ReviewNutrients2013
Methoxistasis: integrating the roles of homocysteine and folic acid in cardiovascular pathobiology.
Review in Nutrients, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Homocysteine-lowering interventions for preventing cardiovascular events.The Cochrane database of systematic reviews · 2017Pooled it
- Associations of methyl donor and methylation inhibitor levels during anti-oxidant therapy in heart failure.Journal of physiology and biochemistry · 2021Trial
- Effect of Folic Acid, Betaine, Vitamin B₆, and Vitamin B12 on Homocysteine and Dimethylglycine Levels in Middle-Aged Men Drinking White Wine.Nutrients · 2016Trial
- The complex link of the folate-homocysteine axis to myocardial hypertrophy and heart failure: from mechanistic exploration to clinical vision.Journal of advanced research · 2026Review
- Sex-specific benefits of a combined supplementation of B vitamins, nicotinamide riboside, folate and cobalamin, in a murine model of heart failure.Biology of sex differences · 2025Article
- Association of folate levels with all-cause and cause-specific mortality in patients with arthritis.Clinical rheumatology · 2025Article
- Folate in the United States Population and its Association with Congestive Heart Failure.Reviews in cardiovascular medicine · 2024Article
- Effect of Beer Consumption on Methylation and Redox Metabolism.Physiological research · 2022Article
- The Emerging Role of MTHFD Family Genes in Regulating the Tumor Immunity of Oral Squamous Cell Carcinoma.Journal of oncology · 2022Article
- Metabolic Therapy of Heart Failure: Is There a Future for B Vitamins?International journal of molecular sciences · 2021Review
- Prevalence and risk factors for hyperhomocysteinemia: a population-based cross-sectional study from Hunan, China.BMJ open · 2021Article
- CRIF1 Deficiency Increased Homocysteine Production by Disrupting Dihydrofolate Reductase Expression in Vascular Endothelial Cells.Antioxidants (Basel, Switzerland) · 2021Article
- Article
- Methylation as a key regulator of Tau aggregation and neuronal health in Alzheimer's disease.Cell communication and signaling : CCS · 2021Review
- Serum homocysteine concentration in dogs with immunosuppressant-responsive enteropathy.Journal of veterinary science · 2020Article
- Association of Homocysteine, Methionine, and MTHFR 677C>T Polymorphism With Rate of Cardiovascular Multimorbidity Development in Older Adults in Sweden.JAMA network open · 2020Article
- Micronutrients in Support to The Carbon Cycle Activate Antioxidant Defences and Reduce Sperm DNA Damage in Infertile Men Attending Assisted Reproductive Technology Programs: Clinical Trial Study.International journal of fertility & sterility · 2020Article
- Folic Acid Protects Rat Cerebellum Against Oxidative Damage Caused by Homocysteine: the Expression of Bcl-2, Bax, and Caspase-3 Apoptotic Genes.Neurotoxicity research · 2020Article
- Potential Role of Tocotrienols on Non-Communicable Diseases: A Review of Current Evidence.Nutrients · 2020Review
- Exhaustive Exercise and Post-exercise Protein Plus Carbohydrate Supplementation Affect Plasma and Urine Concentrations of Sulfur Amino Acids, the Ratio of Methionine to Homocysteine and Glutathione in Elite Male Cyclists.Frontiers in physiology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Over the last four decades, abnormalities in the methionine-homocysteine cycle and associated folate metabolism have garnered great interest due to the reported link between hyperhomocysteinemia and human pathology, especially atherothrombotic cardiovascular disease. However, clinical trials of B-vitamin supplementation including high doses of folic acid have not demonstrated any benefit in preventing or treating cardiovascular disease. In addition to the fact that these clinical trials may have been shorter in duration than appropriate for modulating chronic disease states, it is likely that reduction of the blood homocysteine level may be an oversimplified approach to a complex biologic perturbation. The methionine-homocysteine cycle and folate metabolism regulate redox and methylation reactions and are, in turn, regulated by redox and methylation status. Under normal conditions, a normal redox-methylation balance, or "methoxistasis", exists, coordinated by the methionine-homocysteine cycle. An abnormal homocysteine level seen in pathologic states may reflect a disturbance of methoxistasis. We propose that future research should be targeted at estimating the deviation from methoxistasis and how best to restore it. This approach could lead to significant advances in preventing and treating cardiovascular diseases, including heart failure.
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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.