Benfotiamine and Cognitive Decline in Alzheimer's Disease: Results of a Randomized Placebo-Controlled Phase IIa Clinical Trial

J Alzheimers Dis. 2020;78(3):989-1010. doi: 10.3233/JAD-200896.


Background: In preclinical models, benfotiamine efficiently ameliorates the clinical and biological pathologies that define Alzheimer's disease (AD) including impaired cognition, amyloid-β plaques, neurofibrillary tangles, diminished glucose metabolism, oxidative stress, increased advanced glycation end products (AGE), and inflammation.

Objective: To collect preliminary data on feasibility, safety, and efficacy in individuals with amnestic mild cognitive impairment (aMCI) or mild dementia due to AD in a placebo-controlled trial of benfotiamine.

Methods: A twelve-month treatment with benfotiamine tested whether clinical decline would be delayed in the benfotiamine group compared to the placebo group. The primary clinical outcome was the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Secondary outcomes were the clinical dementia rating (CDR) score and fluorodeoxyglucose (FDG) uptake, measured with brain positron emission tomography (PET). Blood AGE were examined as an exploratory outcome.

Results: Participants were treated with benfotiamine (34) or placebo (36). Benfotiamine treatment was safe. The increase in ADAS-Cog was 43% lower in the benfotiamine group than in the placebo group, indicating less cognitive decline, and this effect was nearly statistically significant (p = 0.125). Worsening in CDR was 77% lower (p = 0.034) in the benfotiamine group compared to the placebo group, and this effect was stronger in the APOEɛ4 non-carriers. Benfotiamine significantly reduced increases in AGE (p = 0.044), and this effect was stronger in the APOEɛ4 non-carriers. Exploratory analysis derivation of an FDG PET pattern score showed a treatment effect at one year (p = 0.002).

Conclusion: Oral benfotiamine is safe and potentially efficacious in improving cognitive outcomes among persons with MCI and mild AD.

Keywords: Advanced glycation endproducts; Alzheimer’s disease; benfotiamine; glucose; inflammation; oxidative stress.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / genetics
  • Alzheimer Disease / physiopathology
  • Aniline Compounds
  • Apolipoprotein E4 / genetics
  • Brain / diagnostic imaging*
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / genetics
  • Cognitive Dysfunction / physiopathology
  • Disease Progression
  • Ethylene Glycols
  • Female
  • Fluorodeoxyglucose F18
  • Glycation End Products, Advanced / blood
  • Humans
  • Male
  • Positron-Emission Tomography
  • Radiopharmaceuticals
  • Thiamine / analogs & derivatives*
  • Thiamine / therapeutic use
  • Treatment Outcome


  • Aniline Compounds
  • Apolipoprotein E4
  • Ethylene Glycols
  • Glycation End Products, Advanced
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • florbetapir
  • Thiamine
  • benphothiamine