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ARTICLE |

Brain Serotonin Neurotoxicity and Fenfluramine and Dexfenfluramine FREE

Philip D. Lipetz, PhD
JAMA. 1997;278(24):2141-2141. doi:10.1001/jama.1997.03550240031020
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To the Editor.  —Recently the serotonin-enhancing diet drugs, fenfluramine and dexfenfluramine, were withdrawn from the market in the United States. These drugs appear to deplete the brain of serotonin, suggesting that normal physiology during treatment may require constant replenishment of serotonin.1 Brain serotonin is synthesized from tryptophan. The rate-limiting step in brain serotonin synthesis is entry of tryptophan into the brain. Such entry is proportionate to the ratio of plasma tryptophan to other large neutral amino acids (Trp/ LNNA) that compete with tryptophan for passage past the blood-brain barrier. A higher Trp/LAA ratio corresponds to a greater capacity to synthesize brain serotonin.In women, but not in men, dieting has been repeatedly demonstrated to decrease plasma tryptophan levels and Trp/ LNAA ratios by Cowen and colleagues (see reference for citations).2 Four other laboratories have confirmed lower Trp/ LNAA ratios in dieting women.3-6Long-term dexfenfluramine treatment is accompanied

REFERENCES

McCann UD, Seiden LS, Rubin LJ, Ricaurte GA.  Brain serotonin neurotoxicity and primary pulmonary hypertension from fenfluramine and dexfenfluramine: a systematic review of the evidence . JAMA . 1997;;278:666-672.
Walsh AES, Oldman AD, Franklin M, Fairburn CO, Cowen PJ.  Dieting decreases plasma tryptophan and increases the prolactin response to d-fenfluramine in women, but not men . J Affect Disord . 1995;;33:89-97.
Barrio AS, Fernandez-Quintela A, Rocandio A, Latorre PM, Vazquez JA.  Effects of dexfenfluramine on weight loss and serum amino acids profile in obese subjects . Nutr Res . 1996;;16:1671-1678.
McCargar LJ, Clandinin MT, Fawcett DM, Johnson JL.  Short-term changes in energy intake and serum insulin, neutral amino acids, and urinary catecholamine excretion in women . Am J Clin Nutr . 1988;;47:932-941.
Schweiger U, Laessle R, Kittl S, Dickhaut B, Schweiger M, Pirke KM.  Macronutrient intake, plasma large amino acids and mood during weight-reducing diets . Neural Transm . 1986;;67:77-86.
Wolfe BE, Metzger ED, Stollar C.  The effects of dieting on plasma tryptophan concentration and food intake in healthy women . Physiol Behav . 1997;;61:537-541.

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McCann UD, Seiden LS, Rubin LJ, Ricaurte GA.  Brain serotonin neurotoxicity and primary pulmonary hypertension from fenfluramine and dexfenfluramine: a systematic review of the evidence . JAMA . 1997;;278:666-672.
Walsh AES, Oldman AD, Franklin M, Fairburn CO, Cowen PJ.  Dieting decreases plasma tryptophan and increases the prolactin response to d-fenfluramine in women, but not men . J Affect Disord . 1995;;33:89-97.
Barrio AS, Fernandez-Quintela A, Rocandio A, Latorre PM, Vazquez JA.  Effects of dexfenfluramine on weight loss and serum amino acids profile in obese subjects . Nutr Res . 1996;;16:1671-1678.
McCargar LJ, Clandinin MT, Fawcett DM, Johnson JL.  Short-term changes in energy intake and serum insulin, neutral amino acids, and urinary catecholamine excretion in women . Am J Clin Nutr . 1988;;47:932-941.
Schweiger U, Laessle R, Kittl S, Dickhaut B, Schweiger M, Pirke KM.  Macronutrient intake, plasma large amino acids and mood during weight-reducing diets . Neural Transm . 1986;;67:77-86.
Wolfe BE, Metzger ED, Stollar C.  The effects of dieting on plasma tryptophan concentration and food intake in healthy women . Physiol Behav . 1997;;61:537-541.
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