Effects of seabuckthorn juice consumption on erythropoietin production, fatigue, and quality of life in women: a randomized, placebo-controlled, double-blind, parallel-group study

Abstract

Background: Seabuckthorn (Hippophae rhamnoides L.) has attracted interest for mitigating transient fatigue, but clinical evidence remains limited. Although a few preliminary reports suggest potential benefits for fatigue and quality of life, high-quality clinical data are scarce: prior studies have often been small, nonrandomized or open-label, short in duration, and used heterogeneous endpoints with a risk of bias, and preregistered RCTs are rare. This study aimed to address these gaps.

Objective: To evaluate the effects of seabuckthorn juice on fatigue and quality of life (QOL) in premenopausal women and to explore a mechanistic link via erythropoietin (EPO) induction.

Methods: We conducted an 8-week, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the anti-fatigue and quality-of-life effects of seabuckthorn juice. Sixty healthy premenopausal women (20–50 years) with stable menstrual cycles, desk-bound jobs, and transient fatigue with decreased vitality were randomized 1:1 to seabuckthorn juice or a matched control juice. The primary endpoint was Profile of Mood States 2 (POMS2) scores. Secondary endpoints included hematologic indices (hemoglobin [Hb], ferritin, iron-binding capacity), serum erythropoietin (EPO), visual analog scale (VAS) fatigue after a Kraepelin test load, and Stress Response Scale-18 (SRS-18). A mechanistic in-vitro substudy tested isorhamnetin (a seabuckthorn flavonol) for EPO induction in HepG2 cells.

Results: Compared with placebo, seabuckthorn juice significantly improved POMS2 outcomes at week 8, showing lower Total Mood Disturbance, fatigue-related scores, higher vitality/energy, and friendliness subscales. Hematologic endpoints favored seabuckthorn: ferritin, Hb, and EPO were significantly higher at weeks 4 and 8, with greater changes from baseline versus placebo. VAS-rated fatigue after the Kraepelin task was significantly reduced in the seabuckthorn group at weeks 4 and 8. In vitro, isorhamnetin increased EPO production in HepG2 cells, supporting biological plausibility.

Conclusion: Eight weeks of seabuckthorn juice consumption improved mood-related fatigue metrics and quality of life, enhanced blood health via increased EPO and Hb, and reduced work-related fatigue in premenopausal women; in-vitro findings suggest isorhamnetin-mediated EPO induction as a potential mechanism.

Keywords: saji; sea buckthorn; QOL; POMS2; Hb; erythropoietin