Table of Contents
Phenylalanine is a highly bio-available essential amino acid. Your body naturally converts L-Phenylalanine into the amino acid L-Tyrosine which is then converted into L-DOPA. Decarboxylation of L-DOPA results in synthesis of the neurotransmitter dopamine.[i]
Once converted into dopamine, the enzyme dopamine-beta-hydroxylase converts dopamine into the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline). This triad of neurotransmitters are collectively referred to as “catecholamines”.
As a nootropic supplement, you may find several different forms of Phenylalanine available. L-Phenylalanine is the natural form found in proteins. D-Phenylalanine is a mirror image of L-Phenylalanine that is made in the lab. And DL-Phenylalanine is a combination of the two forms.[ii]
L-Phenylalanine can be a highly effective nootropic for boosting cognitive function because it boosts norepinephrine and dopamine production. Resulting in increased attention, motivation and working memory.
D-Phenylalanine (but not L-Phenylalanine) has been used to treat chronic pain although the clinical research in this area is sparse.
L-Phenylalanine also stimulates the production of thyroid hormones T3 (triiodothyronine) and T4 (thyroxine) which are crucial in maintaining both overall physical and cognitive health.
Phenylalanine helps:
- Cognitive Stress. L-Phenylalanine helps produce the catecholamine-triad of neurotransmitters dopamine, norepinephrine and epinephrine. Sleep deprivation and extreme stressors like heat and cold can deplete catecholamine levels. L-Phenylalanine restores them to preserve optimal cognition.[iii]
- Neurotransmitters. Phenylalanine is a necessary precursor for dopamine, norepinephrine and epinephrine. As your dopamine levels increase, you’re better able to concentrate, organize your thoughts, and stay productive.
- Attention Deficit Disorder (ADHD). L-Phenylalanine can be an effective treatment for some with ADHD symptoms. L-Phenylalanine works in synergy with pharmaceutical drugs like Ritalin and Adderall by boosting extracellular levels of dopamine. Helping these drugs be more effective. And mitigating side effects like crashes when the drug wears off.
Overview
L-Phenylalanine is an essential amino acid that you get from food or a supplement. The enzyme phenylalanine hydroxylase converts Phenylalanine in your liver into the amino acid L-Tyrosine.[iv]
Phenylalanine is found in protein-rich foods like soybeans, cheese, nuts, seeds, beef, lamb, chicken, pork, fish, eggs, dairy, beans, and whole grains. The artificial sweetener aspartame also contains Phenylalanine.
Your brain converts L-Tyrosine to L-DOPA which then produces the neurotransmitter dopamine. The unused dopamine is then further converted into the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline). This triad of neurotransmitters are collectively referred to as “catecholamines”.
Many neurohackers prefer L-Phenylalanine over other catecholamine precursors because it supports neurotransmitter production without directly increasing neurotransmitter levels.
This last part is key because indiscriminately increasing neurotransmitters across the board can lead to imbalances and tolerance. Which can defeat the purpose of taking the nootropic in the first place.
For example, not enough epinephrine can decrease cognition. And too much norepinephrine can decrease attention, processing speed and executive function.[v]
L-Phenylalanine vs. D-Phenylalanine: What’s the Difference?
L-Phenylalanine is an essential amino acid which means you must get if from food. Or as a supplement. Your body cannot synthesize Phenylalanine on its own.
L-Phenylalanine (LPA) is converted into the amino acid L-Tyrosine in your liver. Once L-Tyrosine crosses the blood-brain barrier, it is converted into L-DOPA. Which is further converted into the neurotransmitters dopamine, norepinephrine (noradrenaline) and epinephrine (adrenaline).
D-Phenylalanine (DPA) is a synthetic version of, and mirror image of L-Phenylalanine created in the lab. DPA has a different mechanism of action in the body than LPA.
D-Phenylalanine (DPA) slows the action of the enzymes carboxypeptidase A or endorphinase and enkephalinase. These enzymes degrade endorphins. Slowing down these enzymes that reduce endorphins can help reduce pain.[vi]
DL-Phenylalanine is a 50/50 combination of L-Phenylalanine and D-Phenylalanine. By combining the two in theory you get the best of both an antidepressant and pain reducer.
How does L-Phenylalanine work in the Brain?
L-Phenylalanine boosts brain health and function in several ways. But two in particular stand out.
- L- Phenylalanine decreases depression. L-Phenylalanine is converted into L-Tyrosine which in turn is converted into L-DOPA in the brain. L-DOPA is then used to make the feel good neurotransmitter dopamine. So depression could be the result of not getting enough of the first amino acid (L-Phenylalanine) in the chain of events needed to produce dopamine.
In one study done in Germany, 20 depressed patients received from 75-200 mg per day of DL-Phenylalanine for 20 days. At the end of the trial 12 of the depressed patients could be discharged without any further treatment. 4 of the patients had a moderate decrease in depressive symptoms. And 4 patients showed no response.[vii]
- L-Phenylalanine boosts neurotransmitters. L-Phenylalanine turns into L-Tyrosine once taken as a supplement. It then converts into the neurotransmitter dopamine. Dopamine is used to control movement in your body, is fundamental to memory, attention and problem solving.
The unused dopamine can then convert into the neurotransmitters norepinephrine (noradrenaline) and epinephrine (adrenaline).
Norepinephrine is important for attentiveness, emotions, sleeping, dreaming and learning.
Epinephrine drives your ‘flight-or-flight’ response. It’s what prompts your reaction to dangerous circumstances, emergency situations, or in stressful situations or environments.
This balance in neurotransmitters is critical to the fully optimized, healthy brain. And why some neurohackers choose L-Phenylalanine to allow the body to make the neurotransmitters it needs. Instead of causing an imbalance by boosting one neurotransmitter over another.
A study in Venezuela investigated ADHD and autism, and the implications of amino acids on these neuropsychiatric disorders. 40 subjects affected by autism and 11 with ADHD along with 41 healthy subjects were included in this study.
The researchers found that those with ADHD had decreasing Phenylalanine and increasing glycine which disrupted their inhibitory neurotransmission system. Not enough phenylalanine and increasing lysine was present in those with autism.[viii]
Another study at Ohio State University looked at amino acids in 28 ADHD patients. And found all subjects with ADHD had significantly lower levels of the amino acids phenylalanine, tyrosine, tryptophan, histidine, and isoleucine. The researchers concluded each subject had a general deficit in amino acid transport, absorption or both.[ix]
How things go bad
As we get older, our brain and body chemistry and energy metabolism changes.
↓ Dopaminergic neurons are damaged or die
↓ Neurotransmitter levels decline
↓ Thyroid hormones decline
↑ Stress levels increase
↓ Working memory and mood decline
All of these changes are often attributed to aging. But could be a result of dietary and lifestyle choices. Unchecked, they could lead to neurodegenerative diseases like Parkinson’s, a drop in quality of life and depression.
L-Phenylalanine benefits
L-Phenylalanine can boost levels of the neurotransmitters dopamine, norepinephrine and epinephrine. And can help a sluggish thyroid produce more T4 and T3.
L-Phenylalanine can help boost cognition especially in stressful situations. It helps improve decision making, ‘flow state’ and creativity, cognitive flexibility, and working memory.
L-Phenylalanine converts into L-Tyrosine which then converts into L-DOPA to produce dopamine. L-DOPA is also used to make melanin in your body. This conversion process helps in the removal of neurotoxic quinones. And chelates heavy metals like mercury and lead which can accumulate in and damage neurons.
The dopamine that is not used by your brain is available to produce norepinephrine (noradrenaline) which is important for attentiveness, emotions, sleeping, dreaming and learning.
L-Phenylalanine may be an effective nootropic when stacked with ADHD/ADD meds like Ritalin or Adderall. It helps supply extracellular dopamine needed to improve the effectiveness of stimulants used to boost the uptake of dopamine in your brain.
How does L-Phenylalanine feel?
Keep in mind that L-Phenylalanine is a precursor to catecholamines. So if you’re not ‘low’ on dopamine, norepinephrine or epinephrine – you may not ‘feel’ anything.
Many neurohackers report a lift in mood, better focus, concentration, increased energy, and an overall sense of well-being. L-Phenylalanine can help readjust your motivation levels. It can help lower anxiety levels, especially social anxiety.
Supplementing with L-Phenylalanine can help bring your blood pressure down if its elevated from a stressful situation or environment. Take it before the stressful event if you can.
L-Phenylalanine helps buffer the effects of stimulants like caffeine or amphetamines. It helps potentiate and prolong the effects of Ritalin or Adderall, and reduces the crash.
If you’re into athletics or do manual work, you’ll find that supplementing with L-Phenylalanine before a workout or construction job can leave you feeling great afterwards. It may help mitigate many of the effects of acute stress caused by short-term stressors.
And L-Phenylalanine helps your body produce L-Tyrosine which helps to produce melanin, so you may find it easier to get a tan while at the beach.
L-Phenylalanine Clinical Research
Phenylalanine as an Antidepressant
Several studies have investigated using Phenylalanine for the treatment of depression. One study published in the journal Arzneimittel-Forschung looked at using DL-Phenylalanine in a small group of patients who failed to respond to popular antidepressants like MAOIs.
In this study, researchers worked with 23 patients diagnosed with depression and who had not responded to standard antidepressants. They were given 50 or 100 mg of Phenylalanine daily for 15 days. The researchers found that Phenylalanine completely improved mood in 17 of the patients. Within 13 days of the 15-day trial.[x]
Another study in the Journal of Neural Transmission studied DL-Phenylalanine use with 20 depressed patients. The subjects were given 75 – 200 mg/day of DL-phenylalanine for 20 days.
The study found that 8 patients completely recovered from depression. And another 4 experienced a significant improvement in mood. Another 4 patients saw mild to moderate improvements, and another 4 did not respond to treatment.
This study shows that Phenylalanine has considerable antidepressant properties. And is effective for the majority of people suffering from depression.[xi]
Phenylalanine for ADHD
Phenylalanine for ADHD seems at first glance as a natural solution for ADHD symptoms. It’s a precursor to the neurotransmitter dopamine which is targeted with stimulants like Ritalin and Adderall. But the very limited clinical evidence tell a different story for practical use.
In this double-blind crossover study, 19 patients with ADD were given DL-phenylalanine or a placebo for 2 weeks. 13 of the ADD patients experienced a significant improvement in ADD symptoms compared to the placebo. And patients saw an improvement in mood.
But the patients who did respond to DL-Phenylalanine lost all positive benefits within 3 months. And it’s interesting that a later study with ADHD patients using L-phenylalanine (not DL-Phenylalanine) produced no clinical benefit.[xii]
Another study from 1987 treated 11 hyperactive boys for 2 weeks with D-Phenylalanine. There was no significant improvement or deterioration in behavior.[xiii]
There is a modern school of thought that there are several different types of ADD and ADHD. And the symptoms are caused by malfunctions in different parts of the brain depending on the ‘type’ of ADHD.
The bottom line is some dealing with ADHD may benefit from supplementing with Phenylalanine. And that DL-Phenylalanine may be the best option. Try it and see if it works for you.
L-Phenylalanine Recommended Dosage
L-Phenylalanine suggested dosage for cognitive benefit is 500 mg up to 3-times per day.
You may find your body responds to smaller doses. Or even more if your stacking it with stimulants like ADHD meds. Listen to your body and see how you react.
Since L-Phenylalanine is an amino acid, for best absorption and so it’s not competing with other amino acids, take it at least an hour before food. L-Phenylalanine works best on an empty stomach.
And take L-Phenylalanine with Vitamin B6 and Vitamin C to further maximize absorption. And give your body what it needs to produce the neurotransmitters dopamine, norepinephrine and epinephrine.
L-Phenylalanine is also needed along with L-Tyrosine to synthesize the CoQ10 needed to create fuel within your brain’s mitochondria.
L-Phenylalanine Side Effects
L-Phenylalanine quickly turns into the non-essential amino acid L-Tyrosine once you take it. So is considered non-toxic and very safe. Most neurohackers don’t have any negative side effects.
Important Caution: People with phenylketonuria (PKU), and women who are breastfeeding or are pregnant, should not take phenylalanine supplements. PKU is an inherited condition where excess phenylalanine can build up in your body. Aspartame, found in artificial sweeteners such as NutraSweet, is a source of phenylalanine. People with PKU should not use aspartame. If you are pregnant, ask your doctor about using this artificial sweetener.[xiv]
At higher doses there are reports of stomach issues and migraines. Experts say that L-Phenylalanine is toxic in doses above 5000 mg. And higher doses will not give you any added benefit.
If you try recommended doses of L-Phenylalanine and do not feel any benefit, then this nootropic may not be right for you. You could try L-Tyrosine or NALT instead.
L-Phenylalanine can increase your thyroid hormones. So if you’re hyperthyroid you shouldn’t use L-Phenylalanine.
And if you’re taking MAO inhibitors (MAOI’s) like selegiline, Azilect, Marplan or Nardil you should not use L-Phenylalanine. MAOI’s work in your brain and affect neurotransmitters. So using L-Phenylalanine in combination with MAOI’s could throw off the delicate balance of neurotransmitters needed for optimal brain health and cognition. And taking L-Phenylalanine with MAOI’s could cause a severe increase in blood pressure which could lead to a heart attack or stroke.
Other sides effects which can accompany unusually high doses of phenylalanine can include anxiety, rapid heart beat, restlessness, heart palpitations or high blood pressure. If you are dealing with or on medication for high blood pressure you should not use L-Phenylalanine.
Type of Phenylalanine to buy
L-Phenylalanine is available in powder, capsule and tablet form. Capsules and tablets are usually 500 mg.
Phenylalanine is also available as D-Phenylalanine and the 50/50 combined form of DL-Phenylalanine. You may find one form works better for you than another.
Ensure you read labels carefully, and stick with manufacturers who follow Good Manufacturing Practices (GMP). And are GMP-Certified.
Nootropics Expert Recommendation
L-Phenylalanine 500 mg up to 3-times per day
I recommend using L-Phenylalanine as a nootropic supplement.
Your body does synthesize some L-Tyrosine from phenylalanine which comes from high-protein foods like chicken, fish, almonds, avocados and bananas.
But most of us don’t get enough L-Phenylalanine from our diet. So supplementation will help. And L-Phenylalanine is a highly bioavailable, natural form of this amino acid. So you should feel its effects faster.
L-Phenylalanine is helpful for most neurohackers to combat stress and sleep deprivation. It’ll boost dopamine, norepinephrine and epinephrine levels.
It’s particularly helpful if you take L-Phenylalanine prior to a stressful situation, workout or physically demanding job.
L-Phenylalanine could be helpful to those dealing with ADHD/ADD. It’s a great compliment to stack with stimulant meds like Ritalin or Adderall. L-Phenylalanine will provide the dopamine your brain needs. It will help smooth out and prolong the effects of stimulant meds. And help prevent the associated crash when they wear off.
You can safely use up to 1,500 mg per day when stacking with ADHD meds. But dosed throughout your day.
Join The Discussion - 135 comments
Mike
November 9, 2022
is there a natural amino acid we can take for pain, or is the “lab” version l-phenylalanine the only option?
David Tomen
November 9, 2022
Mike, Use the search function top right above the top menu and search for the keyword pain. And you will get a list of supplements that help with pain including taurine, L-Glutamine and Alpha Lipoic Acid.
Acci
September 26, 2022
Can you take DLPA and CoQ10 as part of a morning stack together? I can’t seem to find information on taking them both at the same time. (CoQ10 60mg and DLPA 500mg). Thanks for this post!
David Tomen
September 27, 2022
Acci, you cannot find anything on using them together likely because it is not a problem.
Morten Ruby
July 11, 2022
Hi David
I’m tapering off buprenorfine. Right now I’m down to 0.2 mg each morning. The withdrawal is hard and soon I will hit 0 and 10 years of opiates addiction is over. I read that DLPA can help with withdrawal, but I’m also taking Sertralin so I wonder if DLPA will interact in a bad way with Sertralin as it is SSRI and NOT MAOI?
Thanks for your time
Morten
David Tomen
July 12, 2022
Morten, Sertraline also affects the dopamine transporter. Its contradiction with L-DOPA is considered “moderate”. Phenylalanine also boosts dopamine although it takes a little longer to do it compared to L-DOPA.
So, I suggest being careful if you decide to try DLPA. Start with the lowest dose at first and see how you react. Then go from there.
Cindy
May 12, 2022
I have a question where I can’t seem to find the answer anywhere. I was doing some research and I get the impression that taking L-Phenylalanine alone is more effective than the DLPA version. If I were to obtain the best results from both the L and D, should I take them separately and at different times from each other? I’m asking because I do need the benefits of both types. If it is better to take them independent from each other, how does that work? The timing around the other? Dosage of each? Any and all information is appreciated. Thank you!
David Tomen
May 15, 2022
Cindy, try the 50/50 combined form of DL-Phenylalanine and see how if works for you.
Gary Smith
March 15, 2022
Hi David, I’m curious as to your opinion on trying DL-phenylalanine or L-phenyalanine. I’m mostly interested from an anxiety, depression and insomnia perspective. Thanks!
David Tomen
March 17, 2022
Gary, scroll up to this section: “L-Phenylalanine vs. D-Phenylalanine: What’s the Difference?“. You will do best with L-phenylalanine unless you want it for pain control.
Gary Smith
March 19, 2022
Hi David, I bought NOW L-Phenylanine 500 mg. The bottle says to take it in between meals. Would you recommend taking it before breakfast or in between breakfast and lunch? I am going to start with one pill to make sure it doesn;t negatively affect my sleep. Thanks.
David Tomen
March 19, 2022
Gary, they recommend taking it between meals because theoretically it competes for the same transporters as the amino acids you get from food. I wouldn’t worry too much about it however because the dose you are taking by using this supplement is far more than what you’ll get from food. And it will win that competition.
The half-life is short so try taking it both in the morning and at noon.
Darcy
March 5, 2022
Wanted to report that I found nasal phenylalanine, not sure what lead me to it. I take a lot of nootropics, including l-phenylalanine but when I started taking the nasal phenylalanine, it made a huge difference in my productivity.
I’m housebound and useless. This has helped me to cook, and even clean, a bit. If there are any supporting supplements, I’d love to hear about them, so that I continue to receive these results.
Just FYI; The labels says to take only 1 spray, as a dose, and to take 1 pump every 4 hours. The first day, I felt the affects, and took 3 pumps total for that day. I got a headache late in the day. The next day I took only 1 pump to see if the headache would return, it did not. I do have a bloody nose, not dripping out, but if I blow my nose, there’s blood, and I sneeze a lot throughout the hour after taking a dose. This nootropic, as a nasal spray only, has made the biggest difference for me but we are all battling different variables. I’m on day 7 now so granted, that’s not a lot of time but I’ve been productive, to some extent, every one of those days.
I am eating like a maniac but that may or may not be related. I’ve had hunger issues for years but I’m really out of control lately. It may be a contributing factor. If only I could find a supplement that helped that.
David Tomen
March 5, 2022
Darcy, the only supplement I know of that tackles satiety is this prebiotic: https://bit.ly/2KzeQi2
Many prefer L-Phenylalanine over other catecholamine precursors (like L-Tyrosine and L-DOPA) because it supports neurotransmitter production without directly increasing neurotransmitter levels.
This last part is key because indiscriminately increasing neurotransmitters across the board can lead to imbalances and tolerance. Which can defeat the purpose of taking the nootropic in the first place.
So, you have two things going on here that could be contributing to your newfound productivity. L-Phenylalanine goes on to make L-Tyrosine which eventually turns into more dopamine in your brain. AND L-Tyrosine helps produce thyroid hormones. You could be thyroid deficient and not even know it. Many are.
I assume you are already using a bioactive B-Complex and magnesium because they are cofactors in the production of dopamine. And you need selenium and Iodine to make thyroid hormones.
Moe
February 22, 2022
Hello David,
This is great resource and I greatly appreciate how active you are with your audience.
I had a CDiff infection, after which my cognitive functions became extremely compromised. Generally speaking I am extremely disciplined and have strong will power. After this infection I lost my self control and my brain felt like a brain of a drug addict even though I never used any substances.
I had test done that indicated I had excess dopamine in my brain. It turns out CDiff inhibits DBH which is needed for the conversion of dopamine to norepinephrine. So dopamine is not being converted in my brain.
I was considering taking L- phenylalanine to help convert the dopamine, but I want to convert dopamine not increase it, as that would only make the issue worse.
So what would your recommendation be to help convert this extra dopamine and reduce this build up?
Here is some info regarding this condition from the Great Lakes laboratory (They perform the OATS test that tests for such imbalances):
-certain Clostridia metabolites have the ability to inactivate dopamine beta-hydroxylase, which is needed for the conversion of dopamine to norepinephrine…
Clostridia metabolites common in autism significantly decreases brain dopamine beta hydroxylase activity.
-norepinephrine /epinephrine production by catecholamine producing neurons in the central nervous system, sympathetic nervous system, and adrenal gland. The most common reason for an elevation of the HVA/VMA ratio is a decreased conversion of dopamine to norepinephrine. The enzyme responsible for this conversion, dopamine beta-hydroxylase (DBH), is copper and vitamin C dependent so an elevated ratio could be due to deficiencies of these cofactors . The most common reason for this elevated ratio is inhibition of this enzyme by Clostridia byproducts
David Tomen
February 22, 2022
Moe, according to this study (https://www.sciencedirect.com/science/article/pii/S1658361216300385) you can try black seed oil (2%) and Myrrh water extract to eliminate Clostridium difficile. Or you can try Sulforaphane , Taurine and/or Saffron for norepinephrine.
Jman
January 29, 2022
Hello
How long half-life does DL-phenylalanine have?
David Tomen
January 29, 2022
2-3 hours.