PurposeAlthough the pathogenesis of stroke is not yet completely elucidated, factors such as oxidative stress and inflammation have been shown to play an important role in this regard. The purpose of this paper is to investigate the effects of whey protein plus lipoic acid on the inflammatory and oxidative stress markers and the prognosis in acute ischemic stroke (AIS) patients.Design/methodology/approachA double-blind, randomized controlled clinical trial was conducted among 42 patients with the first episode of AIS at the Imam Reza Hospital of the Tabriz University of Medical Sciences. The blind research staff randomly assigned patients to two groups of receiving usual hospital gavage (control group) and 1,200 mg of lipoic acid plus 20 g of whey protein in addition to usual hospital gavage (intervention group) for midday meal. Levels of albumin, Interleukin-6 (IL-6), tumor necrosis factor (TNF-α), high-sensitivity C-reactive protein (hs-CRP) and clinical outcomes including severity of neurologic damage according to National Institutes of Health Stroke Scale (NIHSS) and functional state based on modified Rankin Scale (mRS) were evaluated initially and three weeks later.FindingsThere were no significant differences in demographic and baseline characteristics between the two groups (p> 0.05). After three weeks, hs-CRP (p<* 0.01), IL-6 (p= 0.02) and TNF-α(p= 0.01) levels significantly reduced in the intervention group, but no significant changes were observed in cases of albumin, malondialdehyde (MDA) and total antioxidant capacity (TAC) in this group (p> 0.05). Instead, only IL-6 decreased significantly in the control group (p<* 0.01). In addition, comparing changes of assessed variables between two groups showed no significant improvement in the whey protein plus lipoic acid supplementation group vs the control group (p > 0.05). While there was significant betterment in clinical prognosis parameters within groups, no significant changes were found between groups.Originality/valueThe investigation implied that whey protein plus lipoic acid supplementation has no significant effects on inflammatory and oxidative stress markers compared to the control group of AIS patients. More studies in this field are needed to approve the result.