GRAPEFRUIT JUICE IMPROVES GLYCEMIC CONTROL BUT EXACERBATES METFORMIN-INDUCED LACTIC ACIDOSIS IN NON-DIABETIC RATS

Recent clinical studies have indicated that grapefruit juice (GFJ) improves insulin resistance and reduces weight gain in humans. The effect of GFJ on glucose tolerance and metformin-induced lactic acidosis in normal, non-diabetic in rots is hereby investigated. Three groups (A, B, Q of 20 mole Wistar rots each, were treated with stepwise, escalated oral doses of 0, 1.0, 2.0, 3.0 (group A), and 3.0 ml/kg body weight (groups B and C) of GFJ. Croup C rots additionally received 250 mg/kg body weight of metformin. All the animals were sacrificed after 74 days of treatment. Fasting blood glucose levels were significantly (P < 0.0001) lower in GFJ-treated test (2.9 +/- 0.4 mmol/L)compared with control (3.7 +/- 0.39 mmol/L) rots, but 1.5-hr plasma insulin levels were similar GFJ alone or in combination with metformin, significantly (P < 0.05) lowered blood glucose levels compared with control animals. Blood lactic acid levels were similar in GFJ-treated test (2.81 +/- 1.4 mmol/L) and control (2.54 +/- 0.7 mmol/L) rots, respectively, but were significantly increased (P = 0.0079) in rots that were treated with either metformin alone (5.38 +/- 2.53 mmol/L) or in combination with GFJ (8.37 +/- 3.48 mmol/L). Metformin concentration in liver tissue was significantly higher (P < 0.05) in GFJ-treoted (397 +/- 79 mu g/g) than in control (280 +/- 75 mu g/g) rots, respectively. Plasma metformin levels were comparable between the control (95 +/- 8.1 mu g/ml) and GFJ-treated test (708 +/- 20 mu g/ml) rots, respectively. Liver tissue metformin concentrations and plasma lactic acid levels showed significant correlation in both control (P = 0.0722; r(2) = 0.9080) and GFJ-treoted test rots (P = 0.0005; r(2) = 0.9893). Although GFJ may be beneficial to diabetic patients, it may exacerbate lactic acidosis in diabetic patients taking metformin concurrently