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Neurology 2003;60:690-695
© 2003 American Academy of Neurology
Medical Hypothesis

Will caloric restriction and folate protect against AD and PD?

Mark P. Mattson, PhD

From the Laboratory of Neurosciences, National Institute on Aging, Gerontology Research Center, Baltimore, MD.

Address correspondence and reprint requests to Dr. Mark P. Mattson, Laboratory of Neurosciences, National Institute on Aging, Gerontology Research Center 4F01, 5600 Nathan Shock Drive, Baltimore, MD 21224; e-mail: mattsonm{at}grc.nia.nih.gov

Recent epidemiologic studies of different sample populations have suggested that the risk of AD and PD may be increased in individuals with high-calorie diets and in those with increased homocysteine levels. Dietary restriction and supplementation with folic acid can reduce neuronal damage and improve behavioral outcome in mouse models of AD and PD. Animal studies have shown that the beneficial effects of dietary restriction result, in part, from increased production of neurotrophic factors and cytoprotective protein chaperones in neurons. By keeping homocysteine levels low, folic acid can protect cerebral vessels and can prevent the accumulation of DNA damage in neurons caused by oxidative stress and facilitated by homocysteine. Although further studies are required in humans, the emerging data suggest that high-calorie diets and elevated homocysteine levels may render the brain vulnerable to neurodegenerative disorders.




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