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

2025-10-31
International journal of molecular sciences 26(21)
- Maria T Bayo Jimenez
- Lorenzo Rivas-García
- Cristina Sánchez-González
- Giuseppe Grosso
- Vivian Lipari
- Laura Vera-Ramírez
- Maurizio Battino
- Francesca Giampieri
- José L Quiles
- Tamara Y Forbes-Hernández

PubMed: 41226670
DOI: 10.3390/ijms262110631

Study Design

Type: Systematic Review
Sample size: n = 3,582
Population: 3582 participants aged 50-90
Duration: 8 weeks to 2 years

Rigorous Journal

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.

Research Insights

Aloe Vera→Improved Cognitive Function
resveratrol showed mixed outcomes with some side effects
Effect
Neutral
Effect size
Small
Ginkgo→Improved Cognitive Function
resveratrol showed mixed outcomes with some side effects
Effect
Neutral
Effect size
Small
Ginseng→Improved Cognitive Function
resveratrol showed mixed outcomes with some side effects
Effect
Neutral
Effect size
Small
Lemon Balm→Improved Cognitive Function
resveratrol showed mixed outcomes with some side effects
Effect
Neutral
Effect size
Small
Red Grape→Improved Cognitive Function
resveratrol showed mixed outcomes with some side effects
Effect
Neutral
Effect size
Small
Resveratrol→Improved Cognitive Function
resveratrol showed mixed outcomes with some side effects
Effect
Neutral
Effect size
Small
Spirulina→Improved Cognitive Function
resveratrol showed mixed outcomes with some side effects
Effect
Neutral
Effect size
Small
Turmeric→Improved Cognitive Function
resveratrol showed mixed outcomes with some side effects
Effect
Neutral
Effect size
Small

Adverse Events Reported

Resveratrol→Overall tolerability
resveratrol showed mixed outcomes with some side effects
Finding
Reported