FIRKO-isation without all the hassle?

OK, I've treated myself to a few hours at the blog.

If we look at Veech's 2011 paper we can see that he is driving towards a drug which induces ketosis, side stepping all of that starvation or very low carbohydrate eating normally required, outstripping octanoate for carbohydrate defying ketosis. You can even FIRKO-ise your mice without all that standing around on a hill top in mid winter. It would, essentially, allow all of the benefits of ketosis on metabolic efficiency while still consuming a diet of utter crap. That's not something which interests me terribly much, though I can completely see where he is coming from. It will do some good but probably do very little to influence the underlying progress of the disease.

We had friends of friends round to supper the other day. They were interested (as Veech is) in ketosis as a tool to try and modify the progress of Parkinson's disease. So we had a baked mushroom each, filled with bacon and melted soft cheese with a smidge of fried onions and a micro smidge of spinach then topped with half a round of goat cheese for starters, belly pork goulash with soured cream, broccoli and asparagus for main course and Optimal ice cream (minimal dose of honey, no sugar) with a few raspberries for desert. Coffee and double cream. Modest red wine portions. The funniest part was trying to explain to them that serious researchers/nutritionists genuinely explained away the reduced appetite on LC diets as being due to either boredom or lack of palatability.

As Veech commented:

"Further, to achieve effective ketosis with KG diets, almost complete avoidance of carbohydrates is required to keep blood insulin levels low to maintain adipose tissue lipolysis. Such high-fat, no-carbohydrate diets are unpalatable, leading to poor patient compliance."

Eeeh, the stuff people come up with. Personally, I think Veech should sack his chef. Or stop eating F3666 and hire a chef.

The other gem from the paper was this line here, talking about his ketone ester fed mice:

"The ketone levels are similar to those found in humans during prolonged fasting (33, 34) and are 3- to 5-fold higher than the levels reported for mice fed KG diets (13, 15)."

It's the last section of that quote that really made me sit up. Both ref 13 and ref 15 are sitting on my hard drive. They use F3666, 8.6% protein, 3.2% carbs and lots of fat. They found ketone levels of 1.3mmol/l and 1.6mmol/l.

That is amazing. Amazingly pathetic ketosis. Nine percent protein, minimal carbs, the rest fat. If you or I ate this diet for more than a few days we would be peeing brilliant purple on our Ketostix.

What is really special about this Veech study and the other two mouse ketosis papers is not what they tell us about how to get in to ketosis (or not), it's much more what they tell us about C57BL/6 mice. That's right, C57BL/6 mice.

These mice are very special.

I've long thought that these poor rodents behave, when fed a high fat diet, rather like MSG lesioned, ventromedial hypothalamic lesioned or gold thioglucose lesioned animals. Their VMH breaks. They develop neuronally mediated acute insulin hypersensitivity in their adipocytes, they then abnormally store fat at low levels of insulin, increase eating to compensate for this calorie loss in to adipocytes and eventually develop adipocyte distention induced insulin resistance, which shows as metabolic syndrome.

It is impossible to over emphasise how important these ketosis studies are to C57BL/6 mice. Especially if you happen to be a C57BL/6 mouse.

BUT let's pretend none of us is a C57BL/6 mouse, just imagine you are a Wistar rat on 11% protein added to your traditional diet of neat Crisco (Mmmmm, Crisco, yumeeee). You will be in to ketosis with a beta hydroxybutyrate at 4.8mmol/l, and probably develop another mmol/l of AcA, within days and stay there. Are humans more like C57BL/6 mice or Wistar rats? I have no doubt that a human can damage their VMH by the same process by which they become obese. I doubt very much that this has anything to do with eating fat. Sucrose is much more likely. But even if you are obese and have damaged your VMH while becoming obese, you can still get your BHB over 7mmol/l. It may take some time, or even a little water fasting, but you can do it.

BTW Crisco induced ketosis is neuroprotective although I'd personally rather do the same with butter!

If you are a human looking to manage Parkinsons you can quite easily get to 6mmol/l of ketones in your bloodstream. You are not a C57BL/6 mouse. You don't even need Crisco, selected Food will do it.

The massive benefit of a ketogenic diet over the "SAD spiked with ketone esters" approach is that ketogenic diets avoid hyperglycaemic episodes. If you think hyperglycaemia is good for neurons you are probably well in to some nasty neurodegenerative disease!

Peter

BTW Apologies for the total lack of contribution to conversation in the comments. I have the choice between the occasional post or trying to get comments answered and a lot of the time neither gets done. Here's the occasional post. Obviously the next step, given time, is back to Veech 1995 where he talks electron transport chain, mitochondrial inner membrane voltages, proton leakage and a whole load more about very basic concepts, some of which are quite fascinating. Including the benefits of insulin. He then is talking in Nick Lane territory. And I hope everyone noticed that Stan has been to Nick Lane's website and has linked to this publication. I just loved this quote about the acetyl CoA pathway:

It's "a free lunch that you're paid to eat," in the words of Everett Shock.

My own light reading at the moment is this one, as a kid I thought tunnel diodes were cool.