18 ms·

Why cancer cells waste so much energy

341 points by chmaynard 6y ago

deskamess 6y ago
So the cancer cells went with the non-blocking, albeit slower algorithm. With aerobic, pipelines could get filled with ATP and end up blocking the essential NAD+. So the optimization was a loosely decoupled slower fermentation process over the faster aerobic process. Back pressure avoided and all that. So tempting to go with analogies we are familiar with.
- blakesterz 6y ago
  "The findings suggest that drugs that force cancer cells to switch back to aerobic respiration instead of fermentation could offer a possible way to treat tumors. Drugs that inhibit NAD+ production could also have a beneficial effect, the researchers say." And hopefully that's a path to follow that will help treat/cure some types of cance? This all just barely makes sense to me, but my first question was "Does this help beat cancer in a new way?" and I guess the answer is... maybe?
  - loceng 6y ago
    It sounds like there's speculation that yes it potentially could, in theory, but it needs to be tested.
  - ben_w 6y ago
    Article also says that other cells using this process include immune cells, so I wouldn’t be on this being a silver bullet.
  - segfaultbuserr 6y ago
    It is a basic research question - it doesn't produce directly usable results, but the better understanding may be helpful in the long run.
  - majkinetor 6y ago
    Or maybe not because cancer cells do not exist in vacuum but are part of the body. You will force your own cells to do so: red blood cells, certain immune cells etc. We already do something along those lines - reducing sugar input via diet and sugar neogensis via metformin. Be all that as it may, the finding is astounding.
  - datavirtue 6y ago
    I'm waiting for them to suggest starving the cancer. That wouldn't keep the cancer industry going though. X
- inglor_cz 6y ago
  There is a relatively new theory saying that malignant, metastatic cancer cells behave like single cell organisms, and that cancer basically represents an unwanted return to our genetic roots; multicellular organisms used to be single cell organisms a billion years ago and the original genes might carry on within our DNA until today. But they should be switched off. Once they are switched on, the cells will stop cooperating with the rest of the tissue and start acting "selfishly", at others' expense. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474827/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474827/ This is known as "atavistic theory of cancer" and it is rather controversial, there are people who utterly hate it, not least because the original authors are not specialists in cancer treatment. Part of this theory is that cancer cells "cannot help but switch to the previous single-celled metabolism, very inefficient compared to ours".
  - deleted 6y ago
    [deleted]
  - im3w1l 6y ago
    > There is a relatively new theory saying that malignant, metastatic cancer cells behave like single cell organisms, This is the track they are on, but given how shortlived they are, they never get the chance to do much evolution. They only have time to learn a few tricks. Simple things like turning stuff of or up/downregulating existing systems. It's a strange step to "cannot help but switch to the previous single-celled metabolism, very inefficient compared to ours". Theory in article seems much more likely.
    - jetrink 6y ago
      > given how shortlived they are, they never get the chance to do much evolution There is a very rare category of cancers for which this is not true, clonally transmissible cancers[1]. They can move from individual to individual like other pathogens. One example is the devil facial tumor disease[2] that has killed around 95% of Tasmanian devils. 1. https://en.wikipedia.org/wiki/Clonally_transmissible_cancer https://en.wikipedia.org/wiki/Clonally_transmissible_cancer 2. https://en.wikipedia.org/wiki/Devil_facial_tumour_disease https://en.wikipedia.org/wiki/Devil_facial_tumour_disease
bfieidhbrjr 6y ago
YSK, cancer as a metabolic disease, and tripping over the truth, are excellent books about this, and why we got cancer wrong since watson and crick.
- chaganated 6y ago
  "Tripping Over The Truth," seconded.
  - antoniuschan99 6y ago
    I’m listening to his other books now, Ketones. There’s also Emperor of All Maladies (and his other book Genes) from another author that may be of interest.
    - avaldeso 6y ago
      > There’s also Emperor of All Maladies (and his other book Genes) from another author that may be of interest. Author name's Siddhartha Mukherjee. Great book, focused more on history of oncology than the biology of cancer though.
- dimitrios1 6y ago
  So I know that Gundry's book "Plant Paradox" is probably rife with some scientific hyperbole, but it's enticing for me to at least follow a system with this principle in mind: that you want to essentially mellow out your metabolism.
- LinuxBender 6y ago
  Here is a video on "Cancer as a Metabolic Disease: Implications for Novel Therapies" [1] by Prof. Thomas Seyfried that may be related. I think their research is very promising. [1] - https://www.youtube.com/watch?v=06e-PwhmSq8 https://www.youtube.com/watch?v=06e-PwhmSq8 [video]
  - PIKAL 6y ago
    I find the metabolic cancer hypothesis to be extremely compelling. Did you happen to find this link on HN originally?
foxhop 6y ago
At the end of the day life is a series of ever complex systems of inputs and outputs. I'm not surprised by the findings and the resolution to this paradox. When we look at apparent inefficiencies of life systems (singletons and complete systems) we have to take into account setting and environmental factors as well as the various layers of abstraction. Looking down at cancer (similar to a defect in software) and questioning why it behaves in seemingly counter intuitive ways makes it all the more appearent that we are still at the tip of our scientific and spiritual understanding for models of healthy systems, both cellularly and holistically as life on our planet. As above so below. Based on this research cancer switches to a process which accepts the inputs at hand and processes outputs for growth (often rapid growth). Regardless of how it looks as a spectator, the cells inside you make billions of individual decisions each second and those decisions may have eventual degrgations over time with enough entropy. The cell has blueprints and is on a mission, sometimes it's mission is corrupted or the order of operations is abnormal. I like how they make mention yeast fermentation as a similar process and I didnt know our cells could run both processes. I wonder why? Do we use fermentation at various parts of our human development?
- adrian_b 6y ago
  Most animals (actually not only the animals but most eukaryotic cells) can produce energy (in the form of ATP) by transforming glucose into lactic acid, exactly like in the lactic fermentation of milk into yogurt. (Some animals and some other eukaryotic organisms use other fermentation variants, e.g. alcoholic fermentation by yeasts or fermentation of glucose + water into acetic acid + carbon dioxide + dihydrogen in cells with hydrogenosomes.) The energy produced thus is many times lower than the energy that could be produced by oxidizing the same quantity of glucose into water and carbon dioxide. While the energy is low, the power is very high, because the fermentation is done by a simpler sequence of reactions and a much larger quantity of glucose can be fermented in a given time than the quantity that could be fully oxidized. So the difference between using glucose fermentation and using the oxidation of either glucose or fat is like the difference between using supercapacitors and using batteries. Some devices are optimized for high power but lower energy storage capacity, while others are optimized for low power but much higher energy capacity. In most cells there is a more complex hierarchy of energy-producing mechanisms, which are ordered from the highest power and lowest energy capacity to the lowest power and the highest energy capacity. For example, in the muscles of vertebrates, you have, in the order from above, ATP hydrolysis, phosphocreatine hydrolysis, glucose fermentation and finally glucose & fat oxidation. The vertebrates are actually much better than most other animals at glucose fermentation, which gives them a significant advantage. Because of that, the vertebrates are able of short bursts of activity that use a very high power, e.g. running short distances or jumping or catching a prey, before having to reduce the power to the lower level that can be sustained for a long time by the aerobic oxidation.
deleted 6y ago
[deleted]
yholio 6y ago
This is the type of fundamental research that private labs do not typically pursue, yet might yield revolutionary treatments.
- zaroth 6y ago
  Was it public or private labs that did all the amazing mRNA research?
  - PeterisP 6y ago
    50/50 - as with most things, the initial breakthroughs took 10+ years in public labs (e.g. the work by Kariko & Weissman), and one it was clear that the new idea works and roughly how it could be used, it took 10 or so years in private labs to make it practical and scalable. Also, it's not exactly accurate to view something as "developed in public lab" or "developed in private lab", as often (also in this case) the research is done by the same people but they do the early stage in a public lab and then move on to (or create) a private lab for the later stage of technological readiness.
whalesalad 6y ago
I’m curious to see how fasting might influence cancer treatment. I know in other parts of the world it is seen as a legitimate treatment, while also potentially considered to be a hippy dippy homeopathic treatment. Anecdotally it seems you can starve certain cancers to death pretty easily by severely limiting your caloric intake. I sense a relationship between that and this study.
- dplgk 6y ago
  This didn't work for Steve Jobs
  - simplemen 6y ago
    He wasn't fasting, he was on fruits diet.
    - Technically 6y ago
      What's the metabolic difference between major and complete fasting? I honestly have no idea.
    - jaywalk 6y ago
      Yeah, and he also had a highly treatable form of cancer and access to the best medical care in the world. Unfortunately his arrogance got the best of him.
    - dplgk 6y ago
      He drank carrot juice which I'd say is severely limiting your caloric intake.
      - Dirlewanger 6y ago
        Limiting your caloric intake is not the same as fasting.
      - teknopurge 6y ago
        Also keep in mind that sugar is the enemy. Your body has chemistry to make sugar - there is no-need to ingest it.
balthasar 6y ago
Cancer is bad
aszantu 6y ago
I've been thinking and came to the conclusion that cancer might be a way of the body to get rid of excess sugar and maybe other toxins. Many cancers seem to respond well when ppl go keto for example
- shishy 6y ago
  That’s.... backwards. Excess sugars and toxins promote environments that are favorable for cancer promotion (eg by weakening immune system by down regulating certain cells within the tumor microenvironment or activating metabolic pathways that should be inhibited and so on).
  - datavirtue 6y ago
    Yep. The guys who did that China Study were feeding aflotoxins (difficult to detect mold toxins) to rats and then fed them milk casin to trigger cancer. Then they would stop feeding them the casin to turn off the cancer.
- majkinetor 6y ago
  Seems a bit extreme don't you think ? Getting rid of the sugar by getting rid of the host, sounds like those AI fatalistic movies where curing misery involves killing all humans.
- hoka-one-one 6y ago
  Can we have one health thread where no one shills their fad eating disorder diet? Just one?
- crubier 6y ago
  In this thread: Web engineers turned Cancer specialists.
  - shishy 6y ago
    Well I used to do Cancer research at the NCI before going back to software! :)
hlfy_hn 6y ago
Dichloroacetate influences NAD+ level (but increases)
calebkaiser 6y ago
The research around NAD+ production and cancer proliferation may also give some causal explanation--or at least, a place to start looking--for the correlation between B vitamin supplementation (edit: folic acid, specifically) and increased cancer rates/fatalities in certain high-risk populations: https://www.webmd.com/cancer/news/20091117/folic-acid-b12-may-increase-cancer-risk https://www.webmd.com/cancer/news/20091117/folic-acid-b12-ma...
- majkinetor 6y ago
  Not B vitamins, but folic acid (just one of them). Folic acid is required for stable DNA, something that cancer doesn't need at all (it needs mutations for plasticity). Its also needed for DNA production, but many more cells need it, those that have short lifespan - cells lining the stomach for example, sperm cells, some immune cells etc.
  - calebkaiser 6y ago
    Good point--I amended my original comment to specify folic acid. What you're saying about stable DNA makes sense. I'm curious, though, if the supplementation helps the body generate more NAD+ (relative to someone with a deficiency), and if that could help cancer proliferate in its earliest stages (hence why the correlation is most pronounced in people already likely to develop cancer--smokers).
    - majkinetor 6y ago
      That is the whole problem - everything that benefits your body, benefits cancer and vice-versa. Cancer forms all the time - body should handle it when functioning correctly (via immune system). NAD is essential for many functions, especially longevity as sirtuins require it for proper function. As far as I know only massive Vitamin C doses uniquely influence cancer in negative manner and get pretty much no effect on non cancer cells. Massive vitamin C infusions (which work via mechanism similar to chemotherapy) while can't cure cancer per se, have potential to make life span and quality of life much longer (toward chronic disease).
jgilias 6y ago
Very interesting. Another result showing how increased NAD+ levels 'benefit' cancer cells casting a shadow on the idea of NAD+ boosting supplementation to increase healthspan and lifespan. But then, it's not like this means that heightened NAD+ levels cause cancer. Just that it is plausible that it makes it more aggressive, once you have it.
- majkinetor 6y ago
  Why doubt? It only proves that supplements work as indented in prolonging eycariotic cell life. Its just that you don't want everything in your body to be boosted, just some - cancer is just one of those, you don't want various constituents of your body flora influenced as well, like parasites, harmful microbiota etc.
  - jgilias 6y ago
    So the trick is figuring out how to boost the things you want to boost without boosting or preferably even inhibiting things you don't want to boost. Actually, this echoes what is sometimes said about curing cancer. That it's pretty easy to kill cancer. The problem is in keeping people alive in the process. In either way, I'm pretty excited by all the recent findings and breakthroughs in both fields - longevity and figuring out cancer.
majkinetor 6y ago
Obligatory: https://imgs.xkcd.com/comics/cells_2x.png https://imgs.xkcd.com/comics/cells_2x.png (not because of article which describes mechanism, but because of people who will jump to conclusion)
tyingq 6y ago
This is why PET scans work well for highlighting cancer as bright spots. The injected 18F-FDG marker looks like glucose to the cancer cells, and is consumed by them for the energy.
- majkinetor 6y ago
  Yeh, PET scans are eye opening.
vmception 6y ago
If they really take this approach of targeting NAD+ production, which other types of "fast growing cells" will this kill? People will still go bald?
mncharity 6y ago
I enjoyed Zhaoqi Li's associated thesis defense "Bioenergetics and Metabolism of Eukaryotic Cell Proliferation" a few weeks ago. I don't quickly find his defense or thesis available online yet, but this paper[1] (open access) looks similar. Here's his twitter.[2] And a profile[3]. Someday we'll need to address the issue that talks, with their more extensive and accessible graphics and explanations, are less available to the public than papers. [1] https://www.sciencedirect.com/science/article/pii/S1097276520309047 https://www.sciencedirect.com/science/article/pii/S109727652... [2] https://twitter.com/zhaoqili https://twitter.com/zhaoqili [3] https://biology.mit.edu/graduate/why-mit-biology/graduate-testimonials/profile-zhaoqi-li/ https://biology.mit.edu/graduate/why-mit-biology/graduate-te...
wombatmobile 6y ago
In 2017, Berridge and Neuzil reported that stromal cells can donate healthy mitochondria to respiration-deficient tumor cells, restoring normal respiration as well as their ability to form tumors in mice. https://onlinelibrary.wiley.com/doi/full/10.1111/1440-1681.12764 https://onlinelibrary.wiley.com/doi/full/10.1111/1440-1681.1...
oedmarap 6y ago
Worth noting that unlike the cells of the human body, cancer cells are unable to utilize ketones as an energy source[0][1], hence the benefits of a ketogenic diet. A ketogenic diet can also be ideally coupled with intermittent fasting[2] in order to engage/enhance autophagy within the body. [0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842847/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842847/ [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/ [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257056/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257056/
- dpatrick86 6y ago
  Your point may be broadly true but subject to important caveats. Cancer is a very heterogeneous disease. There is evidence that _some_ cancers can use, for example, acetoacetate. https://www.sciencedaily.com/releases/2017/01/170112141359.htm https://www.sciencedaily.com/releases/2017/01/170112141359.h...
- mehrzad 6y ago
  Back when I had cancer in 2015, I read about this effect but I also read there was some potential danger in the cancer cells adapting to ketosis and accelerating their growth, so I thought it seemed too risky. It seems like the research may have improved since then though to suggest some benefit.
  - mkrishnan 6y ago
    Congrats.
  - eloff 6y ago
    I don't follow your logic there, cancer cells have an effective metabolism by default, so the chance that they can adapt to ketosis seems much better odds than the 100% that they're already adapted to your diet. But I'm very glad that whatever your decision, you're still among the living! Cancer is a terrifying diagnosis.
- wonder_er 6y ago
skadamou 6y ago
Here is an NCBI article about the Warburg effect that I found illuminating https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783224/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783224/
jacobn 6y ago
Does the difference in metabolic pathway lead to e.g. different waste products present in the blood? I.e. could you do a blood test to detect elevated levels of fermentation-based metabolism, indicating that it might be time to do a deeper cancer screen?
- paxswill 6y ago
  Lactate Dehydrogenase (LDH) is one test that uses this effect and it is used for monitoring some cancers. It's non-specific to cancer, but elevated levels can be cause by a range of not-great conditions. https://en.wikipedia.org/wiki/Lactate_dehydrogenase#Testing_in_cancer https://en.wikipedia.org/wiki/Lactate_dehydrogenase#Testing_...
pazimzadeh 6y ago
The summary is that NAD+ is limited for cancer cells, so NAD+ depletion could be a promising cancer therapy. On the other hand, a recent paper shows that NAD+ replenishment reverts tumor resistance to immunotherapy, so those therapies shouldn't be combined. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30554-4 https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)...
mountainboy 6y ago
I suggest that anyone interested in this topic research Johanna Budwig and her Budwig Protocol. She was a world expert on essential fats as well as a physicist. Her work directly followed on that of Otto Warburg, and it is said she cured many many people of Cancer. Having tried her "Budwig Protocol" myself at a time when my energy levels were so low that I had to quit my job and focus only on recovering my health, I can attest that it truly works for delivering more oxygen and thus energy and vitality to one's cells. Today I am healthy and feel much better than I did 5 years ago.
kypro 6y ago
I take a daily dose of NMN to boost NAD+ levels. I was aware that NAD+ could accelerate cancer growth, but does anyone know if there's any evidence to suggest NAD+ could cause cancer or at least increase the likelihood of developing it? From what I understand most experts seem to think it's probably safe and will extend health & life span, but the cancer risk is something that concerned me when I started. Surely if healthspan was as easy as just raising NAD+ levels the body would have already evolved this trait?
thornjm 6y ago
I posted this in a few cancer threads with good response: the seminal work on cancer is actually a really quite approachable and short free paper - “Hallmarks of Cancer” by Hanahan and Weinberg. For anyone wishing to understand the fundamental features and survivorship bias that all cancer cells go through I highly recommend it. I think this is an updated version: https://www.cell.com/fulltext/S0092-8674(11)00127-9 https://www.cell.com/fulltext/S0092-8674(11)00127-9

341 points by chmaynard 6y ago

So the cancer cells went with the non-blocking, albeit slower algorithm. With aerobic, pipelines could get filled with ATP and end up blocking the essential NAD+. So the optimization was a loosely decoupled slower fermentation process over the faster aerobic process. Back pressure avoided and all that. So tempting to go with analogies we are familiar with.

blakesterz 6y ago
"The findings suggest that drugs that force cancer cells to switch back to aerobic respiration instead of fermentation could offer a possible way to treat tumors. Drugs that inhibit NAD+ production could also have a beneficial effect, the researchers say." And hopefully that's a path to follow that will help treat/cure some types of cance? This all just barely makes sense to me, but my first question was "Does this help beat cancer in a new way?" and I guess the answer is... maybe?
- loceng 6y ago
  It sounds like there's speculation that yes it potentially could, in theory, but it needs to be tested.
- ben_w 6y ago
  Article also says that other cells using this process include immune cells, so I wouldn’t be on this being a silver bullet.
- segfaultbuserr 6y ago
  It is a basic research question - it doesn't produce directly usable results, but the better understanding may be helpful in the long run.
- majkinetor 6y ago
  Or maybe not because cancer cells do not exist in vacuum but are part of the body. You will force your own cells to do so: red blood cells, certain immune cells etc. We already do something along those lines - reducing sugar input via diet and sugar neogensis via metformin. Be all that as it may, the finding is astounding.
- datavirtue 6y ago
  I'm waiting for them to suggest starving the cancer. That wouldn't keep the cancer industry going though. X
inglor_cz 6y ago
There is a relatively new theory saying that malignant, metastatic cancer cells behave like single cell organisms, and that cancer basically represents an unwanted return to our genetic roots; multicellular organisms used to be single cell organisms a billion years ago and the original genes might carry on within our DNA until today. But they should be switched off. Once they are switched on, the cells will stop cooperating with the rest of the tissue and start acting "selfishly", at others' expense. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474827/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5474827/ This is known as "atavistic theory of cancer" and it is rather controversial, there are people who utterly hate it, not least because the original authors are not specialists in cancer treatment. Part of this theory is that cancer cells "cannot help but switch to the previous single-celled metabolism, very inefficient compared to ours".
- deleted 6y ago
  [deleted]
- im3w1l 6y ago
  > There is a relatively new theory saying that malignant, metastatic cancer cells behave like single cell organisms, This is the track they are on, but given how shortlived they are, they never get the chance to do much evolution. They only have time to learn a few tricks. Simple things like turning stuff of or up/downregulating existing systems. It's a strange step to "cannot help but switch to the previous single-celled metabolism, very inefficient compared to ours". Theory in article seems much more likely.
  - jetrink 6y ago
    > given how shortlived they are, they never get the chance to do much evolution There is a very rare category of cancers for which this is not true, clonally transmissible cancers[1]. They can move from individual to individual like other pathogens. One example is the devil facial tumor disease[2] that has killed around 95% of Tasmanian devils. 1. https://en.wikipedia.org/wiki/Clonally_transmissible_cancer https://en.wikipedia.org/wiki/Clonally_transmissible_cancer 2. https://en.wikipedia.org/wiki/Devil_facial_tumour_disease https://en.wikipedia.org/wiki/Devil_facial_tumour_disease

bfieidhbrjr 6y ago

YSK, cancer as a metabolic disease, and tripping over the truth, are excellent books about this, and why we got cancer wrong since watson and crick.

chaganated 6y ago
"Tripping Over The Truth," seconded.
- antoniuschan99 6y ago
  I’m listening to his other books now, Ketones. There’s also Emperor of All Maladies (and his other book Genes) from another author that may be of interest.
  - avaldeso 6y ago
    > There’s also Emperor of All Maladies (and his other book Genes) from another author that may be of interest. Author name's Siddhartha Mukherjee. Great book, focused more on history of oncology than the biology of cancer though.
dimitrios1 6y ago
So I know that Gundry's book "Plant Paradox" is probably rife with some scientific hyperbole, but it's enticing for me to at least follow a system with this principle in mind: that you want to essentially mellow out your metabolism.
LinuxBender 6y ago
Here is a video on "Cancer as a Metabolic Disease: Implications for Novel Therapies" [1] by Prof. Thomas Seyfried that may be related. I think their research is very promising. [1] - https://www.youtube.com/watch?v=06e-PwhmSq8 https://www.youtube.com/watch?v=06e-PwhmSq8 [video]
- PIKAL 6y ago
  I find the metabolic cancer hypothesis to be extremely compelling. Did you happen to find this link on HN originally?

foxhop 6y ago

At the end of the day life is a series of ever complex systems of inputs and outputs. I'm not surprised by the findings and the resolution to this paradox. When we look at apparent inefficiencies of life systems (singletons and complete systems) we have to take into account setting and environmental factors as well as the various layers of abstraction. Looking down at cancer (similar to a defect in software) and questioning why it behaves in seemingly counter intuitive ways makes it all the more appearent that we are still at the tip of our scientific and spiritual understanding for models of healthy systems, both cellularly and holistically as life on our planet. As above so below. Based on this research cancer switches to a process which accepts the inputs at hand and processes outputs for growth (often rapid growth). Regardless of how it looks as a spectator, the cells inside you make billions of individual decisions each second and those decisions may have eventual degrgations over time with enough entropy. The cell has blueprints and is on a mission, sometimes it's mission is corrupted or the order of operations is abnormal. I like how they make mention yeast fermentation as a similar process and I didnt know our cells could run both processes. I wonder why? Do we use fermentation at various parts of our human development?

adrian_b 6y ago
Most animals (actually not only the animals but most eukaryotic cells) can produce energy (in the form of ATP) by transforming glucose into lactic acid, exactly like in the lactic fermentation of milk into yogurt. (Some animals and some other eukaryotic organisms use other fermentation variants, e.g. alcoholic fermentation by yeasts or fermentation of glucose + water into acetic acid + carbon dioxide + dihydrogen in cells with hydrogenosomes.) The energy produced thus is many times lower than the energy that could be produced by oxidizing the same quantity of glucose into water and carbon dioxide. While the energy is low, the power is very high, because the fermentation is done by a simpler sequence of reactions and a much larger quantity of glucose can be fermented in a given time than the quantity that could be fully oxidized. So the difference between using glucose fermentation and using the oxidation of either glucose or fat is like the difference between using supercapacitors and using batteries. Some devices are optimized for high power but lower energy storage capacity, while others are optimized for low power but much higher energy capacity. In most cells there is a more complex hierarchy of energy-producing mechanisms, which are ordered from the highest power and lowest energy capacity to the lowest power and the highest energy capacity. For example, in the muscles of vertebrates, you have, in the order from above, ATP hydrolysis, phosphocreatine hydrolysis, glucose fermentation and finally glucose & fat oxidation. The vertebrates are actually much better than most other animals at glucose fermentation, which gives them a significant advantage. Because of that, the vertebrates are able of short bursts of activity that use a very high power, e.g. running short distances or jumping or catching a prey, before having to reduce the power to the lower level that can be sustained for a long time by the aerobic oxidation.

deleted 6y ago

[deleted]

yholio 6y ago

This is the type of fundamental research that private labs do not typically pursue, yet might yield revolutionary treatments.

zaroth 6y ago
Was it public or private labs that did all the amazing mRNA research?
- PeterisP 6y ago
  50/50 - as with most things, the initial breakthroughs took 10+ years in public labs (e.g. the work by Kariko & Weissman), and one it was clear that the new idea works and roughly how it could be used, it took 10 or so years in private labs to make it practical and scalable. Also, it's not exactly accurate to view something as "developed in public lab" or "developed in private lab", as often (also in this case) the research is done by the same people but they do the early stage in a public lab and then move on to (or create) a private lab for the later stage of technological readiness.

whalesalad 6y ago

I’m curious to see how fasting might influence cancer treatment. I know in other parts of the world it is seen as a legitimate treatment, while also potentially considered to be a hippy dippy homeopathic treatment. Anecdotally it seems you can starve certain cancers to death pretty easily by severely limiting your caloric intake. I sense a relationship between that and this study.

dplgk 6y ago
This didn't work for Steve Jobs
- simplemen 6y ago
  He wasn't fasting, he was on fruits diet.
  - Technically 6y ago
    What's the metabolic difference between major and complete fasting? I honestly have no idea.
  - jaywalk 6y ago
    Yeah, and he also had a highly treatable form of cancer and access to the best medical care in the world. Unfortunately his arrogance got the best of him.
  - dplgk 6y ago
    He drank carrot juice which I'd say is severely limiting your caloric intake.
    - Dirlewanger 6y ago
      Limiting your caloric intake is not the same as fasting.
    - teknopurge 6y ago
      Also keep in mind that sugar is the enemy. Your body has chemistry to make sugar - there is no-need to ingest it.

balthasar 6y ago

Cancer is bad

aszantu 6y ago

I've been thinking and came to the conclusion that cancer might be a way of the body to get rid of excess sugar and maybe other toxins. Many cancers seem to respond well when ppl go keto for example

shishy 6y ago
That’s.... backwards. Excess sugars and toxins promote environments that are favorable for cancer promotion (eg by weakening immune system by down regulating certain cells within the tumor microenvironment or activating metabolic pathways that should be inhibited and so on).
- datavirtue 6y ago
  Yep. The guys who did that China Study were feeding aflotoxins (difficult to detect mold toxins) to rats and then fed them milk casin to trigger cancer. Then they would stop feeding them the casin to turn off the cancer.
majkinetor 6y ago
Seems a bit extreme don't you think ? Getting rid of the sugar by getting rid of the host, sounds like those AI fatalistic movies where curing misery involves killing all humans.
hoka-one-one 6y ago
Can we have one health thread where no one shills their fad eating disorder diet? Just one?
crubier 6y ago
In this thread: Web engineers turned Cancer specialists.
- shishy 6y ago
  Well I used to do Cancer research at the NCI before going back to software! :)

hlfy_hn 6y ago

Dichloroacetate influences NAD+ level (but increases)

calebkaiser 6y ago

The research around NAD+ production and cancer proliferation may also give some causal explanation--or at least, a place to start looking--for the correlation between B vitamin supplementation (edit: folic acid, specifically) and increased cancer rates/fatalities in certain high-risk populations: https://www.webmd.com/cancer/news/20091117/folic-acid-b12-may-increase-cancer-risk https://www.webmd.com/cancer/news/20091117/folic-acid-b12-ma...

majkinetor 6y ago
Not B vitamins, but folic acid (just one of them). Folic acid is required for stable DNA, something that cancer doesn't need at all (it needs mutations for plasticity). Its also needed for DNA production, but many more cells need it, those that have short lifespan - cells lining the stomach for example, sperm cells, some immune cells etc.
- calebkaiser 6y ago
  Good point--I amended my original comment to specify folic acid. What you're saying about stable DNA makes sense. I'm curious, though, if the supplementation helps the body generate more NAD+ (relative to someone with a deficiency), and if that could help cancer proliferate in its earliest stages (hence why the correlation is most pronounced in people already likely to develop cancer--smokers).
  - majkinetor 6y ago
    That is the whole problem - everything that benefits your body, benefits cancer and vice-versa. Cancer forms all the time - body should handle it when functioning correctly (via immune system). NAD is essential for many functions, especially longevity as sirtuins require it for proper function. As far as I know only massive Vitamin C doses uniquely influence cancer in negative manner and get pretty much no effect on non cancer cells. Massive vitamin C infusions (which work via mechanism similar to chemotherapy) while can't cure cancer per se, have potential to make life span and quality of life much longer (toward chronic disease).

jgilias 6y ago

Very interesting. Another result showing how increased NAD+ levels 'benefit' cancer cells casting a shadow on the idea of NAD+ boosting supplementation to increase healthspan and lifespan. But then, it's not like this means that heightened NAD+ levels cause cancer. Just that it is plausible that it makes it more aggressive, once you have it.

majkinetor 6y ago
Why doubt? It only proves that supplements work as indented in prolonging eycariotic cell life. Its just that you don't want everything in your body to be boosted, just some - cancer is just one of those, you don't want various constituents of your body flora influenced as well, like parasites, harmful microbiota etc.
- jgilias 6y ago
  So the trick is figuring out how to boost the things you want to boost without boosting or preferably even inhibiting things you don't want to boost. Actually, this echoes what is sometimes said about curing cancer. That it's pretty easy to kill cancer. The problem is in keeping people alive in the process. In either way, I'm pretty excited by all the recent findings and breakthroughs in both fields - longevity and figuring out cancer.

majkinetor 6y ago

Obligatory: https://imgs.xkcd.com/comics/cells_2x.png https://imgs.xkcd.com/comics/cells_2x.png (not because of article which describes mechanism, but because of people who will jump to conclusion)

tyingq 6y ago

This is why PET scans work well for highlighting cancer as bright spots. The injected 18F-FDG marker looks like glucose to the cancer cells, and is consumed by them for the energy.

majkinetor 6y ago
Yeh, PET scans are eye opening.

vmception 6y ago

If they really take this approach of targeting NAD+ production, which other types of "fast growing cells" will this kill? People will still go bald?

mncharity 6y ago

I enjoyed Zhaoqi Li's associated thesis defense "Bioenergetics and Metabolism of Eukaryotic Cell Proliferation" a few weeks ago. I don't quickly find his defense or thesis available online yet, but this paper[1] (open access) looks similar. Here's his twitter.[2] And a profile[3]. Someday we'll need to address the issue that talks, with their more extensive and accessible graphics and explanations, are less available to the public than papers. [1] https://www.sciencedirect.com/science/article/pii/S1097276520309047 https://www.sciencedirect.com/science/article/pii/S109727652... [2] https://twitter.com/zhaoqili https://twitter.com/zhaoqili [3] https://biology.mit.edu/graduate/why-mit-biology/graduate-testimonials/profile-zhaoqi-li/ https://biology.mit.edu/graduate/why-mit-biology/graduate-te...

wombatmobile 6y ago

In 2017, Berridge and Neuzil reported that stromal cells can donate healthy mitochondria to respiration-deficient tumor cells, restoring normal respiration as well as their ability to form tumors in mice. https://onlinelibrary.wiley.com/doi/full/10.1111/1440-1681.12764 https://onlinelibrary.wiley.com/doi/full/10.1111/1440-1681.1...

oedmarap 6y ago

Worth noting that unlike the cells of the human body, cancer cells are unable to utilize ketones as an energy source[0][1], hence the benefits of a ketogenic diet. A ketogenic diet can also be ideally coupled with intermittent fasting[2] in order to engage/enhance autophagy within the body. [0] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842847/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842847/ [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375425/ [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257056/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6257056/

dpatrick86 6y ago
Your point may be broadly true but subject to important caveats. Cancer is a very heterogeneous disease. There is evidence that _some_ cancers can use, for example, acetoacetate. https://www.sciencedaily.com/releases/2017/01/170112141359.htm https://www.sciencedaily.com/releases/2017/01/170112141359.h...
mehrzad 6y ago
Back when I had cancer in 2015, I read about this effect but I also read there was some potential danger in the cancer cells adapting to ketosis and accelerating their growth, so I thought it seemed too risky. It seems like the research may have improved since then though to suggest some benefit.
- mkrishnan 6y ago
  Congrats.
- eloff 6y ago
  I don't follow your logic there, cancer cells have an effective metabolism by default, so the chance that they can adapt to ketosis seems much better odds than the 100% that they're already adapted to your diet. But I'm very glad that whatever your decision, you're still among the living! Cancer is a terrifying diagnosis.
wonder_er 6y ago

skadamou 6y ago

Here is an NCBI article about the Warburg effect that I found illuminating https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783224/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4783224/

jacobn 6y ago

Does the difference in metabolic pathway lead to e.g. different waste products present in the blood? I.e. could you do a blood test to detect elevated levels of fermentation-based metabolism, indicating that it might be time to do a deeper cancer screen?

paxswill 6y ago
Lactate Dehydrogenase (LDH) is one test that uses this effect and it is used for monitoring some cancers. It's non-specific to cancer, but elevated levels can be cause by a range of not-great conditions. https://en.wikipedia.org/wiki/Lactate_dehydrogenase#Testing_in_cancer https://en.wikipedia.org/wiki/Lactate_dehydrogenase#Testing_...

pazimzadeh 6y ago

The summary is that NAD+ is limited for cancer cells, so NAD+ depletion could be a promising cancer therapy. On the other hand, a recent paper shows that NAD+ replenishment reverts tumor resistance to immunotherapy, so those therapies shouldn't be combined. https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30554-4 https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)...

mountainboy 6y ago

I suggest that anyone interested in this topic research Johanna Budwig and her Budwig Protocol. She was a world expert on essential fats as well as a physicist. Her work directly followed on that of Otto Warburg, and it is said she cured many many people of Cancer. Having tried her "Budwig Protocol" myself at a time when my energy levels were so low that I had to quit my job and focus only on recovering my health, I can attest that it truly works for delivering more oxygen and thus energy and vitality to one's cells. Today I am healthy and feel much better than I did 5 years ago.

kypro 6y ago

I take a daily dose of NMN to boost NAD+ levels. I was aware that NAD+ could accelerate cancer growth, but does anyone know if there's any evidence to suggest NAD+ could cause cancer or at least increase the likelihood of developing it? From what I understand most experts seem to think it's probably safe and will extend health & life span, but the cancer risk is something that concerned me when I started. Surely if healthspan was as easy as just raising NAD+ levels the body would have already evolved this trait?

thornjm 6y ago

I posted this in a few cancer threads with good response: the seminal work on cancer is actually a really quite approachable and short free paper - “Hallmarks of Cancer” by Hanahan and Weinberg. For anyone wishing to understand the fundamental features and survivorship bias that all cancer cells go through I highly recommend it. I think this is an updated version: https://www.cell.com/fulltext/S0092-8674(11)00127-9 https://www.cell.com/fulltext/S0092-8674(11)00127-9