Homocysteine and vitamin therapy in stroke prevention and treatment: a review.

Abstract

Homocysteine (Hcy), a sulfur amino acid, is the only direct precursor for L-methionine synthesis through a reaction that requires vitamin B₁₂, representing a connection with "one-carbon" units metabolism. Hcy catabolism requires vitamin B₆ and as a consequence, alteration in folic acid and B vitamins status impairs Hcy biotransformation. Numerous studies have indicated that Hcy is an independent risk factor for cardio- and cerebrovascular diseases. In the last decade, several clinical trials have investigated the possible correlation between the use of folic acid and vitamins B₆ and B₁₂ for lowering Hcy plasma concentration and the reduced risk of stroke or its recurrence. This review is aimed to present some aspects of Hcy biochemistry, as well as the mechanisms through which it exerts the toxic effects on the vascular endothelium. We also discuss the results of some of the clinical trials developed to investigate the beneficial effects of vitamin therapy in the prevention and management of stroke.

The Molecular and Cellular Effect of Homocysteine Metabolism Imbalance on Human Health

“…The concentration of tHcy can also be assessed through capillary electrophoresis with a suitable detection system. Different methods used to assess tHcy and Hcy-thiolactone concentration in biological samples (plasma, urine) are very nicely summarized by Manolescu et al [19]. …”

“…In addition, Hcy acts an agonist for both groups of glutamate receptors, metabotropic (groups I and III) and ionotropic (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)) receptors, as well as for N -methyl- d -aspartate receptor (NMDA) [43]. Overstimulation of these receptors results in increased level of cytoplasmic calcium, higher production of free radicals and activation of caspases leading to apoptosis [19,43,46]. Hcy mediated NMDA receptor induction of neuronal cells could lead to their death due to transient activation of extracellular signal-regulated kinases (ERKs), mitogen-activated protein kinase (MAPK) and p38 MAPK [47,48] that is different from downstream signaling pathways triggered by other NMDA receptor agonists.…”

“…It has been estimated that a 2.5 µM rise in plasma tHcy concentrations is associated with 10% increase in CVD risk [66]. Moreover, it was shown that increased plasma tHcy levels (above 20 μM) should be associated with nine-fold increase of myocardial infarction and also with subsequent stroke risk comparing to concentration below 9 μM [19]. A key issue that remains to be resolved is whether a condition of hHcy has a direct, causal impact on vascular diseases, or exists as a biomarker that reflects another changes in metabolism for the adverse effects on vascular function.…”

Elevated homocysteine is associated with poorer self-perceived physical health in older men: The Health in Men Study

“…These could conceivably cause muscle weakness and atrophy, leading to progressive physical decline. At the molecular level, B-vitamin deficiency may be mediated via hyperhomocysteinaemia through mechanisms of oxidative stress [10], or by homocysteinylation [11] which involves covalent binding of tHcy to proteins. These modified proteins or neoantigens can trigger the inflammatory cascade, resulting in vascular endothelium damage and subsequently cerebro-or cardiovascular events, leading to functional and physical deterioration.…”

Tetrahydrocurcumin Ameliorates Homocysteinylated Cytochrome-c Mediated Autophagy in Hyperhomocysteinemia Mice after Cerebral Ischemia

“…Many studies indicate a plethora of risk factors for cerebral stroke (i.e., hypertension, obesity, smoking, and diabetes mellitus) (Manolescu et al, 2010). Nevertheless, cerebrovascular events can occur sometimes in individuals without any of the previously mentioned risk factors.…”