Dietary Amino Acids and Proteins Influence Serotonin Synthesis in Brain Neurons
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1 Dietary Amino Acids and Proteins Influence Serotonin Synthesis in Brain Neurons John D. Fernstrom University of Pi>sburgh School of Medicine
2 Neuronal Serotonin Synthesis & Metabolism
3 Source of Neuronal Tryptophan FOOD
4 PLASMA BRAIN Carbs Protein Plasma TRP (nmol/ml) Carbs Fasting Protein Fasting Brain TRP (nmol/gram) Time (hours) Time (hours)
5 Source of Neuronal Tryptophan FOOD * * Serum TRP/ΣLNAA
6 Serotonin synthesis in brain neurons is influenced by normal changes in brain TRP levels Brain TRP levels are influenced by changes in blood levels of TRP and the other LNAA: BBB compe++on is important! Carbohydrates raise brain TRP (and 5HT) while protein does not: compe++on explains dichotomy.
7 The bovine protein α-lactalbumin increases the plasma ratio of tryptophan to the other large neutral amino acids, and in vulnerable subjects raises brain serotonin activity, reduces cortisol concentration, and improves mood under stress 1-3 C Rob Markus, Berend Olivier, Geert EM Panhuysen, Jan Van der Gugten, Martine S Alles, Adriaan Tuiten, Herman GM Westenberg, Durk Fekkes, Hans F Koppeschaar, and Edward EHF de Haan Am J Clin Nutr 2000; 71:
8 Source: Feurte S et al., Nutr Neurosci 4: , 2001
9 Extracellular 5HT levels from hypothalamus in rats ingesting either casein (white bars) or lactalbumin (black bars) diets. * P<0.05 or *** P<0.001 vs day 0; ++ P<0.01 vs casein diet. From: Orosco M et al, Behav Brain Res 148: 1-10, 2004.
10 In Vivo Microdialysis in Rat Brain From: Davarsh AS et al. Expert Opin Drug Discov 6(2): , 2011
11 Meal ingestion, amino acids and brain neurotransmitters: Effects of dietary protein source on serotonin and catecholamine synthesis rates SuJean Choi, Briana DiSilvio, Madelyn H. Fernstrom, John D. Fernstrom Physiology & Behavior 98: , Give rats a meal containing 17% protein at dark onset. 2. Meal contains no protein (carbs + 5% fat only) or the same formulation with one of 5 proteins (Lactalbumin, Casein, Gluten, Soy Protein, Zein). 3. Two hr after meal presentation, inject a drug to allow 5HT synthesis to be measured. 4. Sacrifice rats 30 minutes later.
12 Effects of Single Meals Containing Different Proteins: Rat Study LACTALBUMIN Brain TRP (nmol/gram) Carbohydrates Soy Protein CASEIN Gluten Zein Time (minutes) Source: Choi S et al., Physiol Behav 98: , 2009
13 Effects of Single Meals Containing Different Proteins: Rat Study Cortex TRP (nmol/gram) Brain TRP (nmol/gram) r = C F LACTALBUMIN Carbohydrates Soy Protein CASEIN Gluten Zein L Fasting Soy Protein Lactalbumin Zein Gluten Carbohydrate Casein Time (minutes) Serum TRP Ratio Source: Choi S et al., Physiol Behav 98: , 2009
14 Effects of Single Meals Containing Different Proteins: Rat Study Hypothalamic 5HTP (pmol/gram/min) r = 0.87 C F L Fasting Soy Protein Lactalbumin Zein Gluten Carbohydrate Casein Cortical TRP (nmol/gram) Source: Choi S et al., Physiol Behav 98: , 2009
15 Effects of Chronic Diets Containing Different Proteins: Rat Study Source: Choi S et al., Neurochem Res 36: , 2011
16 Effects of Chronic Diets Containing Different Proteins: Rat Study Soy Gluten Lactalbumin Casein Zein Source: Choi S et al., Neurochem Res 36: , 2011
17 Dietary Protein IngesIon has the same plasma effects in humans & rats 0.3 Rats Humans 0.20 Serum TRP Ratio Plasma TRP Ratio Lactalbumin Zein 0.05 Gluten Carbs Time (minutes) Time (minutes) Choi S et al., Physiol Behav 98: , 2009 Fernstrom JD et al., Clin Nutr 32: , 2013
18 Speculation Trends in Pharmacological Sciences 29(9): , 2008.
19 Acute Tryptophan DepleIon: Depression Depressed Px (n=18) in remission on meds. ATD + 9AM. 1, 2, 3, 4, 6, 8 Hr. Balanced, cross-over design. 2-7 days between tests. From: Delgado PL et al., Serotonin function & the mechanism of antidepressant action. Reversal of antidepressant-induced remission by rapid depletion of plasma tryptophan. Arch. Gen. Psychiat. 47: , 1990.
20 Acute Tryptophan DepleIon: Biochemistry Healthy subjects (n=6) admitted to CRC. Low monoamine & low TRP diet from day 1. Lumbar catheter placed on day 8. ATD drink ingested on day 9 and samples drawn. From: Williams WA et al., Effects of acute tryptophan depletion on plasma & cerebrospinal fluid tryptophan & 5-HIAA in normal volunteers. J. Neurochem. 72: , 1999.
Physiology & Behavior
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