2016 Ancestral Health Meetup - Stavia's blog

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Julie G
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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby Julie G » Tue Aug 16, 2016 5:21 pm

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.

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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby JulieAnnie » Tue Aug 16, 2016 8:36 pm

Dementogens? Wait... Not so fast.

Background: Astrocytes and cerebral endothelial cells are important components of the blood-brain barrier (BBB). Disruption to this barrier through inflammation is a major contributor to Alzheimer’s disease (AD) pathology. The amyloid beta (Aβ) protein is known to exist in several forms and is a key modulator of AD that is known to cause inflammation and changes to BBB function. While one of these forms, fibrillary Aβ (fAβ), is known to cause endothelial cell death at the BBB, no studies have looked specifically at its role on inflammation in a model of the human BBB. Aims: To determine if fAβ is inflammatory to the human BBB. As statins have been shown to be anti-inflammatory and protective in AD, we also tested if these could inhibit the inflammatory effect of fAβ. Methods: Using cultured cerebral endothelial cells and astrocytes we determined changes in cytokine release, cell toxicity and barrier function in response to fibrillary β-amyloid1–42 (fAβ1–42) alone and in combination with statins. Results: fAβ1–42 induced inflammatory cytokine release from endothelial cells in the absence of cell toxicity. It also induced astrocyte cytokine release and cell death and caused a loss of barrier integrity. Statin treatment inhibited all of these effects. Conclusions: We conclude that fAβ1–42 has both inflammatory and cytotoxic effects on the BBB and the protective effect of statins in AD may in part be through inhibiting these effects.

PMID: 27309956

PMCID: PMC4911157
URL - http://www.ncbi.nlm.nih.gov/pubmed/2730 ... t=Citation

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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby Julie G » Tue Aug 16, 2016 9:30 pm

JulieAnnie, use our search engine to find lots of info on the relationship between statins, cholesterol, and Alzheimer's disease. This area is far from settled. While the Cochrane report has concluded that statins do not reduce risk of AD nor treat it, their utility in terms of addressing established atherosclerosis is undeniable albeit still controversial in terms of further impairing mitochondrial function in our genotype. FWIW, I was referring to a single paper by Bredesen that points to some statins being more dangerous than others based upon their ability to induce the C-terminal cleavage of AβPP that leads to associated cell death and dementia.

Induction of the C-terminal proteolytic cleavage of AβPP by statins.
http://www.ncbi.nlm.nih.gov/pubmed/?ter ... A+21422530

Abstract
Statins are drugs commonly used to inhibit cholesterol synthesis, with the goal of reducing vascular diseases such as myocardial infarction and stroke. Statins have also been suggested as a therapeutic option for Alzheimer's disease (AD), although their benefit in AD remains controversial. We have previously shown that the intracellular C-terminal cleavage of the amyloid-β protein precursor (AβPP) is a major contributor to the neuronal toxicity seen in AD, and that this cleavage can be induced by amyloid-β. We now report that certain brain permeable statins are also able to induce the C-terminal cleavage of AβPP and associated cell death, whereas other statins do not. This statin effect on AβPP exceeded the effects of all other FDA-approved drugs in a library composed of these compounds, suggesting that this effect on AβPP cleavage is unique to a subset of the statins. Furthermore, the greatest effect occurred with cerivastatin, which has previously been shown to be the statin associated with the greatest risk of rhabdomyolysis. These results may have implications for the choice of which statins to evaluate in AD therapeutic trials; furthermore, the results may inform statin choice in individuals who are at high risk for the development of AD, such as those with an apolipoprotein E ε4 allele. [Empasis mine.]

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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby TheresaB » Tue Aug 16, 2016 9:32 pm

If anyone had a problem with the links in my previous posts in trying to listen to the Q&A sessions with Dr Gundry and/or Dr Bredesen, try again. Someone with a Mac complained they couldn't due to incompatibility. I converted the files to MP3, which is more universal and should work now.

Sorry for any inconvenience, I'm new to audio files.
-Theresa
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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby Russ » Wed Aug 17, 2016 4:56 am

Juliegee wrote:


Gundry & Bredesen’s theorize that is was the difference between primate & human APOE that allowed us to become human.


Julie - Nice post. We are now back on the same page. As to Bredesen's comments on statins in his talk, indeed you know me well enough that this, of course, perked up my ears. Another interesting observation on the subject.
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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby Stavia » Wed Aug 17, 2016 12:13 pm

Breaking news!
Some of the videos are up on YouTube.
Search "AncestryFoundation" channel and subscribe or search "AHS16"

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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby Tincup » Wed Aug 17, 2016 2:36 pm

This should be a link to the search.
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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby TheresaB » Wed Aug 17, 2016 3:25 pm

Here's the link to Dr Steven Gundry's presentation: “Dietary Management of the Apo E 4 Genotype, the True Ancestral Gene” at the Ancestral Health Symposium last week (11 Aug 2016)

https://www.youtube.com/watch?v=Bfr9RPq0HFg
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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby TCat » Wed Aug 17, 2016 4:20 pm

Just wanted to chime in and tell you how much all of your notes, comments and links are appreciated. Thank you soooo much, Stavia and all.

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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby Stavia » Wed Aug 17, 2016 6:24 pm

Very very welcome TCat. I firmly believe that we are strongest if united. Please let us know your thoughts on the presentations as they are loaded onto the channel.


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