ArticleMolecular systems biology2020
The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease.
Article in Molecular systems biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Multi-omics characterization of improved cognitive functions in Parkinson's disease patients after the combined metabolic activator treatment: a randomized, double-blinded, placebo-controlled phase II trial.Brain communications · 2025Trial
- Combined metabolic activators improve cognitive functions in Alzheimer's disease patients: a randomised, double-blinded, placebo-controlled phase-II trial.Translational neurodegeneration · 2023Trial
- Combined metabolic activators therapy ameliorates liver fat in nonalcoholic fatty liver disease patients.Molecular systems biology · 2021Trial
- Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Trial
- Subchronic Tolerance Trials of Graded Oral Supplementation with Phenylalanine or Serine in Healthy Adults.Nutrients · 2021Trial
- Hemochromatosis and Hepatic Complications: A Comprehensive Review of Molecular Mechanisms, Diagnostics, and Emerging Therapeutics.Current molecular medicine · 2026Review
- Gut microbiome composition and metabolic activity in metabolic-associated fatty liver disease.Virulence · 2025Article
- Chrysanthemum morifolium extract improves metabolic dysfunction-associated fatty liver disease by regulating lipid metabolism.Scientific reports · 2025Article
- Emerging strategies, applications and challenges of targeting NADNature aging · 2025Review
- Pathogenesis and Clinical Management of Metabolic Dysfunction-Associated Steatotic Liver Disease.International journal of molecular sciences · 2025Review
- Genome-scale models in human metabologenomics.Nature reviews. Genetics · 2025Review
- Combined Metabolic Activators with Different NAD+ Precursors Improve Metabolic Functions in the Animal Models of Neurodegenerative Diseases.Biomedicines · 2024Article
- Data-driven transcriptomics analysis identifies PCSK9 as a novel key regulator in liver aging.GeroScience · 2023Article
- What is really known about the effects of nicotinamide riboside supplementation in humans.Science advances · 2023Review
- Revisiting the role of serine metabolism in hepatic lipogenesis.Nature metabolism · 2023Article
- Costunolide and Parthenolide Ameliorate MPP+ Induced Apoptosis in the Cellular Parkinson's Disease Model.Cells · 2023Article
- Microbiota Dysbiosis and Gut Barrier Dysfunction Associated with Non-Alcoholic Fatty Liver Disease Are Modulated by a Specific Metabolic Cofactors' Combination.International journal of molecular sciences · 2022Article
- Multiomics Analysis Reveals the Impact of Microbiota on Host Metabolism in Hepatic Steatosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- The CD38 glycohydrolase and the NAD sink: implications for pathological conditions.American journal of physiology. Cell physiology · 2022Review
- Assessment of the neuroprotective potential of d-cycloserine and l-serine in aluminum chloride-induced experimental models of Alzheimer's disease:Frontiers in nutrition · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l-serine, N-acetyl-l-cysteine (NAC), nicotinamide riboside (NR), and l-carnitine by performing a 7-day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.