Fighting Alzheimer’s with Increased Autophagy via Rapamycin + Trehalose

Good news for all the rapamycin autophagy fans here:

In this study, the researchers sought to investigate if targeting mTOR-independent autophagy with trehalose in addition to the mTOR-dependent pathway with rapamycin would bring additional benefit in a mouse model of Alzheimer’s disease.

Trehalose treatment significantly upregulated autophagy in the hippocampus and frontal cortex, while the combined treatment was more efficient in inducing autophagy than monotherapies in the amygdala and dentate gyrus.

Conclusion

This study shows that the induction of autophagy by trehalose alone or in combination with rapamycin in general is more beneficial than rapamycin-only treatment in an animal model of AD. This points out the importance of activating the mTOR-independent pathway to address neurodegeneration.

The authors argue that unlike rapamycin, which acts through mTOR, trehalose affects the expression of several transcription factors, including FOXO1 and TFEB, which, in turn, regulate the expression of autophagy genes. This leads to an increased production of lysosomes.

Read the full story here:

Research paper the above story is based on:

Highlights

•Trehalose but not rapamycin produced pronounced and prolonged autophagy induction.

•Trehalose produced pronounced long-term transcriptional activation of autophagy genes.

•Trehalose and rapamycin effectively prevented Aβ deposition and microglia activation.

•Autophagy inhibitor 3-methyladenine disturbed the effect on Aβ load.

• The autophagy inducers restored behavioral and neuronal deficits in Aβ-injected mice.

More on Trehalose and Autophagy

Its interesting, because trehalose is easily available as a sugar substitute (similar, I think to Allulose, which many will have heard of from Peter Attia). I use Allulose in my house as my sweetener typically, though still use very little.

Trehalose might be something we need to research more:

Trehalose has been widely used in the preservation of food, but has also been used to treat medical diseases due to its ability to enhance autophagy. In healthy middle-aged and older adults, oral trehalose supplements (100 g/day) improved microvascular function by increasing endothelial nitric oxide [21]. The protective effects of trehalose have largely been demonstrated in neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease [22,23,24]. Trehalose enhanced autophagy and reduced abnormal protein aggregation in the brain tissue of mice with Huntington’s disease [24,25].

… the efficacy of orally administered trehalose has been well-documented in neurodegenerative disorders. Trehalose (2%) added to the drinking water was directly bound and inhibited polyglutamine aggregates in a mouse model of Huntington’s disease, and the presence of trehalose in the homogenates of brain and liver tissue has been confirmed, indicating the effectiveness of orally administered trehalose [25]. The long-term administration of 1% trehalose through drinking water over two and a half months reverted the death of dopamine neurons and induced autophagy in a mouse model of parkinsonism [39]. In a mouse model of Lewy body disease, the oral intake of 2% trehalose for one week was associated with increased autophagy in the brain [40].

Source: Effect of Trehalose Supplementation on Autophagy and Cystogenesis in a Mouse Model of Polycystic Kidney Disease

Mechanism of neuroprotection by trehalose: controversy surrounding autophagy induction

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

3 Likes

That’s interesting. I wonder if allulose works the same . Coffee also upregulates autophagy, so some coffee sweetened with allulose and rapamycin down the hatch. I can feel my cells self digesting just thinking about it.

2 Likes

Human studies…

Thirty-two healthy adults aged 50-77 years consumed 100 g/day of trehalose (n=15) or maltose (n=17, isocaloric control) for 12 weeks (randomized, double-blind)

3 Likes

The problem is humans have an enzyme which degrades Trehalose and turns it into glucose…

2 Likes

Would like to read the full study. Most likely a transgenic AD mouse model, which has been an abject failure translating to human AD clinical trials. Consuming a sugar…that’s like kryptonite for me, anti-thesis of all things to avoid for dementia related disorders.

1 Like

From Twitter, but i think he means 300 grams per day.

300g/day? Diabetes anyone? I am extremely leery of any sugar/saccharide.

Although it shows some lower glycemic index response (25g bolus) than glucose.

Glycemic, insulinemic and incretin responses after oral trehalose ingestion in healthy subjects

1 Like

From the paper:

“Therefore consuming trehalose with daily meals
may contribute to the maintenance of good health
through the prevention of hyperglycemia. Also trehalose
may possibly contribute with useful saccharide in prediabetic and type 2 diabetic patients”

Also, it may reverse arterial aging in mice. That would be a major game-changer if it translates to humans.

Since I have been taking rapamycin my fasting glucose keeps creeping up.
I currently use stevia as a sweetener. Now I think I will try trehalose for a while and monitor the results.

2 Likes

If you’re glucose is creeping up due solely to Rapamycin, and not consuming other sugars or diet mediated glucogenic nutrients, adding more glycemic index will just increase your glucose further.

FWIW…

Another molecule/molecules to add, just doing quick surfing will be adding D-Ribose and Modified Citrus Pectin to the Trehalose.

Yes, I am aware there is a marketed product with that mix. Will be mixing my own from bulk.

Trehalose
D-Ribose
Modified Citrus Pectin

Maybe, but it doesn’t spike like sugar and I have just recently added Empagliflozin to my regimen. As I have posted before, at my age, I am willing to experiment until I see which way my markers are heading. Thanks to the relatively cheap self-purchased blood tests available I can get much more frequent testing. I feel empowered by it and I don’t have to argue with my doctor or fight with my insurance company. I am not sure younger people realize what exciting times these are.

5 Likes

If you’re replacing sugar WITH Trehalose, then yes, maybe you reduce glucose. But if nothing has changed in your diet to cause a rise in glucose, then you’re just adding to it.

But run the experiment…I can see the motivation.

I thought you said nothing excited you at 81…you are fighting harder than most of us!

1 Like

I will put my cgm on when i try trehalose. If i am taking empagliflizin i suspect minimal impact.

1 Like

OK - I ordered 2lbs of Trehalose from Amazon (the link in the first post). Maybe I’ll try Trehalose sweetened lemonade?

Does anyone have any other ideas on how to consume 100 grams to 300 grams of trehalose in a day? This seems to be an issue with this compound…

I’m going to test it out over the coming month… with my CGM on (and using a finger prick blood sugar test also) to see how it impacts my blood glucose levels - by itself, then with either Acarbose or empagliflozin.

Also - something to be aware of…

So I will avoid the risk factors (not hard I think - but an issue at higher rapamycin doses I suspect)

Risk Factors for C. diff

C. diff can affect anyone. Most cases of C. diff occur when you’ve been taking antibiotics or not long after you’ve finished taking antibiotics.

There are other risk factors:

  • Being 65 or older
  • Recent stay at a hospital or nursing home
  • A weakened immune system, such as people with HIV/AIDS, cancer, or organ transplant patients taking immunosuppressive drugs
  • Previous infection with C. diff or known exposure to the germs

@Joseph , why D-Ribose and Citrus Pectin?

2 Likes

While surfing looking up Trehalose information{based on your original posting here] I came across a company/popular book published doctor D’Adamo marketing Trehalose with the additional D-Ribose and Modified Citrus Pectin.

Looking further;

Understanding D-Ribose and Mitochondrial Function

Modified citrus pectin anti-metastatic properties: one bullet, multiple targets

Heat-Modified Citrus Pectin Induces Apoptosis-Like Cell Death and Autophagy in HepG2 and A549 Cancer Cells

Modified Citrus Pectin

So I just copied the molecules that are being marketed in his Trehalose product. Will be mixing from bulk, this cost less and you can change the mix.

Ordered bulk;

Trehalose{the PURE Brand, through Amazon, 2lb powder
D-Ribose{the NOW Brand selling the Bioenergy Ribose, 1lb powder
Modified Citrus Pectin{the NOW Brand selling the PectaSol-C MCP 1lb powder

Waiting for delivery

3 Likes

Thanks for the reminder re MCP. Took it years ago for its anti- metastatic properties and just fell out of the habit. The studies are very impressive for a whole range of cancers. I had no side effects but it’s pricey.

1 Like

The lowest price I located is at the All Star Health, web site;
Paid $78.00 for 1 lb, NOW branded selling the PectaSol-C, Modified Citrus Pectin{MCP]

I have no affiliation with ASH, NOW or the PectaSol-C manufacturer/producer, am just a customer.

1 Like

Good to know. Thanks.

I am excited to try D-ribose. It’s something I have come across before from Youtube fitness gurus etc, but have never actually tried it. While I generally feel good, at my age I can always use a little more energy.

Here is one doctor’s energy formula featuring D-ribose:

As an added benefit it appears t be synergetic with coffee for extending the temporary boost you get from coffee and modulating the jittery effects of coffee.

D-ribose – An additive with caffeine

“D-ribose with caffeine may be the substrate to aid in the potential intracellular energy demand, aid in lessening the perceived unpleasant side effects of caffeine, and still preserving the desired benefits of this stimulant consumed by all of us daily.”

2 Likes