APOE4 and Insulin Resistance and many pathways involved

[circular]

That's interesting Harrison. I remember this notion about the metabolic 'no man's land' of eating both higher fat and higher carb. Is there a sort of go-to study showing that high carb/low fat is metabolically safe? This is the way my husband still prefers to eat, and I get nervous he's doing a real number on his metabolic health over the years, and he won't test it sufficiently to know. If there's good science behind what you're saying it might put my mind more at ease.

Do you personally feel that either HCLF or HFLC can be healthy, just don't too HFHC?

[Harrison]

That's interesting Harrison. I remember this notion about the metabolic 'no man's land' of eating both higher fat and higher carb. Is there a sort of go-to study showing that high carb/low fat is metabolically safe? This is the way my husband still prefers to eat, and I get nervous he's doing a real number on his metabolic health over the years, and he won't test it sufficiently to know. If there's good science behind what you're saying it might put my mind more at ease.

Do you personally feel that either HCLF or HFLC can be healthy, just don't too HFHC?

Hi Circular,
Those are some good questions. I think the problem has been that there is no one size fits all nutrition solution. My wife can drink 1 can of full-sugar soda a day with a fasting glucose in the 80s and an a1c of 4.9. If I do the same thing, my fasting glucose is over 110 and my a1c is 5.5. Even cutting out the can of coke, if I eat what she eats (loads of high-carb vegetables), I find myself starving a few hours later and end up snacking. When she eats my diet, she gains weight and doesn't feel great. Meanwhile my numbers look good.

If a person has good looking markers in terms of glucose/a1c, insulin, cholesterol, etc and are otherwise healthy, I can't imagine making a change. The only caveat to this is some of the Kraft data suggesting "hidden" insulin resistance in otherwise healthy people. Unfortunately you need to do a glucose/insulin tolerance test to find that out.

[Searcher]

They used a 60% fat diet (HFD) to induce insulin resistance in mice that carried either E3 or E4. Also had E3 or E4 mice on a 10% fat diet. Further, included a switch from 60% fat to 10% fat. Compared cognition in the various groups. Later, sacrificed the mice and analysed their hippocampi for the epigenome and metabolome.

1) The metabolic and cognitive dysfunction brought on by a high fat diet is magnified by E4,
2) is characterized by a distinct hippocampal epigenome and metabolome,
3) is responsive to a dietary intervention, and
4) may be driven by alterations in metabolic pathways of purine metabolism, glutamate, and the pentose phosphate pathway.

Plus, "E4 HFD mice show a unique profile of DNA hydroxymethylation in the hippocampus."

The paper is rich in detail, highly informative.

http://europepmc.org/articles/PMC5341123/

The approach appears to be pioneering and revealing.

My guess is they used saturated fats [edit: checked, it was largely lard, which includes a fair proportion of saturated fats]. I'm glad to have replaced saturated fats with unsaturated.

I wonder if ketosis offers mainly symptomatic relief in cognitive impairment, rather than "curing" the metabolic basis or stopping the pathology?

[Orangeblossom]

Thanks, Bettylacy. Interesting read, although I do wish the labcoats would stop referring to food that is 19% maltodextrin/sucrose as a 'high fat diet'. Their little picture-flow-chart at the top of page 9 is amusing - the little mice being "rescued" by a low fat diet. Hooray!

It is surprising that they do refer to

"A primary, modifiable contributor to obesity, IR and T2D is caloric excess, particularly in the form of high intake of saturated fats and high glycemic index foods. Consumption of this Western style diet increases the risk of dementia, and the effects may be modulated by APOE genotype

but then seem to base the rest of the paper on the role of the fats not the combination of the diet

Lard contains more monounsaturated fat than saturated, but in combination of a sugary diet that would have been a problem. I agree, poor mice! Glad we are not consuming a SAD...which is what it seems this paper was looking at in it's effects.

Amy Berger's writes well on insulin resistance, and she explains metabolic syndrome here https://books.google.co.uk/books?id=MwF ... sy&f=false