{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T12:26:21Z","timestamp":1762863981516},"reference-count":0,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2001,5,2]],"date-time":"2001-05-02T00:00:00Z","timestamp":988761600000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2001,5]]},"abstract":"Objective<\/jats:title>To examine the in vitro and in vivo attributes of aspartame and to determine its efficacy for treating sickle cell anemia.<\/jats:p><\/jats:sec>Rationale<\/jats:title>Aspartame (L<\/jats:sc>\u2010aspartyl\u2010L<\/jats:sc>\u2010phenylalanine methyl ester) binds with 2 human Bence Jones proteins. The proteins (Mcg and Sea) showed phenylalanine penetrating into hydrophobic binding sites. This aspartame property suggested a potential to interfere with sickle hemoglobin fibril formation.<\/jats:p><\/jats:sec>Methods<\/jats:title>For the in vitro studies, blood from 20 subjects monitored for sickle cell anemia was collected in heparinized tubes. Specimens were divided in thirds and aspartame was added to 2 tubes to yield a 1 mg\/mL or 2 mg\/mL concentration. Sickled cells that were present after a drop from each aliquot was added to a fresh 2% metabisulfite solution were counted 3 times. For the in vivo studies, 23 subjects from the Sickle Cell Clinic (University of Oklahoma Health Sciences Center, Oklahoma City, Okla) consented to participate in a randomized single\u2010dose administration of 1.5, 3.0, or 6 mg\/kg aspartame. Heparinized blood was obtained at 0, 30, 60, 120, 240, 480, and 1440 minutes after aspartame administration. Specimens were counted in a blinded manner by means of the technique used for the in vitro method, but a photomicrograph of 1 field from each triplicate count was made. The pictures were marked and were computer counted.<\/jats:p><\/jats:sec>Results<\/jats:title>For the in vitro studies, sickled cells decreased from 28% to <14% when 1 mg\/mL aspartame was added and decreased further with 2 mg\/mL. For the in vivo studies, a decreased number of sickled cells in homozygous blood (HbSS) were observed after oral administration of aspartame. Sickling was inhibited by 6 mg\/kg aspartame for at least 6 hours in 15 subjects with HbSS anemia.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Further evaluations of the efficacy of aspartame for sickle crisis and crisis prevention appears to be warranted.<\/jats:p>Clinical Pharmacology & Therapeutics<\/jats:italic> (2001) 69<\/jats:bold>, 346\u2013355; doi: 10.1067\/mcp.2001.115141<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1067\/mcp.2001.115141","type":"journal-article","created":{"date-parts":[[2002,7,25]],"date-time":"2002-07-25T04:21:43Z","timestamp":1027570903000},"page":"346-355","source":"Crossref","is-referenced-by-count":14,"title":["Aspartame effect in sickle cell anemia"],"prefix":"10.1111","volume":"69","author":[{"given":"Carl V.","family":"Manion","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and the Department of Crystallography, Oklahoma Medical Research Foundation Department of Pediatrics University of Oklahoma Health Sciences Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Howard","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and the Department of Crystallography, Oklahoma Medical Research Foundation Department of Pediatrics University of Oklahoma Health Sciences Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandi","family":"Ogle","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and the Department of Crystallography, Oklahoma Medical Research Foundation Department of Pediatrics University of Oklahoma Health Sciences Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joan","family":"Parkhurst","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and the Department of Crystallography, Oklahoma Medical Research Foundation Department of Pediatrics University of Oklahoma Health Sciences Center"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen","family":"Edmundson","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and the Department of Crystallography, Oklahoma Medical Research Foundation Department of Pediatrics University of Oklahoma Health Sciences Center"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2001,5,2]]},"container-title":["Clinical Pharmacology & Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1067\/mcp.2001.115141","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,19]],"date-time":"2023-11-19T15:04:38Z","timestamp":1700406278000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1067\/mcp.2001.115141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,5]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2001,5]]}},"alternative-id":["10.1067\/mcp.2001.115141"],"URL":"https:\/\/doi.org\/10.1067\/mcp.2001.115141","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,5]]}}}