Does supplementation with carnosine improve cardiometabolic health and cognitive function in patients with pre-diabetes and type 2 diabetes? study protocol for a randomised, double-blind, placebo-controlled trial

Abstract

IntroductionCarnosine, an over-the-counter food supplement, has a promising potential for the prevention and treatment of chronic diseases such as type 2 diabetes (T2DM), cardiovascular and neurodegenerative diseases through its anti-inflammatory, antiglycation, antioxidative and chelating effects. We have previously shown that supplementation with carnosine preserves insulin sensitivity and secretion in non-diabetic overweight and obese individuals. The effect of carnosine on cardiometabolic risk and related cognitive outcomes in patients with pre-diabetes and T2DM has thus far not been studied. We therefore aim to investigate whether supplementation with carnosine improves cardiometabolic health and cognitive function in patients with pre-diabetes and T2DM.Methods and analysisWe will employ a parallel design randomised controlled trial. Fifty participants with pre-diabetes (impaired fasting glycaemia and impaired glucose tolerance) and T2DM (with HbA1c level < 8%) aged between 18 to 70 years will be randomly assigned to the intervention or control group. At baseline, participants will undergo a medical review and series of tests including anthropometric measurements (body mass index, a dual X-ray absorptiometry and peripheral quantitative computed tomography scan), an oral glucose tolerance test, cardiovascular measurements (central blood pressure, endothelial function and arterial stiffness), cognitive function, physical activity measurement, heart rate variability and liver fibroscan as well as questionnaires to assess dietary habits, sleep quality, depression and quality of life. The intervention group will receive 2 g of carnosine daily in two divided doses while the control group will receive identical placebo capsules for 14 weeks. All baseline measurements will be repeated at the end of the intervention. The change in glycaemic, cardiovascular and cognitive parameters as well as other measures will be compared between the groups.Ethics and disseminationThis study is approved by the Human Research Ethics Committee of Monash Health and Monash University, Australia. The findings will be disseminated via peer-reviewed publications and conference presentations.Trial registrationNCT02917928; Pre-results.

Endogenous dipeptide‐carnosine supplementation ameliorates hypobaric hypoxia‐induced skeletal muscle loss via attenuating endoplasmic reticulum stress response and maintaining proteostasis

“…Human dose is equivalent to the one sixth dose of rats which is multiplied by human body weight 28 . The above‐given dose is safe as the number of clinical trials are in progress to optimizing cardiometabolic health and cognitive functions in diabetic and pre‐diabetic patients 29–32 . These concentrations of carnosine dose are achievable in humans through supplements.…”

Food-Related Carbonyl Stress in Cardiometabolic and Cancer Risk Linked to Unhealthy Modern Diet

“…Conversely, encouraging preliminary results have been obtained in small, randomized clinical trials addressing the effect of the RCS-sequestering agent L-carnosine on obesity and related cardiometabolic disorders [ 50 , 51 , 83 , 84 , 85 , 86 ]. Another trial on the cardiometabolic effect of L-carnosine is in progress [ 87 ]. An advanced preclinical study has also validated the use of the carnosine analogue carnosinol as therapeutic compound, while demonstrating a pathogenic role for RCS in obesity-related metabolic disorders [ 52 ].…”

“…Diabetes and obesity, particularly abdominal obesity, are carbonyl stress-related conditions [ 11 , 143 ], and weight loss induced by energy restriction and Roux-en-Y gastric bypass were recently found to reduce postprandial dicarbonyl stress [ 143 , 144 ]. A number of small randomized controlled trials to evaluate the cardiometabolic protection provided by L-carnosine have been recently completed [ 50 , 51 , 83 , 84 , 85 , 145 ], or are in progress [ 87 ], with encouraging preliminary results ( Table 2 ).…”

“…Overall, these studies suggest a potential role for L-carnosine in the prevention and treatment of obesity-related cardiometabolic disorders and diabetes-induced vascular dysfunction by reducing carbonyl stress and improving glucose and lipid metabolism. Based on these encouraging preliminary data, a randomized, double blind, placebo-controlled trial is in progress to evaluate the effect of L-carnosine intervention on cardiometabolic health and cognitive function in fifty prediabetic and T2D patients [ 87 ]. Finally, a recent preclinical study has investigated the efficiency and safety of a novel carnosine derivative, carnosinol (2S)-20(3-amino propanoylamino)-3-(1H-imidazol-5-yl)propanol, which sequesters RCS but cannot be degraded by the circulating carnosinase-1 enzyme that is naturally present in humans [ 52 , 149 ].…”

Carnosine as a Possible Drug for Zinc-Induced Neurotoxicity and Vascular Dementia

“…Since the olfactory bulb is a gateway for external information and substances, carnosine is considered to be an endogenous neuroprotective substance, namely a 'neuroprotector' [15]. The supplement therapy of carnosine or its analogues are reportedly effective for the treatments of diabetes [16], cataract [17], and brain-related disorders such as depression and Gulf-war illness [18,19]. We have developed a system for quantitative analysis of carnosine using high-performance liquid chromatography (HPLC) [20] and demonstrated here the developmental changes of the amount of carnosine and its analogues in the brain.…”