Omega-3 fatty acids, homocysteine, and the increased risk of cardiovascular mortality in major depressive disorder

Harv Rev Psychiatry. Nov-Dec 2001;9(6):280-93. doi: 10.1080/10673220127910.


Depression is associated with elevated rates of cardiovascular morbidity and mortality. This elevation seems to be due to a significantly increased risk of coronary artery disease and myocardial infarction and, once the ischemic heart disease is established, sudden cardiac death. Recent data suggest that the increased rates of cardiovascular disease in patients with depression may be the result of one or more still-unrecognized underlying physiological factors that predispose a patient to both depression and cardiovascular disease. Two possibly related factors that may have a causal relation with both depressive disorders and cardiovascular disease are an omega-3 fatty acid deficiency and elevated homocysteine levels. We present the available data connecting cardiovascular disease, depression, omega-3 fatty acids, and homocysteine. In addition, we suggest research strategies and some preliminary treatment recommendations that may reduce the increased risk of cardiovascular mortality in patients with major depressive disorder.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism*
  • Cardiovascular Diseases / mortality*
  • Depressive Disorder, Major / diet therapy
  • Depressive Disorder, Major / genetics
  • Depressive Disorder, Major / metabolism*
  • Fatty Acids, Omega-3 / metabolism*
  • Folic Acid / therapeutic use
  • Genetic Predisposition to Disease
  • Homocysteine / adverse effects*
  • Homocysteine / blood
  • Humans
  • Hyperhomocysteinemia / diet therapy*
  • Lipid Peroxidation
  • Randomized Controlled Trials as Topic
  • Rats
  • Risk
  • Vitamin B 12 / therapeutic use
  • Vitamin B 6 / therapeutic use


  • Fatty Acids, Omega-3
  • Homocysteine
  • Vitamin B 6
  • Folic Acid
  • Vitamin B 12