How does folic acid deficiency affect cognitive functioning?

Updated: Sep 14, 2018
  • Author: Katherine Coffey-Vega, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Effects on cognitive function

Several studies have shown that an elevated homocysteine level correlates with cognitive decline. In Herbert's classic study in which a human subject (himself) was in induced folate deficiency from diet restriction, he noted that CNS effects, including irritability, forgetfulness, and progressive sleeplessness, appeared within 4-5 months. Interestingly, all CNS symptoms were reported to disappear within 48 hours after oral folate intake. [38]

Low folate and high homocysteine levels are a risk factor for cognitive decline in high-functioning older adults [39] and high homocysteine level is an independent predictor of cognitive impairment among long-term stay geriatric patients. [40]

Mechanistically speaking, current theory proposes that folate is essential for synthesis of S- adenosylmethionine, which is involved in numerous methylation reactions. This methylation process is central to the biochemical basis of proper neuropsychiatric functioning.

Despite the association of high homocysteine level and poor cognitive function, homocysteine-lowering therapy using supplementation with vitamins B-12 and B-6 was not associated with improved cognitive performance after two years in a double-blind, randomized trial in healthy older adults with elevated homocysteine levels. [41]

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