Wednesday, October 14, 2009

Cancer and ketones

Just a brief post:

Dr Fine is looking at metabolic management of cancers. Cancers express uncoupling protein 2 (UCP2). UCP2 plugs in to the mitochondrial inner membrane, allows protons through, lowers the voltage across the membrane and so reduces both ATP and free radical production by the mitochondria. It might not be as physiological as UCP3, more of a survival tactic in hyper energetic states. UCP2 is not commonly present in normal tissues.

Lack of respiration drives the use of glucose-lactate fermentation, adapted to the the hypoxic environment which is a common location of cancer cells.

Ketone bodies are very special as regards mitochondria. I'll post on this eventually. But they switch on respiration (mitochondrial O2 based ATP production) and switch off glycolysis, ie they cause insulin resistance, but not at the GLUT4 level (post here). Dr Fine points out that cancer cells tend to use GLUT1, not GLUT4, so a non GLUT4 method of glucose deprivation might be a good idea. If a cancer cell's mitochondrial inner membranes are punched full of holes (UCP2s) then ketones cannot generate mitochondrial ATP effectively, but can still inhibit glycolysis. Result: decreased ATP and decreased cell growth. This is an aggressive cancer on a ketogenic diet.

There is no suggestion of apoptosis of the cancer cells, this requires increased free radical production. But slowed cell growth is a better option than runaway growth if you want your immune system to stand a chance of saving your life....

Dr Fine discusses the "model" like nature of his model, and it's flaws, nicely. Just tissue culture at the moment, but the project is aiming to go clinical at some stage soon.

OK, time for a nap before a night shift.



Matt Stone said...

From Melvin Page and Leon Abrams:

“We do not remember seeing a single cancer case who had a correct blood sugar level, yet in most non-cancer cases this easily obtained by means of a sugar-free diet alone.”

Nuff said.

caphuff said...

tangential question: could "metabolic cancer management" also involve the metabolic system having an easier time identifying cancer as nonessential tissue (i.e. when outside calories are scarce or intermittent)than the immune system seems to have identifying it as "foreign" tissue? In other words, would the body "eat" cancer?

Gyan said...

Surely Page and Abrams are incorrect.
My wife got breast cancer last year. Here HbA1c was measured and was 5.1% (on a normal high-carb lacto-vegetarian diet, no stint on saturated fats).

Rick Kiessig said...


HbA1c alone doesn't tell the whole story. You can have significantly high blood glucose peaks, while retaining a normal HbA1c (particularly when eating high-carb). Also, as I understand it, Page and Abrams argument is more around ketosis than simply blood sugar levels. On a high-carb diet, you would definitely not be in ketosis.

In addition, there are certainly multiple causes of cancer -- bypassing one doesn't mean that another won't get you.

caphuff said...

Well, if anyone was wondering, never mind about the body "eating" cancer cells during starvation or fasting. Looks like malignant cells produce a substance that inhibits autophagy . . .

Danyelle said...

Interesting link:
Especially the "further studies" links further down the page.

Peter said...

Hi Danyelle,

Thanks for the links. I've hit a few more along these lines and will get a post up when there is time... Ketones/lactate and glucose within cancer tissue are very interesting. I'm still not sure about cancer being actually "curable" once established, but these ideas are along interesting lines.


Stephanos Pavlides said...

Hi Peter,
I liked your blog! I am a researcher and my recent studies lead our scientific team at Thomas Jefferson University to some very interesting findings!!
You can check out the press release that came out last week, and the announcement from Dr Lisanti (leader of the group)on a video on youtube:

and the press release here:

I hope you enjoy reading about it,


Peter said...

Hi Stephanos,

Interesting and provocative. I will await developments. An initial query is that metabolic syndrome, with diabetes as a facet, is associated with hyperglycaemia without ketosis until the very late stages when pancreatic failure eventually leads to hypo insulinaemia in the aftermath of many years of hyperinsulinaemia. Then there might be ketones. I wasn't aware that ketosis was particularly common in most type 2 diabetics unless they are actively losing weight, a very rare occurrence during modern diabetes management...