SynthesisMolecular medicine (Cambridge, Mass.)2020
Meta-analysis of metabolites involved in bioenergetic pathways reveals a pseudohypoxic state in Down syndrome.
Synthesis in Molecular medicine (Cambridge, Mass.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Handgrip strength measurement protocols in individuals with Down syndrome: a systematic review and meta-regression.Annals of medicine · 2025Pooled it
- Dysregulated calcium signaling underlies hyposalivation and microbial dysbiosis in Down syndrome.Cell reports · 2026Article
- Impact of dietary intervention and supplementation on the physiological profile of individuals with down syndrome.Scientific reports · 2025Article
- Role of cystathionine-β-synthase and hydrogen sulfide in down syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Synergistic mitochondrial impairment by endogenously elevated cyanide and hydrogen sulfide in Down syndrome; commentary on: Cyanide overproduction impairs cellular bioenergetics in Down syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Cyanide overproduction impairs cellular bioenergetics in Down syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Metabolic profiling of amniotic fluid by differentialMetabolomics : Official journal of the Metabolomic Society · 2025Article
- Oxidative Stress and Down Syndrome: A Systematic Review.Antioxidants (Basel, Switzerland) · 2025Review
- Essential role of sulfide oxidation in brain health and neurological disorders.Pharmacology & therapeutics · 2025Review
- Identification of metabolomics-based biomarker discovery in individuals with down syndrome utilizing kernel-tree model-enhanced explainable artificial intelligence methodology.Frontiers in molecular biosciences · 2025Article
- Metabolomics of mothers of children with autism, idiopathic developmental delay, and Down syndrome.Scientific reports · 2024Article
- Consequences of trisomy 21 for brain development in Down syndrome.Nature reviews. Neuroscience · 2024Review
- Neurobehavioral dysfunction in a mouse model of Down syndrome: upregulation of cystathionine β-synthase, HGeroScience · 2024Article
- Multimodal analysis of dysregulated heme metabolism, hypoxic signaling, and stress erythropoiesis in Down syndrome.Cell reports · 2024Article
- Article
- Characterization of mitochondrial and metabolic alterations induced by trisomy 21 during neural differentiation.Free radical biology & medicine · 2023Article
- HCellular and molecular life sciences : CMLS · 2022Article
- Review
- Biochemical Discrimination of the Down Syndrome-Related Metabolic and Oxidative/Nitrosative Stress Alterations from the Physiologic Age-Related Changes through the Targeted Metabolomic Analysis of Serum.Antioxidants (Basel, Switzerland) · 2022Article
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Clinical observations and preclinical studies both suggest that Down syndrome (DS) may be associated with significant metabolic and bioenergetic alterations. However, the relevant scientific literature has not yet been systematically reviewed. The aim of the current study was to conduct a meta-analysis of metabolites involved in bioenergetics pathways in DS to conclusively determine the difference between DS and control subjects. We discuss these findings and their potential relevance in the context of pathogenesis and experimental therapy of DS. Articles published before July 1, 2020, were identified by using the search terms "Down syndrome" and "metabolite name" or "trisomy 21" and "metabolite name". Moreover, DS-related metabolomics studies and bioenergetics literature were also reviewed. 41 published reports and associated databases were identified, from which the descriptive information and the relevant metabolomic parameters were extracted and analyzed. Mixed effect model revealed the following changes in DS: significantly decreased ATP, CoQ10, homocysteine, serine, arginine and tyrosine; slightly decreased ADP; significantly increased uric acid, succinate, lactate and cysteine; slightly increased phosphate, pyruvate and citrate. However, the concentrations of AMP, 2,3-diphosphoglycerate, glucose, and glutamine were comparable in the DS vs. control populations. We conclude that cells of subjects with DS are in a pseudo-hypoxic state: the cellular metabolic and bio-energetic mechanisms exhibit pathophysiological alterations that resemble the cellular responses associated with hypoxia, even though the supply of the cells with oxygen is not disrupted. This fundamental alteration may be, at least in part, responsible for a variety of functional deficits associated with DS, including reduced exercise difference, impaired neurocognitive status and neurodegeneration.
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Registered trials
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