819.16 Pilot clinical trial of curcumin for treating Alzheimer's disease Larry Baum, Stanley K.K. Cheung Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong Introduction Curcumin is a yellow food color comprising about 5% of turmeric. Because of its anti-inflammatory, anti-oxidant, and other potentially protective properties, curcumin has been tested in animal models of Alzheimer's disease (AD). In the Tg2576 APPSw transgenic mouse and amyloid-infused rat models of AD, six months of an oral dose equivalent (as a proportion of body weight) to roughly 1.5 g/day in humans significantly reduced levels of brain amyloid, plaques, oxidized proteins, and isoprostanes (Frautschy 2001, Lim 2001). Treatment with curcumin blocked the development of cognitive deficits in the rat model (Frautschy 2001). Thus we designed a pilot, 6-month, clinical trial of curcumin to examine its safety and effects on biochemical and cognitive measures in humans with AD. Frautschy et al. 2001. Neurobiol Aging 22:993. Lim et al. 2001. J Neurosci 21:8370. curcumin Methods In Hong Kong, 36 AD patients (10 men and 26 women) were recruited for the study between 10/04 and 3/06, with mean age=74.2±9.8 years and mean MMSE score=15.5±6.9. Patients were randomized to receive placebo, 1 g/day, or 4 g/day of curcumin. To match cognition among the three dose groups at baseline, patients were also stratified into low, medium, and high MMSE levels, using 13.5 and 17.5 as the cutoffs because, in the first batch of patients, these values split the patients into 3 groups of roughly equal size. Curcumin was a generous gift of Kancor Flavours. Patients chose whether to receive drug as 10 capsules/day or 1 packet of powder to mix with soft food such as congee. All patients were allowed to continue other drugs and were given 120 mg/day ginkgo leaf extract. Results MMSE score changes between 0 and 6 months did not significantly differ among doses (p=0.3) and showed no significant deterioration with or without curcumin. Data are for 11 patients at 4 g, 10 at 1 g, and 10 at 0 g. Concentrations of 15 metals were measured in serum at 0 and 1 month. Only cadmium showed a change that was different among dose groups at p<0.05: p=0.04. Data are for 11 patients in each dose group. Plasma isoprostane changes between 0 and 6 months did not significantly differ among dose groups (p=0.2). Data are for 10 patients at 4 g, 10 at 1 g, and 7 at 0 g. Plasma isoprostane levels have been reported to differ between and AD and controls in some but not all studies. Isoprostane did not significantly differ between 34 AD patients at 0 months and 15 controls (p=0.4). Mean ages of controls and patients were matched: 78.1±6.9 yr for controls and 74.4±9.9 yr for AD (p=0.2). Sex distribution was matched: controls were 6 men and 9 women; AD patients were 9 men and 25 women (p=0.5) Curcumin was reported to decrease serum cholesterol. In our study, neither total serum cholesterol, HDL-C, LDL-C, nor triglyceride levels significantly differed among dose groups at 0, 1, or 6 months. To explore for potential harmful effects of long-term curcumin treatment, sodium, potassium, urea, creatinine, protein, albumin, bilirubin, ALP, and ALTGPT were measured in blood. Only albumin showed a change between 0 and 6 months that was different among dose groups at p<0.05: p=0.04. Data are for 11 patients at 4 g, 8 at 1 g, and 9 at 0 g. The number of patients who stopped taking the study drug for at least 1 month during the study for any reason did not differ significantly among dose group (p=0.06): 0 at 4 g, 3 at 1 g, and 5 at 0 g. Conclusions Curcumin had no apparent side effects. A longer study may determine whether curcumin slows cognitive decline in AD. Curcumin had no effect on lipid levels. Isoprostane levels did not differ between AD and controls.