Metabolic Theory of Cancer: Speculation on the Causes of Cancer -- and How to Mitigate Them (Pt.5B)

Okay!

I left off last time saying that we have two big issues to address with regard to hypoxia as a cause or exacerbating factor in cancer: 

1. What causes tissue to become hypoxic?
2. Is there a role for hyperbaric oxygen therapy in fighting cancer?

  

Let’s tackle them in order.

To be honest with you, I still don’t know which comes first: low oxygen, or mitochondrial dysfunction. The fact is, even when there’s plenty of oxygen available, if the mitochondria are malfunctioning, they can’t use it. But what if what’s causing the mitochondria to malfunction is insufficient oxygen? (I told you last time this stuff is complicated!)

It almost doesn’t matter, right? The bottom line is, whether the tissue is hypoxic or not, the mitochondria are not using whatever oxygen might be present. (Well, they’re using some of it. Remember, kids, when it comes to biology and biochemistry, there are very rarely any absolutes, yes or no, on or off. Things aren't binary, but rather, there's a balancing act. Even cancer cells have some mitochondria that are okay; it’s just that the majority of them are messed up.)

I just have a hard time wrapping my head around it all. Think about angiogenesis: the creation of blood vessels specifically so that the cancerous tissue ensures it has a steady supply of fuel and nutrients. But what does blood carry besides fuel and nutrients? OXYGEN. So you would think that angiogenesis would give cancer cells more oxygen, not less. So going one step further, this being the case, it seems like the mitochondrial dysfunction comes first, because theoretically, there should be sufficient oxygen delivery to the cancer cells, what with all those blood vessels they created for their own nefarious purposes. So there is sufficient oxygen (“normoxia”), yet we have hypoxia-inducible factors out the yin-yang upregulating all sorts of nasty pathways and reactions in these cells to keep themselves alive because they think they’re hypoxic. And the reason they think they’re hypoxic is because the mitochondria aren’t using the oxygen. (That’s my logic, anyway. I told you there was going to be a lot of wild speculation here, and so it begins.)

Metabolic Theory of Cancer: Speculation on the Causes of Cancer -- and How to Mitigate Them (Pt.5A)

Graphic adapted from Seyfried et al., 2015

OH. EM. GEE!!!!!

It’s baaa-aaaaack!

Today is June 1, 2016. Looking back through the blog archives, I saw that the previous post in this series on the metabolic theory of cancer was published on June 1, 2015. Yes, kids, it’s been a year. A full year! An entire year to the day. If you have been waiting and waiting (and waiting!) for me to get back to this and address some key concepts we haven’t gotten to yet, believe me, nobody wanted me to get back to this more than I did. I absolutely did not plan on it taking a year. But alas. Hopefully, in that time, you’ve learned a thing or two about insulin, stubborn fat loss, and the use of ketogenic diets for Alzheimer’s disease and other neurological conditions. In fact, I am in the process of adding a new installment to the “ITIS/It’s the Insulin, Stupid” series, but when I saw that I was coming up on the one-year anniversary of neglecting the cancer series, I knew I had to get my rear in gear and just DO IT. I really wanted to do the insulin post first, but considering the date, I thought it would be apropos for me to do this one instead.

Also, just to let you know, since the writing of that last post, I have had the honor of meeting Drs. Seyfried, D’Agostino, and Poff in person. {Squee!!}  I also got to meet Dr. Cunnane, Dr. Newport, Dr. Rho, and Dr. Maffetone. Holy moly…it was a nonstop conference of metabolism rock stars.

I am most definitely going to get to the mamma-jamma, granddaddy of all topics we’ve been waiting for in this cancer series—the ketogenic diet—but please be patient. I’ve very recently had more work stuff come up (in a good way), and I am feeling a bit overwhelmed. I will write about ketosis. I can’t promise when, exactly, that will happen, but I promise it won’t take a year. (Maybe just a couple weeks, considering I’m already working on it.)  ;-)

If you’re new to my blog and have no idea what’s going on right now, the series I’ve written on the metabolic theory of cancer is a “fan favorite” – at least, among the people who like to geek out on the science with me. The cancer series is representative of when my blog becomes a free course in (very basic) biochemistry and physiology, and is peppered with links and quotes from the scientific literature. If you prefer my rants, shakedowns of food labels, and other casual-type posts, no prob! Whatever floats your boat. But for those of you who need to kill lots of time at your desk job, or who perhaps need help falling asleep, you might want to start way back at the beginning and work your way toward today’s post. (Actually, that’s sarcasm. The truth is, I think this stuff is fascinating, and perhaps some of my best work. I swear, that hexokinase 2 stuff STILL blows my mind.)

Since it has been a year (!!) since the last installment, I’ll make it easy for you and list all the posts in order, from first to most recent: 

1. Introduction
2. Cells Behaving Badly
3. Cellular Energy Generation 1 - Glycolysis
4. Cellular Energy Generation 2 - Mighty Mitochondria (Krebs Cycle, Electron Transport Chain)
5. Mitochondrial Dysfunction 1
6. Mitochondrial Dysfunction 2 - They ARE Broken
7. Glycolysis Run Amok & Mutant Hexokinase
8. Aerobic Fermentation (a.k.a. "The Warburg Effect")
9. Cancer Cells are Sugar Junkies
10. Mutations vs. Mitochondria
11. Cancer as a Protective Mechanism
12. Speculation on the Causes of Cancer (Pt.1)
13. Video Lesson! (Thomas Seyfried, PhD)
14. Speculation on the Causes of Cancer -- and How to Mitigate Risk (Pt.2)
15. Speculation on the Causes of Cancer -- and How to Mitigate Them (Pt.3 - Viruses)
16. Speculation on the Causes of Cancer -- and How to Mitigate Them (Pt.4 - Carcinogens)

Buckle up and hang on tight, everyone. HERE WE GO!

Podcast Interview - Ketogenic Diets for Neurological Health

For those of you who don’t follow me on Twitter or Facebook and missed the announcement last week, I’ve recorded another episode of the Real World Paleo Podcast with Christine Lehmann, the Reverse Diabetes Coach, and a fellow Nutritional Therapy Practitioner. (In fact, Christine and I met when we were in the same class for our NTP training.) You can check out the details here, and the show is available on iTunes and Stitcher.

You may recall I was on this show a few months ago, talking about ketogenic diets for Alzheimer’s disease. This time, we expanded the discussion to other neurological conditions, including Parkinson’s, ALS, epilepsy, and multiple sclerosis. We briefly touched upon the potential efficacy of ketogenic approaches for psychological conditions as well, such as schizophrenia, anxiety, and bipolar disorder. We also spent a few minutes talking about intermittent fasting and how it might be an additional tool in the arsenal to combat neurological and neurodegenerative conditions.

Why Am I Not Losing Weight on LCHF? (Pt.2 - Nutrients)

This is the second installment in a short-ish series looking at roadblocks to fat loss, even when it seems like you’re doing “all the right things.” If you missed part 1, you can check it out here, and here’s a link to a post about the complexity of weight loss in general.

Since we covered some of the “duh” stuff last time—the stuff that most of you are already aware of and were probably angry with me for even writing—this time, let’s get into some issues that might resonate with more of you, and, perhaps most importantly, provide you with information you can apply immediately if they do resonate.

In the series I wrote about insulin (which general consensus says totally kicked butt, by the way), I frequently used the word lipolysis. I explained that that’s just a fancy way to say “breaking down fat.” (“Lipo” for fat, and “lysis,” for splitting apart.) I further explained that lipolysis is the splitting of a triglyceride into its component pieces: a glycerol molecule and three fatty acids. The reason lipolysis is such an important process is that it is the method by which body fat is released from adipose tissue (fat cells), in order to travel through the blood to arrive at a destination where it can be burned for energy, such as in muscle cells. (10-second refresher: triglycerides are too large to pass through the cell membrane. In order for them to get out of the fat cell—which is what we want and need to happen in order to burn that fat—they have to be broken down into smaller pieces.)

As we also covered in the insulin posts, insulin gets in the way of lipolysis. (Scientifically speaking, insulin inhibits the enzyme hormone-sensitive lipase, which is what starts the lipolysis ball rolling.) This is one of the mechanisms by which low-carb diets work: keep insulin levels low, and lipolysis is free to proceed. Keep insulin levels high, and that fat ain’t goin’ nowhere, no-how.

But here’s the thing. And pay attention, because this is a very big thing:

Alzheimer’s, Ketones, and Kidding Ourselves (Pt.3/3)

I concluded the previous post by introducing the idea that, when it comes to a body and brain being fueled by ketones, the absolute concentration of ketone bodies in the blood might be less important than the body’s ability to use those ketones. I expressed concern that placing the sum total of our faith in high β-OHB levels might take our eyes off the marker we should probably be more interested in: how well an AD patient is functioning. Maybe some AD patients do require ketones at upwards of 4-5mM. But maybe some others would do just great at lower levels.

Here’s my thinking on this...

Alzheimer’s, Ketones, and Kidding Ourselves (Pt.2/3)

I ended the previous post by introducing the idea of using exogenous ketones for improving the signs and symptoms of Alzheimer’s, while not requiring the afflicted individual to make any dietary changes. (Recall that, according to researchers, a very low carb diet is “inconvenient” to prepare and consume.) Is there a place for exogenous ketones in AD therapy? Yes. I believe there is. It depends on the person’s age and severity of illness, but I absolutely acknowledge that exogenous ketones can improve quality of life. BUT: with the exception of some very specific cases, which I’ll mention in a bit, I cannot support them being used as the sole intervention. It’s as bad as telling a type-2 diabetic to use insulin and do nothing else to influence the way their body handles glucose, or, really, insulin, itself.  

Please tell me someone out there is on the same page as me here.

“Alzheimer's disease patients frequently undergo changes in food preference toward sweet, carbohydrate-rich foods, which would make compliance to a ketogenic diet difficult.” (Henderson et al., 2009)

Really? Do they undergo changes in food preference toward sweet, carbohydrate-rich foods after they develop Alzheimer’s disease, or are sugar addicts more likely to develop AD? Which is the chicken, and which is the Cadbury Crème Egg?

Now, here’s where things get deep.

Alzheimer’s, Ketones, and Kidding Ourselves (Pt.1/3)

  

The Setup

Picture the following scenario:

You find yourself walking from one room into another and can’t remember why. And it’s been happening more often.

You’ve been misplacing things. Your phone, your keys, your wallet or purse. And it’s been happening more often.

You’ve been forgetting about important appointments, and that’s happening more often, too.

But this isn’t a big deal, right? You’re just getting older. This is normal. “Senior moments.” Happens to everyone.

But what if things are a little worse than that?

What if you’re out running errands and forget how to get back home?

What if you go for a walk by yourself and get lost in your own neighborhood?

What if you set something on the stove to cook, then wander away for a few minutes, and the only reason you remember you had something cooking is because the smoke alarm goes off and acrid smoke fills the house?

What if you start asking people the same simple question—one they’ve already answered—over and over—and over again?

You’re not just having senior moments. You’re having entire senior days. Senior weeks. Senior months.

You are literally losing your mind.

Maybe it’s gotten so bad you’ve had to stop working.

Maybe your family no longer trusts you to be at home by yourself, or cook for yourself, or drive your car.

Scary, huh?

But what if I told you I could fix things for you?

Metabolic Theory of Cancer: Speculation on the Causes of Cancer -- and How to Mitigate Them (Pt.4)

We’re in the midst of exploring a few potential causes of cancer, and ways to possibly reduce risk. Up today: carcinogens. (If you’re new here, this post is pretty far down the line in a series that started back in November 2014, in which we are exploring the metabolic theory of cancer. Click here for the first post. Each one will end with a link to the next.) 

I have been saying that sometimes, people can do “all the right things,” and still end up developing some pretty gnarly health issues. I have also said that some of the diet and lifestyle factors we suspect might cause cancer (mostly by way of disrupting mitochondrial function) probably apply less to little kids than they do to older folks. So, aside from what we’ve already covered—viruses, age, and freaky mutations to mitochondrial DNA, what else might be causing cancer in babies and other people with no obvious risk factors?

Metabolic Theory of Cancer: Speculation on the Causes of Cancer -- and How to Mitigate Them (Pt.3)

Graphic modified from Seyfried, et al. 

Cancer as a metabolic disease: 

implications for novel therapeutics. 

Carcinogenesis. 2014 Mar; 35(3): 515–527.

VIRUSES

The potential cancer cause we’ll look at today is viruses. Some cancers are known to be viral in origin, and this makes total sense. Viruses hijack a cell’s replication machinery, right? They hijack the replication mechanisms such that the virus’ own DNA or RNA gets copied like crazy, so we’re left with lots of cells that contain tons of viral DNA/RNA. I am not a microbiologist, nor do I play one on TV. But I have to assume that having lots of viral DNA or RNA floating around in a cell probably isn’t good for mitochondria. Either way, if certain viruses do cause cancer, my guess would be that they do so by affecting mitochondrial function.

As a potential cause of cancer, viruses can strike people of any age. I suspect viruses are one of the primary drivers of cancer in children. I can’t imagine much else causing it. Like I said, older people have had many more years to abuse their mitochondria via diet, lifestyle, and unknown environmental exposures. But little kids? Not so much. Something else has got to be driving cancer in younger people. (And like I've said before, it’s entirely possible there’s a role for maternal & paternal health/diet at the time of conception and during gestation, as well as environmental exposures in utero, but, like the authors of the paper I mentioned in an earlier post said, if you think I’m about to blame the parents of a child with cancer for causing that child’s cancer, you are crazier than a vegan at a Brazilian churrascaria.)

In terms of prevention,  We can’t do much about this except to make sure our immune systems are up to snuff. I have said before that most of us probably “get cancer” all the time. We have cells behaving badly and doing wacky things left and right, but our immune systems go to work and kick those misbehaving cells to the curb. (Or the cells engage in apoptosis, commit suicide, and save our immune systems the trouble.) So how might we try to ensure our immune systems are up to the task? I was originally going have a separate post (or two or three!) about cancer prevention, but it seems more logical to address potential prevention/mitigation strategies in the same post as I write about putative causes. (I would be embarrassed to admit how much time I’ve spent going back and forth over this issue, about which most of you probably don’t care one way or the other.)

Metabolic Theory of Cancer: Speculation on the Causes of Cancer -- and How to Mitigate Risk (Pt.2)

If the previous post in this series on cancer (before the video) was unsettling, good! It was supposed to be. It was meant to remind us that cancer is a vile beast, and that it can spring up seemingly from out of nowhere. It strikes people who are total health trainwrecks, and people who, by all accounts, are healthy. (That is, except for the cancer...) It strikes old people, young people, fat people, thin people, rich people, poor people, PhDs, high school dropouts, men, women, and everybody somewhere in between.

We are working under the theory that cancer is a metabolic disease. Something damages mitochondrial function to the point that cellular metabolism is derailed, and all the nefarious things cancer cells do can be understood as logical sequelae of broken mitochondria and cells that are fighting to keep themselves alive. (Anyone else hearing “Eye of the Tiger” playing in their head right now? Hehheh. [BTW…to anyone out there in the Philadelphia area, I did the Broad Street Run several years ago and someone on the sidelines about a mile from the finish line had a boom box and they were playing that song, and it was awesome. Especially because the original Rocky is one of my all-time favorite movies, but I digress. Adrian!!])

I left off last time saying that, according to the metabolic theory of cancer, anything that contributes to mitochondrial dysfunction can be considered a potential cause of cancer. I think the reason older folks tend to have higher rates of cancer is simply that their bodies have been exposed to potential cancer-causing dietary, lifestyle, environmental, and unknown factors for longer than younger people’s bodies have been. That stuff’s gotta add up over time, no? Frankly, in this day and age, I think if you make it to 85 without getting cancer, you’re kind of a living miracle.

But recall that I made a point to emphasize that babies and toddlers get cancer, too, so it’s not only a matter of physiological insults building up over time. And it’s not just eating too much vegetable oil, or slurping down too much sugar, or being sedentary, or smoking, or being exposed to too much radiation, or whatever else we might speculate could cause cancer. There are other factors at work here.

Metabolic Theory of Cancer: Video Lesson!

Since I've fallen behind in churning out new posts in the cancer series on this blog, I wanted to share a little something with you to whet your appetite for more, and to remind you of all the amazing things we've covered so far. (I’ll get back to posting once I’ve written a few and have them in the hopper, ready to go, but I hope you’ll agree that finishing my Alzheimer’s book constitutes a “good cause” for having put things on hold.) 

I have quoted a ton from the work of Thomas Seyfried, PhD, and his colleagues & students. Here, you’ll get to see the man, himself, in action. If you’ve followed along in the series so far, you will be able to understand it all. In fact, you’ll know even more details than Dr. Seyfried goes into here. He only had 55 minutes, after all, and he wasn’t speaking to a room of molecular biologists or biochemists, so he kept things pretty general.  

Still, he managed to cover a lot of ground in less than an hour. He touches on the following, which you are now familiar with:

ANNOUNCEMENT!!

It’s a boy!

It’s a girl!

It’s a book!

I did it! The e-book I’ve been dropping hints about is finally finished and available for sale! Go check it out:

The Alzheimer’s Antidote: A Comprehensive Nutrition and Lifestyle Strategy to Fight Alzheimer’s Disease, Memory Loss, and Cognitive Decline.

I apologize for hawking my wares here, but I’ve got to get the word out, right? Just be thankful I am completely clueless about web design, otherwise you’d have annoying things popping up right in your face the minute my site loads, as you might be familiar with from other sites you frequent.

And since I am the least tech-savvy person alive, before I even tell you anything about the book, I would like to express my deepest and sincerest thanks to Ms. Ellen Davis, for her untiring support and encouragement on this project … and, oh, yeah, by the way, she did all the design and layout. I am not kidding when I say this book wouldn’t exist without her. I sent her all my writing in MS Word, sent all the images I either created or purchased (from iStock Photo, in case anyone’s curious), and she magically transformed them into the e-book that is going to change the way people think about Alzheimer’s and cognitive impairment. Ellen is not just a great designer, however. She is the mastermind behind the Ketogenic Diet Resource, the single best blow-your-mind, one-stop-shop I know of for information on low-carbohydrate and ketogenic diets. (She also happens to have a master’s in nutrition, and is the author of the fantastic, amazing book, Fight Cancer with a Ketogenic Diet. Her most recent project was a collaboration with Keith Runyan, MD, on Conquer Type 2 Diabetes with a Ketogenic Diet.)

Okay. Now that we’re done with the preliminaries, let’s get down to business!

Metabolic Theory of Cancer: Speculation on the Causes of Cancer (Pt.1)

Those of us who are steeped in the ancestral health paradigm sometimes get a little too big for our britches. Because we know a little more about the care and feeding of the human body than the average guy or gal on the street, we tend to think we have an explanation for just about every health-related issue there is. When someone we know is diagnosed with a chronic illness, it’s easy for us to say to ourselves, “If only he had done x, y, and z, this wouldn’t have happened.” Or, “If only she hadn’t done a, b, and c, she wouldn’t have ended up like this.”

And, sure, when it comes to things like type 2 diabetes, heart disease, obesity, difficulty conceiving, and the like, we do have plenty of answers. (Or think we do, anyway.) So we play the blame game. The afflicted individuals brought their conditions upon themselves by engaging in certain behaviors and/or not engaging in others. It’s not that we think they “deserve” whatever conditions they have; it’s just that we can readily identify things they did or did not do, that eventually brought those conditions about. (And in my opinion, in some cases, ignorant doctors hold just as much responsibility as the patients.)

But what about cancer? Anyone out there gutsy enough to say that someone with cancer had it comin’? I’m sure as heck not.

Metabolic Theory of Cancer: Cancer as a Protective Mechanism

“Cancer cells were producing energy in a way that evolution had set aside as an auxiliary pathway, a highly inefficient generator that kicked in when the power went out.” (Christofferson, p.20) 

“Tumors bypass many of the biochemical constraints that regulate metabolism, in order to maximize their survival at great expense to the host.” (Mathupala, Ko, Pedersen, 2010)

The amplified rates of glycolysis “indicate a strategy used by highly malignant tumors to survive as well as thrive within the host using a remarkable set of coordinated molecular mechanisms. These mechanisms, which are very similar to those utilized by some highly successful parasites, indicate a sophisticated strategy devised by tumors to survive even the most inhospitable microenvironments within the host.” (Mathupala, Rempel, Pedersen, 1997)

Throughout this series on the metabolic origins of cancer, I have been hinting that cancer—destructive, devastating, scary cancer—might be an evolutionarily conserved protective mechanism. I realize this is politically incorrect. But when we understand some of the biochemistry and physiology involved, this is actually a fairly logical conclusion to arrive at.   

I have gone to great lengths to explain some of the relevant biochemical pathways involved in how and why cancer cells accomplish all the seemingly horrible things they do. In looking at glycolysis, the shift to hexokinase 2, aerobic fermentation, the upregulation of glucose transporters, and more, we have explored a lot about the how of cancer. And we’ve certainly talked a bit about the why. Today, let’s go a little farther down the rabbit hole of the why, because, as I left off saying last time, if we can figure out why cells become malignant, we might have better odds at preventing cancer. We can certainly develop more effective treatment protocols if we understand the how of cancer, but understanding the why will give us even more of an advantage in devising treatments, as well as creating (potentially) better prevention strategies and strategies to prevent recurrence.    

Metabolic Theory of Cancer: Mutations vs Mitochondria

“Let’s get ready to RUUUUMBLLLLLE!”

“Maybe we’ve mischaracterized the origin of cancer. Maybe cancer is not a genetic disease after all. Maybe we are losing the war against cancer because scientists are chasing a flawed scientific paradigm, and cancer is not a disease of damaged DNA but rather one of defective metabolism.” (Christofferson, xiii)

“If scientists have mischaracterized the origin of cancer, then we have lost three decades trying to target mutations that are a side effect rather than the motor driving the disease. (Christofferson, p.223)

“It is interesting to note that none of the current approaches to brain cancer management discussed at a recent symposium involved strategies to target tumor cell energy metabolism. Several presentations at this symposium discussed the failures associated with current approaches to management. As long as [brain] cancer is viewed as something other than a disease of energy metabolism, the failures will likely continue in our opinion.” (Seyfried et al., 2012)

Metabolic Theory of Cancer: Cancer Cells are Sugar Junkies

“One of the most common and profound phenotypes of cancer cells is their propensity to utilize and catabolize glucose at high rates.” (Mathupala et al, 1997)

“The higher the glucose levels, the faster the tumors grew. As glucose levels fall, tumor size and growth rate falls.” (Seyfried et al., 2012)

“Hyperglycemia was also directly linked to poor prognosis in humans with malignant brain cancer.” (Seyfried et al., 2012)

Cancer cells are sugar junkies.

If those five words, strung together in that order, are a surprise to you, then you haven’t been paying much attention so far. If you’ve been keeping up with the previous posts in this series on the metabolic origins of cancer, you will have seen this coming a mile away. (Or, rather, four or five blog posts away.)

Cancer cells love glucose. They need glucose. And they do everything in their power to suck up as much of it as they possibly can, even at the expense of healthy tissue elsewhere in the body. Short of actually taking control of the motor functions of your arms and hands in order to pour you a giant bowl of sugar-frosted breakfast cereal and cram it down your throat, cancer cells do everything they can to ensure they have access to a never-ending supply of glucose. 

In the past few posts, we’ve looked in detail at the main reason why cancer cells do this, and a few mechanisms for how they do it. I have been saying all along that cancer cells are wily little things, and they perform some stunningly impressive feats of metabolic Twister in order to accomplish the nefarious task of keeping themselves alive by gorging on glucose.

Since it’s been a while since the last post, let’s take a quick look back at what we’ve covered so far, regarding cancer cells’ dependence on glucose as their primary fuel.

Metabolic Theory of Cancer: Aerobic Fermentation (a.k.a. "The Warburg Effect")

Did I blow your mind with that mutated hexokinase stuff in the previous post? (To be honest, it blew my mind, when I first read about it. Still does, actually.)

You can see that as we gather more pieces of this puzzle, cancer cells’ voracious appetite for glucose is starting to reveal itself. So is—for lack of a better term— the intelligence of cancer cells. These little buggers are good at doing whatever they need to in order to stay alive, aren’t they? I mean, their mitochondria are broken. But they need fuel. And because the mitochondria are broken, the only fuel they can use successfully is glucose. So they start using this variation of hexokinase in order to make sure that glycolytic metabolism will never stop. Crazy! (Yet ingenious, no?)

As an aside, I have to mention here that cancer seems to be a metabolic condition every bit as much as Alzheimer’s disease is, but they are opposite sides of the same coin: In both conditions, the mitochondria have lost the ability to effectively generate ATP. In Alzheimer’s, the protective mechanism involves cells shutting off the glucose spigot, whereas in cancer, the spigot is turned on full blast and never shuts off.

Last time, we discussed cancer cells ramping up glycolysis in order to feed themselves. And we left off saying that, as a result of this abnormal amount of glycolysis, we have a ton of pyruvate building up. And the fate of this pyruvate, as I’ve mentioned in past posts, is fermentation—an anaerobic process. But cancer cells do something interesting that most healthy cells don’t: they perform incredible amounts of fermentation even in the presence of oxygen.

Metabolic Theory of Cancer: Glycolysis Run Amok & Mutant Hexokinase

“The ability to sustain an enhanced glycolytic rate represents one of the most consistent and profound biochemical phenotypes of many cancer cells.”
                                            -Mathupala et al, 1997.


Through the previous posts in this series, we have woven a path through an introduction to the metabolic origins theory of cancer, some basic facts about cancer cells, cellular energy generation, mitochondrial structure & function, and potential causes of mitochondrial dysfunction. We have also established that there is a large degree of mitochondrial abnormality in cancer cells. We ended things last time by saying that we would explore cancer's next two most striking calling cards. So here we go. More of the metabolic hallmarks of cancer cells. (And finally, you will start to see why all my blabbing on and on about glycolysis and the Krebs cycle were necessary. I promise!)

Before we get into things today, I’d like to thank anyone who’s still along for the ride. I genuinely believe the metabolic theory of cancer holds an incredible amount of promise, and I consider it a privilege to be able to share with you my understanding—however rudimentary—of the science involved. It has occurred to me that, for the purpose of this series, my blog has become a free course in biochem & physiology, rather than the popular stuff with sensationalist, attention-grabbing headlines about adrenal fatigue, digestion, and women’s hormones. I may be getting far fewer page hits than the big boys and various “gurus” out there, but I sincerely think this could be life-saving information. (And frankly, between you and me…just us friends here…I’m kinda tired of all that adrenal/thyroid/digestion stuff, even if I do find it fascinating most of the time.) Based on the number of page hits, not too many folks are interested in this deep dive into the metabolic origins of cancer. Oh well. Their loss. I like writing about this, and I know there are at least one or two of you out there who value it, so I'll keep going. (And I will try not to be discouraged that other people's posts about “Paleo chocolate chip banana bread” and such generate more buzz than this supremely critical information.)

So to anyone out there who’s still with me, thank you. I hope you continue to find it worth your time.

Metabolic Theory of Cancer: Mitochondrial Dysfunction 2 - They ARE Broken

Class is back in session!

We have covered several hallmarks that make cancer cells different from healthy cells. I’ve been saying there are a few more we’ve been holding off on discussing until we laid a bunch of critical groundwork about cellular energy generation. Well, I'm happy to report that we have emerged from the biochemical weeds, and now, we’re ready to start addressing the first of those remaining hallmarks. 

I have been emphasizing all along that mitochondrial dysfunction is at the heart of the metabolic theory of cancer. Understanding the implications of this is so fundamental to our grasp of cancer as a metabolic disease that we have dedicated a couple of (very long) posts to exploring the structure and function of mitochondria. This was essential groundwork to lay, since we can’t understand what might happen when mitochondria malfunction if we don’t know how things are supposed to work when they’re healthy and everything’s groovy.

The rest of the series will focus on the ramifications of broken mitochondria. Most of the hallmarks of cancer cells make perfect sense as the logical results of mitochondria that are incapable of generating sufficient energy (ATP). But there’s a big, gaping hole in things so far. We haven’t actually established that mitochondria are malfunctioning in cancer cells. I’ve been saying so for a while, but what if I’m making that up? What if I’m just saying any old thing that makes sense because I want you to believe the rest of what I’m going to say? (“These aren’t the droids you’re looking for…”)

So today, let the official record show that mitochondria are abnormal in cancer cells. 

But before we get started, if you’ve just stumbled onto things here, you’ll want to fill yourself in on what we’ve covered so far:

• Introduction: Metabolic Theory of Cancer
• Cells Behaving Badly
• Cellular Energy Generation 1 - Glycolysis
• Cellular Energy Generation 2 - Mitochondrial Structure & Function
• Mitochondrial Dysfunction 1

Metabolic Theory of Cancer: Mitochondrial Dysfunction 1

Welcome to the next installment in my ongoing series exploring the metabolic theory of cancer.

If this is your first visit, you might want to check out the posts leading up to this:

1. Introduction
2. Cells Behaving Badly
3. Cellular Energy Generation 1 - Glycolysis
4. Cellular Energy Generation 2 - Mitochondria

Last time, we started exploring the structure and function of mitochondria, our cells’ main energy generators. I have been saying all along that mitochondrial dysfunction—the inability of mitochondria to generate sufficient energy (ATP)—is at the heart of the metabolic origins theory of cancer. Another leg of this table is mitochondrial insufficiency—too few mitochondria, even if they are functioning perfectly well. For today, though, we’ll focus on dysfunction.

The previous post left off saying we would take a look at a few things that can cause structural damage to mitochondria. And let’s remember: since structure determines function, if mitochondrial structure is compromised, then function will be compromised as well.