Effects of Carnosine Supplementation on Cognitive Outcomes in Prediabetes and Well-Controlled Type 2 Diabetes: A Randomised Placebo-Controlled Clinical Trial.

Trends in global ageing underscore the rising burden of age-related cognitive decline and concomitant cardiometabolic diseases, including type 2 diabetes mellitus (T2DM). Carnosine, a naturally occurring dipeptide with anti-inflammatory, antioxidant and anti-glycating properties, has shown promise in animal models and limited human studies for improving cognitive function, insulin resistance and T2DM, but its therapeutic effects on cognition remain unclear. The aim of this study is to assess the effects of carnosine on cognitive function in individuals with prediabetes or well-controlled T2DM. This is a secondary analysis of a double-blind randomised controlled trial (RCT), whereby 49 adults with prediabetes or early-stage well-controlled T2DM were randomised to receive 2 g of carnosine or identical placebo daily for 14 weeks. At baseline and follow-up, cognitive function was assessed as a secondary outcome using the Digit-Symbol Substitution Test, Stroop test, Trail Making Tests A & B, and the Cambridge Automated Neuropsychological Test Battery (CANTAB). In total, 42 adults (23 males and 19 females) completed the trial. There were no differences in participant anthropometry or cognitive functioning between carnosine and placebo groups at baseline (all > 0.1). After the 14-week supplementation period, there were no differences between carnosine and placebo groups in change and follow-up values for any cognitive measures including Stroop, Digit Symbol Substitution Sest, Trail Making A/B or CANTAB (all > 0.05). Adjustments for baseline cognitive scores, diabetic status, level of education, age or interaction effects with participants' sex did not change the results. Carnosine supplementation did not improve cognitive measures in individuals with prediabetes or T2DM in this study. While larger trials may provide further insights, alternative factors-such as the relatively young and healthy profile of our cohort-may have contributed to the lack of observed effect. Future research should examine individuals with existing cognitive impairment or those at higher risk of cognitive decline to better define the therapeutic potential of carnosine in this context.