Trehalose is a disaccharide (sugar) supplement and food product that is used as a sugar substitute.
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Mechanism of Action: This agent is thought to work at multiple levels by stabilizing membrane and protein structure, and decreasing the levels of toxic fragments.
Rationale for Use in Huntington's: Researchers have shown that trehalose decreases the ability of proteins with polyglutamine stretches, like the protein that causes Huntington's, to aggregate. In mouse studies, trehalose decreased brain damage [Tanaka M 2004]. Further supporting evidence using an HD rat model was reported at a major international conference but has not yet been published in a journal [Nguyen 2006]. It also has been shown to decrease the level of toxic fragments by a process called autophagy [Sarkar S 2007].
Dosage is 25 grams (6 tsp or 2 tbsp) three times per day. Each dose is about 90 calories, so it should be used as a sugar substitute. Trehalose is only 50% as sweet as table sugar, and does not increase blood sugar or levels nearly as much as the same dose of regular sugar.
Side Effects include bloating and diarrhea. Decreasing dosage will prevent these discomforts. This is a safe agent even at very high dosage.
Sources: Trehalose can be obtained online from Amazon at a cost of $15.50 per pound, or about $80 per month.
Tanaka M, Machida Y, Niu S, Ikeda T, Jana NR, Doi H, Kurosawa M, Nekooki M, Nukina N. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat Med. 2004 Feb;10(2):148-54. Epub 2004 Jan 18. PubMed abstract
Nguyen H., Bonin M, Kuhn M, Holzmann C, von Horsten S, and Riess O (2005). Gene expression pattern in HD transgenic rats and HD knock-in mice: Specific effects of trehalose treatment. Abstract Viewer/Itinerary Planner, Society of Neuroscience, Washington D.C. 2005.
Sarkar S, Davies JE, Huang Z, Tunnacliffe A, Rubinsztein DC. Trehalose, a novel mTOR-independent autophagy enhancer, accelerates the clearance of mutant huntingtin and alpha-synuclein. J Biol Chem. 2007 Feb 23;282(8):5641-52. Epub 2006 Dec 20. PubMed abstract