Natural Products in Alzheimer’s Disease: A Systematic Review of Clinical Trials and Underlying Molecular Mechanisms

This systematic review included 31 clinical trial articles examining the effects of natural compounds on Alzheimer’s disease (AD) and mild cognitive impairment (MCI), involving 3582 participants aged 50–90. Treatment durations ranged from 8 weeks to 2 years, with an average of 12.5 months. Notably, 11 studies focused on herbal extracts highlighting their prominence in current research. These extracts showed potential cognitive and neuroprotective benefits, although results varied across compounds and study designs. Other natural compounds—including flavonoids, polyphenols, omega-3 fatty acids, Aloe vera, Spirulina, and citrus phytochemicals—may provide cognitive and neuroprotective benefits, with ginseng and Ginkgo biloba combinations also showing promise. Curcumin and Melissa officinalis had limited effects, resveratrol showed mixed outcomes with some side effects, and matcha green tea may improve cognition and sleep quality. Despite generally favorable results, the studies varied considerably in design and quality; nonetheless, herbal extracts represent a prominent category of natural interventions in AD and MCI, underscoring the need for further large-scale, high-quality clinical trials to confirm their therapeutic potential.