Ketones And Lactate Fuel Tumor Growth And Metastasis

[Edward]

Ketones and lactate “fuel” tumor growth and metastasis: Evidence that epithelial cancer cells use oxidative mitochondrial metabolism
http://www.landesbioscience.com/journal ... cle/12731/

 

[Such_Saturation]

"L-lactate stimulated the formation of lung metastases by ~10-fold" "it may be unwise to use lactate-containing i.v. solutions in cancer patients"

Wow, you think so?

 

[DaveFoster]

So, is this ketones AND lactate, or ketones OR lactate?

 

[TreasureVibe]

J Clin Invest. 2008 Dec;118(12):3930-42. doi: 10.1172/JCI36843. Epub 2008 Nov 20.
Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice.
Sonveaux P1, Végran F, Schroeder T, Wergin MC, Verrax J, Rabbani ZN, De Saedeleer CJ, Kennedy KM, Diepart C, Jordan BF, Kelley MJ, Gallez B, Wahl ML, Feron O, Dewhirst MW.
Author information

Abstract
Tumors contain oxygenated and hypoxic regions, so the tumor cell population is heterogeneous. Hypoxic tumor cells primarily use glucose for glycolytic energy production and release lactic acid, creating a lactate gradient that mirrors the oxygen gradient in the tumor. By contrast, oxygenated tumor cells have been thought to primarily use glucose for oxidative energy production. Although lactate is generally considered a waste product, we now show that it is a prominent substrate that fuels the oxidative metabolism of oxygenated tumor cells. There is therefore a symbiosis in which glycolytic and oxidative tumor cells mutually regulate their access to energy metabolites. We identified monocarboxylate transporter 1 (MCT1) as the prominent path for lactate uptake by a human cervix squamous carcinoma cell line that preferentially utilized lactate for oxidative metabolism. Inhibiting MCT1 with alpha-cyano-4-hydroxycinnamate (CHC) or siRNA in these cells induced a switch from lactate-fueled respiration to glycolysis. A similar switch from lactate-fueled respiration to glycolysis by oxygenated tumor cells in both a mouse model of lung carcinoma and xenotransplanted human colorectal adenocarcinoma cells was observed after administration of CHC. This retarded tumor growth, as the hypoxic/glycolytic tumor cells died from glucose starvation, and rendered the remaining cells sensitive to irradiation. As MCT1 was found to be expressed by an array of primary human tumors, we suggest that MCT1 inhibition has clinical antitumor potential.

Source: Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. - PubMed - NCBI

See following article with PhD doctors refuting the OP study, also make sure to check the comment section:

Do Ketones Fuel Cancer? The Low-Carb Experts Respond « Jimmy Moore's Livin' La Vida Low-Carb Blog

Comment from the comment section:

Just another two-pennyworth:

This paper came out a couple of years ago:

Targeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice. - PubMed - NCBI

I found it fascinating.

Hyperlipid: Glucose, lactate and cancer

What evidence I could find suggests that ketone bodies actually block lactate metabolism, under physiological conditions, in rat brain at least.

Regulation of glucose and ketone-body metabolism in brain of anaesthetized rats. - PubMed - NCBI

It seems plausible that a massive supraphysiological dose of ketones might replace lactate as a fuel for lactate adapted cancer cells in the aerobic areas of tumours, after all they do transport on the same MCTs. But then we’re simply guessing about what is happening in a very third rate study that has relatively little to do with the physiology of ketone production……. I would be very cautious to generalise this study to intact humans.

Peter

Also from the comment section of that last article:

• kevin
  March 3, 2011 at 3:08 pm
  Dr ‘Snuffy’ Myers is a urologist-oncologist who produces short videos to answer questions posed by patients. Someone asked about low carb diets and prostate cancer. His reply was that studies showed poorer regression in tumor size in patients eating low carb diets, compared with those on higher carb diets.
  
  
• Ted Hutchinson
  March 3, 2011 at 4:28 pm
  @ Kevin
  Well whatever Snuffy says
  in this mouse research
  http://onlinelibrary.wiley.com/doi/10.1002/pros.20683/abstract
  84% fat–0% carbohydrate–16% protein kcal-fed mice had significantly reduced tumor growth and prolonged survival relative to Western diet mice and was associated with favorable changes in serum insulin and IGF axis hormones relative to low-fat or Western diet.
  Prostate 68: 11–19, 2008. © 2007 Wiley-Liss, Inc.
  I’m of an age when my mates are all talking about prostate problems so it’s important to me I make the right choices.
  
  Again in
  “Dietary intervention strategies to modulate prostate cancer risk and prognosis” Freeland states “low-carbohydrate diets significantly slow tumor growth independent of weight loss”
  
  So I’m sure you’ll not be surprised I’m sticking with my lowish carb regime.
  
  PS May I also thank Jimmy and his contributors for this valuable contribution to the debate. We are very privileged.

Also a good comment:

Anonymous
August 30, 2011 at 9:11 pm
OK, here’s the study.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3047616/pdf/cc0917_3506.pdf

It states quite plainly that they took a ketone that comes from GLUCOSE-BURNING and injected it into lab mice. So, several points here:

1. Their claim is that ketONES cause cancer, not that ketOSIS causes cancer. Big difference.
2. They did not use a ketone from fat-burning. They used a ketone from sugar-burning.
3. This matters because you would not believe how many types of ketone exist in the world. I did not know you could get ketones from sugar-burning, but clearly you can. You can get several different types of ketones from fat-burning. The smelly stuff in nail polish remover is a ketone. There are several different types of ketones in plant essential oils. All of these serve different purposes and cause different responses in the human body. Some are poisonous, some are burned for fuel, some hardly seem to matter at all.
4. And this experiment wasn’t done on humans. Furthermore, I’m not even sure it was done on mice that were in ketosis. So if they had normal blood sugar, as I think some of the people you quoted above have pointed out, and then this ketone was injected into them, their bodies probably registered that and reacted to it in abnormal ways.

You would not believe the ignorance out there about ketones. I actually read once in an article about lavender essential oil that because it contains ketones, diabetics should not use it. That’s the stupidest thing I’ve ever read in herbal literature, and I’m sure I’ve seen some quack claims made there over the years. It isn’t the ketones that kill a diabetic in ketoacidosis, anyway. It’s the high blood sugar and the metabolic acidosis. The ketones are there because the diabetic has become incapable of burning sugar AT ALL so they have to get energy from somewhere. Yes, the ketones probably contribute to the acidosis–but then so does the glucose!So yeah. Much ado about nothing. I’m annoyed.