Fighting Alzheimer’s with Increased Autophagy via Rapamycin + Trehalose

The reason for trehalose.


I toke 100g Trehalose and 25 Acarbose today, and had bad diarrhea.

My strategy is to take Trehalose with Saccharomyces boulardii next time, Saccharomyces boulardii releases trehalase which helps hydrolyzing Trehalose, but I don’t know if adding Saccharomyces boulardii eliminates the benefit of Trehalose?

The rationale is as shown below. Trehalose can’t be directly absorbed, almost all Trehalose are hydrolyzed to two D-glucose, only less than 0.5% of Trehalose can be absorbed by passive diffusion.

I guess the autophagy effect is not induced by D-glucose, it’s more likely the 0.5% of Trehalose absorbed did the work. Here is the dilemma, people who lacks enzyme trehalase has diarrhea, but people who has abundant enzyme trehalase converts almost all Trehalose to D-glucose, then there is no Trehalose absorbed.

Should I add Saccharomyces boulardii to prevent diarrhea? But Saccharomyces boulardii hydrolyze Trehalose to D-glucose, it’s equivalently drinking the glucose sugar water, does it also activates Autophagy?Any thoughts?

Do you have other strategy to increase the absorption of Trehalose while avoiding the diarrhea?

When ingested, trehalose is not assimilated as a disaccharide
into the blood stream. Rather, it is enzymatically
hydrolyzed in the small intestine by a trehalose-specific
disaccharidase into two D-glucose molecules, which are
subsequently absorbed and metabolized.

In people who can not absorb trehalose normally due to a lack of trehalase it is thought that all absorption that occurs would be via passive diffusion; in regards to disaccharides in general, the amount absorbed by passive diffusion during instances of malabsorption tends to be around 0.5%.

I am a great believer in the Examine reviews of supplements. I took trehalose for a while and dropped it because I just don’t need another fart diarrhea-producing supplement in my daily stack. Acarbose may be worth taking, but it has caused me to drop carbs to a minimum to prevent the unpleasant side effects of acarbose.


I have never seen any good evidence of trehalose being bioavailable in humans. The diarrhea many people experience from taking it supports this, as it is a clear sign of it not being absorbed.


I don’t either but I just bought another kilogram because it actually makes my espresso taste great, autophagy is just an added benefit. I can handle 2 tablespoons/day without diarrhoea


Yes in the worst case scenario the trehalose is acting like slower release glucose because it is broken down to glucose which is then absorbed.


I just got some 3% trehalose eye drops for dry eyes made in France. Probably an insignificant amount, (though 0.5% from intestines might indicate that it only takes a small amount of it to have an effect) but I wonder if any might be absorbed by that alternate route. Or if it improves autophagy of drusen in the retina…

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Stevia is my artificial sweetener of choice. However, stevia extract is so sweet that it has to have an additive to bulk it up and make it reasonably close to sugar for teaspoon-to-teaspoon equivalency. Unfortunately, many brands contain what I deem questionable fillers.

For instance, one brand advertising itself as “Stevia in the Raw” actually contains cane sugar.

How they manage to get zero calories from this is a mystery.

A few brands contain erythritol which is sweet, but much less sweet than stevia extract.

It’s nice that the cheapest brand from Walmart actually contains erythritol as the filler.

So it’s a good way to get some erythritol in our diet. It’s also nice that they list the fat, carbohydrate, and protein on their label. Fat and protein? Of course, the labeling from a giant like Walmart is also confusing. The same label lists 0 protein, then a little further down lists 4 grams of protein. Maybe the top is for the stevia extract and the bottom for the stevia extract + erythritol?


Erythritol is sweet-less for me, I used aspartame, 0.5g aspartame is sweet enough for a 400ml cafe, but I need to put 20g or more erythritol to have the same sweetness, and 20g erythritol made me have mild diarrhea, that’s why I chose aspartame.

The erythritol is just a filler in the sweetener I use.
Why do you choose aspartame over stevia as a sweetener?

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If you like stevia but don’t want the fillers, try these stevia drops from Trader Joe’s. They have the best taste of any stevia, and it’s incredibly easy to get just the right amount. The link is for Amazon, for those unfortunates who don’t have a Trader Joe’s nearby:

I like the one I am using because I want the trehalose content and I have tried the drops before and they don’t work that well except for adding to drinks.

I take 1/2 tsp sublingually, occasionally. Skips the trehalase in the gut. Not as effective as intraperitoneal injection {used in the mouse study (}, but much easier.


Alzforum: Could Calming Overactive Ryanodine Receptor Restore Autophagy? | ALZFORUM.

Autophagy enables microglia to engage amyloid plaques and prevents microglial senescence

Dysfunctional autophagy has been implicated in the pathogenesis of Alzheimer’s disease (AD). Previous evidence suggested disruptions of multiple stages of the autophagy-lysosomal pathway in affected neurons. However, whether and how deregulated autophagy in microglia, a cell type with an important link to AD, contributes to AD progression remains elusive. Here we report that autophagy is activated in microglia, particularly of disease-associated microglia surrounding amyloid plaques in AD mouse models. Inhibition of microglial autophagy causes disengagement of microglia from amyloid plaques, suppression of disease-associated microglia, and aggravation of neuropathology in AD mice. Mechanistically, autophagy deficiency promotes senescence-associated microglia as evidenced by reduced proliferation, increased Cdkn1a/p21Cip1, dystrophic morphologies and senescence-associated secretory phenotype. Pharmacological treatment removes autophagy-deficient senescent microglia and alleviates neuropathology in AD mice. Our study demonstrates the protective role of microglial autophagy in regulating the homeostasis of amyloid plaques and preventing senescence; removal of senescent microglia is a promising therapeutic strategy.

Open Access:

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Metformin and Trehalose-Modulated Autophagy Exerts a Neurotherapeutic Effect on Parkinsonʼs Disease

Therefore, we evaluated the autophagy inducers metformin and trehalose effect in a PD model. Autophagy induced by both molecules was confirmed in the SH-SY5Y dopaminergic cells by detecting increased LC3-II marker and autophagosome number compared to the control by western blot and transmission electron microscopy. Both autophagy inducers showed an antioxidant effect, improved mitochondrial activity, and decreased dopaminergic cell death induced by PQ. Next, we evaluated the effect of both inducers in vivo. C57BL6 mice were pretreated with metformin or trehalose before PQ administration. Cognitive and motor deteriorated functions in the PD model were evaluated through the nest building and the gait tests and were prevented by metformin and trehalose. Both autophagy inducers significantly reduced the dopaminergic neuronal loss, astrocytosis, and microgliosis induced by PQ. Also, cell death mediated by PQ was prevented by metformin and trehalose, assessed by TUNEL assay. Metformin and trehalose induced autophagy through AMPK phosphorylation and decreased α-synuclein accumulation. Therefore, metformin and trehalose are promising neurotherapeutic autophagy inducers with great potential for treating neurodegenerative diseases such as Parkinson’s Disease (PD).

Paper (Paywalled)


Another medication: Nitazoxanide

Activates autophagy in AD model mice.
Improved learning and memory.
Promoted Aβ plaque clearance. (It also inhibits the formation of atherosclerotic plaque in mice).


I have taken trehalose almost daily for a year or two now, but have assumed that it is probably broken down before entering the circulation. I can’t tell from the abstract, but would be nice to know whether it was given orally in this study.

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Another cool fact about trehalose. It is needed for cryptobiosis in worms.

Explained: Scientists ‘Revive’ 46,000-Year-Old Worms Frozen In Ice, How And Why Did They Do It? (

"*The major highlight of the study is that it found that it is possible to stop or pause life for a very long period of time. *

**Researchers identified key genes in the nematode that allow it to achieve the cryptobiotic state, reported NYT. It is a special type of sugar called trehalose.

“This led us, for instance, to understand that they cannot survive without a specific sugar called trehalose. Without this sugar, they just die,” said Teymuras Kurzchalia, Professor Emeritus, Max Planck Institute of Molecular Cell Biology and Genetics in Germany, to NYT."


Unfortunately, like many supplements, it has its good and bad side.

This was generated by Google’s new AI:
"Trehalose is a sugar that may cause more severe infections from Clostridium difficile (C. difficile).
This antibiotic-resistant bacterium can cause diarrhea, colitis, organ failure, and even death.
In one study, trehalose increased the death rate of mice infected with C. difficile by three times.
The increased production and use of trehalose has coincided with a rise in hospital infections from C. difficile.
Trehalose is generally well-tolerated, but some people may experience mild side effects, such as gastrointestinal discomfort, bloating, or flatulence. Trehalose should be used with caution in people with diabetes or insulin resistance.
Trehalose may also help prevent the progression of type II diabetes. It may increase energy expenditure and has potential to prevent obesity. "

I have a pound or more sitting on the shelf. I was an exuberant taker of the initial hype, but trehalose in any significant quantity played havoc with my digestive tract, so I quit taking it.