Dietary Folate, B Vitamins and the Brain: The Homocysteine Connection

  • Mark P. Mattson
  • Inna I. Kruman
  • Wenzhen Duan


It has been known for decades that babies born to women that have a dietary deficiency in folic acid (folate) are at increased risk for birth defects, and that the nervous system is particularly susceptible to such defects. Folate deficiency in adults can increase risk of coronary artery disease, stroke, several types of cancer, and possibly Alzheimer’s and Parkinson’s diseases. Recent findings have begun to reveal the cellular and molecular mechanisms whereby folate counteracts age-related disease. An increase in homocysteine levels is a major consequence of folate deficiency that may have adverse effects on multiple organ systems during aging. Deficiencies of vitamins B6 (pyridoxine) and B12 (cobalamin) may also have adverse consequences for the developing and adult nervous systems, by increasing homocysteine levels. Humans with inherited defects in enzymes involved in homocysteine metabolism, including cystathionine β-synthase and 5, 10-methylenetetrahydrofolate reductase, exhibit features of accelerated aging and a marked propensity for several age-related diseases. Homocysteine enhances accumulation of DNA damage by inducing a methyl donor deficiency state and impairing DNA repair; in mitotic cells such DNA damage can lead to cancer, while in postmitotic cells such as neurons it promotes cell death. The emerging data strongly suggest that elevated homocysteine levels increase the risk of multiple age-related diseases, and point to dietary supplementation with B vitamins as a primary means of normalizing homocysteine levels and increasing the healthspan of the nervous system.


Alzheimer’s disease Apoptosis DNA repair Folic Acid Parkinson’s disease Schizophrenia Stroke Synapse 


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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Mark P. Mattson
    • 1
  • Inna I. Kruman
    • 1
  • Wenzhen Duan
    • 1
  1. 1.Laboratory of NeurosciencesNational Institute on Aging Gerontology Research CenterBaltimoreUSA

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