{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T12:24:44Z","timestamp":1778502284583,"version":"3.51.4"},"reference-count":28,"publisher":"BMJ","issue":"7","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2014,6,27]]},"published-print":{"date-parts":[[2014,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To determine whether valproate (VPA) monotherapy influences homocysteine metabolism in patients with epilepsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Systematic review and meta-analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Data sources<\/jats:title><jats:p>We searched all articles in English through PubMed, Web of Science and EMBASE published up to August 2013 concerning the homocysteine levels in VPA monotherapeutic patients with epilepsy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants<\/jats:title><jats:p>VPA-treated patients with epilepsy (n=266) and matched healthy controls (n=489).<\/jats:p><\/jats:sec><jats:sec><jats:title>Outcome measures<\/jats:title><jats:p>Heterogeneity between studies was assessed using I<jats:sup>2<\/jats:sup>statistics. Pooled standardised mean difference (SMD) and 95% CIs were calculated using a random effect model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of eight eligible studies were enrolled in our meta-analysis. We compared the plasma levels of homocysteine in VPA-treated patients with epilepsy and healthy controls. There was significant heterogeneity in the estimates according to the I<jats:sup>2<\/jats:sup>test (I<jats:sup>2<\/jats:sup>=65.6%, p=0.005). Plasma homocysteine levels in VPA-treated patients with epilepsy were significantly higher than in healthy controls under a random effect model. (SMD, 0.62; 95% CI 0.32 to 0.92). Further subgroup analyses suggested that no signi\ufb01cant differences were present when grouped by ethnicity and age, but the risk of heterogeneity in the West Asian group (I<jats:sup>2<\/jats:sup>=47.4%, p=0.107) was diminished when compared with that of the overall group (I<jats:sup>2<\/jats:sup>=65.6%, p=0.005).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our meta-analysis indicates that VPA monotherapy is associated with the increase in plasma homocysteine levels in patients with epilepsy. Whether this association is influenced by ethnicity needs further research.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2014-004936","type":"journal-article","created":{"date-parts":[[2014,7,17]],"date-time":"2014-07-17T00:24:30Z","timestamp":1405556670000},"page":"e004936","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":28,"title":["Increased homocysteine levels in valproate-treated patients with epilepsy: a 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