Exploring the Efficacy and Safety of Nutritional Supplements in Alzheimer’s Disease

Background: Alzheimer’s disease (AD) represents one of the major challenges of modern medicine, with a growing impact on public health and healthcare systems. In recent years, dietary supplements use has been the subject of increasing interest as a complementary strategy for the prevention and treatment of the disease. Materials and Methods: A Review of reviews was conducted following PRISMA guidelines and REAPPRAISED checklist to evaluate the efficacy and safety of supplement use in AD. The search, performed across major scientific databases, identified 54 relevant articles, including 53 reviews and one mini-review, after applying specific inclusion criteria and removing duplicates. Results: The growing body of evidence suggests that some supplements may help reduce cognitive decline, inflammation, and target mechanisms behind AD. However, many of these supplements are still under investigation, with mixed results highlighting the need for high-quality research. A key challenge is the lack of data on optimal dosages, administration duration, and long-term safety, which limits clinical guidelines. Some studies have reported positive effects from specific regimens, such as curcumin (800 mg/day), omega-3 fatty acids (2 g/day), and resveratrol (600 mg/day). Other supplements, like phosphatidylserine (300 mg/day), multinutrient formulations, probiotics, vitamin E (2000 IU/day), and melatonin (3–10 mg/day), also show benefits, though study variability makes conclusions uncertain. Conclusions: While certain supplements show potential in mitigating cognitive decline in AD, inconsistent findings and gaps in dosage and safety data highlight the need for rigorous, large-scale trials. Future research should focus on personalized, multimodal strategies integrating targeted supplementation, dietary patterns, and microbiota-gut-brain interactions for enhanced neuroprotection.