There are preliminary studies.
Yes, A pilot study, forinstance, showed advanced cancer
patients could tolerate aketogenic diet and it did seem
to reduce glucose availabilityin their tumors, based on PET
scans.
Rachel (10:01):
And animal studies.
Mark (10:02):
Animal studies have often shown more striking results
slowed tumor growth, betterresponse when combined with
chemo or radiation, longersurvival times.
But you know, translating thatto humans is the big hurdle.
Rachel (10:14):
And Seyfried emphasizes it's not just glucose right,
there's glutamine too.
Mark (10:19):
Yes, he stresses that glutamine is a critical second
fuel for many cancers.
They use it alongside glucose,so just cutting glucose might
not be enough for some tumors.
Rachel (10:28):
So how do you target glutamine?
Mark (10:30):
It's trickier.
There are experimental drugscalled glutaminase inhibitors
that block the enzyme cancercells used to process glutamine.
Some people explore strategicfasting protocols which can
lower overall amino acid levels,including glutamine, and there
are older drugs, like Dawn, thatinterfere with glutamine
metabolism, though they can havetoxicity issues.
Rachel (10:49):
So the ideal approach might be hitting both keto for
the glucose, plus something tolimit glutamine.
Mark (10:55):
That's the idea behind a more comprehensive metabolic
strategy, a sort of dual fuelblockade.
It aims to be a less toxicsystem level attack, exploiting
those metabolic weaknesses.
Rachel (11:08):
It sounds like a really different paradigm for treatment
, maybe a foundation, especiallyfor tricky cancers or earlier
stages.
Mark (11:15):
Sievried certainly proposes it could be
foundational, yeah, particularlyfor maybe resistant tumors or
where options are limited.
It's a very different way ofthinking.
Rachel (11:23):
But you said earlier, this isn't fully accepted.
Yet there's debate.
Mark (11:26):
Oh, absolutely.
It's generated a lot ofinterest, but also significant
criticism and skepticism.
It's definitely not mainstreamoncology practice yet.
Rachel (11:34):
So while everyone sort of agrees, metabolism is weird
in cancer, Right.
Mark (11:38):
The Warburg effect is undeniable.
It's whether the mitochondrialdefect is the absolute start of
it all, the primary cause,versus genetic mutations.
That's where the maindisagreement lies.
The traditional SMT view isstill very dominant.
Rachel (11:52):
What are the key arguments for Seyfried's
metabolic view?
What's the evidence supporterspoint to?
Mark (11:56):
Well, number one is that metabolic pattern consistency,
the Warburg effect or somethinglike it, is seen in nearly all
cancers, despite huge geneticvariety.
That suggests a commonmetabolic vulnerability.
Rachel (12:09):
Okay, the universality.
Mark (12:11):
Then there's the reversibility seen in those lab
experiments.
Putting healthy mitochondriaback into cancer cells can
sometimes make them behavenormally again.
That strongly employsmetabolism, as in the driver's
seat.
Rachel (12:22):
Right the nuclear transfer results.
Mark (12:24):
And then there's the early clinical data.
It's limited, sure, smalltrials, case reports, but some
suggest benefits from keto diets, Maybe slowed growth, better
tolerance of other treatments,improved quality of life.
It's suggestive if notdefinitive yet.
Rachel (12:39):
Okay.
And the counter arguments, thecriticisms?
Why isn't everyone jumping onboard?
Mark (12:44):
The biggest one is the lack of large scale randomized,
controlled trials in humans.
That's the gold standard forproving a therapy works, and we
just don't have that formetabolic therapies like KMT as
a primary cancer treatment.
Rachel (12:56):
Yet we need more robust human data.
Mark (12:59):
Definitely.
Critics also point out cancer'sheterogeneity.
Again, maybe not all cancersare that glucose dependent.
Some might adapt, find otherfuels, even on keto.
Brain cancer, pancreatic cancerare often mentioned as
potentially tricky.
Rachel (13:14):
And, practically speaking, sticking to a strict
keto diet.
That's tough for anyone, letalone someone going through
cancer treatment.
Mark (13:21):
Compliance is a real challenge, absolutely.
People feel unwell, lose theirappetite, it's difficult and
finally, many researchers feelit's probably not just
metabolism or just genes.
Rachel (13:31):
It's likely more complex an interaction.
Mark (13:34):
Exactly.
They argue.
Metabolism and genetics likelyinfluence each other in
complicated feedback loops.
It's probably not a simpleone-way street.
So maybe the future isn'tmetabolic versus genetic, but
metabolic and genetic.
That seems like a much morelikely and probably more
productive path forward.
An integrated view is gainingground.
Rachel (13:53):
How would that work?
Maybe mitochondrial issues kickthings off, creating metabolic
stress?
Mark (13:58):
Which then leads to genomic instability, making
mutations more likely, or itcreates an environment where
cells with certain mutationsthrive.
It's plausible.
The initial trigger might vary,but the metabolic dysfunction
becomes a core feature and avulnerability.
Rachel (14:13):
So in this combined model, metabolism is still a key
target, but you don't ignorethe genetic context.
Mark (14:19):
Precisely, metabolism is a driver and a target.
Mutations tell you about thespecifics of that tumor and,
importantly, it brings in thingslike diet and lifestyle as
factors that can influence bothenergy regulation and gene
expression.
Gives you, the listener,potentially more agency.
Rachel (14:37):
Which logically leads to integrative treatments
combining the best of bothworlds.
Mark (14:41):
Absolutely Imagine combining precision medicine,
using genetic info to guidetargeted drugs or immunotherapy,
with metabolic strategies likenutritional ketosis, maybe
calorie restriction, perhapseven drugs targeting glutamine
or therapies to supportmitochondria.
Rachel (14:55):
And maybe things like hyperbaric oxygen exercise,
things that affect metabolismtoo.
Mark (14:59):
Yes, adjunctive therapies that influence the tumor's
metabolic environment could fitinto a broader, more holistic
plan.
The idea is to hit the cancerfrom multiple angles.
Rachel (15:09):
Targeting both the genetic vulnerabilities and
these metabolic dependencies.
That sounds like a powerful wayto potentially overcome
treatment resistance.
Mark (15:18):
That's the hope that by addressing both you get better
outcomes, maybe with lesstoxicity, better quality of life
.
It brings Seyfried's quote backinto focus you need to address
the origin.
If metabolism is part of thatorigin, you need to address
metabolism.
Rachel (15:33):
Okay, so, wrapping this up, the core challenge we've
explored is this idea of canceras primarily a metabolic disease
, shifting focus from just genes.
Mark (15:42):
Right Dr Seyfried's central thesis.
It's a disorder of themitochondria forcing cells into
inefficient fermentation usingglucose and glutamine.
Rachel (15:50):
And genetics isn't irrelevant, but perhaps
secondary the consequence ofthis initial energy crisis.
Mark (15:55):
That's his view.
The mutations are part of theevolution, but the metabolic
problem comes first, or is atleast a critical early step.
Rachel (16:02):
And the really profound implication is that cancer might
be vulnerable to non-toxicdiet-based approaches like
ketogenic therapy.
Mark (16:10):
Yeah, the potential is there.
Animal studies and early humandata show promise slowed growth,
maybe better outcomes, qualityof life improvements.
But we absolutely need morerigorous human trials.
That's critical.
Rachel (16:24):
But looking bigger picture, it suggests cancer
prevention and management mightrely not just on high tech drugs
but also on really supportingour basic metabolic health.
Mark (16:33):
Through diet, maybe fasting, focusing on
mitochondrial health.
It's a more holisticperspective.
Rachel (16:39):
And for those of you listening, interested in your
own metabolic health, oursponsor, quicklab Mobile, does
offer that in-home testing forthings like fasting, insulin,
ketones, glucose, lipids,inflammation markers, letting
you get a clearer picture ofyour own metabolic state.
Mark (16:53):
It really comes down to that powerful closing thought,
doesn't it?
Cancer is complex, yes, butmaybe its fuel source is simpler
.
Rachel (17:00):
Control the fuel.
Mark (17:01):
And you might gain more control over the fire.
It's a compelling idea to thinkabout.
Rachel (17:05):
Definitely food for thought.
Thanks for taking this deepdive with us today.
We hope it gave you a lot toconsider.
Nicolette (17:20):
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 (00:24):
So what if the way we've thought about cancer for well,
for decades, really this ideathat it's all about genetics?
What if that's not the fullpicture?
Mark (00:33):
Right, it's a huge question and it's really being
pushed forward by people like DrThomas Seyfried over at Boston
College.
Seyfried, yeah, His book Canceras a Metabolic Disease at
Boston College, Seyfried, yeah,His book Cancer as a Metabolic
Disease, Exactly.
He makes this well prettycompelling case that cancer is
fundamentally a metabolicproblem about energy.
Rachel (00:52):
Okay, metabolic, so how cells make and use energy.
That's the core idea.
Mark (00:57):
That's it and you know it's not entirely out of the
blue.
It actually connects back tosome really early observations
in science.
Rachel (01:04):
You mean Otto Warburg, way back.
Mark (01:06):
Precisely Warburg won a Nobel Prize and way back in the
1920s he noticed somethingreally odd about how cancer
cells produce energy.
Seyfried's work really buildsright on top of that foundation.
Rachel (01:17):
Interesting.
So okay, for this deep dive.
Our mission is really to unpackthis metabolic theory.
What is it saying?
What's the science?
Mark (01:27):
And crucially yeah, what could it actually mean for
treatment?
Could it lead to maybe lesstoxic approaches?
That's a big part of theinterest.
Rachel (01:30):
And just to be clear for you listening, this isn't
necessarily about throwing outeverything we know about cancer
genetics.
Mark (01:36):
Not at all.
It's more about reframing it,looking at the origin
differently.
Where does the problem start?
And that shift?
Well, it can lead to some realaha moments.
Rachel (01:45):
So, before we dive into Seyfried's view, let's quickly
touch on the standard model, theone that's dominated for the
last 50 years the somaticmutation theory, SMT.
Mark (01:54):
Right, the SMT.
It's been the bedrock.
The basic idea is that cancerkicks off when a normal cell
racks up enough damage to itsDNA, enough mutations.
Rachel (02:04):
Like flipping the wrong switches.
Mark (02:05):
Pretty much.
These mutations might turn ongenes that push growth, on
haggadgenes, or they mightswitch off the brakes, the tumor
suppressor genes.
And if the DNA repair systemsare also hit, things can really
spiral.
Rachel (02:18):
And this model has driven so much right Screening,
like for BRCA.
Mark (02:22):
Yeah, brca, tp53 markers, all that.
And drug development too, thosetargeted therapies aiming at
specific mutations, even how weclassify cancers, you know,
based on their genetic subtypesit's all flowed from the SMT.
Rachel (02:34):
But there must be cracks in that foundation, or we
wouldn't be having thisconversation.
What are the issues?
What doesn't the SMT quiteexplain?
Mark (02:43):
Well, that's the thing.
It's powerful, but it faceschallenges like heterogeneity.
You see two patients with thesame type of cancer, but their
tumors have totally differentmutation sets.
Rachel (02:56):
And even within one tumor.
Mark (02:57):
Yeah, Massive variation sometimes.
Then there's treatmentresistance.
You target one mutation.
The tumor just seems to evolve.
New mutations pop up.
The drug stops working.
Rachel (03:08):
It's frustrating, and I guess the big one is finding
cancers that don't even havethose common mutations you'd
expect.
Mark (03:13):
Exactly.
Sometimes aggressive cancerslack the usual suspects, which
leads to that big question Arethe mutations really the cause,
or are they maybe a symptom, adownstream effect of something
else going wrong?
Rachel (03:24):
first, Okay, so that's the perfect lead-in to Seyfried
and the metabolic hypothesis.
Mark (03:32):
He's taking Warburg's old observations and running with
them.
He really is.
Rachel (03:34):
He's building on that Warburg effect, the aerobic
glycolysis thing Right, thatweird thing where cancer cells
ferment glucose like yeast doeswithout oxygen, but they do it
even when oxygen is available.
Mark (03:45):
Seems backwards inefficient.
It does seem inefficient from apure ATP perspective.
Yeah, and Seyfried's bigargument is this isn't just some
weird side effect, he thinksthis metabolic shift is causal,
it's the driver.
Rachel (03:56):
And the root cause, he says, isn't the DNA in the
nucleus, it's the mitochondria,the cell's power plants.
Mark (04:03):
That's the core hypothesis .
It starts with mitochondrialdysfunction, damage to their
ability to do their main jobrespiration.
Rachel (04:10):
Okay, so break down Seyfried's theory for us.
What are the key steps orprinciples?
Mark (04:14):
All right.
So first, something damages themitochondria, impairs their
respiration.
Second, because they can't makeenergy properly that way, the
cells switch strategy.
They ramp up fermentation usingglucose and also another fuel,
glutamine.
Rachel (04:28):
Glucose and glutamine OK .
Mark (04:29):
Third, this messed up energy system is what fuels the
crazy growth, the genomicinstability, the resistance to
cell death, all that cancerstuff.
Rachel (04:37):
And the mutations?
Where do they fit in?
Mark (04:39):
He sees them as secondary.
They happen, sure, but they'rea consequence of this underlying
metabolic chaos and theoxidative stress it generates,
not the primary cause.
Rachel (04:50):
He really hammers this point in his book right that the
altered metabolism is universalin cancer but specific
mutations aren't always there.
Mark (04:57):
Exactly that.
Universality is a key piece ofhis evidence.
And then there are thosefascinating nuclear cytoplasmic
transfer experiments.
Rachel (05:06):
Oh yeah, Tell us about those.
They sound crucial.
Swapping bits between cells.
Mark (05:10):
Pretty much.
You take the nucleus from acancer cell with all its mutated
genes and pop it into a healthycell cytoplasm, one with
healthy mitochondria.
Rachel (05:18):
And what happens?
Does it become cancerous?
Mark (05:20):
Yep?
Generally it doesn't.
The mutations alone, in thecontext of healthy mitochondria,
were enough to drive cancer.
Rachel (05:27):
Wow, ok, and the reverse Healthy nucleus, but damaged
mitochondria.
Mark (05:31):
That's where it gets really telling.
Put a healthy nucleus intocytoplasm with dysfunctional
mitochondria and the cell startsacting cancerous even with
normal genes.
Rachel (05:41):
So the state of the mitochondria seems to dictate
the cell's behavior more thanthe nuclear DNA itself.
Mark (05:47):
That's the conclusion Seyfried draws.
It's like the mitochondria arethe operating system and they're
corrupted.
Doesn't matter as much whatsoftware the nuclear genes
you're running.
Rachel (05:55):
That's a really different way of looking at it.
It suggests we should befocusing on fixing mitochondria
or maybe cutting off those fuelsthey're forced to use.
Mark (06:03):
Precisely.
It opens up a whole avenue fortherapies that could be, you
know, less toxic, targeting theenergy supply, restoring
function.
Rachel (06:10):
Let's go back to that Warburg effect again.
It seems so central.
Remind us exactly what it isand why Seyfried thinks it
points to mitochondrial failure.
Mark (06:19):
Sure.
So the Warburg effect.
Cancer cells prefer glycolysis.
They ferment glucose intolactate even with oxygen around
Normal cells.
With oxygen would fully oxidizeglucose in the mitochondria for
way more energy.
Rachel (06:35):
Much more ATP that way.
Mark (06:36):
Loads more.
Warburg spotted this nearly 100years ago.
It's a hallmark of most cancers.
Rachel (06:41):
And Seyfried's take is this isn't a choice, it's a
necessity because themitochondria are broken.
Mark (06:46):
That's his interpretation.
Yes, damaged mitochondria justcan't handle the normal
oxidative process efficiently,so the cell compensates.
It ramps up glucose intake,ramps up glutamine intake and
pushes them through fermentationpathways instead.
Rachel (07:01):
But why fermentation If it's less efficient for ATP?
What's the upside for thecancer cell?
Mark (07:06):
Well, several things.
One if your mitochondria arebusted, you don't have much
choice for getting energyquickly.
Glycolysis and glutaminemetabolism give you some ATP.
Two these pathways aren't justabout ATP.
They spin off building blocks.
Rachel (07:19):
Building blocks.
Mark (07:20):
Yeah, the raw materials, nucleotides for dna, lipids for
membranes, amino acids needed tobuild new cells rapidly.
Rachel (07:26):
fermentation is good for that ah, okay, so fuels growth
directly, not just energy right.
Mark (07:32):
And third, it seems to help them survive in low oxygen
areas within a tumor, thehypoxic zones and the
inefficiency in at they justmake up for it by grabbing way
more glucose.
Rachel (07:42):
That's why PE scans light up tumors.
Mark (07:44):
Exactly they become glucose augs.
But there are other potentialperks too.
This metabolic state mightprotect them from oxidative
stress, resist programmed celldeath.
Basically helps them surviveunder tough conditions.
Rachel (07:57):
So Seyfried sees cancer cells as metabolically
inflexible, stuck in thisfermentation mode.
Mark (08:03):
Very much so that inflexibility is key.
Healthy cells can usuallyswitch fuels pretty easily.
Cancer cells, according to thistheory, get locked into,
relying heavily on glucose andglutamine.
Rachel (08:14):
And that inflexibility, that's the weakness, that's the
target.
Mark (08:18):
That's the potential Achilles heel.
Yes, If they're so dependent onthese specific fuels, maybe we
can cut off the supply.
Rachel (08:24):
Which brings us neatly to the therapeutic side.
If cancer is metabolic, maybetreatment should target
metabolism.
Mark (08:30):
Logically yes.
Instead of just focusing on DNAmutations, focus on how the
cancer cell fuels itself, andthis leads directly to metabolic
therapies.
The best known example isprobably ketogenic metabolic
therapy, or KMT.
Rachel (08:43):
The keto diet high fat, super low carb.
How does that target cancermetabolism?
Mark (08:48):
Well, the keto diet forces your body into ketosis.
You start burning fat andproducing ketone bodies for
energy, instead of relying onglucose from carbs.
Rachel (08:58):
Okay.
Mark (08:58):
The theory is, most cancer cells are poorly equipped to
use ketones efficiently for fuel.
They're geared up for glucose,so by drastically cutting carbs
you limit their primary foodsource.
Rachel (09:10):
You essentially starve them of glucose.
Mark (09:12):
That's the goal.
But importantly, your healthycells, especially your brain and
muscles.
They can adapt.
They switch over to usingketones quite well.
Rachel (09:20):
So it's potentially selective hits the cancer cells
harder than the normal cells.
Mark (09:24):
That's the principle Create a metabolic environment
that favors healthy cells andstresses the cancer cells.
Plus, keto might have otherbenefits, like what it could
lower insulin and IGF-1 growthfactors that can push cancer
growth.
It might reduce inflammation,oxidative stress, maybe even
hinder angiogenesis, the growthof new blood vessels tumors need
.
Rachel (09:44):
Has this been tested in people with cancer?
Are there studies?
Mark (09:47):
There are preliminary studies.
Yes, A pilot study, forinstance, showed advanced cancer
patients could tolerate aketogenic diet and it did seem
to reduce glucose availabilityin their tumors, based on PET
scans.
Rachel (10:01):
And animal studies.
Mark (10:02):
Animal studies have often shown more striking results
slowed tumor growth, betterresponse when combined with
chemo or radiation, longersurvival times.
But you know, translating thatto humans is the big hurdle.
Rachel (10:14):
And Seyfried emphasizes it's not just glucose right,
there's glutamine too.
Mark (10:19):
Yes, he stresses that glutamine is a critical second
fuel for many cancers.
They use it alongside glucose,so just cutting glucose might
not be enough for some tumors.
Rachel (10:28):
So how do you target glutamine?
Mark (10:30):
It's trickier.
There are experimental drugscalled glutaminase inhibitors
that block the enzyme cancercells used to process glutamine.
Some people explore strategicfasting protocols which can
lower overall amino acid levels,including glutamine, and there
are older drugs, like Dawn, thatinterfere with glutamine
metabolism, though they can havetoxicity issues.
Rachel (10:49):
So the ideal approach might be hitting both keto for
the glucose, plus something tolimit glutamine.
Mark (10:55):
That's the idea behind a more comprehensive metabolic
strategy, a sort of dual fuelblockade.
It aims to be a less toxicsystem level attack, exploiting
those metabolic weaknesses.
Rachel (11:08):
It sounds like a really different paradigm for treatment
, maybe a foundation, especiallyfor tricky cancers or earlier
stages.
Mark (11:15):
Sievried certainly proposes it could be
foundational, yeah, particularlyfor maybe resistant tumors or
where options are limited.
It's a very different way ofthinking.
Rachel (11:23):
But you said earlier, this isn't fully accepted.
Yet there's debate.
Mark (11:26):
Oh, absolutely.
It's generated a lot ofinterest, but also significant
criticism and skepticism.
It's definitely not mainstreamoncology practice yet.
Rachel (11:34):
So while everyone sort of agrees, metabolism is weird
in cancer, Right.
Mark (11:38):
The Warburg effect is undeniable.
It's whether the mitochondrialdefect is the absolute start of
it all, the primary cause,versus genetic mutations.
That's where the maindisagreement lies.
The traditional SMT view isstill very dominant.
Rachel (11:52):
What are the key arguments for Seyfried's
metabolic view?
What's the evidence supporterspoint to?
Mark (11:56):
Well, number one is that metabolic pattern consistency,
the Warburg effect or somethinglike it, is seen in nearly all
cancers, despite huge geneticvariety.
That suggests a commonmetabolic vulnerability.
Rachel (12:09):
Okay, the universality.
Mark (12:11):
Then there's the reversibility seen in those lab
experiments.
Putting healthy mitochondriaback into cancer cells can
sometimes make them behavenormally again.
That strongly employsmetabolism, as in the driver's
seat.
Rachel (12:22):
Right the nuclear transfer results.
Mark (12:24):
And then there's the early clinical data.
It's limited, sure, smalltrials, case reports, but some
suggest benefits from keto diets, Maybe slowed growth, better
tolerance of other treatments,improved quality of life.
It's suggestive if notdefinitive yet.
Rachel (12:39):
Okay.
And the counter arguments, thecriticisms?
Why isn't everyone jumping onboard?
Mark (12:44):
The biggest one is the lack of large scale randomized,
controlled trials in humans.
That's the gold standard forproving a therapy works, and we
just don't have that formetabolic therapies like KMT as
a primary cancer treatment.
Rachel (12:56):
Yet we need more robust human data.
Mark (12:59):
Definitely.
Critics also point out cancer'sheterogeneity.
Again, maybe not all cancersare that glucose dependent.
Some might adapt, find otherfuels, even on keto.
Brain cancer, pancreatic cancerare often mentioned as
potentially tricky.
Rachel (13:14):
And, practically speaking, sticking to a strict
keto diet.
That's tough for anyone, letalone someone going through
cancer treatment.
Mark (13:21):
Compliance is a real challenge, absolutely.
People feel unwell, lose theirappetite, it's difficult and
finally, many researchers feelit's probably not just
metabolism or just genes.
Rachel (13:31):
It's likely more complex an interaction.
Mark (13:34):
Exactly.
They argue.
Metabolism and genetics likelyinfluence each other in
complicated feedback loops.
It's probably not a simpleone-way street.
So maybe the future isn'tmetabolic versus genetic, but
metabolic and genetic.
That seems like a much morelikely and probably more
productive path forward.
An integrated view is gainingground.
Rachel (13:53):
How would that work?
Maybe mitochondrial issues kickthings off, creating metabolic
stress?
Mark (13:58):
Which then leads to genomic instability, making
mutations more likely, or itcreates an environment where
cells with certain mutationsthrive.
It's plausible.
The initial trigger might vary,but the metabolic dysfunction
becomes a core feature and avulnerability.
Rachel (14:13):
So in this combined model, metabolism is still a key
target, but you don't ignorethe genetic context.
Mark (14:19):
Precisely, metabolism is a driver and a target.
Mutations tell you about thespecifics of that tumor and,
importantly, it brings in thingslike diet and lifestyle as
factors that can influence bothenergy regulation and gene
expression.
Gives you, the listener,potentially more agency.
Rachel (14:37):
Which logically leads to integrative treatments
combining the best of bothworlds.
Mark (14:41):
Absolutely Imagine combining precision medicine,
using genetic info to guidetargeted drugs or immunotherapy,
with metabolic strategies likenutritional ketosis, maybe
calorie restriction, perhapseven drugs targeting glutamine
or therapies to supportmitochondria.
Rachel (14:55):
And maybe things like hyperbaric oxygen exercise,
things that affect metabolismtoo.
Mark (14:59):
Yes, adjunctive therapies that influence the tumor's
metabolic environment could fitinto a broader, more holistic
plan.
The idea is to hit the cancerfrom multiple angles.
Rachel (15:09):
Targeting both the genetic vulnerabilities and
these metabolic dependencies.
That sounds like a powerful wayto potentially overcome
treatment resistance.
Mark (15:18):
That's the hope that by addressing both you get better
outcomes, maybe with lesstoxicity, better quality of life
.
It brings Seyfried's quote backinto focus you need to address
the origin.
If metabolism is part of thatorigin, you need to address
metabolism.
Rachel (15:33):
Okay, so, wrapping this up, the core challenge we've
explored is this idea of canceras primarily a metabolic disease
, shifting focus from just genes.
Mark (15:42):
Right Dr Seyfried's central thesis.
It's a disorder of themitochondria forcing cells into
inefficient fermentation usingglucose and glutamine.
Rachel (15:50):
And genetics isn't irrelevant, but perhaps
secondary the consequence ofthis initial energy crisis.
Mark (15:55):
That's his view.
The mutations are part of theevolution, but the metabolic
problem comes first, or is atleast a critical early step.
Rachel (16:02):
And the really profound implication is that cancer might
be vulnerable to non-toxicdiet-based approaches like
ketogenic therapy.
Mark (16:10):
Yeah, the potential is there.
Animal studies and early humandata show promise slowed growth,
maybe better outcomes, qualityof life improvements.
But we absolutely need morerigorous human trials.
That's critical.
Rachel (16:24):
But looking bigger picture, it suggests cancer
prevention and management mightrely not just on high tech drugs
but also on really supportingour basic metabolic health.
Mark (16:33):
Through diet, maybe fasting, focusing on
mitochondrial health.
It's a more holisticperspective.
Rachel (16:39):
And for those of you listening, interested in your
own metabolic health, oursponsor, quicklab Mobile, does
offer that in-home testing forthings like fasting, insulin,
ketones, glucose, lipids,inflammation markers, letting
you get a clearer picture ofyour own metabolic state.
Mark (16:53):
It really comes down to that powerful closing thought,
doesn't it?
Cancer is complex, yes, butmaybe its fuel source is simpler
.
Rachel (17:00):
Control the fuel.
Mark (17:01):
And you might gain more control over the fire.
It's a compelling idea to thinkabout.
Rachel (17:05):
Definitely food for thought.
Thanks for taking this deepdive with us today.
We hope it gave you a lot toconsider.
Nicolette (17:20):
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.
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