Zero carb diet will help prevent Alzheimer’s

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TheresaB
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Re: Zero carb diet will help prevent Alzheimer’s

Postby TheresaB » Mon Jun 24, 2019 4:20 pm

jgilberAZ wrote:Define "better."


Oxidized LDL (oxLDL) is the problem, it's the LDL that "rusts" i.e oxidizes. APOE4 is associated with LDL cholesterol not being recycled by the liver very well, as a consequence higher concentrations of LDL particles are in the circulatory system for a longer period of time, which then have a higher chance of undergoing inflammatory transformation thus forming oxidized LDL.
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Re: Zero carb diet will help prevent Alzheimer’s

Postby MarcR » Mon Jun 24, 2019 4:34 pm

Exactly (agreeing with jgilberAZ).

On this point, Peter at Hyperlipid has a great new post today in which he uses images of real arteries to illustrate the impossibility of the lipid hypothesis. I recommend the whole thing and the comments. Here's an excerpt:
It is very, very hard to explain how utterly disreputable the lipid hypothesis is. All of this angst about increased LDLc and/or apoB counts on LC diets is based on the assumption that somewhere, somehow, cholesterol is the cause of heart disease. How LDLc "invades" (by active and controlled transcytosis!) the sub-endothelial space, disappears from there and then suddenly appears at over 200micrometres deeper, with none showing in the intervening zone requires a belief tenet which bears no resemblance to reality...

This was bollocks in the 1950s. My question is, as always, at what time did it stop being bollocks?

No one would reasonably doubt that the lipid deep down at the intima/muscularis junction level comes from lipoproteins (though there are other plausible explanations). No one would doubt that loading the lipoproteins with with linoleic acid is likely to be a Bad Thing. No one would doubt that generating oxidative derivatives of the lipids in those lipoproteins might be a Bad Thing.

But trans-endothelial "invasion" is beyond belief.

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Re: Zero carb diet will help prevent Alzheimer’s

Postby MarcR » Mon Jun 24, 2019 4:38 pm

I should link Julie's excellent prior topic:

Rethinking the etiology of CAD

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Re: Zero carb diet will help prevent Alzheimer’s

Postby jgilberAZ » Mon Jun 24, 2019 10:12 pm

Granted, in a high insulin and blood sugar environment, more LDL would lead to more oxidized LDL, which would be bad.

However, keeping insulin and blood sugar low will eliminate that concern.

And in that environment, high LDL is protective against all cause mortality.
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Re: Zero carb diet will help prevent Alzheimer’s

Postby mike » Fri Jun 28, 2019 6:27 am

So if E3 is not the response to additional meat, then what is it a response to? While they now grow many kinds of tubers in Africa, the only native ones are toxic to man. Maybe there used to be others. I find it interesting that where man evolved, tubers evolved to be toxic to man. In the new world the tubers are not toxic. By the time man got to the new world, they were farmers, but in Africa, we were hunter gatherers. If there were other tubers in Africa, they likely went extinct, while the toxic ones thrived. At some point man discovered that if you soaked the tubers, and then cooked them, they were good to eat. New food source. Carbs. When? I think E3 is in response to carbs. Is it really just a coincidence that prevention of AD usually involves low carb diet?
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Re: Zero carb diet will help prevent Alzheimer’s

Postby Julie G » Fri Jun 28, 2019 6:09 pm

mike wrote:So if E3 is not the response to additional meat, then what is it a response to?

I assume you understand that your hypothesis remains unproven (?) You can find some alternative theories here and here.

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Re: Zero carb diet will help prevent Alzheimer’s

Postby mike » Sat Jun 29, 2019 4:56 pm

Julie G wrote:
mike wrote:So if E3 is not the response to additional meat, then what is it a response to?

I assume you understand that your hypothesis remains unproven (?) You can find some alternative theories here and here.

Thanks for the lite reading... ;) I found it particularly interesting that most of the DNA was from more recent time period, yet most were homozygous, whatever allele they had - 4/4 or 3/3 or 2/2, and only one was 3/4. This means that there was not much mixing until more recently... They self selected out most older samples (including Neanderthal), since they only took those where they could get both mutations. Also, they need to include samples from further east to better show the story. If there was little mixing as long as 5,000 years ago, then no reason to try to figure out why the older E4 still exists...

Which theory - that E3 is a response to carbs? Sure, I realize there is not proof. I'm convinced that there is enough evidence to say that it is not a response to meat though...
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Re: Zero carb diet will help prevent Alzheimer’s

Postby mike » Sun Jun 30, 2019 7:02 pm

Julie G wrote:
mike wrote:So if E3 is not the response to additional meat, then what is it a response to?

I assume you understand that your hypothesis remains unproven (?) You can find some alternative theories here and here.

The first article actually has something that I find mind blowing. In section six - APOE Trade-offs where they talk about the various theories as to why E4 still exists, ner the bottom they talk about the DNA analysis that they did. It has some problems, but is striking none the less...

The samples, mapped in Figure 3 and listed in Supplementary Table S5 with details on the place of discovery and cultural context, cover the Euro-Mediterranean area and range from 1500 to 42,000 years ago. The ε3/ε3 genotype was found to be the most frequent (83%), followed by the ε4/ε4 genotype (13%), and the ε2/ε2 genotype (3%). The only heterozygote ε3/ε4 was represented by the Ust’Ishim sample, a 42,000-year old specimen of early hunter-gatherer human found in Siberia. In more detail, the ε2/ε2 individuals are Northern European samples from the Bronze Age. Despite carrying the ancestral genotype, all ε4/ε4 individuals are less than 8000 years old, with most of them being even more recent than 5000 years, while a conspicuous number of ε3/ε3 samples are much older than this, especially in the areas of Caucasus, between the Black Sea, the Caspian Sea, and the Middle East. This temporal and spatial distribution may be coherent with Palaeolithic alleles, like APOE4, having been reintroduced in Europe at higher frequency with the Yamnaya migration from the Steppe during the Bronze age and APOE3 being present at higher frequencies in the Fertile Crescent prior to the Neolithic Revolution, even though both alleles were already present in the European populations as well, as highlighted by the older local specimens [238,243,245]. However, the limited number of samples available across such an extended geographic area and the chance of genotyping errors due to the highly deteriorated ancient DNA hinder the possibility of a thorough factual discussion of the results. In order to draw more elaborate conclusions, it would be useful to recover more complete and evenly distributed ancient data, both in space and in time.


This is basically saying that as recently as 5,000 years ago, There were a bunch of isolated bands and little interaction between them, either because of space or time. The % of the individual zygote type roughly the same as current, except it is now often mixed. Seems the great mixing occurred less than 5,000 years ago, so there has been little time for genetic evolution...
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Re: Zero carb diet will help prevent Alzheimer’s

Postby circular » Sun Jun 30, 2019 10:59 pm

[quote=“mike”]Quoting the paper ...

‘However, the limited number of samples available across such an extended geographic area and the chance of genotyping errors due to the highly deteriorated ancient DNA hinder the possibility of a thorough factual discussion of the results. In order to draw more elaborate conclusions, it would be useful to recover more complete and evenly distributed ancient data, both in space and in time.’
[/quote]
This is why I mentioned holding my breath for the next 20 years. Population genetics research is moving at a pretty fast clip. I do understand the pull to hypothesize though :)
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Re: Zero carb diet will help prevent Alzheimer’s

Postby Fiver » Mon Jul 01, 2019 9:50 am

This is interesting to think about.

But I keep coming back to the here and now. If we had a reliable way to test our status once in a while we could figure out pretty easily which diet works best for each one of us. The "best" diet is probably different for each person, and probably changes over time at different points in our lives. That's what all our N=1 experiments are about, we just struggle to get adequate data to see what's working.
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