Blood methanol concentrations in normal adult subjects administered abuse doses of aspartame

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Abstract
Blood methanol concentrations were measured in 30 normal adult subjects administered aspartame, a dipeptide methyl ester. The doses studied included the 99th percentile of projected daily ingestion (34 mg/kg body wt) and 3 doses considered to be in the abuse range (100, 150 and 200 mg/kg body wt). Methanol concentrations were below the level of detection (0.4 mg/dl) in the blood of the 12 normal subjects who ingested aspartame at 34 mg/kg. They were significantly elevated (P .ltoreq. 0.001) after ingestion of each abuse dose, with mean peak blood methanol concentrations and areas under the blood methanol concentration-time curve increasing in proportion to dose. Mean (.+-. SD) peak blood methanol concentrations were 1.27 .+-. 0.48 mg/dl (100 mg/kg dose), 2.14 .+-. 0.35 mg/dl (150 mg/kg dose) and 2.58 .+-. 0.78 mg/dl at the (200 mg/kg dose). Blood methanol concentrations returned to predosing levels by 8 h after administration of the 100 mg/kg dose. Methanol was still detected in the blood 8 h after the subjects had ingested aspartame at 150 or 200 mg/kg. Blood formate analyses were carried out in 6 subjects who ingested aspartame at 200 mg/kg, since recent studies indicated that the toxic effects of methanol were due to formate accumulation. No significant increase in blood formate concentrations over predosing concentrations was noted. No changes were noted in any blood chemistry profile parameters measured 24 h after aspartame ingestion, compared to values noted before administration. No differences were noted in ophthalmologic examinations carried out before and after aspartame loading.