Activity of Choline Alphoscerate on Adult-Onset Cognitive Dysfunctions: A Systematic Review and Meta-Analysis

Abstract

Background: Choline alphoscerate (alpha glyceryl phosphorylcholine, α-GPC) is a choline-containing phospholipid used as a medicine or nutraceutical to improve cognitive function impairment occurring in neurological conditions including adult-onset dementia disorders. Despite its 1985 marketing authorization, there are still discrepancies between countries regarding its approval as a prescription medicine and discussions about its effectiveness. Objective: This study aimed to evaluate the efficacy of the α-GPC compound for treating cognitive impairment in patients with adult-onset neurological disorders. Methods: Relevant studies were identified by searching PubMed, Web of Science, and Embase. Studies that evaluated the effects of α-GPC alone or in combination with other compounds on adult-onset cognitive impairment reporting cognition, function, and behavior were considered. We assessed the risk of bias of selected studies using the Cochrane risk of bias tool. Results: A total of 1,326 studies and 300 full-text articles were screened. We included seven randomized controlled trials (RCTs) and one prospective cohort study that met our eligibility criteria. We found significant effects of α-GPC in combination with donepezil on cognition [4 RCTs, mean difference (MD):1.72, 95% confidence interval (CI): 0.20 to 3.25], functional outcomes [3 RCTs, MD:0.79, 95% CI: 0.34 to 1.23], and behavioral outcomes [4 RCTs; MD: –7.61, 95% CI: –10.31 to –4.91]. We also observed that patients who received α-GPC had significantly better cognition than those who received either placebo or other medications [MD: 3.50, 95% CI: 0.36 to 6.63]. Conclusion: α-GPC alone or in combination with donepezil improved cognition, behavior, and functional outcomes among patients with neurological conditions associated with cerebrovascular injury.

Choline-Containing Phospholipids in Stroke Treatment: A Systematic Review and Meta-Analysis

“…It has also been reported in a previous study that choline alphoscerate might play a role in acute cerebrovascular diseases by antagonizing the biochemical-functional deficiency of the cholinergic system in cases of ischemia-induced damage [13]. In fact, it has a beneficial effect on patients with neurodegenerative diseases such as Alzheimer's disease (AD), and the study reported that it significantly improved cognitive function in patients with mild to moderate conditions of AD [45]. As neuroinflammation plays an important role in Alzheimer's disease, this may be explained by this compound's potential anti-inflammatory properties [46].…”

Pharmacological enhancement of cholinergic neurotransmission alleviates neuroinflammation and improves functional outcomes in a triple transgenic mouse model of Alzheimer’s disease

“…Our study investigates the potential of choline alphoscerate (α-GPC) in the evolving scenario of AD therapeutics, which is often characterized by treatments with limited disease-modifying properties ( Sheikh et al, 2023 ). Among choline precursors, α-GPC stands out as the most effective in enhancing in vivo Ach release ( Traini et al, 2013 ) and has been suggested as a potential neuroprotective agent for various pathological conditions associated with inflammatory phenomena ( Choi et al, 2020 ; Sagaro and Amenta, 2023 ; Sagaro et al, 2023 ).…”

“…Cholinergic precursors have been among the initial therapeutic strategies attempting to counteract cholinergic impairment and to relieve cognitive decline occurring in dementia disorders. Among these, choline alphoscerate, also known as alpha-glyceryl-phosphoryl-choline (α-GPC), is considered one of the most suitable sources of choline ( Parnetti et al, 2001 ; Traini et al, 2013 ; Sagaro et al, 2023 ). Despite its presence in the pharmaceutical market since 1987, α-GPC experienced a decline in interest following the introduction of cholinesterase inhibitors.…”

“…Despite its presence in the pharmaceutical market since 1987, α-GPC experienced a decline in interest following the introduction of cholinesterase inhibitors. Nevertheless, the last 10 years have witnessed a resurgence of interest in this choline-containing phospholipid, evident in numerous pre-clinical and clinical studies ( Traini et al, 2013 ; Traini et al, 2020 ; Roy et al, 2022 ; Sagaro et al, 2023 ). Indeed, α-GPC, encompassing choline in its structure, seems to have a significant effect in enhancing acetylcholine (Ach) synthesis and release, due to its ability to cross the blood-brain-barrier (BBB) ( Parnetti et al, 2007 ).…”

Adulteration of Brain Health (Cognitive, Mood, and Sleep Enhancement) Food Supplements by the Addition of Pharmaceutical Drugs: A Comprehensive Review of Analytical Approaches and Trends

“…While α-GPC is found as an ingredient in dietary supplements in the U.S. and is a recently approved ingredient by Health Canada’s Food Directorate for use in supplemented foods [ 32 ], it is considered a novel food in the EU since it was not consumed to a significant degree as a food before 15 May 1997, therefore requiring a pre-market authorization [ 33 ]. Moreover, discrepancies in the use of this substance between countries have been reported since it is considered a prescription drug in some EU countries [ 34 ], such as in Italy where it is sold under the brand name Delacit.…”