This study was supported by Davisco Foods International. Shenzhen, April 08. Paolo Mainardi Department of Neuroscience University of Genova

Transcription

1 This study was supported by Davisco Foods International Shenzhen, April 08 Paolo Mainardi Department of Neuroscience University of Genova Italy

2 in intestine in blood in brain - Serotoninergic neurons in all brain areas - Ubiquity of serotonin is phylogenetic - Onthogenically ancient serotoninergic neurons after 5 weeks of pregnancy they increase up until the 10th week serotonin plays an important role in the development of other brain amines brain serotonin levels increase up until the age of 2, then they gradually start decreasing from the age of 5 onwards up to 50 % in adults Shenzhen, April 08 Paolo Mainardi

3 3 The role of 5-HT in CNS: 1) Sleep 2) Appetite 3) Memory 4) Learning 5) Thermo regulation 6) Food 7) Sexual behavior 8) Cardio vascular functions 9) Muscle contration 10)Endocrine regulation Physiologic and behaviour aspect: Food intake, Sleep, Aggressivity Shenzhen, April 08 Pathologies implicated: 1. Depression 2. Schizophrenia 3. Anorexia 4. Bulimia 5. Compulsive and obsessive disorders 6. Migraine 7. Phobic disorders 8. Epilepsy 9. Autism 10. ALS 11. MS 12. alzheimer 13. hypertension 14. Down syndrom Paolo Mainardi

4 4 Tryptophan is what is known as an essential amino acid. It must be ingested through food or supplements, the body cannot make it. It s the only precursor to serotonin, About 10% of tryptophan reach the brain where it s converted to serotonin. Shenzhen, April 08 Paolo Mainardi

5 5 By the late of 80 s about 14 million people were using tryptophan to: Improve mood Reduce irritability Reduce premenstrual symptoms Lessen chronic pain Lose weight Treat alcholism Ameliorate sleep In 1989 FDA stopped it because an eosinophilia myalgia syndrome (EMS) was associated with the use of Trp. Shenzhen, April 08 Paolo Mainardi

6 6 However Trp administration carry out controversial results in severe diseases as depression and epilepsy Shenzhen, April 08 Paolo Mainardi

7 7 LNAAs: tyr, val, ile, leu, phe and trp R= trp/σlnaas

8 8 digestive process of proteins begins in the mouth. limited or complete proteolysis resulting in basic or neutral free-amino acids (40%) or dioctapeptides the brush border peptidases continue to degrade oligopeptide to di-tripeptides and neutral free-amino acids Some peptides are uptaken by the enterocytes whose cytosolic peptidases complete the hydrolysis Proteins rich in trp and poor in the other LNAAs is the best way to increase trp plasma level.

9 9 Alpha-lactalbumin (ALAC) is a whey protein naturally occurring in human milk (2 g/l) it have an hight Trp/LNAAs ratio it s able to increase the Trp-LNAAs ratio of up to 48% compared to casein (Markus CR) fully adsorbed by gastro-intestinal system as short peptides

10 10 Casein protein form curds in the stomach, then rapid hydrolysis and slower gastric emptying Whey proteins do not coagulate under acidic conditions They are considered to be fast proteins They reach the jejunum rapidly after ingestion Kinetic aspect: A slow transit increases hydrolysis, then more free amino acids will be arriving on intestinal membrane

11 11 Markus, 20 g ALAC: 48% increasing in Trp/LNAAs Baulens, 12 g ALAC: 16% increasing in Trp/LNAAs Feurte, S et al. (Nutr Neurosci. 2001;4(5):413-8) found after 5 days of chronically administration of ALAC (as 17% of diet) an 40% increase in plasmatic Trp/LNAA ratio

12 12 Cortisol Trp Depressed pts have high levels of cortisol, then increasing free plasmatic trp, carry out a decreasing of the conversion from trp to brain serotonin. In fact, low doses of trp are most effective than higher doses.

13 R= trp/σlnaas The same trp dose that increases R in autistic pts don t increase it in controls ATD worsened autistic behaviors but it s ineffective in controls ATD worsened aggressively in aggressive subject not in controls, and the more aggressive subject don t worsened ATD decreasing R more in Parkinson s than in controls Trp adiministration can: to be ineffective on R increase it in right way increase it so much to start liver metabolism Could EMS to be linked to individual response to Trp?

14 14 Our own results about the concentration of tryptophan and LNAAs in the blood of epileptic patients in respect to controls (Lunardi G, Mainardi P, Albano C in Allegri Flippini G et al eds, Tryptophan and Epilepsy in Recent advances in tryptophan research Plenum Press, New York). Applying these equations to our data we have found a significant 30% reduction of tryptophan brain uptake rate in epileptic patients in respect to controls.

15 15 R was found low also in: Depressed pts ALS pts MS pts The reliability of clinical trials on Trp as antidepressant has been questioned. Meyers S (2000). "Use of neurotransmitter precursors for treatment of depression". Alternative medicine review : a journal of clinical therapeutic 5 (1): Shaw K, Turner J, Del Mar C (2002). "Tryptophan and 5-hydroxytryptophan for depression". Cochrane database of systematic reviews (Online) (1): CD Clinical trials on 5-Hydroxytryptophan in epilepsy and depression are regarded inconclusive and lacking Turner EH, Loftis JM, Blackwell AD (2006). "Serotonin a la carte: supplementation with the serotonin precursor 5-hydroxytryptophan". Pharmacol Ther 109 (3):

16 16 Serplus (Giofarma Srl) is a food supplement containing 0.75 g ultra pure ALAC / tablet

17 17 P.Mainardi

18 18 Pathologies implicated: 1. Depression 2. Schizophrenia 3. Anorexia 4. Bulimia 5. Compulsive and obsessive disorders 6. Migraine 7. Phobic disorders 8. Epilepsy 9. Autism 10. ALS 11. MS 12. alzheimer 13. Parkinson 14. hypertension