Kinetics of Metabolic Cofactors After Oral Supplementation in Healthy Subjects
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 10
- 试验地点
- 3
- 主要终点
- Changes of plasma levels of nicotinamide riboside measured by mass spectrometry
研究概览
简要总结
There is a strong correlation between major adverse health consequences of obesity and development of non-alcoholic fatty liver disease (NAFLD). NAFLD is characterized by abnormal hepatic accumulation of triglycerides and other lipids. It has become a worldwide health problem that accelerates cirrhosis, type 2 diabetes mellitus (T2DM), and especially premature cardiovascular morbidity and mortality.
The plasma level of glutathione (GSH) is typically depleted in individuals with metabolism related disorders. However, cellular GSH levels cannot be increased by supplementing GSH and it must be synthesized within the liver either de novo or by salvation pathway. The level of GSH is not enough to maintain and regulate the thiol redox status of the liver in subjects with high hepatic steatosis at fasting stage due to the depletion of glycine. Glycine can be synthesized via the interconversion of serine. It has been shown that the serine synthesis is downregulated in patients with NAFLD and supplementation of serine has attenuated alcoholic fatty liver by enhancing homocysteine metabolism in mice and rats. Depleted liver glutathione is also restored by the administration of N-acetylcystein as in acetaminophen poising. L-carnitine and nicotinamide that both stimulate the transfer of fatty acids from cytosol to mitochondria have been identified as two additional cofactors that are depleted in patients with NAFLD.
In this study, the kinetics in blood of pivotal metabolic cofactors, serine, L-carnitine, N-acetylcystein and nicotinamide after single and simultaneous dietary supplementation, are measured.
详细描述
In 10 healthy subjects with BMI <30 kg/m2 the plasma concentrations of 4 natural compounds (nicotinamide riboside, L-carnitine, L-serine and N-acetylcystein) are measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLCMSMS) after individual and combined administration, on five consecutive days and at every hour during 9 hours after administration. The study will start at 8:00 every morning and at each time point, blood samples will be collected.
The taste and any potential sensing of the co-factors such as vertigo, nausea, bowel movement will be recorded.
Each participant will receive one oral dose of Day 1: 1 g nicotinamide riboside; Day 2: 3 g L-carnitine; Day 3: 5 g N-acetylcystein; Day 4: 20 g L-serine; Day 5: combined 1 g nicotinamide riboside, 3 g L-carnitine, 5 g N-acetylcystein, and 20 g L-serine
In addition, untargeted metabolomics analysis as well as O-link proteomics analysis we be performed to study effect of the administered cofactors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy without any medication, no smokers, no obesity
排除标准
- •Any known disease, obesity
研究组 & 干预措施
Intervention
Oral administration of cofactors, 1g nicotinamide riboside, 3g L-carnitine, 20g serine and 5g N-acetylcystein, first as single compounds, then combined, on 5 days
干预措施: Cofactors (Dietary Supplement)
结局指标
主要结局
Changes of plasma levels of nicotinamide riboside measured by mass spectrometry
时间窗: Twenty-four hours after administration
Plasma levels of nicotinamide riboside by UPLCMSMS at 8 time points during 24h after administration
Changes of plasma levels of L-carnitine measured by mass spectrometry
时间窗: Twenty-four hours after administration
Plasma levels of L-carnitine (nM) measured by UPLCMSMS at 8 time points during 24h after administration
Changes of plasma levels of L-serine measured by mass spectrometry
时间窗: Twenty-four hours after administration
Plasma levels of L-serine (nM) measured by UPLCMSMS at 8 times points during 24h after administration
Changes of plasma levels of N-acetylcystein measured by mass spectrometry
时间窗: Twenty-four hours after administration
Plasma levels of N-acetylcystein (nM) measured by UPLCMSMS at 8 times points during 24h after administration
次要结局
- Changes in the plasma level of metabolites associated with the supplementation of metabolic co-factors.(Twenty-four hours after administration of combined cofactors)
- Changes in the plasma level of inflammation-related proteins associated with the supplementation of metabolic co-factors.(Twenty-four hours after administration of combined cofactors)
研究者
Hanns-Ulrich Marschall
Professor, University Hospital Consultant
Sahlgrenska University Hospital, Sweden