The Effect of Carnosine Supplementation on Depressive Symptoms and Health‐Related Quality of Life in Individuals With Prediabetes and Well‐Controlled Type 2 Diabetes: A Randomized Controlled Trial

Type 2 diabetes mellitus (T2DM) is commonly associated with mental health disorders such as depression and anxiety. Carnosine, an over-the-counter food supplement, may improve depressive symptoms through its anti-inflammatory properties; however, its effects on depressive symptoms and quality of life in prediabetes or T2DM remain unexplored. This randomized controlled trial aimed to examine whether carnosine supplementation may improve depressive symptoms and quality of life among individuals with prediabetes and well-controlled T2DM. A total of 38 participants (73.6% male) with a median (IQR) age of 54.8 years (46.2, 59.4) and mean ± SD body mass index (BMI) of 29.0 ± 4.2 kg/m² were randomized to carnosine (<i>n</i> = 18) or placebo (<i>n</i> = 20) for 14 weeks. None of the patients were diagnosed with depression or anxiety or any other chronic disease other than prediabetes (<i>n</i> = 20, 52.6%) and T2DM (<i>n</i> = 18, 47.4%), the latter being well-controlled with diet or metformin only. Depressive symptoms were measured using the patient health questionnaire (PHQ-8) and health-related quality of life was measured with five-dimension EuroQoL three level (EQ-5D-3L) scale. Paired <i>t</i>-tests were employed for within-group comparisons. Analysis of covariance (ANCOVA) was used for between group comparisons adjusted for age, BMI, and baseline values. Carnosine supplementation resulted in improvement of depressive symptoms assessed by total PHQ-8 score (mean difference = -2.0; 95% CI: -3.9, -0.2; <i>p</i> = 0.03), compared with placebo. However, the eight subcomponents of the PHQ-8 scale did not show significant changes (<i>p</i> > 0.05). There were no significant changes both in between-group and within-group comparisons in health-related quality of life scores (<i>p</i> > 0.05). We demonstrated for the first time that carnosine supplementation resulted in a modest improvement in depressive symptoms in individuals with prediabetes or T2DM. Further studies are needed to corroborate these findings in larger cohorts with more diverse baseline risk profiles. <b>Trial Registration:</b> NCT02917928.