L-arginine supplementation at 6 g/day for 8 weeks reduced fatigue severity relative to placebo and was well-tolerated, but mean FSS scores remained above the enrollment threshold, indicating a reduction in, rather than resolution of, persistent fatigue.
L-arginine 6 g/day reduced Fatigue Severity Scale (FSS) scores more than placebo at Week 8, while 3 g/day did not differ from placebo.
The improvement in Checklist Individual Strength (CIS) with 6 g/day did not survive multiplicity adjustment.
Sleep quality (PSQI) improved nominally at both doses of L-arginine.
L-arginine 6 g/day lowered blood lactate measures during and after a standardized submaximal treadmill run compared with placebo.
Resting plasma nitrite did not differ between L-arginine and placebo.
L-arginine was well-tolerated with no serious adverse events.
Mean FSS scores remained above the enrollment threshold after treatment, so L-arginine reduced rather than resolved persistent fatigue.
This study tested whether taking the amino acid L-arginine could ease everyday, ongoing fatigue in working-age adults. 120 people aged 30-59 with persistent fatigue took 3 grams a day, 6 grams a day, or a placebo for 8 weeks, without knowing which one they received. Fatigue was measured with a standard questionnaire, and some participants' blood lactate (a by-product of exertion) was tracked after a standardized treadmill run. The 6 gram daily dose reduced fatigue scores more than placebo (a drop of about 6.4 points versus 2.2), while the 3 gram dose did not. Sleep quality scores improved at both doses, though these results were less statistically firm. At 6 grams, blood lactate was lower overall during exercise and 15 minutes into recovery than with placebo. No serious side effects were reported. This research suggests L-arginine at a higher dose may modestly lessen persistent fatigue, but it did not eliminate it: average scores stayed above the level used to define fatigue at the start. Some secondary measures, such as another fatigue questionnaire, did not hold up after statistical correction. The trial was short (8 weeks), so longer and larger studies would be needed to confirm the findings.
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Upload Your LabsKang E, Hong S, Yoon N, Lee N, Kim B. (2026). Effects of Oral L-Arginine on Everyday Persistent Fatigue, Sleep, and Post-Exercise Lactate Recovery in Community-Dwelling Working-Age Adults: A Double-Blind, Placebo-Controlled Randomized Trial.. Nutrients. https://doi.org/10.3390/nu18203375