The neuroprotective effect of autophagy activation by rapamycin and trehalose was studied in a mouse model of Parkinson’s disease (PD) induced by neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Both rapamycin (10 mg/kg/day, 7 days) and trehalose (2% in drinking water, 7 days) increased the expression of LC3-II (a marker of autophagy activation) in the frontal cortex and striatum of normal C57Bl/6J mice, with signs of an additive effect. Autophagy stimulation in the striatum was confirmed by a lysosomal osmotic test. In the model of MPTP-induced PD, the two drugs were applied starting from the 2nd day after subchronic daily MPTP administration (20 mg/kg/day, 4 days). …
Thus, the autophagy activation through different pathways by the combination of rapamycin and trehalose reverses both neuronal dopaminergic and behavioral deficits in vivo and seems to be a promising therapy for PD-like pathology.
FWIW
There is another thread on this site about trehalose, not with rapamycin.
I have been using trehalose in coffee{coffee is the delivey vehicle] with other added supplements in the coffee.
Review, if you have not seen/read.
Thank you. I do a lot of searching on Google Scholar, but frankly, it never occurred to me to pair trehalose and rapamycin.
Maybe I will dump a bunch of trehalose into my grapefruit juice before I dose with rapamycin.
Seriously, I am going to do it.
I decided to get some, can’t comment on any health benefits yet but I highly recommend from a culinary standpoint: trehalose adds the richness of sucrose (table sugar) to food without the sweetness
Interesting that it is poorly absorbed taken orally but yet in the mice study it was orally ingested through their drinking water.
Does anyone have a source for Lactotrehalose?
Trying it, can’t say I’ve noticed anything. I know it’s already been tested in worms, but thinking about sponsoring this molecule in the million molecule challenge.
Have you considered the low bioavailability. 99 % of trehalose is broken down to two regular glucose molecules in the human gut ( by the enzyme trehalase). How much are you taking?
@John_Loverich Yes - I no longer think Trehalose is beneficial. See the discussion in this thread: The "Clogged Drain" of Aging: Why Exercise is the Plumber for Your Muscle Mitochondria - #10 by cl-user
There have been no published clinical trials that repeat the 100g/day protocol to confirm the vascular benefits. The primary reasons effectively act as a “soft refutation” of the protocol’s viability:
- The “Trehalase Barrier”: A major 2025 study (referenced in recent literature) challenged the oral viability of trehalose, demonstrating that in mice, oral trehalose failed to improve metabolic dysfunction because it was rapidly broken down into glucose by the enzyme trehalase in the gut. This directly contradicts the premise that oral trehalose can reach tissues intact to trigger autophagy, suggesting Kaplon’s results might have been due to gut-signaling or a unique responder effect rather than systemic absorption.
- Caloric & GI Toxicity: The 100g dose (400 calories of sugar) caused significant gastrointestinal distress and weight gain in the original study, which nullified the benefits in many participants. This “therapeutic window” is considered too narrow for clinical recommendation.
- Lower Dose Failures/Equivocal Results: Subsequent human trials testing sustainable doses (e.g., 3.3g/day to 10g/day) have shown mixed results.
- Diabetes/Metabolic Syndrome: A 2020 study (Mizote et al.) found that 3.3g/day improved glucose tolerance in healthy humans, but this effect was metabolic, not vascular.
- Inflammation: A pilot study in Traumatic Brain Injury (TBI) patients (Dehbalaei et al.) noted a reduction in C-Reactive Protein (CRP) with trehalose, but other markers of oxidative stress did not change, leaving the systemic anti-inflammatory effect “inconclusive.”
I’m just using as a sugar substitute, so like a teaspoon. Though I normally don’t use sugar. I do like it because it’s much less sweet.
Yes - thats a good use for it. It also has a much flatter “curve” in terms of its hit on blood glucose levels:
1. The Substance: Trehalose
Trehalose is a non-reducing disaccharide consisting of two glucose molecules linked by an α,α-1,1-glycosidic bond.Unlike sucrose (glucose + fructose) or maltose (glucose + glucose with a standard bond), this specific linkage makes trehalose highly stable and resistant to acid hydrolysis.
2. Clinical Evidence: Glycemic and Insulin Impact
The claim that trehalose has “less impact” on blood sugar is accurate but nuanced. It is not non-glycemic; it is slowlyglycemic.
- Glycemic Index (GI): Trehalose has a GI of approximately 70 (compared to Glucose at 100 and Sucrose at ~65). While often marketed as “low glycemic,” clinically it is considered moderate. However, its Glycemic Loaddynamics differ from table sugar.
- Digestion Kinetics: The enzyme trehalase (located in the intestinal brush border) hydrolyzes trehalose into two glucose units. This enzymatic activity is significantly slower than the hydrolysis of sucrose.
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Insulin Secretion: Clinical data indicates that trehalose elicits a lower insulin spike compared to glucose.
- Study Data: In a randomized, double-blind trial with type 2 diabetic patients, trehalose ingestion (3.3 g/day for 12 weeks) did not significantly lower fasting blood glucose or HbA1c compared to placebo, but it did significantly reduce C-reactive protein (CRP) , a marker of systemic inflammation often linked to insulin resistance.
- Healthy Subjects: In healthy individuals, trehalose demonstrates a flatter glucose curve—avoiding the sharp hyperglycemic spike and subsequent reactive hypoglycemic crash associated with glucose.
Verdict: Trehalose provides a steadier release of energy than glucose, but it is not a calorie-free sweetener. It provides the standard 4 kcal/g. If you are strictly Keto or managing severe diabetes, it will still raise blood glucose.
I’ve purchased trehalose but avoided oral intake due to poor systemic absorption. I plan to use it in homemade skincare. I already use trehalose-based eye drops for lubrication, which work well for my sensitive eyes.
Trehalose shows scientific promise for topical skincare. It protects keratinocytes, might boost autophagy, reduces UV damage, and supports skin barrier function. Cellular studies are strong, early human models are promising, but large RCTs remain limited. Topical effects are easy to assess visually—so why not try it?
If trehalose really can trigger meaningful mTOR-independent autophagy in skin cells, then it would be rather rare in a cheap skincare product? it can stabilize proteins and membranes under stress (UV, osmotic, heat). And evidence from Human Cells show it lowers keratinocyte death and DNA damage after UVB exposure. I know it boosts barrier function and hydration, as seen in eye drops. Maybe someone in the forum already have made experiences from topical use of trehalose.