Carnosine and histidine-containing dipeptides improve dyslipidemia: a systematic review and meta-analysis of randomized controlled trials

Abstract

Context Cardiovascular disease is a major public health problem and represents a significant burden of disease globally. Lifestyle interventions have their limitations and an intervention that will effectively address cardiovascular risk factors to help reduce this growing burden of disease is required. Objective Carnosine and other histidine-containing dipeptides (HCDs) have exerted positive effects on cardiovascular risk factors and diseases in animal and human studies. The authors conducted a systematic review and meta-analysis examining the effects of HCDs on cardiovascular outcomes in line with the PRISMA guidelines. Data Sources The Medline, Medline in process, Embase, Cumulative Index of Nursing and Allied Health, and All EBM databases were searched from inception until January 25, 2019, for randomized controlled trials (RCTs) examining the effects of HCDs on cardiovascular outcomes, compared with placebo or controls. Data Extraction Basic characteristics of the study and populations, interventions, and study results were extracted. The grading of recommendations assessment, development, and evaluation approach was used to assess the quality of evidence for each outcome. Data Analysis A total of 21 studies were included. Of these, 18 were pooled for meta-analysis (n = 913). In low risk of bias studies, HCD-supplemented groups had lower total cholesterol (n = 6 RCTs; n = 401; weighted mean difference [WMD], −0.32 mmol/L [95%CI, −0.57 to −0.07], P = 0.01) and triglyceride levels (n = 6 RCTs; n = 401; WMD, −0.14 mmol/L [95%CI, −0.20 to −0.08], P < 0.001) compared with controls. In studies using carnosine alone, triglycerides levels were also lower in the intervention group vs controls (n = 5 RCTS; n = 309; P < 0.001). There were no significant differences in blood pressure, heart rate, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C) or the total cholesterol to HDL-C ratio between groups. Conclusions Carnosine and other HCDs may have a role in improving lipid profiles. Larger studies with sufficient follow-up are necessary to confirm these findings and explore the use of HCDs in the prevention of cardiovascular diseases. Systemic Review Registration PROSPERO registration no.: CRD42017075354

Novel Relationship Between Plasmalogen Lipid Signatures and Carnosine in Humans

“…[1][2][3] Carnosine (𝛽-alanyl-L-histidine), a naturally occurring dipeptide and over-thecounter food supplement, has recently emerged as a potential strategy for reducing DM2 and CVD risk factors. [4,5] Carnosine is mainly found in human skeletal muscle and carnosine supplementation is shown to improve muscle performance and exercise endurance. [6] Lower concentrations of carnosine are also found in other tissues and cells such as the brain, stomach, and erythrocytes.…”

“…[8] In addition to previously known benefits of carnosine for muscle function, more recent animal studies have shown that carnosine reduces obesity and improves glucose metabolism, chronic lowgrade inflammation, lipid levels and peroxidation, atherosclerotic plaque instability, blood pressure, insulin resistance, and insulin secretion, along with increasing 𝛽-cell mass. [4,[9][10][11][12][13][14][15] We and others have also shown beneficial effects of carnosine supplementation on glucose and lipid metabolism in humans. [5,16,17] Molecular and animal research suggests that the beneficial effects of carnosine on these risk factors occur, at least in part, through its anti-inflammatory, anti-oxidative, and anti-glycating properties.…”

“…[4,[9][10][11][12][13][14][15] We and others have also shown beneficial effects of carnosine supplementation on glucose and lipid metabolism in humans. [5,16,17] Molecular and animal research suggests that the beneficial effects of carnosine on these risk factors occur, at least in part, through its anti-inflammatory, anti-oxidative, and anti-glycating properties. [5,11,12,16,17] Dietary carnosine is usually rapidly degraded to 𝛽-alanine and histidine upon absorption.…”

“…[5,16,17] Molecular and animal research suggests that the beneficial effects of carnosine on these risk factors occur, at least in part, through its anti-inflammatory, anti-oxidative, and anti-glycating properties. [5,11,12,16,17] Dietary carnosine is usually rapidly degraded to 𝛽-alanine and histidine upon absorption. However, carnosine catabolism is less pronounced in individuals with low serum carnosinase-1 (CN-1) activity, resulting in increases in circulating carnosine.…”

Use of carnosine in the prevention of cardiometabolic risk factors in overweight and obese individuals: study protocol for a randomised, double-blind placebo-controlled trial

“… 22 23 Our two recent meta-analysis showed improvements in fasting glucose, haemoglobin A1c (HbA1c) and triglyceride levels in studies using carnosine as a part of the intervention. 24 25 Moreover, other human studies using carnosine reported improved quality of life, physical performance and cognitive function. 20 26 27 Despite several studies showing the beneficial effects of carnosine on cardiometabolic risk factors, several limitations exist in the current literature.…”