Trehalose is a non-reducing disaccharide composed of two glucose molecules linked by an α,α-1,1-glycosidic bond. Its unique structural stability under stress conditions and non-glycating nature give it distinct advantages in medical nutrition, particularly in the context of surgical stress, neurological protection, and metabolic regulation. Trehalose has demonstrated benefits across multiple domains, including glucose homeostasis, protein stabilization, autophagy induction, antioxidant defense, and neuroprotection via the gut-brain axis.

Mechanisms of Action and Benefits

• Trehalose has been shown to produce lower glycemic and insulinotropic responses compared to sucrose, resulting in a flattened postprandial glucose curve. This may help reduce surgical insulin resistance, support metabolic flexibility, and limit complications associated with glucose dysregulation.¹⁻⁵
  
• Trehalose acts as a chemical chaperone, preventing protein misfolding and aggregation under oxidative or metabolic stress. It induces mTOR-independent autophagy, facilitating the clearance of aberrant proteins implicated in neuroinflammation and cognitive dysfunction. This may be relevant for perioperative brain health and postoperative cognitive recovery.⁶⁻⁸
  
• Trehalose exhibits anti-inflammatory activity by suppressing NF-κB signaling and reducing reactive oxygen species (ROS). It promotes Nrf2 translocation, upregulating antioxidant enzymes such as superoxide dismutase, glutathione, and catalase, thereby enhancing the body’s intrinsic defense mechanisms.⁶⁻⁸
  
• Emerging evidence suggests trehalose may influence neurological health by modulating gut microbiota composition and signaling pathways within the gut-brain axis, supporting brain resilience during physiologic stress.⁶
  
• Due to the absence of a reducing end, trehalose does not participate in non-enzymatic glycation,
  minimizing the formation of advanced glycation end-products (AGEs). It
  also protects membrane lipids from oxidative degradation, contributing
  to cellular membrane integrity and vascular health.⁶⁻⁸

References:

1. Zhang Y, DeBosch BJ. Using trehalose to prevent and treat metabolic function: effectiveness and mechanisms. Curr Opin Clin Nutr Metab Care. 2019;22(4):303-310.
2. DeBosch BJ, Heitmeier MR, Mayer AL, et al. Trehalose inhibits solute carrier 2A (SLC2A) proteins to induce autophagy and prevent hepatic steatosis. 2016;9-21. 
3. Xu C, Chen X, Sheng W-B, Yang P. Trehalose restores functional autophagy suppressed by high glucose. Reproductive Toxicology. 2019.
4. Yoshizane C, Mizote A, Arai C, et al. Daily consumption of one teaspoon of trehalose can help maintain glucose homeostasis: a double-blind, randomized controlled trial conducted in healthy volunteers. Nutrition J. 2020.
5. Mizote A, Yamada M, Yoshizane C, et al. Daily intake of trehalose is effective in the prevention of lifestyle-related diseases in individuals with risk factors for metabolic syndrome. J Nutrition Sci Vitaminol. 2016;62:380-7.
6. Lee HJ, Yoon YS, Lee SJ. Mechanism of neuroprotection by trehalose: controversy surrounding autophagy induction. Cell Death Dis. 2018;9(7):712.
7. Welch WJ, Brown CR. Influence of molecular and chemical chaperones on protein folding. Cell Stress & Chaperones. 1996;1:109–115.
8. Khalifeh M, Barreto GE, Sahebkar A. Trehalose as a promising therapeutic candidate for the treatment of Parkinson's disease. Br J Pharmacol. 2019;176(9):1173-1189.