Although it’s mechanistically plausible that folic acid supplementation could improve cognitive function, in clinical trials it does not seem to have a significant effect.
High levels of homocysteine and low levels of folate have been associated with an increased risk of dementia and Alzheimer’s disease.[1][2] While this doesn’t prove that high homocysteine and low folate can cause cognitive decline, mechanistically such an effect could make sense.
Folate deficiency can lead to high levels of homocysteine which in turn can result in oxidative stress and stimulation of N-methyl-D-aspartate (NMDA) receptors, both of which could have toxic effects on neurons.[1] Additionally, folate is involved in the development and repair of nerve cells.[3] Despite this, clinical trials have generally been anticlimactic, and folic acid supplementation has demonstrated little to no benefit on various measures of cognitive function, including memory, in older adults with or without dementia.[4][5]
In fact, folic acid fortification in North America has been associated with an increased risk of cognitive impairment in older adults.[6][7] This may be because folic acid can mask the hematological signs of a vitamin B12 deficiency, potentially leading to an undiagnosed deficiency which may result in irreversible cognitive decline in the long term.[6]
References
- ^Wang Q, Zhao J, Chang H, Liu X, Zhu RHomocysteine and Folic Acid: Risk Factors for Alzheimer's Disease-An Updated Meta-Analysis.Front Aging Neurosci.(2021)
- ^Zhang X, Bao G, Liu D, Yang Y, Li X, Cai G, Liu Y, Wu YThe Association Between Folate and Alzheimer's Disease: A Systematic Review and Meta-Analysis.Front Neurosci.(2021)
- ^Huang L, Zhao J, Chen Y, Ma F, Huang G, Li WBaseline folic acid status affects the effectiveness of folic acid supplements in cognitively relevant outcomes in older adults: a systematic review.Aging Ment Health.(2022-Mar)
- ^David S Wald, Anuradhani Kasturiratne, Mark SimmondsEffect of folic acid, with or without other B vitamins, on cognitive decline: meta-analysis of randomized trialsAm J Med.(2010 Jun)
- ^Camellia Akhgarjand, Sara Ebrahimi Mousavi, Zahra Kalantar, Amir Bagheri, Hossein Imani, Hamid Rezvani, Mahmoud Dehghani Ghorbi, Zahra VahabiDoes folic acid supplementation have a positive effect on improving memory? A systematic review and meta-analysis of randomized controlled trialsFront Aging Neurosci.(2022 Nov 28)
- ^Morris MS, Jacques PF, Rosenberg IH, Selhub JFolate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification.Am J Clin Nutr.(2007-Jan)
- ^Wang B, Sahyoun NR, Shao K, Dutta E, Clarke JAssessment of the Dose-Response Relationship Between Folate Exposure and Cognitive Impairment: Synthesizing Data from Documented Studies.Risk Anal.(2020-Feb)