Ketones Fuel Cancer?!
Ketones and lactate “fuel” tumor growth and metastasis
Previously, we proposed a new model for understanding the “Warburg effect” in tumor metabolism. In this scheme, cancer-associated fibroblasts undergo aerobic glycolysis and the resulting energy-rich metabolites are then transferred to epithelial cancer cells, where they enter the TCA cycle, resulting in high ATP production via oxidative phosphorylation. We have termed this new paradigm “the Reverse Warburg effect.”
Here, we directly evaluate whether the end-products of aerobic glycolysis (3-hydroxy-butyrate and L-lactate) can stimulate tumor growth and metastasis, using MDA-MB-231 breast cancer xenografts as a model system. More specifically, we show that administration of 3-hydroxy-butyrate (a ketone body) increases tumor growth by ~2.5-fold, without any measurable increases in tumor vascularization/angiogenesis. Both 3-hydroxy-butyrate and L-lactate functioned as chemo-attractants, stimulating the migration of epithelial cancer cells. Although L-lactate did not increase primary tumor growth, it stimulated the formation of lung metastases by ~10-fold. thus, we conclude that ketones and lactate fuel tumor growth and metastasis, providing functional evidence to support the “reverse Warburg effect.”
Moreover, we discuss the possibility that it may be unwise to use lactate-containing i.v. solutions (such as lactated Ringer’s or Hartmann’s solution) in cancer patients, given the dramatic metastasis-promoting properties of L-lactate. Also, we provide evidence for the upregulation of oxidative mitochondrial metabolism and the TCA cycle in human breast cancer cells in vivo, via an informatics analysis of the existing raw transcriptional profiles of epithelial breast cancer cells and adjacent stromal cells.
Lastly, our findings may explain why diabetic patients have an increased incidence of cancer, due to increased ketone production, and a tendency towards autophagy/mitophagy in their adipose tissue.
A friend sent me this one recently. I'm mostly passing it along as a PSA of sorts as I'm busy with other interests at the moment. However there have been many blogs and threads on discussion boards discussing the role of glucose and carbs in general in cancer. Also, around a year ago headlines splashed across the web such as Fructose can trigger cancer cells to grow faster, study finds, Cancer cells slurp up fructose, US study finds, and 'Fructose-Slurping' Cancer Could Sour the Soda Business. These sparked innumerable blogs and disco board threads in LC/Paleo/Anti-Sugar-warrior arenas.
Now ketones and lactate aren't dietary agents, let alone the easily demonized HFCS, so it's no mystery why this paper didn't spawn a similar flurry. The metastasis part of this really gives me pause.
Might be interesting to some. Particularly Dr Seyfried's response.
There are bad studies on every side of every fence I suspect :/
I just read through it. I have to say Seyfried's response is disappointing. And a long term low carber included amongst "experts"?
I was also disappointed in the Ottobonis who say: "First, the biochemical logic: Cancer cells require glucose as their source of energy. As far as is known, glucose is their only energy source. Cancer cells cannot survive, grow, and metastasize without energy." And later: "Ketone bodies produced in humans as a result of β-oxidation of fatty acids ... have been shown to be an excellent source of energy for all normal tissues and organs, except the liver." Umm... what do they think cancer cells are? Alien explants? No ... they are human cells gone awry.
I think its more an argument for the evolutionary process than against a diet choice though :)
I'm sure if I was a cancer researcher though, and discovered a new, unknown, source of energy for cancer it'd be worth writing a paper about...
I agree about the lame "long term low carber" bit...
Also, the expression "administration of 3-hydroxy-butyrate " caught my attention. If ketones are not created in the body but artificially added in one form or another it may have different effect and create a diabetic-like environment with abandon nutrition for anything growing.
I am no cancer expert but let me take a whack at this. Most cancers occur among older people. Not all, but most. Since aging is a "disease of civilization," wouldn't it make sense that cancer is more prevalent amongst a population where most people get to live their 3-score and ten?
I have some thoughts on the other comments. Be back in a bit :)
I'll see your invitro study and counter it with a (totally tiny) pilot study showing a keto diet reversing or slowing the growth of tumours. You know the study, why dismiss that even though it is a higher form of evidence than you have posted?
Got a link to the pilot study? I haven't really looked at this much either way.
Ketones and lactate increase cancer cell “stemness”, driving recurrence, metastasis and poor clinical outcome in breast cancer
There is a section on Metformin and cancer cells that concludes and might be relevent (really this is mostly beyond my comprehension far too specialised)
" Finally, it is quite ironic that such a promising anti-cancer drug (metformin) exerts its therapeutic effects by inducing a type of metabolism (aerobic glycolysis) that has been proposed to be the “root-cause” of cancer for the last 85 years. Thus, induction of aerobic glycolysis in cancer cells may not be the “cause of cancer,” but rather it may be the “cure for cancer.”
Not published yet as far as I can see, but still impressive results.
And a good ol' (published) mouse study for good measure:
Although, I don't really know if that tells us absolutely anything because I doubt the mice were eating anything akin to real food.
Paul Jaminet hypothesised that mucin deficiency could lead to gastric cancers in long term VLC, and I find the theory plausible long term but if I would be diagnosed tomorrow (touch wood) I'd hop on a VLC diet stat (I'd prob restrict protein too to be on the safe side re: glutamate issues.)
Dr. Adrienne Scheck's studies reversing cancer on a ketogenic diet have received some attention from the low carb community. But she also used the ketogenic diet in conjunction with chemo and radiation therapy:
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