DL-phenylalanine is an ingredient in Sanesco’s Procite-D™ Targeted Nutritional Therapy. Procite-D is a catecholamine support formula, specifically targeted toward dopamine synthesis. The catecholamines (dopamine, norepinephrine, and epinephrine) are essential for healthy cognition, energy levels, and mood regulation. Depletion of these neurotransmitters can result in depression, apathy, fatigue, cognitive decline, or more serious conditions such as schizophrenia, ADD/ADHD, and Parkinson’s disease.[1]
The use of amino acid precursors and cofactors to increase neurotransmitter synthesis has promising clinical outcomes. Phenylalanine is a precursor to synthesis of dopamine, norepinephrine, and epinephrine.[2] Supplementing with DL-phenylalanine has been shown to boost dopamine levels and function, making it a key ingredient in Procite-D.
D-phenylalanine vs. L-phenylalanine
Phenylalanine is an essential amino acid, meaning humans cannot synthesize phenylalanine on their own.[3] Instead, phenylalanine must come from the food we eat or supplementation. Sanesco uses a combination of D-phenylalanine and L-phenylalanine, called DL-phenylalanine or DLPA. D- and L-phenylalanine are isomers, meaning they are mirror images of one another.
L-phenylalanine is found naturally, while D-phenylalanine must be synthesized in a laboratory.[4] These isomers, while nearly identical, produce different effects in the body. L-phenylalanine is converted to L-tyrosine in the liver. L-tyrosine can cross the blood-brain barrier, where it is then used for catecholamine synthesis.[5]
D-phenylalanine is an inhibitor of enzymes that inactivate enkephalins.[6] Enkephalins are naturally occurring morphine-like peptides that function to reduce pain. By blocking enzymes from degrading enkephalins, D-phenylalanine can reduce pain severity. Phenylalanine is the only amino acid other than methionine in which both isomers, L and D, are readily absorbed.[7] DLPA is 50% D-phenylalanine and 50% L-phenylalanine, making it clinically useful as a neurotransmitter precursor and as a potential pain mediator.
Phenylalanine & Dopamine
Dopamine is perhaps the most well-known neurotransmitter, at is plays a huge role in regulating good mood, sex drive, motivation, reward, cycles of addiction, and satiation. The pathway of catecholamine synthesis is as follows: phenylalanine to tyrosine to L-DOPA tp dopamine to norepinephrine to epinephrine.[8]
When the body is deprived of phenylalanine/tyrosine, such as in the genetic disorder phenylketonuria (PKU) or malnutrition, dopamine synthesis and transmission is greatly reduced.[9] Low dopamine can hinder synthesis of the other catecholamines, cause feelings of depression and lethargy, impede motor function and cognitive abilities, and lead to overeating and addictive behaviors.
Neurotransmitter Precursors
The idea behind Targeted Nutritional Therapy™ (TNT) formulas are to provide the body with the necessary ingredients to synthesize neurotransmitters on its own. There are several issues with using neurotransmitters themselves as supplements.
First, the neurotransmitters would have to make it through the digestive tract and into the brain. Not only is the digestive tract a harsh environment, the blood-brain barrier functions to only allow certain substances into and out of the brain. While some smaller molecules can readily cross this barrier and enter the central nervous system, larger molecules and neurotransmitters may not readily make this transit.[10] Additionally, overloading with neurotransmitters can lead to receptor insensitivity and tolerance.[11] It is estimated that 95% of ingested DLPA is converted to tyrosine.[12]
Supplementing with tyrosine, however, does not appear to produce the clinical outcomes of DLPA supplementation. One study found DLPA to improve mood in 78% of patients with depression, while tyrosine supplementation produced no clinical outcomes.[13] This discrepancy may be due to the poor solubility of tyrosine as a supplement.[14] These factors combined make DLPA supplementation a promising and safe option for neurotransmitter modulation.
Clinical Outcomes of Phenylalanine Supplementation
For people who do not suffer from PKU, DL-phenylalanine supplementation may be a healthy option for treatment of mood, cognitive, behavioral, and motor problems. Depression is one of the most commonly studied mental disorders and the target of many natural and pharmaceutical therapies. Pharmaceutical antidepressants are extremely helpful for many patients. However, these medications, if misused or overprescribed, can result in negative side effects.
Some of the most common side effects associated with SSRI (selective serotonin reuptake-inhibitor) use are decreased libido and apathy.[15] These symptoms may be due to suppression of dopamine, also associated with SSRI use.[16] Depression is commonly associated with inadequate function or synthesis of dopamine, serotonin, and norepinephrine.[17] Some studies have found that supplementing with DLPA produces the same clinical outcomes as the use of tricyclic antidepressants.[18] It has particular use in some patients with crying depression.
Some researchers have even hypothesized that overeating and obesity may be due to inadequate dietary phenylalanine intake.[19] Controlled studies in which patients were deprived of dietary phenylalanine and tyrosine showed decreased cognitive abilities compared to those with normal diets.[20] L-phenylalanine supplementation has even been shown to stimulate thyroid hormone T3 and T4 synthesis, improving overall wellbeing and neuroendocrine balance.[21]
Vitamin B6 is a necessary cofactor in the conversion of L-phenylalanine to L-tyrosine, and the conversion of L-DOPA to dopamine.[22] Therefore, it is typically recommended to take B6 with DLPA supplements. Sanesco’s Procite-D formula contains vitamin B6 (as pyridoxal-5-phosphate), DL-phenylalanine, Mucuna pruriens (standardized to 25% L-DOPA), along with Neuro Support Blend (NSB™) digestive enzymes for optimal absorption.
Learn more about dopamine’s important role in the brain and body.
[1] Larson, M. J., Clayson, P. E., Primosch, M., Leyton, M., & Steffensen, S. C. (2015). The effects of acute dopamine precursor depletion on the cognitive control functions of performance monitoring and conflict processing: an event-related potential (ERP) study. PLoS one, 10(10), e0140770.
[2] Kuhar, M. J., Couceyro, P. R., & Lambert, P. D. (n.d.). Biosynthesis of Catecholamines. In Basic Neurochemistry: Molecular, Cellular and Medical Aspects. (6th ed.).
[3] http://www.anaturalhealingcenter.com/documents/Thorne/monos/DLPA%20mono.pdf
[4] Tomen, D. (2016, July 08). Phenylalanine. Retrieved September 21, 2017, from http://nootropicsexpert.com/phenylalanine/
[5] Tomen, Ibid.
[6] Ehrenpreis, S., & Ehrenpreis, E. (2006). U.S. Patent Application No. 11/479,216.
[7] http://www.anaturalhealingcenter.com/documents/Thorne/monos/DLPA%20mono.pdf
[8] Kuhar, op. cit.
[9] Larson, op. cit.
[10] Tomen, op. cit.
[11] Tomen, Ibid.
[12] http://www.anaturalhealingcenter.com/documents/Thorne/monos/DLPA%20mono.pdf
[13] http://www.anaturalhealingcenter.com/documents/Thorne/monos/DLPA%20mono.pdf
[14] Roberts, S. A., Ball, R. O., Filler, R. M., Moore, A. M., & Pencharz, P. B. (1998). Phenylalanine and tyrosine metabolism in neonates receiving parenteral nutrition differing in pattern of amino acids. Pediatric research, 44(6), 907-914.
[15] Hirschfeld, R. (2000). History and evolution of the monoamine hypothesis of depression. The Journal of clinical psychiatry.
[16] Hirschfeld, Ibid.
[17] Meyers, S. (2000). Use of neurotransmitter precursors for treatment of depression. Alternative Medicine Review, 5(1), 64-71.
[18] Meyers, Ibid.
[19] Acton, Q. A. (Ed.). (n.d.). Catecholamines—Advances in Research and Application (2012 ed.). ScholarlyEditions.
[20] Larson, op. cit.
[21] Tomen, op. cit.
[22] Tomen, op. cit.
Clinical Contributor
Sophie Thompson
Clinical Support Specialist at Sanesco International, Inc.
Sophie recently obtained her degree in Biology from UNCA in Asheville. Born and raised in Asheville, her hobbies include painting, writing and spending quality time with her dog and her family.
