In any case, unless the prior paper I cited is flat our factually inaccurate, I think we can dispense with the idea that the ancestral human APOE4 allele is the same as primate APOE therefore we should eat like primates concept. Can't see how there is room for misinterpretation of something that is simply factually incorrect?
Of course, it's more nuanced than that. Neither Gundry nor Bedesen are suggesting that we eat like primates, but rather that we acknowledge that our genotype appears to represent the bridge between hominids and humans. Comparing the APOE from modern day chimps to modern day humans and definitively declaring no evolutionary relationship feels premature to me. We have strong indications that we share a common ancestor from the hominid family. The extinct humans, denisovan hominin, provide the first known finding of APOE-ε4 (identical phenotype with R61, R112, and R158) as modern day humans. Evolutionary timelines suggest that denisovans are thought to have evolved from homo erectus, who in turn appeared to evolve from the hominids- the group consisting of all modern and extinct great apes.
Gundry & Bredesen’s theorize that is was the difference between primate & human APOE that allowed us to become human. There are multiple theories as to why that might have been. Perhaps the pro-inflammatory nature of APOE-ε4 protected us from infection when we came down from the trees onto the savanna and stepped on dung? It may have also have protected us when we began eating raw meat full of disease causing pathogens? Perhaps APOE-ε4 evolved in response to shifts in diet (a thrifty gene), that allowed for fat accumulation when nutrition access fluctuated? These and other theories can be found in box #2 of Raichlen’s paper.
What sets Gundry & Bredesens' theories apart from others is that they both have independently concluded that utilizing a lipid-based (as opposed to glucose-based) metabolism that honors our genotype's preference for fatty acids as fuel to enhance mitochondrial metabolism and neural efficiency. Our ancestors were likely very often in ketosis whether it was due to famine, exercise, or fat consumption from their increased ability to enhance foraging with occasional meat. The way that Gundry & Bredesen are suggesting we achieve ketosis (through fasting, exercise, a specialized HFLC diet with some animal protein) seems to help align our evolutionary mismatch while humbly acknowledging the unknowns of a diet high in saturated animal fat given our propensity for fat accumulation.
Liu's argument that we drive up LDL and Lp(a) feels a little dangerous to me given the pro-inflammatory nature of APOE-ε4. FWIW, neither Gundry nor Bredesen appear to be focused on lowering cholesterol. After all, both propose a ketogenic diet for our population. Gundry only looks at particle size, not number. And, Bredesen would agree with Liu's assessment of statins. Based upon AD mouse studies that he did with every FDA approved drug looking for "dementogens," he found statins (especially cerivastatin) to top the list.