59vw
#241
@Anthony Rosuvastatin is one of the statins that is not sensitive to GFJ so you don’t need to worry about dosage effects if that is the reason you plan to skip it on days your are experimenting with GFJ.
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I’m now favoring rosuvastatin over other statins for several reasons .
The lack of cyp3a4 effects, the potency, and lack of getting into the brain are excellent qualities. Also it is cheap.
On the downside . . A risk of T2DM and insulin resistance.
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Here is an excellent overview of GLP1, the hormone your body makes - and GLP1-R’s - the receptors which specifically interact with your GLP-1 and the “new” GLP1-RA (agonists) peptides that help this system work better.
https://www.nature.com/articles/s41392-024-01931-z
The linked study below, comprising a review of 23 RCTs and more than 150,000 patients - ONLY GLP-1 agents were associated with a SIGNIFICANT reduction - 45% vs those who received placebo in the incidence of dementia
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I’m sorry, Steve😭, but that’s just a terrible paper. It’s a case making review replete with mechanistic speculation, all piled up higgedly piggedly with studies from all over, animal data randomly with human and just a giant mess. I was wondering why the english was so poor (sample sentence: “These flaws create covertly.” - um, wha??), and why wasn’t this cleaned up, being in dire need of an editor. I looked it up - Indian + Saudi dodgy institutions; PASS. YMMV.
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There are 2 papers in my post, not sure which one you are referring to.
The first link is an overview of how the GLP1 system works in relation to GLP1-RA’s with a lot of good info for people who want to know how that works. There are more than a few misconceptions on GLP1 and GLP1-RA’s
The second one, I think my “headline” was from another article I read but I didn’t post that link, I posted another overview instead. So my headline is definitely misleading. in relation to the actual article I referenced.
This article is a review from 2022 of work completed by others in relation to potential dementia benefits.
Got you. Thanks for clarifying. The first paper I only glanced at, seemed fine.
Xylitol warning from the European Heart Journal.
Xylitol is prothrombotic and associated with cardiovascular risk
https://academic.oup.com/eurheartj/article-abstract/45/27/2439/7683453?redirectedFrom=fulltext
The Swiss say the article’s title is misleading.
We therefore find the title of this publication misleading. It should say: ‘Endogenous xylitol production is elevated in patients with cardiovascular risk’ and ‘Xylitol intake might have a short-term effect on thrombocyte aggregation’
.
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Beth
#248
Since listening to the Wise Athletes dental podcast a month or two ago, I’ve been happily downing bucketloads of cinnamon xylitol … thank you @JuanDaw
I don’t completely understand the paper, as per usual, so @DrFraser, please share if I can continue my new guilty cinnamon pleasure !
The European article says elevated xylitol may promote clotting, which may lead to strokes or other CVD events. The Swiss counter, it is elevated xylitol produced by the body (endogenous) which is associated with the Europeans’ observation, not xylitol consumption. If there is any pro-clotting effect, the Swiss observe that it is short-term. Besides, even exercise and hunger increase thrombocyte aggregation in the short-term.
The authors also report that ex vivo platelet response to stimulation with TRAP6 and ADP 30 min after ingestion of 30 g xylitol in 10 healthy humans was increased. However, with n = 10, the study was small; there was no placebo arm and only a single timepoint after ingestion. Short-term thrombocyte aggregation is e.g. altered in response to physical exertion and acute food intake. The single timepoint after 30 min does not allow drawing any conclusions about how relevant this observation is in the context of other natural fluctuations.
Although xylitol is known as a sweetener, the findings in cohorts with CVD reflect endogenous synthesis, which is unrelated to consumption, as noted by the authors.
The dose is also high - 30 grams. That is 30 xylitol mints in one taking.
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The dose makes the poison. The mints we recommend 2 per day of or maximum 4 per day of (split after each dental hygiene episode) is 1 gram per 2 mints. This is a little different than showing some platelet abnormalities short term after 30 grams. Amazon.com : Epic 100% Xylitol Mints - Aspartame Free, Sugar Free - Peppermint Flavored Mints, 180 Pieces (Pack of 2) : Grocery & Gourmet Food
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Have you considered intranasal insulin?
Yes I have, but it’s not going to make the list at this time. The primary issue in this sphere seems to be insulin resistance. Insulin, at least in the periphery is toxic to blood vessels (not as toxic as hyperglycemia which is why I’d still favor using it once other options are exhausted), but it is unclear on the brain. Right now there are mixed findings on whether this is good or not for MCI or early AD.
I use multiple agents to improve insulin sensitivity in the brain, with the best evidence being for GLP-1’s or GLP-1/GIP agents, and probably some effect indirectly of SGLT2’s.
I’m much happier with Rifampin/Rifampicin intranasal and potentially rapamycin intranasal. It does seem to result in significant levels in the brain via, I believe, the olfactory and trigeminal nerves.
It looks like Rapamycin (and yes this would be a good time for the powder) dissolved in 5% ethanol in distilled or reverse osmosis water is an option intranasal. Dosing is a challenge - I’ve got my views on this and have offered it to patients. I’ll possibly add this to my protocol for those with ApoE4’s.
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Thank you for your detailed and thoughtful reply. I will look into Rifampin/Rifampcin.
I have been taking the intranasal insulin for one week now, and will go to eight weeks to decide whether to continue, and whether to start my husband on it for MCI. I decided to try it myself because there appears to be a correlation between naturally low insulin in women and AD, and, also, I have family history. So intranasal insulin seems worth trying because there seems to be a match between my personal makeup and what intranasal insulin does. Alternatively, when I think about rapamycin, it is less clear how its benefits would work for me personally since I am naturally kind of a catabolic phenotype.
Please keep posting your thoughts about all things AD!
I wonder if someone here have tried coffee fruit extract. Besides HiiT exercise, it seems to be an intervention that significantly increase BDNF apprix 140 %. Cofffee fruit extract is also said to contain chlorogenic acid.
Cognitive short- and long-term effects of coffee cherry extract in older adults with mild cognitive decline: Aging, Neuropsychology, and Cognition: Vol 27, No 6
I also wonder if someone has in formation about Casacara and if it can increase BDNF. Cascara is dried coffee fruits that is used for tea.
NBut HiiT exercise is still nr 1 when it comes to increasing BDNF. But it would be nice to have the effect in a tea,
Fasting for 20 h does not affect exercise‐induced increases in circulating BDNF in humans - Gibbons - 2023 - The Journal of Physiology - Wiley Online Library
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I recommend coffee cherry extract for many of my patients as a sensible supplement. We use the Swanson Brand… very cost effective.
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Neo
#256
I use xylitol gum for oral health optimization
But I spit out after chewing and sloshing it around a bit in my mouth
Not because I was aware of any CVD risks, but because (a) decreasing micro plastics exposure and (b) xylitol is slightly laxative
Is there any value to swallowing xylitol or is it enough to expose the oral cavity to it?
Including @JuanDaw @Beth
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Beth
#257
@neo, @DrFraser @JuanDaw
The moral of the story is I can no longer keep them in the car because I may or may not be easily inhaling 30 grams …. I do not have the willpower to have only 4 mints!!!
I’m glad this came up so you didn’t have to find out I died from a xylitol overdose…
I buy these fwiw… chose them because it was cinnamon oil vs flavor (not sure if it matters)
https://www.amazon.com/dp/B0BXBB4TCM?ref=ppx_yo2ov_dt_b_fed_asin_title&th=1
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There is some research that it helps the microbiome.
Xylitol’s Health Benefits beyond Dental Health: A Comprehensive Review - PMC.
Xylitol is not digested by human enzymes and approximately 50% of the consumed xylitol is absorbed through passive diffusion in the small intestine [6]. The remaining 50% of the dietary xylitol thus enters the colon where it can serve as an energy and carbon source for the intestinal microbiota and leads to the formation of short-chain fatty acids which provide energy to the host and support immune system homeostasis [24]. These properties of xylitol are very similar to what is expected from a prebiotic; a substrate that is selectively utilized by host microorganisms conferring a health benefit [25]. The increased concentration of xylitol in the digesta leads to an increased osmotic pressure which contributes to water retention in the digesta and thus may lead to laxative effects when consumed in excess (>20 g) [8,24]. However, this property of xylitol can also be used to address constipation; which is in line with the prebiotic nature of xylitol.
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The Swiss, in the link above, disagree with the warning of the EU. They state that it is the overproduction of xylitol by the body, that may pose danger, not consumption. Whatever it is, that induces overproduction, that is the likely danger, not the consumption.
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These results suggest that WCCE is associated with acute neurophysiological changes supportive of faster reaction times and increased, sustained attention.
Finally, we examined behavioral performance on two well-known tasks of cognition—the n-back and the go/no-go task. Behaviorally, WCCE resulted in an approximately four times greater reduction in reaction time during the n-back task compared to the placebo. Furthermore, the placebo was associated with a decreased accuracy during the go/no-go task, with participants committing over 50% more errors compared to post-WCCE ingestion. This manifestation within the placebo group may have been due to mental fatigue, decreased alertness, or increased frustration in individuals who, by definition, were untreated and were not availed of the support of the WCCE. These results suggest that WCCE has acute behavioral effects and further corroborates findings demonstrating long-term effects of WCCE administration [35]. Moreover, these acute results may imply longer-term significant effects on cognitive processing, pointing toward an increased efficiency (i.e., reduced reaction time) and potentially protecting against errors through increased sustained attention or other mechanisms. This has been behaviorally supported in recent research [35], also conducted in older adults.
Here, we demonstrated significant improvements in cognition, with concomitant observed changes in neurofunctional brain networks after a single 100 mg dose of WCCE (whole coffee cherry extract), a polyphenol-rich plant-based extract that appears to increase exosomal BDNF, an essential neuroprotein.
Sample size is small - four patients each, WCCE, and placebo.
The dosage used in the study was 100 mg. The Swanson WCCE recommended by Dr Fraser contains 200 mg per capsule.
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