Effects of Supplementation with Folic Acid and Its Combinations with Other Nutrients on Cognitive Impairment and Alzheimer’s Disease: A Narrative Review

Abstract

Cognitive impairment and Alzheimer’s Disease, among other cognitive dysfunctions, has been recognized as a major public health problem. Folic acid is a well-known essential nutrient whose deficiency has been linked to neurocognitive dysfunctions, owing to hyperhomocysteinemia, an independent risk factor for cardio- and cerebrovascular diseases, including cognitive impairment, Alzheimer’s Disease, and vascular dementia. However, to date, there is certain controversy about the efficacy of vitamin supplementation in patients with these pathologies. Therefore, we have reviewed the available dietary intervention studies based on folic acid, either alone or in combination with different vitamins or nutrients into the progression of Alzheimer’s Disease and Cognitive impairment, highlighting the cognition and biochemical markers employed for the evaluation of the disease progression. Undeniably, the compiled information supports the potential benefits of vitamin supplementation in these pathologies, especially relevant to the aging process and quality of life, although more research is urgently needed to confirm these positive findings.

Folic Acid Protects against Hyperuricemia in C57BL/6J Mice via Ameliorating Gut–Kidney Axis Dysfunction

“…27 In addition, it is also found to be associated with the prevention of megaloblastic anemia, cancer, and improving immune system functioning. 28 Recently, emerging lines of evidence indicate that folic acid plays a significant role in regulating gut microbiota dysbiosis 29,30 and delaying the progression of CKD in patients, 31 hinting the crucial effect on the gut−kidney axis. Meanwhile, folic acid and its derivatives have been reported to show an inhibitory activity of XOD, which is responsible for the conversion of the purine xanthine and hypoxanthine to UA.…”

Oxidative stress and antioxidant defenses in mild cognitive impairment: a systematic review and meta-analysis

“…Vitamin B supplements including folate appear to be effective in the prevention of cognitive decline in elderly people (Li et al, 2021). Moreover, folate administration may lower homocysteine levels and O&NS (Zhou and Chen, 2019) and folate administration, as well as the combination of folate with other nutrients, may be beneficial in the treatment of MCI and Alzheimer's disease (Puga et al, 2021). Overall, measurements of O&NS (MDA and homocysteine) and antioxidants (folate and the GSH system, vitamins A and C) should be performed in subjects with MCI, and treatment with GSH-promoting supplements (e.g., NAC), as well as vitamin A, B and C, may improve the redox imbalance and, most likely, MCI.…”

Medicine–food herb:Angelica sinensis, a potential therapeutic hope for Alzheimer's disease and related complications

“…Studies have found that folic acid, either alone or in combination with different vitamins or nutrients, has been shown to intervene and improve cognitive impairment and AD. 7 Wei Xu used meta-analysis to find that four dietary exposures could be as protective factors of AD, three of which were folic acid, vitamin E and vitamin C. 81 The role of dietary folate in providing methyl groups required for the maintenance and modulation of deoxyribonucleic acid methylation makes it an intriguing nutrient in AD. 82 Low folate levels and raised homocysteine levels are risk factors for dementia, AD and depression.…”

“…However, they are useful for symptomatology improvement with little impact on disease progression. 7 In fact, the American Food and Drug Administration has recently given its approval for Adulhem™ (adacanumab-avwa), the first new treatment approved for AD since 2003 and the first therapy that targets the fundamental pathophysiology of the disease. Specifically, adacanumab-avwa action is focused on the reduction of amyloid-β plaques in the brain; some scientists believe that plaque could cause AD.…”