Good afternoon all,
New to the forum, but a 4/4 in life and maniacally obsessed with foregoing AD other associated health issues. Big fan of Peter Attia's work and thought you all might enjoy a paper who co-authored with Bob Kaplan which I didn't see posted on the site.
https://www.frontiersin.org/articles/10 ... 00096/full
Happy reading.
Mechanisms of Risk Reduction in the Clinical Practice of Alzheimer’s Disease Prevention
Re: Mechanisms of Risk Reduction in the Clinical Practice of Alzheimer’s Disease Prevention
Greetings Jegreacen and welcome to our site!jegreacen wrote:Good afternoon all,
New to the forum, but a 4/4 in life and maniacally obsessed with foregoing AD other associated health issues. Big fan of Peter Attia's work and thought you all might enjoy a paper who co-authored with Bob Kaplan which I didn't see posted on the site.
https://www.frontiersin.org/articles/10 ... 00096/full
Happy reading.
I am also a huge fun of Dr. Peter Attia's work thank you for sharing the study with us.
It sounds you are very proactive and serious about your health and wellbeing. To find more health ideas, explanation of science and prevention strategies for ApoE4 carries, but not only, I would like to point you to the PRIMER. It is a true wealth of information written and updated by our member- Dr. Stavia.
viewtopic.php?f=33&t=1418
Also, a great place to visit is our Wiki page here is the link:
https://wiki.apoe4.info/wiki/Main_Page
Happy reading:), and If you find a minute to write a little more about yourself, I invite you to post an introduction in "Our Stories".
Magda
Functional Medicine Certified Health Coach & MS Clinical Nutrition Student
IFM/Bredesen Trained, Reversing Cognitive Decline
IFM/Bredesen Trained, Reversing Cognitive Decline
Re: Mechanisms of Risk Reduction in the Clinical Practice of Alzheimer’s Disease Prevention
Thankyou jegreacen, a most interesting read.
Re: Mechanisms of Risk Reduction in the Clinical Practice of Alzheimer’s Disease Prevention
It was interesting to see a-lipoic acid and Li in Figure 2 as part of the risk reduction strategy. I'm curious to read more about the long-term safety of microdose diet-level Li Orotate supplementation in healthy individuals, looking at thyroid hormones / kidney function / mutagenic concerns. I did read that long-term use might be associated with hypometabolism, but perhaps that's a side effect with higher doses... if Li does reduce AD in spite of glucose hypometabolism, it seems like there's something interesting going on there.
In doing a little more research on ALA, I came across this article (with rats) I hadn't seen before:
https://www.sciencedirect.com/science/a ... 3916000053
"The present results suggest that high fat diet (HFD) induced alterations in central insulin signalling could switch metabolism to produce ketone bodies, which in turn, in the hippocampus, might lead to a decreased expression of VGlut1, and therefore to a decreased release of glutamate and hence, to the glutamatergic deficit described in AD. The ability of α-lipoic acid (LA) treatment to prevent the alterations in insulin signalling in this model of HFD might represent a possible new therapeutic target for the treatment of AD."
I hadn't considered a "glutamatergic deficit" as being associated with AD (something to consider with supplements like oxaloacetate, which is a "glutamate scavanger") -- I've tended to associate excess glutamate to be the potential issue (unless it's also something like excess glutamate eventually leads to a loss in glutamate receptors?)
https://www.ncbi.nlm.nih.gov/pubmed/24220168
"Alzheimer's disease is an age-related neurodegenerative disease characterized by deterioration of cognition and loss of memory. Several clinical studies have shown Alzheimer's disease to be associated with disturbances in glucose metabolism... this hypometabolism was partially or completely restored by lipoic acid feeding. The ability of lipoic acid to restore glucose metabolism and subsequent TCA cycle-related metabolites further substantiates its role in overcoming the hypometabolic state inherent in early stages of Alzheimer's disease."
This one was also interesting (with rats)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942488/
"Alpha-Lipoic Acid Reduces LDL-Particle Number and PCSK9 Concentrations in High-Fat Fed Obese Zucker Rats: Our data further suggests that enhanced hepatic LDLr protein abundance may be mediated through a reduction in serum PCSK9, a mechanism not previously investigated."
It seems like ALA would pair well with a HFLC diet which can carry a side effect of increased LDL particles via lower LDLr. In looking at natural compounds that seem to hedge against the potential for hypometabolism, it sounds like I can add ALA to the list next to Benfotiamine and Oxaloacetate. Although, I have come across some negative theories about ALA in the past, like the potential to redistribute mercury into neural tissue / organs, cardiovascular concerns, or SAMe depletion / increased homocysteine. Tricky.
In doing a little more research on ALA, I came across this article (with rats) I hadn't seen before:
https://www.sciencedirect.com/science/a ... 3916000053
"The present results suggest that high fat diet (HFD) induced alterations in central insulin signalling could switch metabolism to produce ketone bodies, which in turn, in the hippocampus, might lead to a decreased expression of VGlut1, and therefore to a decreased release of glutamate and hence, to the glutamatergic deficit described in AD. The ability of α-lipoic acid (LA) treatment to prevent the alterations in insulin signalling in this model of HFD might represent a possible new therapeutic target for the treatment of AD."
I hadn't considered a "glutamatergic deficit" as being associated with AD (something to consider with supplements like oxaloacetate, which is a "glutamate scavanger") -- I've tended to associate excess glutamate to be the potential issue (unless it's also something like excess glutamate eventually leads to a loss in glutamate receptors?)
https://www.ncbi.nlm.nih.gov/pubmed/24220168
"Alzheimer's disease is an age-related neurodegenerative disease characterized by deterioration of cognition and loss of memory. Several clinical studies have shown Alzheimer's disease to be associated with disturbances in glucose metabolism... this hypometabolism was partially or completely restored by lipoic acid feeding. The ability of lipoic acid to restore glucose metabolism and subsequent TCA cycle-related metabolites further substantiates its role in overcoming the hypometabolic state inherent in early stages of Alzheimer's disease."
This one was also interesting (with rats)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942488/
"Alpha-Lipoic Acid Reduces LDL-Particle Number and PCSK9 Concentrations in High-Fat Fed Obese Zucker Rats: Our data further suggests that enhanced hepatic LDLr protein abundance may be mediated through a reduction in serum PCSK9, a mechanism not previously investigated."
It seems like ALA would pair well with a HFLC diet which can carry a side effect of increased LDL particles via lower LDLr. In looking at natural compounds that seem to hedge against the potential for hypometabolism, it sounds like I can add ALA to the list next to Benfotiamine and Oxaloacetate. Although, I have come across some negative theories about ALA in the past, like the potential to redistribute mercury into neural tissue / organs, cardiovascular concerns, or SAMe depletion / increased homocysteine. Tricky.
