Amazonian and Related Phytotherapy for Cancer-Related Fatigue: A Narrative Review of Clinical and Mechanistic Evidence.

Cancer-related fatigue (CRF) is one of the most debilitating symptoms experienced by cancer patients, with a multifactorial etiology involving inflammatory, metabolic, neuroendocrine, and psychological mechanisms. As pharmacological treatments for CRF remain limited and often ineffective, interest has grown in complementary approaches, including the use of Amazonian and related plant extracts. Plant extracts contain various bioactive compounds with multiple pharmacological activities that may be beneficial in addressing complex multifactorial symptoms such as CRF.

Purpose

This narrative review evaluates the clinical and mechanistic evidence surrounding the use of two Amazonian plants-Paullinia cupana (guaraná) and Uncaria tomentosa (cat's claw)-and one Asian-origin plant naturalized in the Brazilian Amazon-Zingiber zerumbet (bitter ginger)-for the management of CRF. MAJOR

Findings

We discuss their phytochemical profiles, proposed biological effects, and the findings of preliminary clinical studies. A notable limitation of the available evidence is that ten of the twelve clinical studies reviewed originate from the author's home institution (Faculdade de Medicina da Fundação ABC), raising important questions about generalizability that future multicenter trials should address. Although preliminary results suggest potential benefits in CRF symptom control and quality of life, methodological limitations and heterogeneity across studies warrant caution. Importantly, guaraná was associated with worsening outcomes in patients with head and neck cancer undergoing concurrent chemoradiotherapy, underscoring that treatment-type-specific safety must be carefully considered before clinical use.

Conclusions

Further well-powered, placebo-controlled, multicenter trials are essential to validate these findings and support clinical integration.