The Potential of Carnosine Supplementation in Reducing the Cardiometabolic Risk: a Double-blind, Placebo-controlled Trial
试验速览
- 阶段
- 不适用
- 入组人数
- 84
- 试验地点
- 2
- 主要终点
- Change in insulin sensitivity measured by euglycaemic glucose clamp
研究概览
简要总结
The aim of this study is to determine whether carnosine supplementation in overweight/obese individuals can improve insulin secretion and/or insulin resistance by decreasing sub clinical inflammation.
The investigators hypothesise that carnosine supplementation will reduce type 2 diabetes and cardiovascular risk factors by lowering chronic low-grade inflammation (CLI), oxidative stress, advanced glycation end products (AGEs), and advanced lipoxidation end products (ALEs).
Aim :To determine the capacity of carnosine supplementation to decrease major risk factors for type 2 diabetes and cardiovascular disease and identify metabolic pathways involved, specifically by:
- Reducing diabetes risk (insulin sensitivity; secretory function and glucose tolerance)
- Improving cardiovascular risk factors (lipids; arterial (aortic) stiffness; central blood pressure (cBP); endothelial function).
- Decreasing the CLI, oxidative stress, AGEs, and ALEs, and increase detoxification of reactive carbonyl species (RCSs).
详细描述
Cardiovascular risk factors including type 2 diabetes underpin a major threat to the globe and result in a heavy health and financial burden across the healthcare system. Treating type 2 diabetes and cardiovascular disease is expensive and often unsatisfactory. Current medications bring unwanted side effects, and often merely delay rather than prevent type 2 diabetes complications and cardiovascular disease. As a further concern, the micro- and macrovascular complications of type 2 diabetes often start developing before actual diagnosis. Diabetes prevention and treatment through weight loss and exercise programs is a difficult and costly public health measure, leaving the tidal wave of type 2 diabetes to swell even more. An alternative is urgently needed: a low-cost safe approach, easy to implement at population level.
Could carnosine be that alternative? The evidence suggests carnosine has significant metabolic impact and presents such an alternative. A naturally occurring dipeptide, carnosine is already emerging as a human therapy in exercise physiology, heart failure, cataract prevention and treatment, neurology, and psychiatry. A promising further use may derive from its effect on cardiovascular risk factors. Metabolic research, though confined to animal studies, strongly suggests that carnosine supplementation aids the prevention and treatment of obesity, type 2 diabetes, and cardiovascular disease - by virtue of its anti-inflammatory, antioxidative, and anti-glycating effects. The investigators conducted the first pilot data in human and demonstrate relationships among carnosine, obesity, insulin resistance, and dyslipidemia. Put briefly, the pilot weighs strongly in favour of carnosine as a means of reducing cardiovascular risk in humans.
Too good to be true? Apart from its excellent side-effect profile, carnosine is inexpensive and seemingly safe (available as an over-the-counter food additive), making it prima facie ideal for population use. In this setting research is now urgently needed - to test the significant metabolic potential of carnosine to address a major health problem.
The investigators propose a comprehensive double-blind placebo-controlled human trial to investigate the effects of carnosine supplementation on cardiovascular risk factors. If the investigators demonstrate a role in reducing risk factors for type 2 diabetes and cardiovascular disease in overweight and obese non-diabetic humans, the public health implications will be revolutionary, offering the world a genuine low cost, accessible, intervention to curtail the advance of obesity, type 2 diabetes, and cardiovascular disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Age >18 or <60 years,
- •Weight change < 5 kg in last 12 months
- •BMI >25kg/m2 but weight <159kg due to DEXA scan restrictions
- •Non-diabetic, no allergy, non-smoker, no high alcohol use
- •No current intake of medications including vitamin supplements
- •No kidney, cardiovascular, haematological, respiratory, gastrointestinal, endocrine or central nervous system disease, as well as no psychiatric disorders, no active cancer within the last five years; no presence of acute inflammation (by history, physical or laboratory examination)
- •Not pregnant or lactating
排除标准
- •Age <18 or > 60 years
- •Weight change > 5 kg in last 12 months
- •Diabetes (diagnosed or oral glucose tolerance test (OGTT), allergy
- •Current smoking habit, high alcohol use
- •Current intake of medications including vitamin supplements
- •Kidney, cardiovascular, haematological, respiratory, gastrointestinal, endocrine or central nervous system disease, as well as psychiatric disorder, active cancer within the last five years; presence of acute inflammation (by history, physical or laboratory examination)
- •pregnancy or lactation
研究组 & 干预措施
Intervention
Each participant will be given a daily oral dose 2 g of carnosine (2 tablets twice daily) for 14 weeks
干预措施: carnosine (Dietary Supplement)
Control
Each participant will be given a daily oral dose 2 g of identical placebo tablets ( 2 tablets twice daily) for 14 weeks
干预措施: Placebo (Other)
结局指标
主要结局
Change in insulin sensitivity measured by euglycaemic glucose clamp
时间窗: From baseline to 14 weeks
The clamp will be used to measure insulin sensitivity. The clamp is initiated by an intravenous bolus injection of insulin (9milliUnit/kg). Insulin is then constantly infused at a rate of 40 milliUnit.m-2.min-1 for 120 min into an arm vein, whilst glucose is variably infused to maintain euglycaemia. Plasma glucose values will be monitored every 5 minutes during the clamp and the variable infusion rate of glucose is adjusted to maintain blood glucose at a constant value of 5mmol/L.
次要结局
- Change in markers of endothelial dysfunction(From baseline to 14 weeks)
- Change in Resting systolic and diastolic blood pressure(From baseline to 14 weeks)
- Change in Acute Insulin Secretory Response - Intravenous Glucose Tolerance Test(From baseline to 14 weeks)
研究者
Barbora de Courten
Associate Professor
Monash University