Folic Acid Reduces Neuroinflammation and Improves Cognitive Function in Older Adults

by | Feb 27, 2018 | 2016, Alzheimer's Disease, Brain Health, Cognitive Health, Folic Acid & Folate

Written by Angeline A. De Leon, Staff Writer. Twelve months of folic acid supplementation significantly improved cognitive impairment and reduced homocysteine, inflammatory cytokines, and amyloid in the participating subjects compared to conventional treatment group.

agingThe pathophysiology of Alzheimer’s disease (AD) can be traced to various inflammatory processes, the cumulative effects of which result in observable decline of cognitive function. For example, peripheral inflammatory cytokines, positive mediators of inflammation, are recognized as biomarkers of AD and mild cognitive impairment. Evidence suggests that the activation of cytokines, including IL-1β, IL-6, and TNF-α, produces neuroinflammation which plays a role in disease progression 1,2. Peripheral inflammation, if modifiable at early stages, may, therefore, be a key component in designing new strategies to prevent and ameliorate dementia. As nutritional intervention has gained favor as an approach to ameliorating cognitive deficits, so too has interest in folate, a water-soluble B-complex vitamin. In numerous studies, folate, along with other B-vitamins, have been found to lower homocysteine, an amino acid known to cause oxidative stress, high levels of which are linked to dementia 3. Although the mechanism through which homocysteine levels may increase risk of dementia is unknown, its ability to do so is well-supported, as is the capacity of folic acid to reduce homocysteine levels 4,5. Some epidemiological work even propose that low folate levels can induce an inflammatory state, suggesting a link between vitamin B deficiency and risk of cognitive impairment 6. To better understand the effect of folic acid on cognitive function and whether its potential to improve performance is based on its capacity to reduce inflammatory cytokine levels, researchers in Tianjin Medical University in China investigated the association between folic acid intake and changes in both inflammatory cytokines and cognitive performance 7 .

A total of 152 participants (aged 65 years and older) diagnosed with mild cognitive impairment were enrolled in a 12-month, randomized, controlled trial. They were randomly assigned to receive a daily oral dose of 400 µg of folic acid for 12 months or conventional treatment consisting of non-pharmacological interventions for preventing/reducing cognitive decline, along with dietary recommendations. Cognitive function was assessed using the Chinese version of the Wechsler Adult Intelligence Scale-Revised (WAIS-RC), and at baseline, Month 6, and Month 12, fasting blood samples were collected and analyzed for peripheral inflammatory cytokine and folate levels.

After 12 months, folic acid supplementation, relative to conventional treatment, was associated with significant improvement on the Full-Scale Intelligence Quotient (-1.10 vs. 0.85, p = 0.028), Information (-0.61 vs. 1.15, p = 0.031), and Digit Span (1.37 vs. 1.96, p = 0.009) scores on the WAIS-RC. For the folic acid group vs. conventional treatment, significant improvements were also observed for folate (7.01 vs. 9.44, p = 0.011), homocysteine (13.65 vs. 8.21, p = 0.009), peripheral IL-6 (9.48 vs. 7.71, p = 0.025), TNF-α (138.41 vs. 101.09, p = 0.009), and Aβ-42 (amyloid linked to AD, 53.07 vs. 49.16, p = 0.013).

Based on study findings, researchers conclude that through daily administration of oral folic acid, significant improvements in general cognitive function, along with decreases in peripheral inflammatory cytokines which are predictive of dementia, are possible in a population with mild cognitive impairment. Future work using double-blinded randomized trials would be valuable to examine the longer-term effects of folic acid supplementation, particularly in individuals with existing AD. 

Source: Ma, F. et al. Folic acid supplementation improves cognitive function by reducing the levels of peripheral inflammatory cytokines in elderly Chinese subjects with MCI. Sci. Rep. 6, 37486; doi:10.1038/srep37486 (2016).

© The Author(s) 2016 Creative Commons Attribution 4.0 International License. http://creativecommons.org/licenses/by/4.0/ 

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Posted February 27, 2018.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

References:

  1. Tarkowski E, Blennow K, Wallin A, Tarkowski A. Intracerebral production of tumor necrosis factor-α, a local neuroprotective agent, in Alzheimer disease and vascular dementia. Journal of clinical immunology. 1999;19(4):223-230.
  2. Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen AN, Skinhøj P, Pedersen BK. A high plasma concentration of TNF-α is associated with dementia in centenarians. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 1999;54(7):M357-M364.
  3. Seshadri S. Elevated plasma homocysteine levels: risk factor or risk marker for the development of dementia and Alzheimer’s disease? Journal of Alzheimer’s Disease. 2006;9(4):393-398.
  4. Coppieters N, Dragunow M. Epigenetics in Alzheimer’s disease: a focus on DNA modifications. Current pharmaceutical design. 2011;17(31):3398-3412.
  5. Lehmann M, Gottfries C, Regland B. Identification of cognitive impairment in the elderly: homocysteine is an early marker. Dementia and geriatric cognitive disorders. 1999;10(1):12-20.
  6. Das UN. Folic acid and polyunsaturated fatty acids improve cognitive function and prevent depression, dementia, and Alzheimer’s disease—but how and why? Prostaglandins, Leukotrienes and Essential Fatty Acids. 2008;78(1):11-19.
  7. Ma F, Wu T, Zhao J, et al. Folic acid supplementation improves cognitive function by reducing the levels of peripheral inflammatory cytokines in elderly Chinese subjects with MCI. Scientific reports. 2016;6:37486.