Numerous clinical trials involving natural products have been conducted to observe cognitive performances and biomarkers in Alzheimer's Disease (AD) patients. However, to date, no natural-based drugs have been approved by the FDA as treatments for AD. In this review, natural product-based compounds that were tested in clinical trials from 2011 to 2023, registered at www.clinicaltrials.gov were reviewed. Thirteen compounds, encompassing 7 different mechanisms of action were covered. Several observations were deduced, which are: i) several compounds showed cognitive improvement, but these improvements may not extend to AD, ii) compounds that are endogenous to the human body showed better outcomes, and iii) Docosahexaenoic acid (DHA) and cerebrolysin had the most potential as AD drugs among the 13 compounds. Based on the current findings, natural products may be more suitable as a supplement than AD drugs in most cases. However, the studies covered here were conducted in a relatively short amount of time, where compounds acting on AD pathways may take time to show any effect. Given the diverse pathways that these natural products are involved in, they may potentially produce synergistic effects that would be beneficial in treating AD. Additionally, natural products benefit from both physicochemical properties being in more favorable ranges and active transport playing a more significant role than it does for synthetic compounds.
* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.