News from our SFO Meet-up

[Russ]

4. Dr Kraus spoke about the huge uncertainty of the role of lipoproteins in apoe4 as the trials just simply aren't there. He also couldn't give us targets as again the trials just aren't there.
What he could say with certainty was that lipoproteins matter in the absence of IR. Saturated fat should be less than 7% of calories. Saturated fat is a problem with us because we start at a higher LDL than other folks and the sat fat downgrades the LDL receptors thus slowing clearance and large LDL accumulates. Butter and red meat are bad. Milk and cheese neutral. Carbs bad if IR is present and too many small particles.

Thanks for this, Stavia! Maybe someone else has said it before, but this sounds like one of the more coherent strings of reasoning for mechanisms that may allow us to reconcile the apparent lipid dilemma. On the one hand he objectively admits we don't have data on the direct problems of LDL-P per-se (for just us, or others in non-inflamed state?), but (postulates or has data for?) down regulation of LDL receptors due to the presence of too much (longer-chain?) saturated fat consequently leading to reduced clearance and accumulation (and likely oxidation?). I still struggle to align with the evolutionary context of meat-eating hunter gatherers for whom this gene was at least relatively helpful (and possibly vitally important?), but maybe the answer to that lies in variability?

[SusanJ]

Variability, definitely yes.

Here's the thing about ancient diet. My guess is that eating red meat was a more rare occurrence than we think. So they were probably eating opportunistically, eating smaller game and fish with much less saturated fat and different fat profiles, and the occasional big game catch was rare but also provided a fat profile much different than corn-finished beef of today.

Your tag line seems to sum it up well.

[Russ]

Variability, definitely yes.

Here's the thing about ancient diet. My guess is that eating red meat was a more rare occurrence than we think. So they were probably eating opportunistically, eating smaller game and fish with much less saturated fat and different fat profiles, and the occasional big game catch was rare but also provided a fat profile much different than corn-finished beef of today.

Your tag line seems to sum it up well.

Susan - Just underscoring one of several important points you make above and reinserting a graphic I placed in a prior post to emphasize not only different absolute magnitudes, but balance in various fatty acid fractions...

Fatty acid differences of grass fed beef.jpg

[Julie G]

I'll jump in and share my notes from our meeting with Dr. Krauss. His lab was in an older, well manicured, Spanish-style, sprawling commercial building that almost looked like a prep school. Once we got inside, we realized that was precisely what it had been in a previous carnation. We left the grandeur of The Buck and we were back in high school . FWIW, I greatly admire Dr. Krauss for NOT cherry picking and truly following the science. For those who aren't aware of his research background, he had a long history of work advocating a HFLC diet that he has since somewhat backed away from- based upon the results of his work. He is both a researcher and a clinician; a very sweet man, paternalistic, perhaps somewhat shy.

He made it very clear that there were MANY more questions than answers for our population. Quite recently, he's begun to focus his efforts towards the E4 population; especially the relationship between AD and CAD/CVD. We're lucky to have his efforts focused on our dilemma.

Per Dr. Krauss the whole notion of particle size is very much up in the air for our population. As Kit suggested, he shared some very preliminary, unpublished work with us that suggested larger LDL particles may be associated with increased amyloid plaque- CONTRARY to their beneficial role in heart disease. Headspinning Given that, particle number becomes the more important biomarker to track for us. I thought I heard him say that <1200 was a decent goal for us (with all other risk factors minimized.) Alternatively, he had concerns with a patient who presents with primarily small LDL particles even if they had a low LDL-P.

Dr. Krauss recommended that our population especially should minimize SFA; less than 7% of diet. He suggested that all SFA did NOT have the same effect on lipids. Butter and meat, in particular was more detrimental. Of course, we all asked about grain-fed vs. grass-fed. He said he couldn't speak on that as it simply hadn't been trialed. He suggested that cheese and fermented dairy was less detrimental and in response to a question from Stavia, milk was neutral.

Overall, he suggested a low SFA, low carb diet for our population. At one point he said that whole kernel grains may have a positive effect for us. When Stavia pointed out that the vast majority of us replaced vegetables with grains; he backed away from the notion that grains were a "super-food." He simply liked them for their fiber which he freely acknowledged that vegetables also provide. IF the above diet doesn't yield the desired advanced lipids, he doesn't hesitate to use statins on our population. He is not concerned with their effect on cognition and uses both lipophilic and non-lipophilic.

[Stavia]

Fascinating. Bredesen postulated that the e4 evolved when we moved from an arboreal life to the savannah thus exposing us to cuts on our feet, carrion cos we were most likely scavangers, and fighting in competition. The gene is pro inflammatory thus helped kill pathogens. The negative effects would only kick in at later life which we would have been extremely unlikely to make. As we have evolved, e4 has slowly been selected out in favour of the newer e3. Evolution isnt an end game. Perhaps we were not well adapred for longevity as hunter gatherers. Perhaps the diet was optimal for reproduction only. We should not assume that the hunter gatherer lifestyle was well adapted for the e4 allele in terms of our modern purposes which is to prevent LOAD.. Remember the paradigm of the selfish gene.
Just saying. I guess we will never know

[Stavia]

When Dr Kraus spoke to our question as to what he would eat as an e4 - he said low carb. We said tick. He said low sat fat. We said tick. He said heaps of whole grains. We said whut????
There was a moment of cognitive dissonance when he said no no no he means whole grain dense breads. We said but but but NO bread. He said fiber!. We said um veggies veggies veggies.
It turns out that he doesn't think they are necessary per se, but I suspect didn't think there would be a group so disciplined as to replace grains completely with veggies. Go us!!!
It was a very cute moment. So so cute. He is adorable. Totally adorable. I know we arent supposed to talk about the person but the message but I want to highlight this adorability of this brilliant man.

[marthaNH]

Won't let me delete the post, so just ignore it please.

[Tincup]

Until the Buck posts the video of Bredesen's (and Julie's) talk, here is a link to his talk before the California Assembly a few weeks ago. They are similar: https://www.apoe4.info/forums/viewtopic ... bly#p14803 If you are new and haven't read it, here is the paper he published in Sept: http://www.impactaging.com/papers/v6/n9 ... 00690.html

Also I'm uploading a copy of the handout at our talk with a newspaper clipping appended (also a handout).

Bredesen May 2015.pdf

Here is a link to the podcast of the February talk: http://www.buckinstitute.org/podcasts/h ... nt-podcast

[Stavia]

Thank you George!! You are a hunny bunny

[Tincup]

Some posters on the lab wall:

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