Nicolette: 0:01

Welcome to the Health Pulse, your go-to source for quick, actionable insights on health, wellness and diagnostics. Whether you're looking to optimize your well-being or stay informed about the latest in medical testing, we've got you covered. Join us as we break down key health topics in just minutes. Let's dive in.

Rachel: 0:24

So what if the way we've thought about cancer for well, for decades, really this idea that it's all about genetics? What if that's not the full picture?

Mark: 0:33

Right, it's a huge question and it's really being pushed forward by people like Dr Thomas Seyfried over at Boston College. Seyfried, yeah, His book Cancer as a Metabolic Disease at Boston College, Seyfried, yeah, His book Cancer as a Metabolic Disease, Exactly. He makes this well pretty compelling case that cancer is fundamentally a metabolic problem about energy.

Rachel: 0:52

Okay, metabolic, so how cells make and use energy. That's the core idea.

Mark: 0:57

That's it and you know it's not entirely out of the blue. It actually connects back to some really early observations in science.

Rachel: 1:04

You mean Otto Warburg, way back.

Mark: 1:06

Precisely Warburg won a Nobel Prize and way back in the 1920s he noticed something really odd about how cancer cells produce energy. Seyfried's work really builds right on top of that foundation.

Rachel: 1:17

Interesting. So okay, for this deep dive. Our mission is really to unpack this metabolic theory. What is it saying? What's the science?

Mark: 1:27

And crucially yeah, what could it actually mean for treatment? Could it lead to maybe less toxic approaches? That's a big part of the interest.

Rachel: 1:30

And just to be clear for you listening, this isn't necessarily about throwing out everything we know about cancer genetics.

Mark: 1:36

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 real aha moments.

Rachel: 1:45

So, before we dive into Seyfried's view, let's quickly touch on the standard model, the one that's dominated for the last 50 years the somatic mutation theory, SMT.

Mark: 1:54

Right, the SMT. It's been the bedrock. The basic idea is that cancer kicks off when a normal cell racks up enough damage to its DNA, enough mutations.

Rachel: 2:04

Like flipping the wrong switches.

Mark: 2:05

Pretty much. These mutations might turn on genes that push growth, on haggadgenes, or they might switch off the brakes, the tumor suppressor genes. And if the DNA repair systems are also hit, things can really spiral.

Rachel: 2:18

And this model has driven so much right Screening, like for BRCA.

Mark: 2:22

Yeah, brca, tp53 markers, all that. And drug development too, those targeted therapies aiming at specific mutations, even how we classify cancers, you know, based on their genetic subtypes it's all flowed from the SMT.

Rachel: 2:34

But there must be cracks in that foundation, or we wouldn't be having this conversation. What are the issues? What doesn't the SMT quite explain?

Mark: 2:43

Well, that's the thing. It's powerful, but it faces challenges like heterogeneity. You see two patients with the same type of cancer, but their tumors have totally different mutation sets.

Rachel: 2:56

And even within one tumor.

Mark: 2:57

Yeah, Massive variation sometimes. Then there's treatment resistance. You target one mutation. The tumor just seems to evolve. New mutations pop up. The drug stops working.

Rachel: 3:08

It's frustrating, and I guess the big one is finding cancers that don't even have those common mutations you'd expect.

Mark: 3:13

Exactly. Sometimes aggressive cancers lack the usual suspects, which leads to that big question Are the mutations really the cause, or are they maybe a symptom, a downstream effect of something else going wrong?

Rachel: 3:24

first, Okay, so that's the perfect lead-in to Seyfried and the metabolic hypothesis.

Mark: 3:32

He's taking Warburg's old observations and running with them. He really is.

Rachel: 3:34

He's building on that Warburg effect, the aerobic glycolysis thing Right, that weird thing where cancer cells ferment glucose like yeast does without oxygen, but they do it even when oxygen is available.

Mark: 3:45

Seems backwards inefficient. It does seem inefficient from a pure ATP perspective. Yeah, and Seyfried's big argument is this isn't just some weird side effect, he thinks this metabolic shift is causal, it's the driver.

Rachel: 3:56

And the root cause, he says, isn't the DNA in the nucleus, it's the mitochondria, the cell's power plants.

Mark: 4:03

That's the core hypothesis. It starts with mitochondrial dysfunction, damage to their ability to do their main job respiration.

Rachel: 4:10

Okay, so break down Seyfried's theory for us. What are the key steps or principles?

Mark: 4:14

All right. So first, something damages the mitochondria, impairs their respiration. Second, because they can't make energy properly that way, the cells switch strategy. They ramp up fermentation using glucose and also another fuel, glutamine.

Rachel: 4:28

Glucose and glutamine OK.

Mark: 4:29

Third, this messed up energy system is what fuels the crazy growth, the genomic instability, the resistance to cell death, all that cancer stuff.

Rachel: 4:37

And the mutations? Where do they fit in?

Mark: 4:39

He sees them as secondary. They happen, sure, but they're a consequence of this underlying metabolic chaos and the oxidative stress it generates, not the primary cause.

Rachel: 4:50

He really hammers this point in his book right that the altered metabolism is universal in cancer but specific mutations aren't always there.

Mark: 4:57

Exactly that. Universality is a key piece of his evidence. And then there are those fascinating nuclear cytoplasmic transfer experiments.

Rachel: 5:06

Oh yeah, Tell us about those. They sound crucial. Swapping bits between cells.

Mark: 5:10

Pretty much. You take the nucleus from a cancer cell with all its mutated genes and pop it into a healthy cell cytoplasm, one with healthy mitochondria.

Rachel: 5:18

And what happens? Does it become cancerous?

Mark: 5:20

Yep? Generally it doesn't. The mutations alone, in the context of healthy mitochondria, were enough to drive cancer.

Rachel: 5:27

Wow, ok, and the reverse Healthy nucleus, but damaged mitochondria.

Mark: 5:31

That's where it gets really telling. Put a healthy nucleus into cytoplasm with dysfunctional mitochondria and the cell starts acting cancerous even with normal genes.

Rachel: 5:41

So the state of the mitochondria seems to dictate the cell's behavior more than the nuclear DNA itself.

Mark: 5:47

That's the conclusion Seyfried draws. It's like the mitochondria are the operating system and they're corrupted. Doesn't matter as much what software the nuclear genes you're running.

Rachel: 5:55

That's a really different way of looking at it. It suggests we should be focusing on fixing mitochondria or maybe cutting off those fuels they're forced to use.

Mark: 6:03

Precisely. It opens up a whole avenue for therapies that could be, you know, less toxic, targeting the energy supply, restoring function.

Rachel: 6:10

Let's go back to that Warburg effect again. It seems so central. Remind us exactly what it is and why Seyfried thinks it points to mitochondrial failure.

Mark: 6:19

Sure. So the Warburg effect. Cancer cells prefer glycolysis. They ferment glucose into lactate even with oxygen around Normal cells. With oxygen would fully oxidize glucose in the mitochondria for way more energy.

Rachel: 6:35

Much more ATP that way.

Mark: 6:36

Loads more. Warburg spotted this nearly 100 years ago. It's a hallmark of most cancers.

Rachel: 6:41

And Seyfried's take is this isn't a choice, it's a necessity because the mitochondria are broken.

Mark: 6:46

That's his interpretation. Yes, damaged mitochondria just can't handle the normal oxidative process efficiently, so the cell compensates. It ramps up glucose intake, ramps up glutamine intake and pushes them through fermentation pathways instead.

Rachel: 7:01

But why fermentation If it's less efficient for ATP? What's the upside for the cancer cell?

Mark: 7:06

Well, several things. One if your mitochondria are busted, you don't have much choice for getting energy quickly. Glycolysis and glutamine metabolism give you some ATP. Two these pathways aren't just about ATP. They spin off building blocks.

Rachel: 7:19

Building blocks.

Mark: 7:20

Yeah, the raw materials, nucleotides for dna, lipids for membranes, amino acids needed to build new cells rapidly.

Rachel: 7:26

fermentation is good for that ah, okay, so fuels growth directly, not just energy right.

Mark: 7:32

And third, it seems to help them survive in low oxygen areas within a tumor, the hypoxic zones and the inefficiency in at they just make up for it by grabbing way more glucose.

Rachel: 7:42

That's why PE scans light up tumors.

Mark: 7:44

Exactly they become glucose augs. But there are other potential perks too. This metabolic state might protect them from oxidative stress, resist programmed cell death. Basically helps them survive under tough conditions.

Rachel: 7:57

So Seyfried sees cancer cells as metabolically inflexible, stuck in this fermentation mode.

Mark: 8:03

Very much so that inflexibility is key. Healthy cells can usually switch fuels pretty easily. Cancer cells, according to this theory, get locked into, relying heavily on glucose and glutamine.

Rachel: 8:14

And that inflexibility, that's the weakness, that's the target.

Mark: 8:18

That's the potential Achilles heel. Yes, If they're so dependent on these specific fuels, maybe we can cut off the supply.

Rachel: 8:24

Which brings us neatly to the therapeutic side. If cancer is metabolic, maybe treatment should target metabolism.

Mark: 8:30

Logically yes. Instead of just focusing on DNA mutations, focus on how the cancer cell fuels itself, and this leads directly to metabolic therapies. The best known example is probably ketogenic metabolic therapy, or KMT.

Rachel: 8:43

The keto diet high fat, super low carb. How does that target cancer metabolism?

Mark: 8:48

Well, the keto diet forces your body into ketosis. You start burning fat and producing ketone bodies for energy, instead of relying on glucose from carbs.

Rachel: 8:58

Okay.

Mark: 8:58

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 food source.

Rachel: 9:10

You essentially starve them of glucose.

Mark: 9:12

That's the goal. But importantly, your healthy cells, especially your brain and muscles. They can adapt. They switch over to using ketones quite well.

Rachel: 9:20

So it's potentially selective hits the cancer cells harder than the normal cells.

Mark: 9:24

That's the principle Create a metabolic environment that favors healthy cells and stresses the cancer cells. Plus, keto might have other benefits, like what it could lower insulin and IGF-1 growth factors that can push cancer growth. It might reduce inflammation, oxidative stress, maybe even hinder angiogenesis, the growth of new blood vessels tumors need.

Rachel: 9:44

Has this been tested in people with cancer? Are there studies?

Mark: 9:47

There are preliminary studies. Yes, A pilot study, for instance, showed advanced cancer patients could tolerate a ketogenic diet and it did seem to reduce glucose availability in 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, better response when combined with chemo or radiation, longer survival times. But you know, translating that to 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 drugs called glutaminase inhibitors that block the enzyme cancer cells used to process glutamine. Some people explore strategic fasting protocols which can lower overall amino acid levels, including glutamine, and there are older drugs, like Dawn, that interfere with glutamine metabolism, though they can have toxicity issues.

Rachel: 10:49

So the ideal approach might be hitting both keto for the glucose, plus something to limit glutamine.

Mark: 10:55

That's the idea behind a more comprehensive metabolic strategy, a sort of dual fuel blockade. It aims to be a less toxic system level attack, exploiting those metabolic weaknesses.

Rachel: 11:08

It sounds like a really different paradigm for treatment, maybe a foundation, especially for tricky cancers or earlier stages.

Mark: 11:15

Sievried certainly proposes it could be foundational, yeah, particularly for maybe resistant tumors or where options are limited. It's a very different way of thinking.

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 of interest, but also significant criticism and skepticism. It's definitely not mainstream oncology 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 mitochondrial defect is the absolute start of it all, the primary cause, versus genetic mutations. That's where the main disagreement lies. The traditional SMT view is still very dominant.

Rachel: 11:52

What are the key arguments for Seyfried's metabolic view? What's the evidence supporters point to?

Mark: 11:56

Well, number one is that metabolic pattern consistency, the Warburg effect or something like it, is seen in nearly all cancers, despite huge genetic variety. That suggests a common metabolic vulnerability.

Rachel: 12:09

Okay, the universality.

Mark: 12:11

Then there's the reversibility seen in those lab experiments. Putting healthy mitochondria back into cancer cells can sometimes make them behave normally again. That strongly employs metabolism, 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, small trials, 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 not definitive yet.

Rachel: 12:39

Okay. And the counter arguments, the criticisms? Why isn't everyone jumping on board?

Mark: 12:44

The biggest one is the lack of large scale randomized, controlled trials in humans. That's the gold standard for proving a therapy works, and we just don't have that for metabolic 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's heterogeneity. Again, maybe not all cancers are that glucose dependent. Some might adapt, find other fuels, even on keto. Brain cancer, pancreatic cancer are often mentioned as potentially tricky.

Rachel: 13:14

And, practically speaking, sticking to a strict keto diet. That's tough for anyone, let alone someone going through cancer treatment.

Mark: 13:21

Compliance is a real challenge, absolutely. People feel unwell, lose their appetite, it's difficult and finally, many researchers feel it'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 likely influence each other in complicated feedback loops. It's probably not a simple one-way street. So maybe the future isn't metabolic versus genetic, but metabolic and genetic. That seems like a much more likely and probably more productive path forward. An integrated view is gaining ground.

Rachel: 13:53

How would that work? Maybe mitochondrial issues kick things off, creating metabolic stress?

Mark: 13:58

Which then leads to genomic instability, making mutations more likely, or it creates an environment where cells with certain mutations thrive. It's plausible. The initial trigger might vary, but the metabolic dysfunction becomes a core feature and a vulnerability.

Rachel: 14:13

So in this combined model, metabolism is still a key target, but you don't ignore the genetic context.

Mark: 14:19

Precisely, metabolism is a driver and a target. Mutations tell you about the specifics of that tumor and, importantly, it brings in things like diet and lifestyle as factors that can influence both energy regulation and gene expression. Gives you, the listener, potentially more agency.

Rachel: 14:37

Which logically leads to integrative treatments combining the best of both worlds.

Mark: 14:41

Absolutely Imagine combining precision medicine, using genetic info to guide targeted drugs or immunotherapy, with metabolic strategies like nutritional ketosis, maybe calorie restriction, perhaps even drugs targeting glutamine or therapies to support mitochondria.

Rachel: 14:55

And maybe things like hyperbaric oxygen exercise, things that affect metabolism too.

Mark: 14:59

Yes, adjunctive therapies that influence the tumor's metabolic environment could fit into a broader, more holistic plan. The idea is to hit the cancer from multiple angles.

Rachel: 15:09

Targeting both the genetic vulnerabilities and these metabolic dependencies. That sounds like a powerful way to potentially overcome treatment resistance.

Mark: 15:18

That's the hope that by addressing both you get better outcomes, maybe with less toxicity, better quality of life. It brings Seyfried's quote back into focus you need to address the origin. If metabolism is part of that origin, you need to address metabolism.

Rachel: 15:33

Okay, so, wrapping this up, the core challenge we've explored is this idea of cancer as primarily a metabolic disease, shifting focus from just genes.

Mark: 15:42

Right Dr Seyfried's central thesis. It's a disorder of the mitochondria forcing cells into inefficient fermentation using glucose and glutamine.

Rachel: 15:50

And genetics isn't irrelevant, but perhaps secondary the consequence of this initial energy crisis.

Mark: 15:55

That's his view. The mutations are part of the evolution, but the metabolic problem comes first, or is at least a critical early step.

Rachel: 16:02

And the really profound implication is that cancer might be vulnerable to non-toxic diet-based approaches like ketogenic therapy.

Mark: 16:10

Yeah, the potential is there. Animal studies and early human data show promise slowed growth, maybe better outcomes, quality of life improvements. But we absolutely need more rigorous human trials. That's critical.

Rachel: 16:24

But looking bigger picture, it suggests cancer prevention and management might rely not just on high tech drugs but also on really supporting our basic metabolic health.

Mark: 16:33

Through diet, maybe fasting, focusing on mitochondrial health. It's a more holistic perspective.

Rachel: 16:39

And for those of you listening, interested in your own metabolic health, our sponsor, quicklab Mobile, does offer that in-home testing for things like fasting, insulin, ketones, glucose, lipids, inflammation markers, letting you get a clearer picture of your own metabolic state.

Mark: 16:53

It really comes down to that powerful closing thought, doesn't it? Cancer is complex, yes, but maybe 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 think about.

Rachel: 17:05

Definitely food for thought. Thanks for taking this deep dive with us today. We hope it gave you a lot to consider.

Nicolette: 17:20

Thanks for tuning into the Health Pulse. If you found this episode helpful, don't forget to subscribe and share it with someone who might benefit. For more health insights and diagnostics, visit us online at wwwquicklabmobilecom. Stay informed, stay healthy and we'll catch you in the next episode.