D-Phenylalanine: Benefits, Side Effects, Best Time to Take It & More

D-Phenylalanine

(DPA)

Evidence: High
Possible Benefits: Reasonable
Safety: Reasonable

What is D-phenylalanine?

D-phenylalanine is a synthetic form of phenylalanine, one of 9 essential amino acids. As a supplement, phenylalanine comes in 3 forms (D-, L-, and DL-phenylalanine) and is often used for enhancing cognition and well-being. Unfortunately, D-phenylalanine doesn’t share most of the benefits that the L- and DL- forms provide. This article is about the main benefits of D-phenylalanine, its potential side effects, the best time to take it, and more.

What does phenylalanine do for the body?

This amino acid mainly plays a role in adrenergic and dopaminergic neurotransmission.

The body converts L-phenylalanine into L-Tyrosine, which is then converted into L-DOPA. Decarboxylation of L-DOPA results in the synthesis of dopamine. Dopamine can then convert into adrenaline and noradrenaline through the dopamine-beta-hydroxylase enzyme.

An increase in these neurotransmitters can lead to a variety of pleasant and unpleasant effects.

It can result in increased attention, motivation, and working memory. On the other hand, too much dopamine, adrenaline, and noradrenaline can cause mild mania, jitteriness, difficulty falling asleep, and more.

L-phenylalanine also stimulates the production of thyroid hormones T3 (triiodothyronine) and T4 (thyroxine).

D-phenylalanine 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.

Possible benefits

It is important to note that all of the potential benefits mentioned below are dose-dependent. Generally, the higher the dose, the more pronounced the effects are. However, they do reach a plateau at a certain point. We will discuss the best dosing protocol later in this article.

Major benefits

Reduced pain – D-phenylalanine (DPA) slows the action of the enzymes carboxypeptidase A or endorphinase and enkephalinase, which can directly reduce pain. The research on this effect is rather limited.

Minor benefits

Reduced stress – L-phenylalanine is somewhat effective at reducing acute stress when taken at low doses. Higher doses may actually increase stress response because of elevated adrenaline levels. This effect may and may not apply to D-phenylalanine as well.
Reduced symptoms of depression – This benefit has mainly been observed in L-phenylalanine but may apply to D-phenylalanine as well to a lesser degree. The main reason behind this effect is an increase in dopamine levels. About 80% of those who take the supplement notice an improvement in their well-being. It is important to note that this improvement happens in the short term and likely won’t last once you stop taking the supplement.
Improved well-being – This effect applies mainly to those with depression but also to non-depressed individuals experiencing mild forms of stress.

Possible side effects

These side effects are dose-dependent. The risk for them increases (often linearly but sometimes exponentially) as you increase the dose. Some of the side effects only apply to very high doses.

Amino acid imbalance – All essential and non-essential amino acids need to be kept in balance as they act synergistically in many ways. Too much of one amino acid can sometimes cause side effects without enough of another amino acid. That is most notably the case for glycine and methionine, but the principle applies to other amino acids, such as lysine and arginine, and the BCAA trio. Using a single amino acid supplement may lead to a negative nitrogen balance, which can lessen how well your metabolism works. A protein powder is usually a better choice for getting enough amino acids unless you have a specific goal in mind targeted by a specific amino acid/s.
Allergic reactions – Phenylalanine supplements can trigger allergic reactions that can cause itching, tingling in the mouth, swelling of the face or hands, and trouble breathing.
Toxicity – While acute toxicity has never been reported, taking high amounts of L-phenylalanine could lead to chronic toxicity over time and cause some health problems, such as nerve damage, headaches, dizziness, nausea, heartburn, anxiety, mild forms of mania, and jitteriness. To prevent chronic toxicity, it is best to stay below 5 grams a day unless you have a great reason to take more.
Contamination – Contaminated supplements are uncommon in the USA and other well-regulated countries. However, if you wish to buy products from China, India, or other countries without strict regulations, beware that the supplements may be contaminated. Either way, you need to choose the brand you order from wisely. It is highly recommended to check the certificates or read through some reviews for the specific product before you buy it. The FDA (Food and Drug Administration) has the power to regulate dietary supplements but can only do so after they have been on the market for a while. That’s because supplement companies are not obligated to announce to the FDA when releasing a new product on the market. The FDA has to discover the product and test it for potential impurities, which can take a lot of time. During that time, the supplement can be sold on the market even if it’s impure. Also, supplement companies can change their manufacturers without announcing it to the FDA.

Who should not take D-phenylalanine?

You should probably avoid taking the supplement if you:

suffer from schizophrenia (taking this amino acid can lead to a movement disorder called tardive dyskinesia in schizophrenics)
have phenylketonuria (PKU), a condition in which your body can’t break down phenylalanine
have high blood pressure and-or take drugs for high blood pressure
have difficulty sleeping
eat high amounts of protein from food (most whole foods contain at least some amount of each essential amino acid)
experience a severe adverse reaction after taking the amino acid
often get anxious
are pregnant or breastfeeding (we don’t yet know if the supplement is safe for the child)
are on a tight supplement budget (since there are more cost-effective supplements on the market for most people)

Who will benefit the most?

You should consider taking the supplement if you:

experience a lot of physical pain
suffer from depression
are looking for a cognitive boost to increase concentration, motivation, and working memory
have ADHD or autism
consume too low amounts of protein (less than 0.3 grams/pound of body weight)

Types of phenylalanine supplements

The different types of phenylalanine supplements include:

L-Phenylalanine – This is the natural form found in food. It converts into L-tyrosine, indirectly causing an increase in dopamine, adrenaline, and noradrenaline levels in the brain.
D-Phenylalanine – This form is synthetic and not as researched as the L- form. The main benefit of D-phenylalanine is that it seems to have mild pain-reducing effects.
DL-Phenylalanine – This is a combination of D- and L-phenylalanine.

Of these supplemental types, L-phenylalanine appears to be the safest while DL-phenylalanine is potentially more beneficial. D-phenylalanine is the least safe and beneficial of these types and should be avoided unless you have a great reason to take it.

How much D-phenylalanine should you take?

The combined RDA (recommended daily allowance) for phenylalanine and tyrosine is 33 mg/kg/day for all adult men and most adult women. This is enough for the majority of people to prevent any symptoms of deficiency.

The RDA increases to 44 and 51 mg/kg/day for pregnant and lactating women, respectively.

Since this amino acid is in almost every food, you probably already get sufficient amounts from food alone. About 0.36 grams of protein/pound of body weight should be enough to prevent a deficiency.

If you plan to take D-phenylalanine as a supplement, 300 mg appears to be the best daily target for most people. Ideally, you would want to take 300 mg of either L-phenylalanine or DL-phenylalanine instead. This amount should provide most of the benefits without meaningful side effects.

Some people may benefit from doses higher than 300 mg. These include people with autism, ADHD, and depression.

The upper safety limit for this amino acid is not well-established. To stay on the safe side, don’t take more than 5 grams daily unless you have a great reason to do so. Higher amounts may cause problems if you take the supplement for a prolonged period.

Food sources of phenylalanine

This amino acid is found in all whole foods that contain dietary protein in a form of L-phenylalanine.

The amount of phenylalanine per gram of protein varies from food to food but a general rule of thumb is that the more protein you eat, the more phenylalanine you are getting from food.

The easiest way to find out exactly how much phenylalanine or other amino acids you are getting from food is with Cronometer.com. This free app allows you to track all vitamins, minerals, and more.

Best time to take D-phenylalanine

Like most other amino acids, D-phenylalanine is water-soluble, so you don’t have to take it with food to absorb it well. Taking the supplement with food is better if it causes stomach upset when you take it on an empty stomach.

To maximize the benefits, take D-phenylalanine in the morning or before you work on a cognitively demanding task.

This amino acid works much better when you take it early in the day. Taking D-phenylalanine at night should only be considered if you cannot fall asleep because of physical pain.

If you practice time-restricted eating, take this amino acid during your eating window to guarantee it won’t break your fast.

Unless it feels too impractical, spread the daily dose into 2+ smaller doses throughout the day.

Interactions

Other amino acids
All essential and non-essential amino acids need to be kept in balance as they act synergistically in many ways. Too much of one amino acid can sometimes cause side effects without enough of another amino acid. That is most notably the case for glycine and methionine, but the principle applies to other amino acids, such as lysine and arginine, and the BCAA trio. Using a single amino acid supplement may lead to a negative nitrogen balance, which can lessen how well your metabolism works. A protein powder is usually a better choice for getting enough amino acids unless you have a specific goal in mind targeted by a specific amino acid/s.
Vitamin B6
Vitamin B6 might increase the effects of this amino acid. The same also applies to vitamin C.
Sedatives
D-phenylalanine might potentiate the effects and side effects of sedatives.
MAOIs
β-phenylethylamine (PEA) is metabolized by monoamine oxidase B (MAO-B). When both MAO-A and MAO-B are inhibited, PEA can cause side effects that would not otherwise occur, such as an increase in blood pressure.

Where to buy D-phenylalanine

Amazon is the best option for ordering phenylalanine supplements in most countries. They offer some very affordable products backed by many positive reviews. Also, you can choose from a wide range of brands without having to search through other markets on the internet.

Beware some brands display the dosage per serving instead of per pill or capsule. Therefore, you may accidentally buy something less potent than you intended. Do not fall for this marketing trick.

FAQ

You can take the supplement daily and do not need to cycle it. However, it is certainly not a problem if you don’t take it daily. Not taking the supplement every once in a while could lead to better absorption. That is yet to be proven or disproven.

All of these options are fine. The two most important things to consider are the price and dosing. Powders are almost always the cheapest form. However, you may need a highly accurate scale to dose them correctly (preferably 0.001g). You can get one for as little as $20 from Amazon. Dosing the powders also takes some time that can add up over months or years. The disadvantage of capsules is that they often contain bovine gelatin, which rarely comes from an ethical source.

This amino acid works much better when you take it in the morning. Taking D-phenylalanine at night should only be considered if you cannot fall asleep because of physical pain.

This amino acid should not become harmful once it exceeds the expiration date but can lose potency over time.

Keep the supplement in a cold, dark, and dry place, and it should remain just as potent for many months or even years.

While toxicity is rare, too much D-phenylalanine in the system can cause some health problems, often related to causing an imbalance in other amino acids. It is best to stay below 5 grams a day to prevent these side effects.

You may need more of this amino acid if you:
– don’t eat enough protein (less than 0.3 grams/pound of body weight)
– suffer from depression due to a lack of dopamine
– wish to optimize aspects of cognition related to dopamine, adrenaline, and noradrenaline (such as memory, attention, and motivation)
– have been diagnosed with ADHD or autism

The half-life of phenylalanine in the body is about 2-3 hours. This amino acid stays in your system for about 10 hours after you ingest it.

You should notice the benefits almost immediately after you take the supplement.

Amino acid supplements often come from animal products, but they do not have to be since all whole plant foods contain all essential amino acids. You can easily find vegan-friendly L-phenylalanine powders but always check the label to be sure. If you buy the amino acid in a capsulated form, beware that the capsules often contain animal-based gelatin. Instead, find a brand that puts its products into cellulose capsules.

Like most other amino acids, D-phenylalanine is water-soluble, so you don’t have to take it with food to absorb it well.

While low doses may not break a fast, higher doses might do so. If you practice time-restricted eating, take this amino acid during your eating window so it doesn’t break your fast.

This amino acid comes in 3 primary forms: D-, L-, and DL-phenylalanine. Of these forms, L-phenylalanine has the best safety profile while DL-phenylalanine can be more beneficial. D-phenylalanine is the least safe and beneficial of these types and should be avoided unless you have a great reason to take it.

References

Most of the information provided in this guide is supported by scientific research that can be found and verified in the PubMed medical library. We highly encourage you to use the library to verify anything said in this article. We excluded from consideration studies that are either confounded or have a high conflict of interest.

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