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Mouse experiments link folic acid deficiency to Parkinson's disease



January 10, 2002

NIA Press Office | 301-496-1752 | nianews3@mail.nih.gov



Mouse experiments suggest that folic acid deficiency could increase the brain's susceptibility to Parkinson's disease, according to scientists at the National Institute on Aging. In the finding, published in the January 2002 issue of the Journal of Neurochemistry , the investigators fed one group of mice a diet that included folate, while a second group was fed a diet lacking this vitamin. They then gave the mice moderate amounts of MPTP, a chemical that can cause Parkinson-like symptoms. In the mice fed folate, MPTP caused only mild symptoms of disease. But mice fed the folate-deficient diet developed severe Parkinson-like symptoms.

The scientists found that mice with low amounts of dietary folic acid had elevated levels of homocysteine in the blood and brain. They suspect that increased levels of homocysteine in the brain caused damage to the DNA of nerve cells in the substantia nigra, an important brain structure that produces dopamine. Loss of dopamine causes the nerve cells to dysfunction, leaving patients unable to direct or control their movement in a normal manner. In mice fed adequate amounts of folate, dopamine-producing nerve cells were able to repair damaged DNA and counteract the adverse effects of homocysteine. However, similar nerve cells in folate-deficient mice could not repair extensive DNA damage. As a result, these cells died.

"This is the first direct evidence that folic acid may have a key role in protecting adult nerve cells against age-related disease," said Mark Mattson, Ph.D., chief of the NIA's Laboratory of Neurosciences. "It is clear from this study that a deficiency of this vitamin is associated with increased toxin-induced damage to the dopamine-producing neurons in the mouse brain."

People who have Parkinson's disease often have low levels of folic acid in their blood, but it is not clear whether this a result of the disease process or if they are simply malnourished due to their illness. But based on this study, Dr. Mattson speculates that consuming adequate amounts of folic acid—either in the diet or by supplementation—could help protect the aging brain against Parkinson's and other neurodegenerative diseases. Green leafy vegetables, citrus fruits and juices, whole wheat bread and dry beans are good sources of the vitamin. Food and Drug Administration (FDA) regulations require the addition of folic acid to enriched breads, cereals, flours, corn meals, pastas, rice, and other grain products.

Parkinson's disease occurs when certain nerve cells die or become impaired and can no longer produce dopamine. Without it, individuals can develop tremor or trembling in hands, arms, legs, jaw, and face; rigidity or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability or impaired balance and coordination. Patients may also have difficulty walking, talking, or completing other simple tasks. The disease is both chronic and progressive. Parkinson's is not usually inherited, but incidence of the disease increases with age, with an average onset at about 60 years. It afflicts about 50,000 Americans annually.

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