Saturday, April 25, 2009
Feed a cold, starve a cancer
Why fasting may lead to more comfortable and effective chemotherapy.
9 Comments:
By 
JPMcT, at
Sun Apr 26, 01:32:00 AM:
Beware of medical blogs that cite "known for years" factoids and yet fail to include a bibliography.
This is the old "Frogs with no legs are deaf" scenario.
Starve yourself until you become ketotic. What happens to wound healing?...well, actually, nothing. Could it be that starved patients preferentially survive high dose chemotherapy because the chemotherapy is LESS potent...and therefore less effective?
How was the study set up? It would have been impossible to be double blind. Were the starved patients seen and evaluated more often and more thoroughly than the "fatties"?
Why the contemptuous remarks about pharmaceutical companies? Good Lord...there would be NO chemotherapy AT ALL without them!!
Naaah...I'm not buying it.
By 
, at
Sun Apr 26, 07:45:00 AM:
I've done dose-dense chemo, and it wasn't necessary to fast because it was hard to eat anything -- even with the anti-nausea meds. Like JPMcT, I have my doubts about this research. It is an interesting thought, but my best advice to people with cancer is to listen to their doctors. My Sloan-Kettering team gave me plenty of advice about what I should be eating. They never recommended starvation.
Four years later, I'm healthy and need to lose weight, but such is a small problem!
By TigerHawk, at
Sun Apr 26, 08:25:00 AM:
FWIW, that's not a medical blog. It is, however, written by my sister, who is both a professor of biology and a cancer survivor. Usually she does put in a bibliography, and has been very methodical in her research into her own disease. Not denying your comments, just pointing out that the author has more qualifications (both professional and personal) than many medical bloggers.
By Elise, at
Sun Apr 26, 03:30:00 PM:
My guess is that the lack of citation for the claim that "[f]or decades, it has been known that 'calorie restriction' (fasting) in many species extends lifespan" is because it's commonly conceded. (See this for example which I found by looking at "Calorie restriction" in Wikipedia.) It may be that citing references for the claim would be like TH citing references for a claim that the Left is generally less supportive of the Iraq war than the Right.
There were no "patients": this research did NOT involve human trials ("[t]he research was conducted both in isolated cells and in mice"). I will grant that Bioblog's statement about efficacy - "at high doses of the drugs, far more individuals survived when they had been starved before treatment" - is somewhat ambiguous since it's not clear if the survival refers to surviving the treatment or surviving the cancer. However if you skim the cited Raffaghello, et. al., paper the authors explicitly say that the starvation routine did NOT reduce the efficacy of the chemotherapy with regard to cancer cells.
This is exciting research and I hope it is aggressively pursued. I though one of the most interesting results was this:
Remarkably, STS [Short-term starvation]-pretreated mice, which lost 20% of their weight during the 48 h of starvation, regained most of the weight in the 4 days after chemotherapy (Fig. 4 B), whereas in the same period, the control mice lost ≈20% of their weight.If this means what I think it means, the mice that were starved beforehand were more able than the control mice to eat normally after chemotherapy. As someone who simply stopped eating for about 2 months following extremely high-dose chemotherapy, all I can say is, "Oh, frabjous day!"
By JPMcT, at
Sun Apr 26, 07:03:00 PM:
While maintaining a near normal BMI is good for your health, the eveidence that it prolongs human life is still wanting. Obesity clearly shortens lifespan as does starvation...so, by definition, there is a middle ground somewhere where people will probably do better than the others.
It clearly works in rats.
Cancer research in rats is a bit of a boondoggle since the results vary with species, especially those that have been bred for certain types of oncocytic predisposition.
The bottom line is: Anything that works in rats deserves a human trial...but how to do that?? It should be a simple matter to calcuate BMI data in large groups of patients and correlate that with survival. If a lower BMI conveys an advantage, then more specific studies can be proposed.
If I were a researcher, I would set a fellow loose on this. Sincebody weight calculations are done rountinely to dose chemotherapy...all the foot work is already there...somebody just needs to mine the data.
By Elise, at
Sun Apr 26, 09:26:00 PM:
If a lower BMI conveys an advantage, then more specific studies can be proposed.I'm pretty sure that's not what the research suggests. It's not the weight a person is when they receive chemotherapy that makes the difference: it's fasting beforehand. The theory is that normal cells respond to being deprived of nutrition by going into "stress-resistance mode"; cancer cells don't. It's as if the normal cells hunker down in their foxholes while the cancer cells are still tap-dancing across the battlefield. The chemo can reach the cancer cells but the normal cells are harder to hit.
The "stress-resistance mode" isn't triggered by being thin (or fat) but by how much nutrition the body is currently receiving.
I think it would be relatively easy to design a study to check this although I agree the double-blindness would be difficult. I suspect the problem is going to be the firm conviction that getting as much nutrition as possible down chemo patients is absolutely crucial. It's going to be hard to convince oncologists to deliberately withhold nutrition from patients prior to a chemotherapy treatment. Especially since for some patients the period right before the next treatment is when they are most able to keep food down and to have an appetite.
By JPMcT, at
Mon Apr 27, 07:12:00 AM:
Hmmm...one could induce ketosis pharmacologically...but that would have to get by a human research committee.
The concept of biologically selecting cancer cells is not new and is the basis for FolFOX and methotraxate based therapies where Folate "rescue" or enhancement is used since cancer cells can't use folate (vit B9) like normal cells do.
The key thing is to drill down and find out WHICH biochemical response to fasting is the one that hypothetically conveys an advantage. Is it BMI related? Is it ketosis? Dehydration? Insulin levels? Lipid related? Acute vitamin deficiency (insert one of a dozen here)? THEN....reproduce the same "state" pharmocologically prior to chemotherapy.
That could keep somebody busy for a decade or two, but I've seen good money spent for grants based on far more bizarre propositions.
By Elise, at
Mon Apr 27, 12:04:00 PM:
The key thing is to drill down and find out WHICH biochemical response to fasting is the one that hypothetically conveys an advantage.I only scanned briefly but it looks to me like people have been trying for 70 years to figure out why calorie restriction extends life span in some species and haven't yet got the answer. It's an interesting question and I'm sure there are drug companies working their little lab tubes off on it in hopes of creating a longevity pill - and good luck to them.
But there's no need to go that route in order to help chemotherapy patients. We can test the fasting protocols themselves without knowing why they work. Simple, cheap, no hideous side-effects. After all, humans used aspirin and its precursors for 5000 years without understanding why they magically made headaches vanish.
Oh, and apologies. I re-read the BioBlog post and you are quite right that a human trial are underway. I was so excited about those little mice that I missed that on my first reading. It does not look like the trial is double-blind (I'm not even sure it's single-blind) but the study is going to be looking for measurable outcomes (like white blood cell count) rather than simply for reports that patients feel better. I found a brief description of the study here. I hope BioBlog will keep us all updated on the results.
By JPMcT, at
Mon Apr 27, 07:39:00 PM:
Elise, thanks for the information. I work with a few oncologists that are among the smartest people I know. I will definitely bring this up in the next conversation I have with them.
