Aim: To describe two cases of diabetic ketoacidosis in newly diagnosed type 1- and type-2-diabetic individuals associated with Metabolife-356(R). Methods: We report the acute hospitalizations and clinical courses of two individuals with diabetic ketoacidosis taking Metabolife-356(R). Results: Both patients presented without a previous diagnosis of diabetes mellitus. One patient clinically has type 1 diabetes (positive islet cell antibodies and subnormal pancreatic beta cell function to glucagon stimulation) and is treated with insulin. The second patient, after 5 days of treatment with intravenous insulin of up to 25 units per hour, is now treated with oral medications. Several possible mechanisms may exist, including the increases in catecholamines and in blood glucose after ingestion of the ingredients of these supplements. Recent clinical trial data shows an increase in blood glucose (in non-diabetics) with these supplements despite significant weight loss at 8 weeks, although no association with diabetes mellitus has been shown in these closely monitored studies. Conclusions: Although no precipitating factor of diabetic ketoacidosis was found in these individuals, the dietary supplement Metabolite cannot be established as a precipitant. However, patients with diabetes should take this supplement only after consultation with their health care provider, as stated on the product label. Most individuals using this supplement meet the current criteria for screening to detect undiagnosed diabetes mellitus and should consider these tests.