DLPA – An Overview
DLPA (DL-phenylalinine) is a more bioavailable form of the essential amino acid phenylalanine.
DLPA is commonly taken as a nootropic supplement for:
- Mental Sharpness
- Pain Relief
There are plenty of reports that DLPA can improve cognition and general feelings of well-being, and there is some clinical evidence that backs up these claims.
DLPA is made from combining D-phenylalanine and L-phenylalanine. 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.
DLPA, provides the best of both worlds as its a combination of both of these isomers.
As Phenylalanine is a precursor for tyrosine, dopamine, norepinephrine, epinephrine, and the skin pigment melanin, DLPA can have various nootropic and health effects.
In this article, we will provide a detailed overview of DLPA, explain how it is made, how it works, and how it goes about affecting depression, anxiety, pain, obesity, alcohol withdrawal, and so much more.
We will also explain the daily recommended dosage of DLPA, as well as some side effects that you should look out for.
What Makes DL-Phenylalanine An Essential Amino Acid
L-Phenylalanine is a part of a special class of molecules called essential amino acids.
While our body can produce many things (including other amino acids), it cannot produce L-phenylalanine or any other essential amino acids.
Thus, DLPA, and other essential aromatic amino acids, must be obtained through dietary sources.
The Importance of Bioavailable Amino Acids
“DLPA” (DL-phenylalanine) is a more bioavailable form of phenylalanine.
Higher bioavailability means that this compound form will be absorbed more readily by the body compared to less bioavailable forms of the same compound.
How is DLPA made?
There are two different forms of phenylalanine: D-phenylalanine and L-phenylalanine.
These two forms exist as isomers. Isomers are two different forms of the same compound that occur as mirror images.
L-phenylalanine can be obtained from natural sources; however, D-phenylalanine must be artificially synthesized in a laboratory.
DL-phenylalanine (DLPA) is thus made by combing the 2 forms in a laboratory making this synthesized phenylalanine supplement oozing with mental health benefits!2Tomislav Jukić , Bojan Rojc, Darja Boben-Bardutzky, Mateja Hafner, Alojz Ihan, The use of a food supplementation with D-phenylalanine, L-glutamine and L-5-hydroxytriptophan in the alleviation of alcohol withdrawal symptoms Coll Antropol. 20113Julia J Rucklidge,Jeanette Johnstone &Bonnie J Kaplan, Nutrient supplementation approaches in the treatment of ADHD Expert Review of Neurotherapeutics. 20094R. H. Cormane, A. H. Siddiqui, W. Westerhof & R. B. H. Schutgens Phenylalanine and UVA light for the treatment of vitiligo, Archives of Dermatological Research. 1985
Benefits Of Supplementing With The Essential Amino Acid DLPA
Much evidence points to DLPA’s ability to improve mental health by boosting cognition and general feelings of well-being.
In recent years many people have found it useful specifically for the treatment of attention deficit disorder.5Julia J Rucklidge,Jeanette Johnstone &Bonnie J Kaplan Nutrient supplementation approaches in the treatment of ADHD Expert Review of Neurotherapeutics. 2009
However, the range of benefits that DLPA presents extends beyond just mental health.
Scientific evidence suggests that phenylalanine supplementation improves our immune system 6Tomislav Jukić , Bojan Rojc, Darja Boben-Bardutzky, Mateja Hafner, Alojz Ihan, The use of a food supplementation with D-phenylalanine, L-glutamine and L-5-hydroxytriptophan in the alleviation of alcohol withdrawal symptoms, Coll Antropol. 2011
as well as skin issues like vitiligo.7R. H. Cormane, A. H. Siddiqui, W. Westerhof & R. B. H. Schutgens Phenylalanine and UVA light for the treatment of vitiligo, Archives of Dermatological Research. 1985
Below are some examples of how the research suggests DLPA can be beneficial!
DLPA Benefits for ADHD
There are some initial findings that indicate DLPA can improve attention and possibly treat symptoms of attention deficit disorder, or ADHD.8R. H. Cormane, A. H. Siddiqui, W. Westerhof & R. B. H. Schutgens Phenylalanine and UVA light for the treatment of vitiligo, Archives of Dermatological Research. 1985
It is one of the plasma amino acids involved in the production of neurotransmitters.
DLPA is specifically a building block for the neurotransmitter dopamine.
Many researchers believe that low levels of dopamine may cause ADHD.
Since L-phenylalanine is a precursor of dopamine, a phenylalanine deficiency could develop symptoms of ADHD.
Therefore, nutrient supplementation approaches with D-phenylalanine may alleviate ADHD symptoms by enabling a higher rate of dopamine production.
A small double-blind study showed an improvement of ADHD symptoms after a few weeks of supplementing with DLPA. However, these results have not been successfully replicated.9Wood DR, Reimherr FW, Wender PH.Treatment of attention deficit disorder with DL-phenylalanine Psychiatry Res. 1985 Sep
Still, some nootropics enthusiasts swear by DLPA for attention.
Their reports are anecdotal but suggest that further research on this subject is needed.
Some users also claim that DLPA can prolong the effects and ease the crash associated with traditional ADHD meds like Ritalin and Adderall.
This would make sense, considering DLPA can help the brain produce more dopamine as Adderall triggers its release.
The future looks bright for ADHD treatment
Due to the lack of concrete clinical data, it is difficult to either establish the health benefit or the risk of using DLPA.
Still, many nootropics enthusiasts stand by DLPA. While their reported benefits are anecdotal, they are worthy of consideration.
There are even reports of DLPA being able to prolong the effects of ADHD medications and make the crash associated with them a little easier to handle.
Considering that DLPA can help the brain produce more dopamine as Adderall triggers its release, this would make sense.
DLPA Benefits for Depression
Over 1.5 million people are receiving treatment for it currently, and about 30 million people are at risk of experiencing the symptoms at least once in their lifetime.11Billie J. SahleyPh.D, DLPA for Chronic Pain and Depression, Pain and Stress Publication. 2001
Since DLPA is known to increase the amount of dopamine flowing throughout the brain, this makes it a potential potent mood enhancer.
Evidence for DLPA benefits in depression
In fact, some research suggests that DLPA can act as a potent antidepressant.
Several double-blind, placebo-controlled trials have indicated the antidepressant effect of DLPA.
Researchers believe that this could be due to the well-known effect of DLPA in increasing the amount of dopamine in our bodies.
In fact, in a comparison of DL-phenylalanine versus imipramine (a drug used to treat depression), DLPA was found to be as effective as imipramine for treating depression.
However, none of these studies used particularly large sample sizes, so these results may not be that robust. Hopefully there will be larger-scale studies in the future that can confirm these results.13Beckmann H, et al DL-phenylalanine versus imipramine: a double-blind controlled study Arch Psychiatr Nervenkr (1970)14H. Spatz, et al. Effects of D phenylalanine on clinical picture and phenethylaminuria in depression Biological Psychiatry 197515Cordonnier L1, Sanchez M, Roques BP, Noble F. Facilitation of enkephalins-induced delta-opioid behavioral responses by chronic amisulpride treatment. Neuroscience. 2005 16Fischer E, Heller B, Nachon M, Spatz H.. Therapy of depression by phenylalanine. Preliminary note Arzneimittelforschung. 1975
On the other hand, an animal study suggests that phenylalanine supplementation does NOT actually increase dopamine levels, as many have theorized.
If this is true, then there may not be a mechanism for DLPA to raise mood, and the previous studies only showed a placebo effect. Again, more study is needed on DLPA for mood disorders.17Fernstrom MH1, Baker RL, Fernstrom JD.. In vivo tyrosine hydroxylation rate in retina: effects of phenylalanine and tyrosine administration in rats pretreated with p-chlorophenylalanine. Brain Res. 1989
DLPA Benefits For Pain Relief
DLPA may significantly reduce the feeling of acute pain even in chronic pain patients.
Some users report that it can be used as a substitute for opiates (which come with significant risks.)
Researchers suspect it works by activating the ‘endogenous analgesia system’ (EAS). The EAS is your body’s internal painkiller system. DLPA produces an elevation in brain enkephalins.
Enkephalins are compounds in the brain that are closely related to fight-or-flight and pain responses.
They bond to mu-opioid pain receptors.
Clinical data supporting DPLA’s role in pain relief
Multiple clinical trials show that DLPA can significantly decrease pain with few adverse side-effects. It is significantly more effective than placebo.18Nurmikko T, Pertovaara A, Pöntinen PJ. Attenuation of tourniquet-induced pain in man by D-phenylalanine, a putative inhibitor of enkephalin degradation Acupunct Electrother Res. 1987 19Kitade T, Odahara Y, Shinohara S, et al Studies on the enhanced effect of acupuncture analgesia and acupuncture anesthesia by D-phenylalanine (2nd report)–schedule of administration and clinical effects in low back pain and tooth extraction. Acupunct Electrother Res. 1990 20S.Ehrenpreis R.C.Balagot S.Myles C.Advocate J.E.Comaty. FURTHER STUDIES ON THE ANALGESIC ACTIVITY OF D-PHENYLALANINE (DPA) IN MICE AND HUMANS International Narcotic Research, 1979
DLPA May Make Opiate Use Safer
Interestingly, the effects of DLPA are reversible by naloxone, which is an opiate overdose prevention drug.
This seems to indicate that DLPA is working on the same biological pathways as opiates, but with far less danger.21Ehrenpreis S.. Analgesic properties of enkephalinase inhibitors: animal and human studies Prog Clin Biol Res. 1985
DLPA may amplify the analgesic effects of opiate therapy while enabling dosage reductions that minimize opiate side effects.
In other words, it makes drugs work better while helping to lower the number of drugs needed. Thus, DLPA can lower the odds of side effects.
This could be extremely beneficial to people who must use opiates to manage chronic pain. It may also complement acupuncture.22Russell AL, McCarty MF. DL-phenylalanine markedly potentiates opiate analgesia – an example of nutrient/pharmaceutical up-regulation of the endogenous analgesia system. Med Hypotheses. 2000
DLPA could help with opioid withdrawal
DLPA may also alleviate symptoms of opioid withdrawal.23Grossman A, Clement-Jones V. Opiate receptors: enkephalins and endorphins. Clin Endocrinol Metab. 1983 Mar 24Ehrenpreis S.. D-phenylalanine and other enkephalinase inhibitors as pharmacological agents: implications for some important therapeutic application Acupunct Electrother Res. 1982
DLPA Benefits For Parkinson’s disease
Parkinson’s disease is another disease caused by disruption to dopamine production in our bodies, leading to reduced dopamine production.
Since L-phenylalanine is a precursor of dopamine and can raise its levels in the body, people with Parkinson’s disease might also feel better after treatment with L-phenylalanine.
There is some clinical evidence that DLPA increased people’s motor function with Parkinson’s disease.25B Heller, E Fischer, R Martin, Therapeutic action of D-phenylalanine in Parkinson’s disease, Arzneimittelforschung. 1976
Thus, phenylalanine supplements could be a potential area for investigation in the future for the development of therapies for people with Parkinson’s disease.
Not beneficial for children with PKU
Research suggests that at higher than normal phenylalanine levels, DLPA can even lead to ADHD symptoms.
A maternal phenylketonuria collaborative study found that children with PKU who received dietary treatment of D-phenylalanine either prenatally or postnatally, at a level higher than normal, were at risk of development of symptoms of ADHD.26Kevin M. Antshel & Susan E. Waisbren , Developmental Timing of Exposure to Elevated Levels of Phenylalanine Is Associated with ADHD Symptom Expression, Journal of Abnormal Child Psychology. 2003
Thus, perhaps like with everything else, too much D-phenylalanine can also be a bad thing for children with different health conditions.
This also suggests that inherited metabolic aberration can worsen through dietary influences.
DPLA Benefits for Alcohol withdrawal
This might be a little unlikely, but a study has shown that treatment with food supplements using phenylalanine and other amino acid precursors can help in relieving alcohol withdrawal symptoms.27Tomislav Juki, Bojan Rojc, Darja Boben-Bardutzky, Mateja Hafner and Alojz Ihan, The Use of a Food Supplementation with D-Phenylalanine, L-Glutamine and L-5-Hydroxytriptophan in the Alleviation of Alcohol Withdrawal Symptoms, Coll. Antropol. 2011
DLPA Benefits for Anxiety
Some research suggests that DLPA can also be beneficial for anxiety. Knowing how pressing this condition is for many people these days it’s important to stratify the scientific evidence based on sex.
Evidence in males
There is some evidence that indicates that L-phenylalanine may be useful for individuals with anxiety as well. In a controlled, double-blind trial with 12 male volunteers, it was observed that phenylalanine boosted mood and memory.28Eugenio H. Grevet, Marcos R. Tietzmann, Flávio M. Shansis, Behavioural effects of acute phenylalanine and tyrosine depletion in healthy male volunteers, Journal of Psychopharmacology. 2002
The subjects that were a part of the group that didn’t receive phenylalanine showed reduced word recalling ability and a decrease in alertness. 29Eugenio H. Grevet, Marcos R. Tietzmann, Flávio M. Shansis, Behavioural effects of acute phenylalanine and tyrosine depletion in healthy male volunteers, Journal of Psychopharmacology. 2002
On the other hand, subjects that did receive phenylalanine showed better memory and had increased scores of alertness.30Eugenio H. Grevet, Marcos R. Tietzmann, Flávio M. Shansis, Behavioural effects of acute phenylalanine and tyrosine depletion in healthy male volunteers, Journal of Psychopharmacology. 2002
Evidence in females
A separate study found that reducing the amount of tryptophan (through phenylalanine deficient diet) in females leads to a reduction in their energy and mood while simultaneously making them more irritable in response to aggressive psychological stress.31M.LeytonPh.D.S.N.YoungPh.D.cR.O.PihlPh.D.bS.Etezadi C.LauzeR.N.P.BlierM.D., Ph.D.G.B.BakerPh.D.dC.Benkelf tM.D, Effects on Mood of Acute Phenylalanine/Tyrosine Depletion in Healthy Women, Neuropsychopharmacology. 2000
Healthy volunteers were given three different forms of diets: one containing phenylalanine as per dietary reference intakes, another deficient in tryptophan, and the third one without phenylalanine and tyrosine.
The researchers found that after over 5 hours, women who received the diet that lacked phenylalanine, tyrosine, or L-tryptophan had lower energy and were in a worse mood.32M.LeytonPh.D.S.N.YoungPh.D.cR.O.PihlPh.D.bS.Etezadi C.LauzeR.N.P.BlierM.D., Ph.D.G.B.BakerPh.D.dC.Benkelf tM.D, Effects on Mood of Acute Phenylalanine/Tyrosine Depletion in Healthy Women, Neuropsychopharmacology. 2000
Moreover, it was also discovered that the women who received the altered diet were prone to developing higher irritability in response to psychological stress, as compared to those who received the normal proportions of phenylalanine.33M.LeytonPh.D.S.N.YoungPh.D.cR.O.PihlPh.D.bS.Etezadi C.LauzeR.N.P.BlierM.D., Ph.D.G.B.BakerPh.D.dC.Benkelf tM.D, Effects on Mood of Acute Phenylalanine/Tyrosine Depletion in Healthy Women, Neuropsychopharmacology. 2000
Researchers have hypothesized that this could be due to the reduced production of serotonin in the brains of these women. Since phenylalanine is a precursor for serotonin production, it is likely that the lack of it can cause a higher state of irritability while simultaneously reducing the energy of the subjects.
DLPA Benefits For Exercise & Weight Loss
DLPA may be a valuable supplement for people trying to lose weight and improve athletic performance. This may be due to a couple of factors.
One small study indicates that DLPA could increase fat oxidization, at least in young athletic males. This could lead to accelerated weight loss.
However, it was a very small study, so it’s difficult to say how applicable the results are. More research needs to be done.34Keisuke Ueda, Chiaki Sanbongi,1 Makoto Yamaguchi. The effects of phenylalanine on exercise-induced fat oxidation: a preliminary, double-blind, placebo-controlled, crossover trial J Int Soc Sports Nutr. 2017
DLPA Benefits for Diabetes Mellitus
DLPA has been shown to help in decreasing insulin resistance and the subsequent diabetes mellitus, adding to its profile as an important factor in weight loss and overall health.35Nuttall FQ, Schweim KJ, Gannon MC.. Effect of orally administered phenylalanine with and without glucose on insulin, glucagon and glucose concentrations. Horm Metab Res. 2006 Aug 36A Alamshah, et al. l-phenylalanine modulates gut hormone release and glucose tolerance, and suppresses food intake through the calcium-sensing receptor in rodents Int J Obes (Lond). 2017
There is also evidence that phenylalanine may promote feelings of satiety and fullness. This could decrease appetite and prevent overeating.
Researchers suspect that this is because phenylalanine is an amino acid that is usually broken down from protein. When you take it as a supplement, your body reads it as intake from a protein source. 37Veldhorst M, et al. Protein-induced satiety: effects and mechanisms of different proteins Physiol Behav. 2008 38Moran TH. Cholecystokinin and satiety: current perspectives Nutrition. 2000
DLPA Benefits for Skin
DLPA is a building block for a pigment known as melanin.
Melanin helps in giving color to our skin. Thus, by taking DLPA, we can build more of this pigment.
This would help with skin-color disorders like vitiligo.
Vitiligo is a skin-condition that is characterized by the appearance of differently-colored patches on the skin. This is caused by the death of melanocytes – a group of specialized cells that produce the color pigment melanin.
Evidence for DLPA being effective against skin disorders
It has been observed that orally taking phenylalanine can restore pigmentation up to 77%.
This could be further improved by oral and topical phenylalanine application.
This is no surprise because skin conditions are much more likely to be treated with topical L-phenylalanine applications.39Siddiqui AH, et al. L-phenylalanine and UVA irradiation in the treatment of vitiligo Dermatology. 1994 40Schulpis CH, Antoniou C, Michas T, Strarigos J. Phenylalanine plus ultraviolet light: preliminary report of a promising treatment for childhood vitiligo Pediatr Dermatol. 1989
How DLPA Works In The Brain
DLPA is a combination of two phenylalanine isomers, a left handed (L) and right handed (R) version. They are mirror images of each other and have slightly different effects, but are both precursors for catecholamines.
Catecholamines refers to important neurotransmitters like dopamine, norepinephrine, and epinephrine.
Once DLPA enters your system, your body breaks it down and converts it into l-tyrosine. Then it converts l-tyrosine into dopamine, which eventually converts to norepinephrine and then epinephrine.
These neurotransmitters are heavily involved in mood, reward, arousal, attention, and other critical processes.
It’s important to note that DLPA provides the building blocks for these neurotransmitters, but does not stimulate their production directly like, say, Adderall.
It has even been shown to be involved in melanin biosynthesis.
How Much DLPA Should I Take?
The typical dose is about 1,000 to 2,000 mg DLPA a day, divided into 2 or 3 doses throughout the day.
DLPA Potential Side Effects
Generally, there are no side effects with this nootropic. Some research shows nausea at extremely high doses, but this is atypical.
That said, it is important to note that there are some dangerous interactions to look out for with DLPA. People with phenylketonuria should not take DLPA. This condition can cause a dangerous buildup of phenylalanine in the body.
People with healthy bodies process phenylalanine; their body naturally breaks L-phenylalanine, usually having no trouble with it.
However, those with PKU cannot metabolize L-phenylalanine, which could increase their blood phenylacetic acid concentration.
Therefore, the people affected by PKU are kept on a low phenylalanine diet to avoid too much phenylalanine from entering their bodies in the first place.
There may also be negative interactions between DLPA and MAOI inhibitors.
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