Testing homocysteine-induced neurotransmitter deficiency, and depression of mood hypothesis in clinical practice

Age Ageing. 2011 Nov;40(6):702-5. doi: 10.1093/ageing/afr086. Epub 2011 Jul 18.


Background: high total plasma homocysteine (tHcy) levels may cause neurotransmitter deficiency, and consequently depression of mood. We have recently shown that mixed oral nutritional supplements containing B-group vitamins led to a statistically significant benefit on depressive symptoms. The aim of this report was to examine the association between elevated plasma tHcy and symptoms of depression in older patients.

Methods: two-hundred and thirty-six hospitalised acutely ill older patients, who were part of a randomised double-blind placebo-controlled trial, were assigned to receive daily mixed oral nutritional supplements containing B-group vitamins or a placebo for 6 weeks. Outcome measures included symptoms of depression measured using Geriatric Depression score and plasma tHcy levels.

Results: the mean tHcy concentration fell by 22% among patients given the supplements compared with the placebo group (mean difference 4.1 ┬Ámol/l (95% CI: 0.14-8.03), P = 0.043). tHcy concentrations was divided into four quartiles and analysed against depression scores. tHcy concentrations in the first relative to the fourth quartile of the distribution were associated with a lower depression symptoms at the end of the supplement period (Geriatric depression score r = -0.20, P = 0.042).

Conclusions: lower plasma tHcy concentrations were associated with reduced depression symptoms in older patients recovering from acute illness.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / blood*
  • Critical Illness / psychology
  • Depression / blood
  • Depression / drug therapy*
  • Dietary Supplements
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Homocysteine / blood*
  • Humans
  • Incidence
  • Inpatients*
  • Male
  • Mood Disorders / drug therapy*
  • Neurotransmitter Agents / deficiency*
  • Outcome Assessment, Health Care
  • Treatment Outcome
  • Vitamin B Complex / administration & dosage
  • Vitamin B Complex / therapeutic use*


  • Biomarkers
  • Neurotransmitter Agents
  • Homocysteine
  • Vitamin B Complex