Efficacy of Phytotherapy for Cancer-Related Fatigue: A Systematic Review and Meta-Analysis of Randomized Controlled...

Cancer-related fatigue (CRF) is one of the most common and burdensome symptoms faced by patients with cancer, yet effective drug-based treatments remain limited. In recent years, phytotherapeutic agents have drawn attention as complementary options, supported by plausible anti-inflammatory, antioxidant, and immunomodulatory mechanisms.

We performed a systematic review and meta-analysis to quantitatively synthesize randomized controlled trial evidence on the efficacy of phytotherapeutic interventions for cancer-related fatigue and to assess the certainty of evidence. Databases were searched from inception, with the final search update completed in October 2025. Eligible studies included adults with CRF and compared herbal interventions with placebo controls. Standardized mean differences (SMDs) were pooled using a DerSimonian-Laird random-effects model. We also evaluated risk of bias (RoB 2), publication bias, and certainty of evidence using GRADE. This systematic review and meta-analysis was conducted in accordance with the PRISMA 2020 guidelines.

Fourteen trials were included, studying agents such as Paullinia cupana, Panax ginseng, multi-herbal Traditional Chinese Medicine formulations, and other botanical extracts. Overall, phytotherapy provided a modest improvement in CRF (SMD = 0.31; 95% CI, 0.08-0.53; p = 0.022), though heterogeneity was substantial (I² = 56.7%). In subgroup analyses, only the group of "other formulations" demonstrated significant benefit; ginseng and guaraná did not demonstrate statistically significant effects. Most trials had high or unclear risk of bias, and the certainty of evidence was rated very low.

Current evidence does not firmly support phytotherapeutic agents as effective treatments for CRF, hindered largely by methodological weaknesses, heterogeneous interventions, and imprecise effect estimates. Even so, the biological rationale and the variability in clinical responses point toward an opportunity for the emerging field of precision herbal oncology. Well-designed, multicenter trials are essential to determine whether phytotherapy can meaningfully contribute to CRF management.