Phenylalanine for Chronic Pain: Research Review

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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:

  1. L-phenylalanine: Found in food proteins
  2. D-phenylalanine: Man-made version
  3. 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


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

  1. It may stop the breakdown of enkephalins, which are natural pain-fighters in your body.

  2. L-phenylalanine can change into other chemicals in the brain that affect mood and pain.

  3. 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:

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:

  1. Visual scale: Patients marked their pain level on a line
  2. 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:

  1. DPA didn’t seem to work well for any type of long-lasting pain.
  2. 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.
  3. 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
Feeling tired
Upset stomach
Hard stools
Feeling dizzy
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



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


  • 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


  • 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


  • 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:

  1. Use many CFS/ME patients
  2. Find the best amount and time to take phenylalanine
  3. Check if it’s safe to use for a long time
  4. Use the same ways to measure pain relief
  5. 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:

  1. Big studies with many CFS/ME patients
  2. How safe and helpful phenylalanine is when used for a long time
  3. The best amount to take and for how long
  4. How phenylalanine works with other CFS/ME treatments
  5. 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:

  1. Find out who it might help most
  2. Learn how it works in the body
  3. Figure out the best amount to take and for how long
  4. 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.

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