Unlocking the Vitamin Puzzle: Investigating Levels in People With Alzheimer's Disease Versus Healthy Controls Through Systematic Review and Network Meta-Analysis

The progression of Alzheimer's disease (AD) is intricately tied to the impairment of neurons, crucial for neurological functions. Despite extensive research, the precise mechanism underlying AD development remains elusive due to its multifaceted aetiology. Vitamin deficiency has emerged as a notable contributor to AD onset and progression, exerting a significant influence on brain function. To explore this link, we conducted a thorough review using PubMed, Web of Science and MEDLINE databases to gather literature on average vitamin concentrations in people with AD and healthy controls. Applying frequentist network meta-analysis techniques, we calculated standardised mean differences (SMDs) in vitamin concentrations between AD and control groups, both directly and indirectly. Our analysis, based on 67 articles, revealed statistically significant findings for various vitamins. Notably, vitamin C displayed the most substantial difference in average concentration between AD and control groups, supported by a high p-score of 0.92. Other vitamins that showed significant differences included vitamin D, folate, vitamin E, vitamin A and vitamin B12. Moreover, by considering alternative reference groups of vitamins, we derived indirect estimates, which further emphasised the role of vitamins in AD pathology. The ranking of vitamins based on their discrepancy in concentration between AD and control groups underscored the importance of vitamin C, followed by vitamin D, vitamin E, folate, vitamin A and vitamin B12. In conclusion, our comprehensive analysis highlights the potential significance of vitamin levels in understanding AD pathology. This underscores avenues for further research and potential therapeutic interventions targeting vitamin deficiencies in people with AD, potentially offering new strategies for managing the disease.

Trial Registration: CRD42023447203