CerefolinNAC Therapy of Hyperhomocysteinemia Delays Cortical and White Matter Atrophy in Alzheimer's Disease and Cerebrovascular Disease

J Alzheimers Dis. 2016 Oct 4;54(3):1073-1084. doi: 10.3233/JAD-160241.


We examined whether using a medical food therapy for hyperhomocysteinemia (HHcy) in patients with Alzheimer's disease (AD) or cognitive impairment due to cerebrovascular disease (CVD) with Cerefolin®/CerefolinNAC® (CFLN: L-methylfolate, methylcobalamin, and N-acetyl-cysteine) slowed regional brain atrophy. Thirty HHcy patients with AD and related disorders (ADRD) received CFLN (HHcy+CFLN: duration [μ ± σ] = 18.6±16.1 months); a sub-sample of this group did not receive CFLN for varying periods of time (HHcy+NoCFLN: duration [μ ± σ] = 12.6±5.6 months). Thirty-seven NoHHcy patients with ADRD did not receive CFLN (NoHHcy+NoCFLN: duration [μ ± σ] = 13.3±17.7 months). No participant took supplemental B vitamins. Regional brain volumes were measured at baseline and end of study, and covariate-adjusted rates of hippocampal, cortical, and forebrain parenchymal (includes white matter) atrophy were predicted. The HHcy+CFLN group's hippocampal and cortical atrophy adjusted rates were 4.25 and 11.2 times slower than those of the NoHHcy+NoCFLN group (p < 0.024). The HHcy+CFLN group's forebrain parenchyma atrophy rate was significantly slower only for CVD; the rate of slowing was proportional to the degree of homocysteine lowering (p < 0.0001). CFLN was associated with significantly slowed hippocampal and cortical atrophy rates in ADRD patients with HHcy, and forebrain parenchymal atrophy rates in CVD patients with HHcy. The present results should be further validated.

Keywords: B12; brain atrophy; circadian rhythm; cognitive impairment; dementia; folate; hippocampus; vascular; volumetrics; white matter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / administration & dosage*
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / diet therapy
  • Atrophy
  • Cerebral Cortex / diagnostic imaging*
  • Cerebrovascular Disorders / diagnostic imaging*
  • Cerebrovascular Disorders / diet therapy
  • Dietary Supplements
  • Female
  • Humans
  • Hyperhomocysteinemia / diagnostic imaging*
  • Hyperhomocysteinemia / diet therapy
  • Male
  • Middle Aged
  • Tetrahydrofolates / administration & dosage
  • Vitamin B 12 / administration & dosage
  • Vitamin B 12 / analogs & derivatives
  • Vitamin B Complex / administration & dosage*
  • White Matter / diagnostic imaging*


  • Tetrahydrofolates
  • Vitamin B Complex
  • mecobalamin
  • Vitamin B 12
  • 5-methyltetrahydrofolate
  • Acetylcysteine