Trehalose Information

1) Conditions Trehalose Has Been Studied For:

Trehalose has been studied for a variety of conditions, including:

• Neurodegenerative diseases such as Huntington's, Parkinson's, and Alzheimer's disease.
• Dry eye syndrome.
• Various infections as an immunomodulatory agent.
• Metabolic disorders.
• Protection against oxidative stress.

2) Efficacy in Treating Those Conditions:

While research on trehalose is ongoing, some studies have shown promise in certain applications:

• It may help stabilize proteins and cells in neurodegenerative diseases, although human studies are limited.
• Its moisturizing effect may provide relief for dry eye symptoms.
• There is not enough evidence to conclusively determine its effectiveness as an immunomodulatory agent against infections.
• Its impact on metabolic disorders is still under investigation.

3) Health Benefits of Trehalose:

Trehalose is associated with several health benefits, such as:

• Acting as a source of glucose after enzymatic hydrolysis.
• Functioning as an antioxidant.
• Potentially reducing the aggregation of misfolded proteins in certain diseases.
• Providing protection to cells against environmental stress.

4) Potential Downsides of Trehalose:

While trehalose is generally considered safe, there are some potential downsides:

• Excessive consumption can lead to an increase in blood sugar levels.
• There are concerns that it could potentially enhance the virulence of certain bacteria like Clostridium difficile.
• It may not be easily digested by everyone, potentially leading to gastrointestinal issues.

5) Impact on Specific Genetic Variations:

The impact of trehalose on specific genetic variations is not well understood and requires more research. However, some points to consider include:

• Individuals with a deficiency in the trehalase enzyme may have difficulty digesting trehalose, leading to gastrointestinal symptoms.
• Genetic variations that affect carbohydrate metabolism might influence how trehalose is processed in the body.

Research Summary on Trehalose

Effectiveness in Treating Dry Eye Syndrome

Trehalose eyedrops have been compared to hyaluronan or hydroxyethylcellulose drops for treating moderate-to-severe dry eye syndrome. A 4-week clinical trial involving 36 patients showed trehalose eyedrops significantly improved ocular surface staining and tear film breakup time. After 8 weeks, trehalose was preferred by more patients and showed better objective signs.

Role in Enhancing Autophagy in Neurodegenerative Diseases

Trehalose, a disaccharide, has been found to enhance autophagy, a cellular cleaning process, without involving the mTOR pathway. This action helps break down proteins linked to Huntington's disease and Parkinson's disease. When combined with rapamycin, trehalose showed an additive effect in clearing protein aggregates and offered protection against cellular death.

Protective Properties in Organisms and Medical Applications

Trehalose protects cells in non-mammalian organisms from desiccation and oxidative stress. It is used in the food industry and for medical applications, including potential treatments for neurodegenerative disorders and ocular conditions like dry eye syndrome.

Trehalase Activity in Diabetics

A study compared trehalase activity in healthy individuals and diabetic patients, revealing a higher average activity in diabetics. High plasma trehalase activity was associated with an increased risk of developing diabetes.

UVB Radiation Protection for the Cornea

Research on rabbits showed trehalose treatment prevented oxidative damage and inflammation in the cornea caused by UVB radiation, maintaining corneal health.

Understanding Trehalose's Protective Mechanism

A review of trehalose's physicochemical properties aimed to explain its ability to stabilize proteins and provide antioxidant effects, aiding survival under harsh conditions.

Historical Significance of Trehalose

Trehalose was first isolated from trehala, a sweet natural product created by insects, and presented to Western Europe in 1855. It was later linked to a sugar found in a fungus, leading to scientific interest in its properties.

Potential Treatment for Polyglutamine Diseases

Trehalose has been effective in reducing protein aggregates and improving symptoms in a mouse model of Huntington disease, indicating its therapeutic potential.

Sugar-Absorption Test for Intestinal Permeability

A study established the sugar-absorption test as a reliable diagnostic tool for evaluating intestinal permeability and enteropathy in children and adults.

Trehalose as a Treatment for ALS

Trehalose induced autophagy in mouse models of ALS, extending lifespan and reducing symptoms by clearing mutant SOD1 protein aggregates.

Protective Effects Against UVB-Induced Corneal Damage

Trehalose-treated rabbit corneas showed reduced damage from UVB radiation compared to saline-treated corneas, suggesting trehalose's potential in mitigating UVB effects on the cornea.

Impact on Endoplasmic Reticulum Stress in Huntington's Disease

A study found that targeting UPR transcription factors, specifically XBP1, could promote neuronal survival and reduce Huntington's disease symptoms by increasing macroautophagy.

Physical and Chemical Properties of Trehalose-Water System

An analysis of the thermodynamics and structural characteristics of trehalose aimed to provide insights into its protective action in living organisms.

Enhancing Clearance of α-Synuclein in Parkinson's Disease

Research showed that trehalose increased autophagy and helped clear A53T mutant α-Synuclein in cellular models, suggesting its potential for treating Parkinson's disease.

Alpha,alpha-Trehalase Deficiency and Probiotic Treatment

An evaluation of alpha,alpha-trehalase activity in patients with abdominal symptoms found a prevalence of enzyme deficiency. Probiotic Saccharomyces boulardii was suggested as a beneficial treatment.

Enhancing Cell Survival in Cryopreservation

Introducing trehalose inside mammalian cells improved their survival rates during freezing, indicating its use as an intracellular cryoprotectant.

Autophagy Inhibition by 3-Methyladenine

3-Methyladenine was shown to inhibit autophagy in rat liver cells, providing a method to study the pathway's role in cellular processes.

Trehalose Treatment for Dry Eye Disorders

Application of trehalose eye drops on mice with dry eye induced by low-humidity air showed improvements in corneal health, suggesting its effectiveness for this condition.

Understanding the Degradation of Tau Protein in Alzheimer's Disease

Stimulation of autophagy by trehalose led to a reduction in tau protein levels, indicating its potential as a therapeutic agent for Alzheimer's disease and related tauopathies.

Trehalose Eye Drops in Dry Eye Syndrome Clinical Trial

A dose-ranging controlled trial found trehalose eye drops to be an effective and safe treatment for patients with moderate to severe dry eye syndrome.

Mushroom Trehalose Intolerance Case

A case of trehalose malabsorption leading to an intolerance to mushrooms was reported, highlighting the digestive issues associated with this sugar.

Trehalase Deficiency in Greenlanders

An analysis of small-intestinal biopsies from Greenlanders showed a prevalence of trehalase deficiency but indicated it has minimal nutritional consequences.

New Mouse Model for Studying Dry Eye

Research developed a mouse model for dry eye using controlled environmental conditions, which successfully replicated human dry eye symptoms and promoted apoptosis on the ocular surface.

References:

1. Trehalose versus hyaluronan or cellulose in eyedrops for the treatment of dry eye
2. Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein
3. Trehalose: an intriguing disaccharide with potential for medical application in ophthalmology
4. Plasma trehalase activity and diabetes mellitus
5. Favorable effects of trehalose on the development of UVB-mediated antioxidant/pro-oxidant imbalance in the corneal epithelium, proinflammatory cytokine and matrix metalloproteinase induction, and heat shock protein 70 expression
6. Thermodynamic, hydration and structural characteristics of alpha,alpha-trehalose
7. [Trehala, a meeting point between zoology, botany, chemistry, and biochemistry]
8. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease
9. Repeatability of the sugar-absorption test, using lactulose and mannitol, for measuring intestinal permeability for sugars
10. Trehalose delays the progression of amyotrophic lateral sclerosis by enhancing autophagy in motoneurons
11. Reduced UVB-induced corneal damage caused by reactive oxygen and nitrogen species and decreased changes in corneal optics after trehalose treatment
12. Targeting the UPR transcription factor XBP1 protects against Huntington's disease through the regulation of FoxO1 and autophagy
13. Reversible dehydration of trehalose and anhydrobiosis: from solution state to an exotic crystal?
14. Effect of trehalose on PC12 cells overexpressing wild-type or A53T mutant α-synuclein
15. Characterization of alpha,alpha-trehalase released in the intestinal lumen by the probiotic Saccharomyces boulardii
16. Intracellular trehalose improves the survival of cryopreserved mammalian cells
17. 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes
18. Trehalose protects against ocular surface disorders in experimental murine dry eye through suppression of apoptosis
19. Trehalose tolerance test. Its value as a test for malabsorption
20. Autophagic degradation of tau in primary neurons and its enhancement by trehalose
21. Tauroursodeoxycholate (TUDCA), chemical chaperone, enhances function of islets by reducing ER stress
22. Apical trehalase expression associated with cell patterning after inducer treatment of LLC-PK1 monolayers
23. Mutant superoxide dismutase 1 overexpression in NSC-34 cells: effect of trehalose on aggregation, TDP-43 localization and levels of co-expressed glycoproteins
24. Disaccharide digestion and maldigestion
25. Cellular toxicity of mutant SOD1 protein is linked to an easily soluble, non-aggregated form in vitro
26. Trehalose treatment accelerates the healing of UVB-irradiated corneas. Comparative immunohistochemical studies on corneal cryostat sections and corneal impression cytology
27. Control of autophagy as a therapy for neurodegenerative disease
28. New insights on trehalose: a multifunctional molecule
29. Trehalose eye drops in the treatment of dry eye syndrome
30. Trehalose malabsorption causing intolerance to mushrooms. Report of a probable case
31. Trehalase deficiency in Greenland
32. A murine model of dry eye induced by an intelligently controlled environmental system

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