Phenylalanine for Chronic Pain: Research Review → BurnoutNutrition.com

Here’s what you need to know about phenylalanine for chronic pain:

D-phenylalanine (DPA) doesn’t seem to work much better than a placebo for chronic pain
In the main study:
- 25% said DPA helped more
- 22% said placebo helped more
- 53% saw no difference
DPA appears safe with few side effects, but long-term safety is unknown
It may have potential for CFS/ME patients, but more research is needed
Current evidence doesn’t strongly support using DPA for chronic pain

Quick comparison of pain treatments:

Treatment	Effectiveness	Side Effects	Mechanism
D-phenylalanine	25% said it helped	Few reported	May inhibit pain enzyme breakdown
Placebo	22% said it helped	None	No active mechanism
Opioids	Can be very effective	Addictive, constipation	Binds to pain receptors
Electroacupuncture + D-amino acids	Synergistic effects	Few	Enhances endogenous pain relief

More large-scale, long-term studies on DPA for chronic pain in CFS/ME patients are needed before drawing firm conclusions about its effectiveness.

2. About Phenylalanine

2.1 Different Forms of Phenylalanine

Phenylalanine comes in three forms:

L-phenylalanine: Found in food proteins
D-phenylalanine: Man-made version
DL-phenylalanine: Mix of L- and D-forms

L-phenylalanine helps make proteins in the body. It can turn into other amino acids and brain chemicals that affect mood and might help with pain.

2.2 Where Phenylalanine is Found

Your body can’t make phenylalanine, so you need to get it from food. Here are some good sources:

Food Type	Examples
Meats and Dairy	Beef, chicken, fish, eggs, milk
Grains	Wheat, oats, quinoa
Beans	Lentils, chickpeas, black beans
Nuts and Seeds	Almonds, pumpkin seeds
Other	Veggie burgers, some sugar-free gum

Eating different protein-rich foods usually gives you enough phenylalanine and other important amino acids.

2.3 How Phenylalanine May Help with Pain

Pain

Phenylalanine, especially the D-form, might help with pain in these ways:

It may stop the breakdown of enkephalins, which are natural pain-fighters in your body.
L-phenylalanine can change into other chemicals in the brain that affect mood and pain.
It can turn into phenylethylamine, which might boost mood and change how you feel pain.

Some studies show good results, but we need more research to know for sure how well phenylalanine works for long-lasting pain.

3. How We Reviewed the Research

3.1 How Studies Were Chosen

We picked studies that looked at how well D-phenylalanine works for long-term pain. We focused on:

Double-blind studies
Randomized controlled trials
Studies that compared D-phenylalanine to a placebo

These types of studies give the most trustworthy results.

3.2 Where We Found the Studies

We looked at well-known medical journals, including:

Archives of Physical Medicine and Rehabilitation
Pain (Journal)

These journals are known for publishing good quality research about pain management.

3.3 When the Studies Were Done

The main studies we looked at were from the 1980s. Here’s a quick look at when they were published:

Study Topic	Year Published
D-phenylalanine for long-term pain	1986
D-phenylalanine tested on primates for short-term pain	1986

While these studies are older, they were the first to look at how D-phenylalanine might help with pain. It would be good to have newer studies to check if these findings still hold true today.

4. Main Studies Reviewed

4.1 Study Setup

The main study we looked at was set up like this:

Double-blind: Neither patients nor researchers knew who got which treatment
Crossover: Patients tried both treatments
Randomized: Patients were put into groups by chance
Parallel design: Groups were compared side by side

This type of study is very good for testing if a treatment works.

4.2 Study Participants

The study included 30 people with long-lasting pain:

All had pain that other treatments didn’t help
The pain came from different causes
These people represented many types of chronic pain

4.3 Phenylalanine Use

Here’s how they used D-phenylalanine (DPA):

Detail	Amount
Dose	250mg
Times per day	4
Weeks of treatment	4

They also used a fake pill (placebo) the same way. After 4 weeks, the groups switched treatments for another 4 weeks.

4.4 Measuring Pain Relief

They checked pain relief in two ways:

Visual scale: Patients marked their pain level on a line
Cold water test: Patients put their hand in cold water to test pain tolerance

They also asked patients questions about their pain.

4.5 Study Results

Here’s what they found:

Result	Percentage of Patients
DPA helped more	25%
Placebo helped more	22%
No difference	53%

For the lowest pain levels:

47% had lowest pain on DPA
53% had lowest pain on placebo

The researchers said DPA didn’t seem to help chronic pain more than a fake pill. This means DPA might not be a good treatment for long-lasting pain, even though some people thought it might work before.

5. Combining Study Results

5.1 Overall Findings

When we look at all the data from the main study on D-phenylalanine (DPA) for long-lasting pain, the results aren’t very promising:

Result	Percentage of Patients
DPA helped more	25%
Placebo helped more	22%
No difference	53%

These numbers show that DPA might not work better than a fake pill for most people with long-lasting pain. The small 3% difference between DPA and placebo suggests any benefits might just be due to people thinking it will help.

5.2 How Good the Study Was

The study was set up well:

No one knew who got which treatment
Everyone tried both treatments
People were put in groups by chance

This makes the results more trustworthy. But, the study only had 30 people, which is a small number. A bigger study might give clearer answers about whether DPA works for long-lasting pain.

5.3 Different Groups of People

The study didn’t give much info about different groups, but we can guess that:

DPA didn’t seem to work well for any type of long-lasting pain.
It didn’t matter if people said how much pain they felt or if the researchers measured it – DPA still didn’t work better than a fake pill.
No group of people seemed to benefit more from DPA than others.

Based on this, DPA might not be a good treatment for long-lasting pain, no matter what’s causing the pain or who has it. But we need more studies with more people to be sure.

6. How Well Phenylalanine Works for Chronic Pain

6.1 Overall Results

A study with 30 chronic pain patients tested D-phenylalanine (DPA) against a placebo. The results were not very promising:

Treatment	Patients Feeling Less Pain
DPA	25%
Placebo	22%
No difference	53%

These numbers suggest DPA might not help much with long-lasting pain.

6.2 DPA vs. Placebo

When comparing DPA to a fake pill:

25% of people felt better with DPA
22% felt better with the fake pill
53% didn’t notice a difference

For the lowest pain levels:

47% had their least pain while taking DPA
53% had their least pain while taking the fake pill

These findings show that DPA may not work better than a fake pill for managing ongoing pain.

6.3 How Much to Take

The study used:

Detail	Amount
DPA dose	250mg
Times per day	4
Weeks of treatment	4

Key points about the dose:

This amount didn’t seem to help much with pain
We need more studies to check if other amounts might work better
Everyone’s body is different, so the effects might vary
Always talk to a doctor before trying new pain treatments

7. Safety and Side Effects

7.1 Reported Side Effects

Phenylalanine is usually safe when eaten in normal food amounts. But taking it as a supplement might cause problems for some people:

Common Side Effects
Heartburn
Feeling tired
Upset stomach
Hard stools
Feeling dizzy
Headache
Feeling worried or too excited
Trouble sleeping

Warning: Taking more than 5,000 mg a day might hurt your nerves.

7.2 Long-term Safety

We don’t know much about taking phenylalanine supplements for a long time. It’s safe in food, but be careful with supplements. Short studies show few problems with up to 12 grams per day. We need more research to know if it’s safe for long-term use.

7.3 Who Shouldn’t Take It and Drug Interactions

Some people should not take phenylalanine supplements:

1. People with PKU: They can’t process phenylalanine, which can hurt their brain.

2. Pregnant and breastfeeding women: It might harm the baby.

3. People with tardive dyskinesia: It might make their condition worse.

Phenylalanine can affect how some medicines work:

Medicine	What Happens
MAOIs	Can raise blood pressure a lot
Baclofen	Body might not absorb the medicine well
Levodopa	Might not work as well
Antipsychotics	Might cause movement problems
Blood pressure pills	Might not work as well
Sleep medicines	Might make you too sleepy

Important: Talk to your doctor before taking phenylalanine supplements, especially if you take other medicines or have health problems.

8. Phenylalanine for CFS/ME Patients

8.1 Results for CFS/ME Patients

A study by McGregor (2019) looked at phenylalanine in people with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME). It found that:

Lower blood phenylalanine levels were linked to worse post-exertional malaise (PEM)
PEM is a main symptom of CFS/ME

8.2 Possible Benefits

Phenylalanine might help CFS/ME patients in these ways:

Benefit	Description
Less PEM	More phenylalanine might reduce PEM symptoms
Pain relief	May help with pain, as seen in other conditions
Better metabolism	Could support overall body function

8.3 Drawbacks

There are some issues to think about:

Drawback	Explanation
Not enough research	We need more studies on phenylalanine for CFS/ME
Different results	It may not work the same for everyone
Side effects	Some people might get headaches or stomach problems
Medicine interactions	It could affect other treatments CFS/ME patients use

CFS/ME patients should talk to their doctor before trying phenylalanine. While some new treatments look good, we need more research to know if phenylalanine is safe and helpful for CFS/ME.

9. Comparing Phenylalanine to Other Pain Treatments

9.1 Comparison Chart

Treatment	How Well It Works	Side Effects	How It Works
D-phenylalanine	25% said it helped more	Few reported	Might stop pain-fighting chemicals from breaking down
Fake pill	22% said it helped more	None	Does nothing
Strong pain pills	Can work well for some	Can be addictive, cause constipation	Attaches to pain receptors
Electric acupuncture with D-amino acids	Works well together	Few	Helps body’s own pain relief

9.2 Good and Bad Points

D-phenylalanine

Good:

Might help some people with long-term pain
Few side effects
Might make strong pain pills work better

Bad:

Doesn’t work much better than a fake pill
Works differently for different people
We need more studies to know if it really helps

Other Pain Treatments

Good:

Strong pain pills can help a lot
Mixing treatments (like D-amino acids and electric acupuncture) might work well
Many choices to fit different needs

Bad:

Strong pain pills can be addictive and cause problems
Some treatments don’t work for all types of pain
Different people respond differently to treatments

When we look at D-phenylalanine next to other pain treatments, we see it doesn’t work much better than a fake pill. Only 25% of people said it helped more, compared to 22% for the fake pill. This means it might help a little, but not a lot.

Other treatments, like strong pain pills, can help more but have bigger risks. Mixing treatments, like using D-amino acids with electric acupuncture, looks good and might help in more ways.

10. Gaps in Current Research

10.1 What’s Missing in Current Studies

Current studies on phenylalanine for chronic pain in CFS/ME lack:

Big studies with many people
Long-term follow-ups
Focus on CFS/ME patients specifically

Most studies are small, making it hard to apply results to everyone.

10.2 Problems with Study Methods

Issues with current studies include:

Problem	Explanation
Poor control groups	Many studies don’t compare to fake treatments well
Different doses	Studies use different amounts, making it hard to find the best dose
Varied ways to measure pain	Makes it hard to compare results between studies

10.3 Need for More Research

We need more studies that:

Use many CFS/ME patients
Find the best amount and time to take phenylalanine
Check if it’s safe to use for a long time
Use the same ways to measure pain relief
Look at how phenylalanine works with other CFS/ME treatments

We also need to understand better how phenylalanine might help with pain in CFS/ME. This means looking more at how it affects tiredness after activity and other body processes.

11. What to Study Next

11.1 Topics for Future Research

Future studies on phenylalanine for chronic pain should look at:

Big studies with many CFS/ME patients
How safe and helpful phenylalanine is when used for a long time
The best amount to take and for how long
How phenylalanine works with other CFS/ME treatments
How phenylalanine helps with pain in CFS/ME patients

These studies would give us better information about using phenylalanine for pain in CFS/ME.

11.2 How to Make Future Studies Better

To make future research on phenylalanine for chronic pain more useful, studies should:

Improvement	How to Do It
Study Design	Use studies where no one knows who gets the real treatment
Number of People	Use more than 100 people in each study
How Long to Study	Check on people for 6-12 months after treatment
Measuring Pain	Use the same ways to measure pain in all studies
How Much to Take	Try different amounts to find what works best

12. Wrap-up

12.1 Main Points

The studies on D-phenylalanine for long-lasting pain show mixed results:

Result	Percentage of Patients
D-phenylalanine helped more	25%
Fake pill helped more	22%
No difference	53%

These numbers show that D-phenylalanine might not work well for most people with long-lasting pain. Some people felt better, but overall, it didn’t work much better than a fake pill.

12.2 What We Think

The studies don’t strongly support using D-phenylalanine to treat long-lasting pain. We need more research to:

Find out who it might help most
Learn how it works in the body
Figure out the best amount to take and for how long
Check if it’s safe to use for a long time

Keep in mind that the studies we have are small and done in different ways, so we can’t be sure about the results.

12.3 What This Means for Treatment

Here’s what to think about when deciding whether to use D-phenylalanine for long-lasting pain:

Thing to Consider	What to Do
How well it works	It might help some people, but not most
Who should try it	People who haven’t found help with other treatments
Watching for problems	Keep track of pain levels and side effects
Using with other treatments	It might work better when used with other pain treatments
Safety	Most people don’t have problems, but watch for side effects
What to expect	Don’t expect it to work miracles

If you have long-lasting pain, including CFS/ME, talk to your doctor about D-phenylalanine. It might be part of a bigger plan to manage pain, but it shouldn’t be the only treatment you use.

13. References

Here’s a list of the main studies and papers we looked at:

Author(s)	Year	Study Title	Journal
McGregor, N. R.	2019	Post-exertional malaise is associated with hypermetabolism, hypoacetylation and purine metabolism deregulation in ME/CFS cases	Journal of Translational Medicine
Walsh, N. E., et al.	1986	Analgesic effectiveness of D-phenylalanine in chronic pain patients	Archives of Physical Medicine and Rehabilitation
Halpern, L. M., & Dong, W. K.	1986	d-Phenylalanine: a putative enkephalinase inhibitor studied in a primate acute pain model	Pain
Freeman, T. B., et al.	1990	Augmented analgesic effects of L-tryptophan combined with low current transcranial electrostimulation	Life Sciences
Fischer, E., et al.	1975	Therapy of depression by phenylalanine. Preliminary note	Arzneimittel-Forschung
Beckmann, H., et al.	1977	DL-phenylalanine in depressed patients: an open study	Journal of Neural Transmission
Adema, D.	n.d.	Milk Thistle to Enhance Liver Function and Drug Therapy	Clinical recommendation

These studies cover different aspects of phenylalanine use, including:

Its effects on chronic pain
How it might work in the body
Its use for other health issues like depression
How it might help people with CFS/ME

The list includes both older and newer studies, giving a broad view of phenylalanine research over time.

Phenylalanine for Chronic Pain: Research Review