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L-Tryptophan Effects on Weight Reduction, Cravings and Diabetes in GLOBESITY Bootcamp for the Obese

Effects of L-Tryptophan on Weight Reduction

Authors: Marcus Free MD, Rouzbeh Motiei-Langroudi MD, Waqar Ahmad PhD, Kelly Daly RDN, and Don Juravin (Don Karl Juravin).

Abstract (Research Summary)

  • L-Tryptophan is a precursor for the neurotransmitter serotonin (aka 5-hydroxytryptamine or 5HT) (Attenburrow 1999, Noach 1994).
  • Serotonin is an important regulator for appetite and food constituents. High serotonin levels reduce appetite and cause higher protein and lower carbohydrate intake (Aguilera 2000, Noach 1994).
  • Carbohydrate consumption increases serotonin release through increasing plasma tryptophan, which provides a feedback mechanism that regulates carbohydrate and protein intake (Wurtman 1995).
  • Plasma tryptophan to large neutral amino acid ratio is reduced by 18-25% in obese individuals (Ashley 1985).
  • In obese individuals, plasma tryptophan to large neutral amino acids ratio fails to rise after carbohydrate consumption, resulting in reduced satiety (Caballero 1988).
  • Endogenous tryptophan suppresses carbohydrate-craving (Gendall 2000, Wurtman 1988b, Wurtman 1986).

L-Tryptophan Effects on Weight Reduction

L-Tryptophan, acting via serotonergic neurons in hypothalamic feeding center, alters satiety and food preference, decreases carbohydrate cravings, carbohydrate intake, and daily energy intake, and promotes weight loss.

  • L-Tryptophan supplementation decreases carbohydrate intake, finally resulting in weight loss (Caballero 1988).
  • Tryptophan depletion increases carbohydrate calorie intake (Pagoto 2008).
  • In obese individuals, plasma ratio of tryptophan to large neutral amino acids fails to rise after carbohydrate consumption, finally resulting in reduced satiety (Caballero 1988).
  • Dieting lowers the ratio of tryptophan to large neutral amino acids, resulting in decreased entry of tryptophan to the brain (Attenburrow 1999).
  • Decreased tryptophan availability to the brain decreases serotonin synthesis, resulting in decreased satiety and binge eating (Attenburrow 1999).
  • Direct or indirect activation of serotonin receptors halts eating episode and maintains satiety (Blundell 1984).

L-Tryptophan Effects on Cravings

L-Tryptophan, either endogenous or exogenous, decreases craving. Tryptophan levels are reduced in obese individuals (by 18-25%) and dietary tryptophan administration suppresses carbohydrate craving (by 40%).

  • Plasma tryptophan to large neutral amino acids ratio is reduced by 18-25% in obese individuals, decreasing brain serotonin neurotransmission, and finally resulting in cravings for carbohydrates (Ashley 1985).
  • Endogenous tryptophan decreases carbohydrate cravings and binge eating (Gendall 2000).
  • Endogenous tryptophan suppresses carbohydrate-craving (Wurtman 1988b, Wurtman 1986).
  • D-Fenfluramine (a drug that enhances tryptophan and serotonin-mediated transmission in the brain) suppresses carbohydrate-craving by 40% (Wurtman 1988a, Wurtman 1988b, Wurtman 1986).

L-Tryptophan Effects on Diabetes

L-Tryptophan increases insulin and incretins secretion. The effect results in better glycemic control in diabetics.

  • Free and protein-bound plasma tryptophan is decreased in type 1 diabetic children (by 67% and 23%, respectively) (Herrera 2003).
  • Tryptophan activates a receptor in the pancreas and the gastrointestinal tract, resulting in an increase in the secretion of insulin and incretins (Lin 2016).
  • Tryptophan deficiency causes insulin resistance and diabetes (Oxenkrug 2013).
  • Tryptophan-derived hormone melatonin influences the development of diabetic complications by neutralizing the production of reactive oxygen species and protecting pancreatic beta cells (Zephy 2015).
  • Tryptophan-derived hormone melatonin increases insulin secretion and prevents diabetes (Zephy 2015).

Benefits, Side Effects, Drug Interactions

Benefits

  • L-Tryptophan can be used in the treatment of sleep disorders (insomnia), depression (1 to 3 g per day), obsessive-compulsive disorder, and mood swings of premenstrual syndrome (PMS) in women.

Safety

L-Tryptophan does not have safety regulations by FDA.

Side effects

  • Serotonin syndrome: The most important side effect of L-Tryptophan, especially seen when co-administered with serotonergic drugs, is the serotonin syndrome. It causes delirium (change in mental state), severe muscle spasms, increased body temperature, and coma.
  • Blurred vision: L-Tryptophan may cause blurring in vision.
  • Dizziness and drowsiness: L-Tryptophan may cause a sense of drowsiness, dizziness, lightheadedness, and vertigo.
  • Nausea: L-Tryptophan may cause stomach upset and nausea.
  • Palpitations: L-Tryptophan may cause strong pounding heart-beats.
  • Tremor: L-Tryptophan may cause tremor in limbs.
  • Loss of muscle coordination and muscle stiffness
  • Sweating
  • Fatigue
  • Hives

Drug interactions

  • Antidepressants: Do not use L-Tryptophan if you take selective serotonin reuptake inhibitor (SSRI, including fluoxetine, paroxetine, citalopram, sertraline, etc.) or monoamine oxidase inhibitor (MAOI, including selegiline, phenelzine, tranylcypromine, etc.) antidepressants.

Caution

  • Pregnancy: It is recommended to use L-Tryptophan supplements with caution in pregnant women.
  • Cirrhosis: Cirrhotic patients (a condition with liver scarring and failure) should not take L-Tryptophan.

References

  1. Aguilera, A., Selgas, R., Codoceo, R., et al. (2000). Uremic anorexia: a consequence of persistently high brain serotonin levels? The tryptophan/serotonin disorder hypothesis. Journal of the International Society for Peritoneal Dialysis [online], 20 (6), pp. 810–6. Available from: http://pdiconnect.com/content/20/6/810 [Accessed 21.07.2016].
  2. Ashley, D., Fleury, M., Golay, A., et al. (1985). Evidence for diminished brain 5-hydroxytryptamine biosynthesis in obese diabetic and non-diabetic humans. The American Journal of Clinical Nutrition [online], 42 (6), pp. 1240–5. Available from: http://ajcn.nutrition.org/content/42/6/1240 [Accessed 21.07.2016].
  3. Attenburrow, M., Williams, C., Odontiadis, J., et al. (1999). The effect of a nutritional source of tryptophan on dieting-induced changes in brain 5-HT function. Psychological Medicine [online], 33 (8), pp. 1381–6. Available from: http://europepmc.org/abstract/med/14672246 [Accessed 22.07.2016].
  4. Blundell, J. (1984). Serotonin and appetite. Neuropharmacology [online], 23 (12, Part 2), pp. 1537–51. Available from: http://www.sciencedirect.com/science/article/pii/0028390884900984 [Accessed 22.07.2016].
  5. Caballero, B., Finer, N., Wurtman, R. (1988). Plasma amino acids and insulin levels in obesity: response to carbohydrate intake and tryptophan supplements. Metabolism: Clinical and Experimental [online], 37 (7), pp. 672–6. Available from: http://wurtmanlab.mit.edu/static/pdf/758.pdf [Accessed 22.07.2016].
  6. Gendall, K., Joyce, P. (2000). Meal-induced changes in tryptophan:LNAA ratio: effects on craving and binge eating. Eating Behavior [online], 1 (1), pp. 53-62. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15001067 [Accessed 22.07.2016].
  7. Herrera, R., Manjarrez, G., Nishimura, E., et al. (2003). Serotonin-related tryptophan in children with insulin-dependent diabetes. Pediatric Neurology [online], 28 (1), pp. 20–3. Available from: http://www.sciencedirect.com/science/article/pii/S0887899402004629 [Accessed 23.07.2016].
  8. Lin, H., Efanov, A., Fang, X., et al. (2016). GPR142 Controls Tryptophan-Induced Insulin and Incretin Hormone Secretion to Improve Glucose Metabolism. PLoS one [online], 11 (6), pp. 0157298. Available from: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0157298 [Accessed 23.07.2016].
  9. Noach, E. (1994). Appetite regulation by serotoninergic mechanisms and effects of d-fenfluramine. Netherland Journal of Medicine [online], 45 (3), pp. 123-33. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7969665 [Accessed 22.07.2016].
  10. Oxenkrug, G. (2013). Insulin resistance and dysregulation of tryptophan-kynurenine and kynurenine-nicotinamide adenine dinucleotide metabolic pathways. Molecular Neurobiology [online], 48 (2), pp. 294–301. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779535/pdf/nihms500086.pdf [Accessed 23.07.2016].
  11. Pagoto, S., Spring, B., McChargue, D., et al. (2009). Acute tryptophan depletion and sweet food consumption by overweight adults. Eating Behaviors [online], 10 (1), pp. 36–41. Available from: www.ncbi.nlm.nih.gov/pmc/articles/PMC2663793/ [Accessed 22.07.2016].
  12. Wurtman, R., Wurtman, J. (1986). Carbohydrate craving, obesity and brain serotonin. Appetite [online], 7, pp. 99-103. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3527063 [Accessed 22.07.2016].
  13. Wurtman, J. (1988a). Carbohydrate craving, mood changes, and obesity. Journal of Clinical Psychiatry [online], 49, pp. 37-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3045110 [Accessed 22.07.2016].
  14. Wurtman, R., Wurtman, J. (1988b). Do carbohydrates affect food intake via neurotransmitter activity? Appetite [online], 11 (Suppl 1), pp. 42-7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/2903717 [Accessed 22.07.2016].
  15. Wurtman, R., Wurtman, J. (1995). Brain serotonin, carbohydrate-craving, obesity and depression. Obesity Research [online], 3 (Suppl 4), pp. 477-80. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8697046 [Accessed 22.07.2016].
  16. Zephy, D., Ahmad, J. (2015). Type 2 diabetes mellitus: Role of melatonin and oxidative stress. Diabetes and Metabolic Syndrome [online], 9 (2), pp. 127–31. Available from: http://www.sciencedirect.com/science/article/pii/S1871402114000952 [Accessed 23.07.2016].

Footnote

This research was sponsored by GLOBESITY FOUNDATION (nonprofit organization) and managed by Don Juravin. GLOBESITY Bootcamp for the obese is part of GLOBESITY FOUNDATION which helps obese with 70 to 400 lbs excess fat to adopt a healthy lifestyle and thereby achieve a healthy weight.

Tags: l-tryptophan, weight reduction, GLOBESITY FOUNDATION, weight loss, cravings, diabetes, healthy weight