Healthy
Conditions
Keywords
nicotinamid riboside, L-carnitine, L-serine, N-acetylcystein
Brief summary
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.
Detailed description
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.
Interventions
DIETARY_SUPPLEMENTCofactors
Oral administration of 1g nicotinamide riboside, 3g L-carnitine, 20g serine and 5g N-acetylcystein, first as single compounds, then combined, on 5 days
Sponsors
Karolinska Institutet
Chalmers University of Technology
Sahlgrenska University Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy without any medication, no smokers, no obesity
Exclusion criteria
Any known disease, obesity
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes of plasma levels of nicotinamide riboside measured by mass spectrometry | 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 | 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 | 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 | Twenty-four hours after administration | Plasma levels of N-acetylcystein (nM) measured by UPLCMSMS at 8 times points during 24h after administration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in the plasma level of metabolites associated with the supplementation of metabolic co-factors. | Twenty-four hours after administration of combined cofactors | Untargeted metabolomic analysis using mass spectrometry. (Untargeted = not pre-specified in terms of outcome) |
| 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 | Changes in the plasma level of inflammation related proteins associated with the supplementation of metabolic co-factors. |
Countries
Sweden
Outcome results
None listed