Research

Alzheimer's Research & Therapy

, 4:43

Open Access This content is freely available online to anyone, anywhere at any time.

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

  • John M RingmanAffiliated withMary S. Easton Center for Alzheimer’s Disease Research, David Geffen School of Medicine at UCLAUCLA Department of Neurology, David Geffen School of Medicine at UCLA Email author 
  • , Sally A FrautschyAffiliated withMary S. Easton Center for Alzheimer’s Disease Research, David Geffen School of Medicine at UCLAUCLA Department of Neurology, David Geffen School of Medicine at UCLAUCLA Department of MedicineGeriatric Research Education and Clinical Center, W LA Veterans Administration Medical Center
  • , Edmond TengAffiliated withMary S. Easton Center for Alzheimer’s Disease Research, David Geffen School of Medicine at UCLAUCLA Department of Neurology, David Geffen School of Medicine at UCLAUCLA Department of MedicineGeriatric Research Education and Clinical Center, W LA Veterans Administration Medical Center
  • , Aynun N BegumAffiliated withUCLA Department of Neurology, David Geffen School of Medicine at UCLAUCLA Department of Medicine
  • , Jenny BardensAffiliated withMary S. Easton Center for Alzheimer’s Disease Research, David Geffen School of Medicine at UCLAUCLA Department of Neurology, David Geffen School of Medicine at UCLA
  • , Maryam BeigiAffiliated withMary S. Easton Center for Alzheimer’s Disease Research, David Geffen School of Medicine at UCLA
  • , Karen H GylysAffiliated withMary S. Easton Center for Alzheimer’s Disease Research, David Geffen School of Medicine at UCLAUCLA School of Nursing
  • , Vladimir BadmaevAffiliated withAMH Corporation
  • , Dennis D HeathAffiliated withMoores UCSD Cancer Center
    • , Liana G ApostolovaAffiliated withMary S. Easton Center for Alzheimer’s Disease Research, David Geffen School of Medicine at UCLAUCLA Department of Neurology, David Geffen School of Medicine at UCLA
    • , Verna PorterAffiliated withUCLA Department of Neurology, David Geffen School of Medicine at UCLA
    • , Zeba VanekAffiliated withUCLA Department of Neurology, David Geffen School of Medicine at UCLA
    • , Gad A MarshallAffiliated withCenter for Alzheimer Research and Treatment, Harvard Medical School
    • , Gerhard HellemannAffiliated withUCLA Semel Institute for Psychiatry and Human Behavior
    • , Catherine SugarAffiliated withUCLA Semel Institute for Psychiatry and Human Behavior
    • , Donna L MastermanAffiliated withF. Hoffman-La Roche, Ltd
    • , Thomas J MontineAffiliated withDepartment of Neuropathology, University of Washington Medical Center
    • , Jeffrey L CummingsAffiliated withCleveland Clinic Lou Ruvo Center for Brain Health
    • , Greg M ColeAffiliated withMary S. Easton Center for Alzheimer’s Disease Research, David Geffen School of Medicine at UCLAUCLA Department of Neurology, David Geffen School of Medicine at UCLAUCLA Department of MedicineGeriatric Research Education and Clinical Center, W LA Veterans Administration Medical Center

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.