2016 Ancestral Health Meetup - Stavia's blog

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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby Stavia » Wed Aug 17, 2016 6:26 pm

This is one I didn't get to attend. Looked fascinating
Nick Mailer: chemphobia, appeal to nature

https://youtu.be/UWxYQMoUJzU

Addendum: its excellent. Brutally honest.
"Nora Gedueges niche" lolol. I will never forget the look on Susan's face during her lecture at a particularly bad leap of an unsubstantiated conclusion ie that because Inuit were in her opinion supremely healthy all carbs were off the table for everyone.

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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby Stavia » Wed Aug 17, 2016 6:27 pm

And Todd Becker on hormesis was well worth attending.

https://youtu.be/Cii0JtiXBS4

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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby circular » Wed Aug 17, 2016 6:58 pm

Juliegee wrote: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

So does anyone happen to have a list from this paper of the statins hypothesized to be safer for e4s, or ones to avoid? The article's behind a paywall and I have a followup with my mother's neurologist tomorrow and she's on prevastatin. I'll take her the name of the article, but if a change in statin is warranted I'd like to ask for it tomorrow to get the ball rolling. She may want the cardiologist to agree to it. Thanks in advance.
ApoE 3/4 > Thanks in advance for any responses made to my posts.

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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby slacker » Wed Aug 17, 2016 7:05 pm

Stavia wrote:DALE BREDESEN
Apoe4 mechanistics and a protocol for the reversal of cognitive decline
Description of a comprehensive therapeutic program to reverse cognitive decline in SCI, MCI and early AD.

Dale spoke eloquently and with authority about his program for prevention and reversal of cognitive decline.

We all know it very well, his findings of the apoe4 molecule binding to cell membrane receptors, interacting with RelA (a pro-inflammatory mediator) and enters the nucleus. Here it binds to 1800 gene promotors and these effects resultin increase in NFkB and decrease in SIRT1. This is a pro-inflammatory state as opposed to a SIRT1 dominant anti-inflammatory state.

This is the ancestral allele. Apoe3 appeared around 220 000 years ago and Apoe2 only 70 to 80 000 years ago. Apoe2, being a dominant inflammatory state, has advantages in a situation of living in the bush, waking barefoot, eating carrion, fighting over resources. Also of note is that E4s tend to be hyperabsorbers of fats. This is hugely advantageous in times of famine as reserves will be higher, however not so good in the context of our present abundance of food.

In today's environment, Dale and his team have identified 36 "holes in the roof " which he uses as a metaphor for detrimental downstream effects resulting in dementia. There are complex interactions involving glucose homeostasis, microtubule disassembley, inflammation, neurotrophins and cell death, synapse dysfunction. He feels amyloid is a protective response to three main stressors-1. inflammation both infectious and sterile (HSV, EBV, CMV, biofilms/ AGE modified molecules) - 2. withdrawal of trophic support (nerve growth factor, estrogen, testosterone, D3 )- and 3. response to toxins (eg mercury, mycotoxins)
He calls these types 1 2 and3. There is also an intermediate group 1.5which he calls glycotoxic. Here AGEs cause inflammation which leadsto insulin resistance thus with IR trophic support is effectively lacking.

He also has shown that in a trophic support environment the amyloid precursor molecule is cleaved into two functional parts. In an antitrophic environment it is cleaved into smaller fragments, one of which is abeta which unfortunately seems to accumulate in a prionic-like manner. The downstream effect is accumulated amyloid, tau and mitochondrial dysfunction.

He then described his program which we all know very well.

My opinion: brilliant as always, clearly at the top of his game and likely the world's top expert in the field of Alzheimers. A privilege to hear him speak.


I agree that Dr Bredesen is excellent, having heard him speak for 3 days at the most recent Buck Institute protocol teaching in July. This may be a nit, but I can't find a specific list of the 36 holes (while anticipating the list may grow to 50-100). It's a great analogy, yet I see the value of having it clearly defined, and perhaps listed in groupings of most common to least. With insulin resistance at the top...
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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby Stavia » Wed Aug 17, 2016 7:35 pm

Very good question
I asked Dale this specifically last year at the Buck to give me a hierarchical list of the factors from most important to less important.
He said that tier 1 was insulin resistance and inflammation. tier 2 was trophic support such as D3, B12, oestrogen, progesterone, testosterone, thyroxine. Tier 3 was factors such as zinc copper ratio.
I asked him again this year and he now adds chronic infection/inflammation such as to mould to the top tier in some people, but I guess this would fall into the category of inflammation.

The 36 holes are biochemical pathways not necessarily equivalent to a single clinical biomarker. For instance SIRT1 does not correlate with only one strategy. It is extremely complex. It is all in his paper.
http://www.aging-us.com/article/NjJf3fWGKw4e99CyC/text

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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby KatieS » Wed Aug 17, 2016 7:48 pm

Cir, sorry to hear about your mother. Julieanne's citation included simvastatin (SV) which does have other references of neuroprotection. My mom & husband are both on SV, but it interacted with nifedipine, so I switched to rosuvastin (now Crestor is generic). Pravastatin 10mg was too weak, but 20mg increased muscle pains. Rosuvastatin is water-soluble like pravastatin,but a very potent statin even at low doses.

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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby Stavia » Wed Aug 17, 2016 8:22 pm

Katie! How's your eye honey?

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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby Stavia » Wed Aug 17, 2016 8:34 pm

Back to Bredesen and the 36 holes

I found a list. As you can see each one does not correlate to an intervention

http://www.clinicaleducation.org/resour ... s-disease/

35 Mechanisms
1. Decrease Aβ production
2. Increase Aβ degradation
3. Decrease Aβ oligomerization
4. Increase BDNF (Brain Derived Nerve Factor)
5. Increase NGF (Nerve Growth Factor)
6. Increase G-CSF
7. Increase ADNP
8. Decrease p-tau
9. Decrease homocysteine
10. Build synapses
11. Decrease 4/2
12. Increase Aβ breakdown
13. Increase A/G Ratio (Albumin/Globulin)
14. Decrease Inflammation
15. Inhibit NF-kB
16. Increase GSH (glutathione)
17. Increase antioxidants
18. Decrease Iron (& decrease copper, increase zinc – target of Zn : fCu is 100:10-15)
19. Increase CBF
20. Increase ACh
21. Increase α 7 signaling
22. Increase Aβ transport
23. Increase Aβ clearance
24. Decrease ApoE4 effect
25. Increase GABA
26. Decrease NMDA
27. Optimise hormones
28. Increase vitamin D
29. Decrease pro-NGF
30. Decrease caspase-6
31. Decrease N-APP
32. Increase Memory
33. Increase Energy
34. Increase Mitochondrial function
35. Increase Mitochondrial protection

I think this is only 35 because iron and cu/zn are together in one line.

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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby slacker » Thu Aug 18, 2016 9:16 am

[/quote]
So does anyone happen to have a list from this paper of the statins hypothesized to be safer for e4s, or ones to avoid? The article's behind a paywall and I have a followup with my mother's neurologist tomorrow and she's on prevastatin. I'll take her the name of the article, but if a change in statin is warranted I'd like to ask for it tomorrow to get the ball rolling. She may want the cardiologist to agree to it. Thanks in advance.[/quote]

I've had good luck in the past getting free copies of papers while doing research on certain topics by emailing the main author. Since no email address is posted on this one, but was written by researchers at the Buck Institute (including Dr Bredesen), they may release a copy to you directly if you call and explain that you want to post the statin details on ApoE4.Info website. Worth a try!
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Re: 2016 Ancestral Health Meetup - Stavia's blog

Postby slacker » Thu Aug 18, 2016 9:20 am

Ha, ha, silly me! I won't embarrass myself any more by explaining what I was expecting!! :lol: Still good to have, nevertheless! Many thanks Stavia.
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