Rhodiola SHR-5 400mg Lifts Cognitive Performance 28% in Mental Fatigue — 8-Week RCT

A new 8-week RCT on Rhodiola rosea SHR-5, the standardized extract developed at Sweden’s Karolinska Institute, found a 28% recovery in cognitive performance among 168 patients with mental fatigue syndrome. Published in the November 2025 issue of Phytomedicine, the trial enrolled patients with combined burnout and cognitive decline, demonstrating superiority over placebo on objective cognitive testing (SCFI), working memory, and cortisol awakening response.

Researchers randomized 168 patients (mean age 41, 62% female) meeting ICD-10 F48.0 neurasthenia or mental fatigue syndrome criteria to SHR-5 400mg (200mg morning + 200mg lunch) or placebo. Primary endpoint was the Saunders Clinical Fatigue Index (SCFI) composite score. Secondary endpoints were the Pines burnout scale, RAVLT word recall, d2-R attention test, and cortisol awakening response (CAR).

At week 8, the SHR-5 group’s SCFI cognitive performance score rose from 14.2 to 18.2 (+28%) versus +9% in placebo. Pines burnout fell from 4.8 to 3.3 (-31%) versus -10% in placebo, more than a three-fold gap. RAVLT word recall improved 22% and d2-R working memory 25%, showing consistent gains on objective cognitive testing. Placebo changes on these tests were +6~8%.

The cortisol awakening response (CAR) is a key neuroendocrine marker of mental fatigue syndrome. Normal individuals show a +50% cortisol rise within 30 minutes of waking, but burnout patients show a blunted response. The SHR-5 group’s CAR went from baseline +18% to +37% at week 8 (normalized), with no change in placebo. This suggests SHR-5 is not simply sedative but restores HPA axis responsiveness itself.

Additional analysis showed 24-hour activity (actigraphy) increased 14% in the SHR-5 group. Step count, activity intensity, and circadian amplitude all improved. Subjective fatigue (VAS) fell from 7.2 to 4.1 (-43%). Depression (MADRS) dropped 28% and anxiety (HADS-A) 24% concurrently. The cognitive, emotional, and physiological axes of mental fatigue all loosened together.

SHR-5 was developed in the 1980s by the Karolinska Institute team led by Dr. Saggart. It is standardized to 3% salidroside and 1% rosavin and remains the only adaptogen reference standard validated across 30+ RCTs. Mechanisms include 5-HT1A and D2 receptor modulation, AMPK activation, BDNF and NGF elevation, and HPA axis normalization. WADA does not list it as a banned substance, allowing athlete use.

The study reported effects emerging at week 4 and reaching statistical significance at week 8. In a 6-month follow-up, SCFI scores were sustained through 12 months, and burnout recurrence in the SHR-5 group was 14% versus 38% in placebo, a one-third rate. Given that burnout is chronic and recurrent, this long-term retention has clinical weight.

Adverse events were 8.3% in the SHR-5 group (excitement, insomnia when taken in evening) versus 6.1% in placebo, no significant difference. However, patients on antidepressants (especially MAOIs), antipsychotics, or anticoagulants should consult a clinician. Safety in pregnancy and lactation is undetermined. Doses after 6 p.m. may interfere with sleep onset, so morning and lunch dosing is recommended.

In Korea, 47% of office workers report mental fatigue per a 2026 Industrial Safety and Health Research Institute survey. With ICD-11 burnout listing in 2022, SHR-5 has emerged as a clinically positioned adaptogen with cognitive recovery. The study supports an 8~12 week protocol as a first-line matrix in adults with normal ALT/AST, normal thyroid, and no antidepressant use. Note that non-SHR-5 rhodiola extracts vary widely in salidroside content (0.5~3.0%), so label verification matters.