Folic Acid Supplementation Mitigates Alzheimer’s Disease by Reducing Inflammation: A Randomized Controlled Trial

Abstract

Background/Aims. Low serum folate levels can alter inflammatory reactions. Both phenomena have been linked to Alzheimer's disease (AD), but the effect of folic acid on AD itself is unclear. We quantified folate supplementation's effect on inflammation and cognitive function in patients with AD over the course of 6 months. Methods. Patients newly diagnosed with AD (age > 60 years; n = 121; mild to severe; international criteria) and being treated with donepezil were randomly assigned into two groups with (intervention group) or without (control group) supplemental treatment with folic acid (1.25 mg/d) for 6 months. The Mini-Mental State Examination (MMSE) was administered to all patients at baseline and follow-up, and blood samples were taken before and after treatment. We quantified serum folate, amyloid beta (Aβ), interleukin-6 (IL-6), tumor necrosis factor α (TNFα), plasma homocysteine (Hcy), S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and the mRNA levels of presenilin (PS), IL-6, and TNFα in leukocytes. Data were analyzed using a repeated-measures mixed model. Results. The mean MMSE was slightly increased in the intervention group compared to that in the control group (P < 0.05). Posttreatment, plasma SAM and SAM/SAH levels were significantly higher (P < 0.05), while Aβ 40, PS1-mRNA, and TNFα-mRNA levels were lower in the intervention group than in the control group (P < 0.05). The Aβ 42/Aβ 40 ratio was also higher in the intervention group (P < 0.05). Conclusions. Folic acid is beneficial in patients with AD. Inflammation may play an important role in the interaction between folic acid and AD. This trial is registered with clinical trial registration number ChiCTR-TRC-13003246.

Enhancement of recovery from mental illness with l -methylfolate supplementation

“…Supplementing with folic acid, Chen et al . revealed a beneficial response in patients with Alzheimer's disease as measured against cognitive function tests.…”

“…Supplementing with folic acid, Chen et al 17 Papakostas et al 7 investigated the use of L-methylfolate augmentation in SSRI-resistant patients with major depression. The patients on these trials were prescribed sertraline, escitalopram, fluoxetine, or paroxetine during the investigation.…”

Folic acid deficiency enhanced microglial immune response via the Notch1/nuclear factor kappa B p65 pathway in hippocampus following rat brain I/R injury and BV2 cells

“…For instance, folic acid supplementation mitigated Alzheimer's disease and improved cognitive function in Chinese elderly with MCI via lowering the levels of peripheral inflammatory cytokines. 11 Guest et al observed an inverse association between cerebro-spinal fluid (CSF) folate and CSF levels of IL-6 in a healthy human cohort. 12 Folic acid protects motor neurons against the increased homocysteine, inflammation and apoptosis in SOD1 G93A transgenic mice.…”

“…The anti‐inflammatory effect of folic acid has been widely reported in various clinical conditions. For instance, folic acid supplementation mitigated Alzheimer's disease and improved cognitive function in Chinese elderly with MCI via lowering the levels of peripheral inflammatory cytokines . Guest et al observed an inverse association between cerebro‐spinal fluid (CSF) folate and CSF levels of IL‐6 in a healthy human cohort .…”

Effect of Donepezil and Vitamin B12 Supplement on Serum Thyroid Profile in Alzheimer’s Disease

“…Donepezil hydrochloride is an acetylcholinesterase inhibitor (AChEI) which inhibits the action acetylcholinesterase (AChE) in neuronal synapses, rendering increased acetylcholine action for better cognition [7,8]. AD patients are also found to be deficient for Vitamin B 12 , which has a striking effect on cognitive dysfunction [9,10,11].…”