Researchers from Japan found that supplementation of folate significantly improves average Mini-Mental State Examination (MMSE) scores from 20.1 (baseline) to 22.2.
MMSE is a neuropsychological examination, where a score of 25 to 30 represents no dementia, 20 to 24 mild dementia and 13 to 19 indicates moderate dementia.
Researchers said this improvement may be due to folate’s ability to reduce homocysteine (Hcy) levels.
In this study, 45 patients (mean age of 79.7 years old) with folate deficiency (<3.6 ng/mL) and cognitive impairment (mean MMSE scores of 20.1 ± 4.7) were recruited from the dementia outpatient clinic at the University of Fukui Hospital and Nakamura Hospital.
At baseline, the mean concentration of folate was 2.7 ± 0.6 ng/mL (normal range 3.6 to 12.9), Hcy was 25.0 ± 18.0 nmol/mL (3.7 to 13.5), and vitamin B12 was 558.4 ± 406.5 pg/mL (233 to 914).
Participants were tasked to take folate supplements supplied by Nihon Pharmaceutical (Foliamin tablets, 5mg folic acid) daily for two months.
Blood samples were collected to assess folate and vitamin B12 levels, and MMES tests conducted at day 28 and 63.
Improved cognition scores
The mean MMSE scores after folate administration significantly changed from 20.1 ± 4.7 to 22.2 ± 4.3 (p<0.001).
The mean folate level also significantly increased changed from 2.7 ± 0.6 ng/mL to 173.3 ± 257.2 ng/mL (p<0.001).
The mean Hcy level was significantly reduced from 25.0 ± 18.0 to 11.0 ± 4.3 nmol/mL (p<0.001) after folate supplementation.
Hcy leads to DNA breakdown, oxidative damage, and the apoptotic process, and high Hcy levels are an indicator of oxidative stress. In addition, oxidative stress inhibits methionine synthase activity which has been proposed to play a key role in attention and cognition
Studies have reported folate deficiency associated with hyperhomocysteinemia, although research on recovery of cognitive function by folate supplementation is limited.
Researchers said one possibility for improved MMSE scores could be due to folate’s ability to lower Hcy levels.
They explained that folate supplementation could improve cognitive function in patients with folate deficiency in the short term, improvement of cognition needs to take into account several effects including exercise effects, placebo effects, or mood improvement with folic acid.
In addition, there was no control group in this study. “Without doing a randomised study looking at other patients in the similar situation/category who did not have folate deficiency, then it cannot be automatically assumed that the folate is what improved the dementia scores and not some other forms of care given to the patients.”
For this study, only serum folate was measured which is an indicator of short-term status. Researchers recommended future trials with older adults experiencing cognitive decline with a larger sample size, as well measuring red blood cell (RBC) folate level which is an indicator for long-term status.
“In this study, only the folate level was measured, but it can increase to normal after a couple of folate-rich meals and/or taking folate vitamins. If the RBC folate level was measured, more patients with folate deficiency may have been found. This should be performed in the future study.”
In addition, as this study was performed in Japan, the findings may not be applicable to countries with government-mandated folic acid fortification of flour.
“Influences of Folate Supplementation on Homocysteine and Cognition in Patients with Folate Deficiency and Cognitive Impairment”
Authors: Yuka Hama, et al.