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Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study

John M Ringman12*, Sally A Frautschy1234, Edmond Teng1234, Aynun N Begum23, Jenny Bardens12, Maryam Beigi1, Karen H Gylys15, Vladimir Badmaev6, Dennis D Heath7, Liana G Apostolova12, Verna Porter2, Zeba Vanek2, Gad A Marshall8, Gerhard Hellemann9, Catherine Sugar9, Donna L Masterman10, Thomas J Montine11, Jeffrey L Cummings12 and Greg M Cole1234

Author Affiliations

1 Mary S. Easton Center for Alzheimer's Disease Research, David Geffen School of Medicine at UCLA, 10911 Weyburn Ave., #200, Los Angeles, CA 90095-7226, USA

2 UCLA Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA

3 UCLA Department of Medicine, 757 Westwood Plaza, Los Angeles, CA 90095, USA

4 Geriatric Research Education and Clinical Center, W LA Veterans Administration Medical Center, 11301 Wilshire Blvd., Bldg. 113, Room 312, Los Angeles, CA 90073, USA

5 UCLA School of Nursing, Box 956919, 6-2668 Factor Bldg., Los Angeles, CA 90095-6919, USA

6 AMH Corporation, 1440-6 Forest Hill Road, Staten Island, NY 10314, USA

7 Moores UCSD Cancer Center, 3855 Health Sciences Drive, La Jolla, CA 92093-0901, USA

8 Center for Alzheimer Research and Treatment, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA

9 UCLA Semel Institute for Psychiatry and Human Behavior, Box 951759, C9-432 Semel, Los Angeles, CA 90095-1759, USA

10 F. Hoffman-La Roche, Ltd, Grenzacherstrasse 183, Bldg/Room 74/3W.306B, 4070 Basel, Switzerland

11 Department of Neuropathology, University of Washington Medical Center, Room C-516, Box 357470, Seattle, WA 98195, USA

12 Cleveland Clinic Lou Ruvo Center for Brain Health, 888 W. Bonneville, Las Vegas, NV 89106, USA

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Alzheimer's Research & Therapy 2012, 4:43  doi:10.1186/alzrt146

Published: 29 October 2012

Abstract

Introduction

Curcumin is a polyphenolic compound derived from the plant Curcuma Long Lin that has been demonstrated to have antioxidant and anti-inflammatory effects as well as effects on reducing beta-amyloid aggregation. It reduces pathology in transgenic models of Alzheimer's disease (AD) and is a promising candidate for treating human AD. The purpose of the current study is to generate tolerability and preliminary clinical and biomarker efficacy data on curcumin in persons with AD.

Methods

We performed a 24-week randomized, double blind, placebo-controlled study of Curcumin C3 Complex® with an open-label extension to 48 weeks. Thirty-six persons with mild-to-moderate AD were randomized to receive placebo, 2 grams/day, or 4 grams/day of oral curcumin for 24 weeks. For weeks 24 through 48, subjects that were receiving curcumin continued with the same dose, while subjects previously receiving placebo were randomized in a 1:1 ratio to 2 grams/day or 4 grams/day. The primary outcome measures were incidence of adverse events, changes in clinical laboratory tests and the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) at 24 weeks in those completing the study. Secondary outcome measures included the Neuropsychiatric Inventory (NPI), the Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) scale, levels of Aβ1-40 and Aβ1-42 in plasma and levels of Aβ1-42, t-tau, p-tau181 and F2-isoprostanes in cerebrospinal fluid. Plasma levels of curcumin and its metabolites up to four hours after drug administration were also measured.

Results

Mean age of completers (n = 30) was 73.5 years and mean Mini-Mental Status Examination (MMSE) score was 22.5. One subject withdrew in the placebo (8%, worsened memory) and 5/24 subjects withdrew in the curcumin group (21%, 3 due to gastrointestinal symptoms). Curcumin C3 Complex® was associated with lowered hematocrit and increased glucose levels that were clinically insignificant. There were no differences between treatment groups in clinical or biomarker efficacy measures. The levels of native curcumin measured in plasma were low (7.32 ng/mL).

Conclusions

Curcumin was generally well-tolerated although three subjects on curcumin withdrew due to gastrointestinal symptoms. We were unable to demonstrate clinical or biochemical evidence of efficacy of Curcumin C3 Complex® in AD in this 24-week placebo-controlled trial although preliminary data suggest limited bioavailability of this compound.

Trial registration

ClinicalTrials.gov Identifier: NCT00099710.