Clinical trial NCT03838822: Kinetics of Metabolic Cofactors in NAFLD
Official title: Kinetics of Metabolic Cofactors After Oral Supplementation in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Healthy
Keywords: nicotinamid riboside
L-carnitine
L-serine
N-acetylcystein
Lead sponsor: Sahlgrenska University Hospital
Sponsor class: OTHER
Collaborators: name: Karolinska Institutet
name: Chalmers University of Technology
First posted: 2019-02-12
Enrollment: 10
Sex: MALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

Healthy without any medication, no smokers, no obesity

Exclusion Criteria:

Any known disease, obesity

Primary outcomes:
measure: Changes of plasma levels of nicotinamide riboside measured by mass spectrometry
timeFrame: Twenty-four hours after administration
measure: Changes of plasma levels of L-carnitine measured by mass spectrometry
timeFrame: Twenty-four hours after administration
measure: Changes of plasma levels of L-serine measured by mass spectrometry
timeFrame: Twenty-four hours after administration
measure: Changes of plasma levels of N-acetylcystein measured by mass spectrometry
timeFrame: Twenty-four hours after administration
Secondary outcomes:
measure: Changes in the plasma level of metabolites associated with the supplementation of metabolic co-factors.
timeFrame: Twenty-four hours after administration of combined cofactors
measure: Changes in the plasma level of inflammation-related proteins associated with the supplementation of metabolic co-factors.
timeFrame: Twenty-four hours after administration of combined cofactors
Other outcomes:
Locations:
city: Göteborg
country: Sweden
facility: Hanns-Ulrich Marschall
city: Göteborg
country: Sweden
facility: Sahlgrenska Academy
Study officials:
affiliation: Sahlgrenska University Hospital
name: Hanns-Ulrich Marschall, Prof
role: PRINCIPAL_INVESTIGATOR
References: