Fighting Alzheimer’s with Increased Autophagy via Rapamycin + Trehalose

Genetic Determinants of Trehalose Utilization Are “Not Associated” With Severe Clostridium difficile Infection outcome. https://academic.oup.com/ofid/article/7/1/ofz548/5696590

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Whether it is useful and might even be more effective in some areas than rapamycin remains TBD, but pretty cool potential for just a spoonful of sugar…! The only challenge is to figure out how to replace sugar already in the diet, rather than adding more.

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Trehalose and Alulose are the only sweeteners I use in my house.

More good news on Trehalose:

Therapeutic promise of combined use of trehalose

The therapeutic effect of trehalose is largely attributable to the activation of the mTOR-independent pathway of autophagy. Such inducers work effectively even during the active phosphorylated state of mTORC1, which inhibits autophagy by the mTOR-dependent mechanism [175], [176]. In this regard, rapamycin can stimulate autophagy even at high levels of inositol or inositol-1,4,5-triphosphate inhibiting mTOR-independent autophagy [177]. Thus, both pathways do not seem to interact with each other

Trehalose has a therapeutic effect in various experimental models of diseases. This glucose disaccharide with a flexible α-1-1′-glycosidic bond has unique properties: induction of mTOR-independent autophagy (with kinase AMPK as the main target) and a chaperone-like effect on proteins imparting them natural spatial structure. Thus, it can reduce the accumulation of neurotoxic aberrant/misfolded proteins. Trehalose has an anti-inflammatory effect and inhibits detrimental oxidative stress partially owing to the enhancement of endogenous antioxidant defense represented by the Nrf2 protein. The disaccharide activates lysosome and autophagosome biogenesis pathways through the protein factors TFEB and FOXO1. Here we review various mechanisms of the neuroprotective action of trehalose and touch on the possibility of pleiotropic effects.

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There is no doubt that Trehalose should be part of my daily regimen, for the neuro-protective effects alone.

Have you found an article that recommends a daily therapeutic dose for humans?
I am looking for some guidance on the lowest therapeutic dose.

Apparently from one study of using trehalose in the treatment of Parkinson’s disease, there appears to be an unknown effective dose. Of course, taking too high a dose results in diarrhea.

“Therefore, it appears that the lowest effective dose and duration of maximum neuroprotective effect need to be defined to avoid the adverse effects of a high dosage.”

Trehalose as a promising therapeutic candidate for the treatment of Parkinson’s disease
https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.14623

Sorry if you have already addressed this.

The catch-22, of course, is that most of us have trained ourselves to not indulge our sweet tooth, so rarely “add” sugar to anything, other than maybe coffee which is problematic since it is in the morning and breaks our fast if we do. In our house, for treats, we usually add dried fruit. Any clever ideas for “replacement,” or are we just doomed to add the calories and insulin spike if we want the possible benefits?

Well, it definitely spikes your blood sugar. I do time-restricted feeding so I don’t add it to my coffee until later in the morning. I like my coffee black and not sweet, but trehalose is not too sweet. I have a convenient little scoop that came with some other supplement.
One scoop is ~8 grams of trehalose, which I add to my coffee. I am going to keep track of my A1C. I don’t expect trehalose to have much effect. The literature is extensive on the benefits of trehalose. I am most interested in the neurological benefits, but it also is good for maintaining healthy glucose levels.

“Daily consumption of one teaspoon of trehalose can help maintain glucose homeostasis: a double-blind, randomized controlled trial conducted in healthy volunteers”
Previously referenced by @rapadmin

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Perhaps you don’t realize the control group in this study. Almost ANYTHING will result in an improvement over 25g of sucrose/DAY. Not quite a can of coke every day, but close.

“This was a randomized, double-blind, placebo-controlled study of healthy Japanese participants (n = 50). Each consumed 3.3 g of trehalose (n = 25) or sucrose (n = 25) daily for 78 days.”

Why did they even bother, oh wait, a totally corporate sponsored study!

Affiliations

  • 1Hayashibara Co. Ltd., 675 Fujisaki, Naka-ku, Okayama, 702-8006, Japan. chiyo.yoshizane@hb.nagase.co.jp.
  • 2Hayashibara Co. Ltd., 675 Fujisaki, Naka-ku, Okayama, 702-8006, Japan.

Founded as a starch syrup manufacture in 1883

In their breakdown of business units, I noticed Trehalose was not included in the “health foods” ingredients unit.

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Allulose has been reported to lower blood sugar via a mechanism that’s been suggested to be similar to SGLT2 inhibitors. So, if you want to avoid a spike in blood sugar allulose may be one way to go.

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This study is just as bad…as suspected, sponsored by yet another Japanese starch conglomerate. “The study was funded by Matsutani Chemical Industry Co”

From the study.

50g of sucrose was part of the base dosing escalation.

"Our study was the largest to test the effects of D-allulose in Westerners, including white and African-American, and results can be summarized as follows:

(1) D-allulose administered in addition to a standard 50g sucrose load led to a dose-dependent reduction of plasma glucose at 30 min compared with placebo;
(2) although plasma glucose was not reduced at the other time points and AUC was similar between D-allulose and placebo, there was a dose-dependent reduction in plasma glucose excursion compared with placebo;
(3) the effects of D-allulose on insulin levels and insulin excursion were similar to those on plasma glucose;
(4) D-allulose effects appeared to be consistent in both white and African-American subjects;
(5) the administration of escalating doses of D-allulose appeared to be safe.

When you pick apart these studies, they are just a corporate mirage. Call it “ose-washing”.

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As I have posted many times: I never suggest or recommend to anyone else to take anything or do anything that I am doing.

Bottom line: If you don’t like it don’t take it.

Having said that, I think the evidence is heavily favored for some people to make Trehalose a part of their healthspan supplement stack.

Also, as I said, I added Trehalose to my supplement stack for neurological protection and other benefits, but, I am not dismissing the glycemic control benefits

"Facts
Trehalose has been shown to be neuroprotective in animal models of various neurodegenerative diseases, such as Parkinson and Huntington diseases.

Autophagy induction and aggregate clearance have been the primary hypothesis for the mechanism of neuroprotection by trehalose.

Trehalose blocks autophagic flux from autophagosome to autolysosome in cell models.

Trehalose may exert the neuroprotective effects through indirect mechanisms at the systemic levels, e.g., through influencing gut microbiota."

https://www.nature.com/articles/s41419-018-0749-9

“In mice fed with HFD, they also found that trehalose intake mitigated insulin resistance, reduced mRNA expression of plasminogen activator inhibitor-1 (PAI-1) (Arai et al. 2010), and increased serum high molecular weight (HMW) adiponectin (Arai et al. 2013). HMW adiponectin may decrease insulin resistance by up-regulating the expression of IRS-1 and IRS-2 mRNA in the muscle (Arai et al. 2013)”

“Trehalose potentially prevents the development of the metabolic syndrome and improves glucose tolerance in humans. Maki et al. (2009) showed that the consumption of trehalose by obese men effectively reduces postmeal insulin bursts”

" Sarkar et al. (2007) identified trehalose as an autophagic enhancer"
.https://www.tandfonline.com/doi/full/10.1080/10408398.2021.1895057

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The trehalose study and the allulose study were designed differently.

In the trehalose study above, trehalose was compared with glucose. In that study trehalose alone seemed to have some blood sugar raising affect, although mild in comparison to the sugar it was compared with.

In the allulose study I linked, the researchers compared sucrose plus placebo with sucrose plus allulose and reported that allulose plus sucrose had some blood sugar lowering effect compared to sucrose alone. In other studies researchers have reported allulose to lower post prandial glucose in comparison to placebo.

d-Allulose enhances postprandial fat oxidation in healthy humans

A pilot study on the effect of D-allulose on postprandial glucose levels in patients with type 2 diabetes mellitus during Ramadan fasting

These studies in conjunction with a couple others point towards allulose as a blood sugar lowering agent on it it’s own as opposed to a sweetener that raises blood sugar to a lesser extent than traditional sugars.

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Hi everyone,

can anybody give me a quick summary of what the data says about which sweetener is best for those who have blood sugar issues? My fasting glucose tends to be high-ish, A1c is 5.3% and HOMA-IR score is 0.8, so not panicking just yet but want to find ways to keep blood sugar in check as best I can.

I use a sweetener 3 times a week to sweeten my home made 24 hour yoghurt (which is very sour!). I have a big sweet tooth, and it takes quite a lot of sweetener to get the taste to my liking.

I used to use Stevia but switched to allulose after reading an article by Peter Attia.

Any thoughts?

thanks

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I tested allulose on myself with a CGM a couple of years ago. Mug of coffee with it and a mug without. Both lines on the CGM looked the same, whilst sugar clearly spiked it. Allulose works for this n=1 to avoid blood sugar spikes. I’ve used Allulose ever since and not a single blood draw has shown hba1c to be high.

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@RPS that is excellent news.

It’s twice as expensive as Stevia (at least here in Australia), and half as sweet - so I have to use a lot.

But well worth it if it’s the best option.

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Does stevia cause your glucose to spike. If not, you could use some of each.

FWIW the study was using trehalose alone or in combination with rapamycin in targeting mTOR-independent autophagy.

It is not/did not using/used “Allulose”

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As I have posted before, I take trehalose for its possible life-extension and neurological benefits, not as a substitute for other sugars.

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Stevia doesn’t seem to cause an increase in glucose, insulin, or A1C levels.

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True, but stevia tastes nasty!:laughing: I mean it’s ok, but for instance i gag on stevia-sweetened coffee. Allulose actually tastes like sugar, moreso than any other noncaloric (or minimally caloric) sweetener IMO.

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@rivasp12 I haven’t tested it. But will do, thanks.