title: Oral curcumin for Alzheimer's disease: tolerability and efficacy in a 24-week randomized, double blind, placebo-controlled study.
abstract: BACKGROUND
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov Identifier: NCT00099710.
authors.affiliation: 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 ; UCLA Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Ringman
authors.affiliation: 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 ; UCLA Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA ; UCLA Department of Medicine, 757 Westwood Plaza, Los Angeles, CA 90095, USA ; Geriatric Research Education and Clinical Center, W LA Veterans Administration Medical Center, 11301 Wilshire Blvd., Bldg. 113, Room 312, Los Angeles, CA 90073, USA.
authors.forename: Sally A
authors.initials: SA
authors.lastname: Frautschy
authors.affiliation: 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 ; UCLA Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA ; UCLA Department of Medicine, 757 Westwood Plaza, Los Angeles, CA 90095, USA ; Geriatric Research Education and Clinical Center, W LA Veterans Administration Medical Center, 11301 Wilshire Blvd., Bldg. 113, Room 312, Los Angeles, CA 90073, USA.
authors.forename: Edmond
authors.initials: E
authors.lastname: Teng
authors.affiliation: UCLA Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA ; UCLA Department of Medicine, 757 Westwood Plaza, Los Angeles, CA 90095, USA.
authors.forename: Aynun N
authors.initials: AN
authors.lastname: Begum
authors.affiliation: 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 ; UCLA Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.
authors.forename: Jenny
authors.initials: J
authors.lastname: Bardens
authors.affiliation: 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.
authors.forename: Maryam
authors.initials: M
authors.lastname: Beigi
authors.affiliation: 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 ; UCLA School of Nursing, Box 956919, 6-2668 Factor Bldg., Los Angeles, CA 90095-6919, USA.
authors.forename: Karen H
authors.initials: KH
authors.lastname: Gylys
authors.affiliation: AMH Corporation, 1440-6 Forest Hill Road, Staten Island, NY 10314, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Badmaev
authors.affiliation: Moores UCSD Cancer Center, 3855 Health Sciences Drive, La Jolla, CA 92093-0901, USA.
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Heath
authors.affiliation: 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 ; UCLA Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.
authors.forename: Liana G
authors.initials: LG
authors.lastname: Apostolova
authors.affiliation: UCLA Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.
authors.forename: Verna
authors.initials: V
authors.lastname: Porter
authors.affiliation: UCLA Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA.
authors.forename: Zeba
authors.initials: Z
authors.lastname: Vanek
authors.affiliation: Center for Alzheimer Research and Treatment, Harvard Medical School, 221 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: Gad A
authors.initials: GA
authors.lastname: Marshall
authors.affiliation: UCLA Semel Institute for Psychiatry and Human Behavior, Box 951759, C9-432 Semel, Los Angeles, CA 90095-1759, USA.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Hellemann
authors.affiliation: UCLA Semel Institute for Psychiatry and Human Behavior, Box 951759, C9-432 Semel, Los Angeles, CA 90095-1759, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Sugar
authors.affiliation: F. Hoffman-La Roche, Ltd, Grenzacherstrasse 183, Bldg/Room 74/3W.306B, 4070 Basel, Switzerland.
authors.forename: Donna L
authors.initials: DL
authors.lastname: Masterman
authors.affiliation: Department of Neuropathology, University of Washington Medical Center, Room C-516, Box 357470, Seattle, WA 98195, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
authors.affiliation: Cleveland Clinic Lou Ruvo Center for Brain Health, 888 W. Bonneville, Las Vegas, NV 89106, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Cummings
authors.affiliation: 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 ; UCLA Department of Neurology, David Geffen School of Medicine at UCLA, 710 Westwood Plaza, Los Angeles, CA 90095-1769, USA ; UCLA Department of Medicine, 757 Westwood Plaza, Los Angeles, CA 90095, USA ; Geriatric Research Education and Clinical Center, W LA Veterans Administration Medical Center, 11301 Wilshire Blvd., Bldg. 113, Room 312, Los Angeles, CA 90073, USA.
authors.forename: Greg M
authors.initials: GM
authors.lastname: Cole