1. Plasma concentration of homocysteine was found to not be associated with incident stroke in a case-control, nested study.
2. Both methionine concentration and methionine to homocysteine ratio were associated with a lower risk of incident stoke.
Evidence Level Rating: 2 (Good)
Stroke is a leading cause of morbidity and mortality worldwide, and homocysteine, formed from the metabolism of methionine, has been recognized as the major sulfur-containing amino acid linked to cardiovascular disease, including stroke, though the pathogenesis is somewhat unclear. Furthermore, due to the relationship between homocysteine and other sulfur-containing compounds, there is a risk of confounding variables. This nested case-control study of the EPIC (European Prospective Investigation Into Cancer and Nutrition)-Norfolk study examined the association of plasma concentration of individual sulfur-containing compounds as well as the ratio of methionine to homocysteine – which represents the activity of one-carbon metabolism – with the incidence of stroke. From the original EPIC-Norfolk study (n = 25,639), 480 cerebrovascular disease cases (mean [SD] age = 67.4 [7.3] years, 52.3% female) and 480 matched controls (mean [SD] age = 67.2 [7.3] years, 52.3% female) were evaluated. It was found that higher plasma concentrations of homocysteine were significantly associated with incident stroke; this associated, though, was attenuated after adjustment. In contrast, higher plasma concentrations of methionine and a higher methionine to homocysteine ratio were both associated with a lower risk of incident stroke, with odds ratios per 1 SD of 0.83 (95% CI 0.72 to 0.96) and 0.82 (95% CI 0.71 to 0.95), respectively. This association persisted after adjusting for homocysteine and other potential variables like lipid levels and blood pressure. Other sulfur-containing compounds like cystathionine, cysteine, glutathione, and taurine were not associated with a risk of stroke. In all, though the plasma concentration of homocysteine was not found to be associated with incident stroke, there may be a potential role for methionine in the prevention of cerebrovascular disease.
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