A Phase II Randomized Clinical Trial of a Nutritional Formulation for Cognition and Mood in Alzheimer's Disease

J Alzheimers Dis. 2015;45(2):395-405. doi: 10.3233/JAD-142499.


Background: Increasing evidence points toward the efficacy of nutritional modifications in delaying cognitive decline and mood/behavioral difficulties in Alzheimer's disease (AD). Nutritional supplementation with individual agents has shown varied results suggesting the need for combinatorial intervention.

Objective: We set out to determine whether nutritional intervention could positively impact cognitive performance and behavioral difficulties for individuals diagnosed with AD.

Methods: A double-blind, multi-site, phase II study (ClinicalTrials.gov NCT01320527; Alzheimer's Association Trialmatch) was conducted in which 106 individuals with AD were randomized to a nutraceutical formulation (NF; folate, alpha-tocopherol, B12, S-adenosyl methioinine, N-acetyl cysteine, acetyl-L-carnitine) or placebo for 3 or 6 months, followed by an open-label extension where participants received NF for 6 additional months.

Results: The NF cohort improved versus the placebo cohort within 3 months (Clox-1 p = 0.0083, 95%CI [0.4481, 2.9343]; Dementia Rating Scale p = 0.0266, 95%CI [0.1722, 2.7171]). Caregivers reported non-significant improvements in Neuropsychiatric Inventory. Both cohorts improved or maintained baseline performance during open-label extensions. Activities of Daily Living did not change for either cohort.

Conclusions: These findings extend phase I studies where NF maintained or improved cognitive performance and mood/behavior.

Keywords: Acetyl-L-carnitine; Alzheimer's disease; B vitamins; N-acetyl cysteine; S-adenosyl methionine; behavioral difficulties; cognitive decline; nutrition; supplement; vitamin E.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications*
  • Caregivers / psychology
  • Cognition Disorders / diet therapy*
  • Cognition Disorders / etiology*
  • Cohort Studies
  • Dietary Supplements*
  • Double-Blind Method
  • Female
  • Folic Acid / administration & dosage
  • Humans
  • Male
  • Middle Aged
  • Mood Disorders / diet therapy*
  • Mood Disorders / etiology*
  • Time Factors
  • Vitamin B 12 / administration & dosage
  • alpha-Tocopherol / administration & dosage


  • Folic Acid
  • alpha-Tocopherol
  • Vitamin B 12

Associated data

  • ClinicalTrials.gov/NCT01320527