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In the present study, we sought to determine the joint influence of serum folate and vitamin B\n                    <jats:sub>12<\/jats:sub>\n                    concentrations on two functional indicators of vitamin B\n                    <jats:sub>12<\/jats:sub>\n                    status, total homocysteine (tHcy) and methylmalonic acid (MMA), among adult participants in phase 2 of the NHANES III (1991\u20131994) and the NHANES 1999\u20132002. Exclusion of subjects who were &lt;20 years old, were pregnant, had evidence of kidney or liver dysfunction, or reported a history of alcohol abuse or recent anemia therapy left 4,940 NHANES III participants and 5,473 NHANES 1999\u20132002 participants for the study. Multivariate analyses controlled for demographic factors, smoking, alcohol use, body mass index, self-reported diabetes diagnosis, and serum concentrations of creatinine and alanine aminotransferase revealed significant interactions between serum folate and serum vitamin B\n                    <jats:sub>12<\/jats:sub>\n                    in relation to circulating concentrations of both metabolites. In subjects with serum vitamin B\n                    <jats:sub>12<\/jats:sub>\n                    &gt;148 pmol\/liter (L), concentrations of both metabolites decreased significantly as serum folate increased. In subjects with lower serum vitamin B\n                    <jats:sub>12<\/jats:sub>\n                    , however, metabolite concentrations increased as serum folate increased starting at \u224820 nmol\/L. These results suggest a worsening of vitamin B\n                    <jats:sub>12<\/jats:sub>\n                    's enzymatic functions as folate status increases in people who are vitamin B\n                    <jats:sub>12<\/jats:sub>\n                    -deficient.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0709487104","type":"journal-article","created":{"date-parts":[[2007,12,4]],"date-time":"2007-12-04T21:55:42Z","timestamp":1196805342000},"page":"19995-20000","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":188,"title":["In vitamin B\n                    <sub>12<\/sub>\n                    deficiency, higher serum folate is associated with increased total homocysteine and methylmalonic acid concentrations"],"prefix":"10.1073","volume":"104","author":[{"given":"Jacob","family":"Selhub","sequence":"first","affiliation":[{"name":"*Vitamin Metabolism Laboratory 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