Just a brief post on the development of NASH in long term ketogenic fed mice because I've been side tracked by some other papers: Starvation (Ethan), metformin (tripped over this one myself, things are moving forward from PSS and Oxygen), UCPs and fat oxidation (kindke)...
NASH, it all comes down to this paper (thanks Liz).
Does sustained ketosis produce NASH? Well yes, or at least something like it. Just look at the picture:
The dark staining patch is made up of neutrophils. You don't want clumps of them aggregating in your liver.
That's what you get if you feed F3666 to C57BL/6 mice. It is, undoubtedly, intensely ketogenic. But is it anything else?
"These are typical amounts of nutrients calculated from
available information. Actual assay results may vary.
For more information contact Jaime Lecker, Ph.D."
The paper (and the F3666 pdf) specifies 16% of PUFA in the fat, which seems rather low considering that USA produced lard (the main ingredient) appears to have 32% PUFA (almost all omega 6) but, even at only 16%, these PUFA are 16% of 95% of your total calories. That's an awful lot of PUFA...
Do PUFA matter for the development of NASH? Probably. From this N and M paper:
"The lipid composition of the different diets which induce steatohepatitis (see Table 4) [19,20,51,52,54], were lard and corn oil, both oils rich in unsaturated fatty acids. We can observe that fat of all the diets inducing steatosis and inflammation (Table 4) were richer in MUFA and PUFA (>30% and >20% of total fat respectively) as compared to our diet (5% and 2%). The injurious effect of unsaturated fatty acids, and particularly n-6 polyunsaturated fatty acids, was associated with enhanced lipid peroxidation and decreased concentrations of antioxidant enzymes, implicating oxidative stress as a causal factor. Indeed, different studies showed the pro-inflammatory effect of polyunsaturated n-6 fatty acids which exacerbate liver oxidative stress [60,61] and promote the development of NASH."
So there is a message: If you are going to eat a very high fat diet in the long term, you should pay serious attention to PUFA creep. Having cirrhosis is not likely to help you make old bones in good shape. Perhaps go easy on the commercial mayonnaise and just spread some butter on your cheese... Actually I tend to add butter to my beef if it's too lean (only happens when eating out, no way we would choose lean beef to cook at home!)...
It makes me wonder about saturophobes who might be swilling PUFA to lower their LDL and triglycerides, with or without a LC diet... More potential victims of the cholesterol hypothesis I suppose.