L-Phenylalanine for Gut Health

Overseen By Aurelia Li, MS

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Weill Medical College of Cornell University

Must not be taking: Antibiotics, Antifungals, MOAI, others

Disqualifiers: Gastrointestinal conditions, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests how the supplement L-Phenylalanine affects gut health by observing changes in a specific metabolite and fungal populations in the gut. Participants will take the supplement daily for two weeks. It is particularly suitable for healthy adults without a history of gut issues, such as inflammatory bowel disease, who haven't recently taken antibiotics, and who aren't allergic to L-Phenylalanine. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits more patients.

Will I have to stop taking my current medications?

You may need to stop taking certain medications that interact with L-Phenylalanine, like Monoamine Oxidase Inhibitors (MOAI), L-DOPA, and some antipsychotic drugs. A complete list of these medications will be provided during screening.

What is the safety track record for L-Phenylalanine?

Research has shown that L-Phenylalanine is generally safe for short-term use. It has been used in special medical foods for over a year and is usually well-tolerated. Some individuals might experience mild side effects, such as anxiety or headaches. L-Phenylalanine is an amino acid, a building block of protein. Most people can take it without issues, but those with certain genetic conditions should exercise caution. Overall, based on available information, the treatment appears safe. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

L-Phenylalanine is unique because it uses an amino acid to potentially improve gut health, which is different from typical treatments like probiotics or dietary changes. This compound is a building block for proteins and may support gut function in a novel way. Researchers are excited about its potential to offer a simple, capsule-based approach that could work in just two weeks, providing a quicker and more convenient option for enhancing gut health.

What evidence suggests that L-Phenylalanine might be an effective treatment for gut health?

Research has shown that L-Phenylalanine, the treatment under study in this trial, might significantly affect the gut's balance of microorganisms. A recent study found that this amino acid could alter the types of fungi in the gut, potentially impacting gut health. Another study discovered that individuals with certain health conditions process L-Phenylalanine differently than healthy individuals. This suggests that L-Phenylalanine might influence gut health by altering its metabolism. While evidence exists of its effects on the gut, researchers continue to study its exact impact on producing specific substances like phenylpropionic acid (PPA). ^{5 6 7 8 9}

Who Is on the Research Team?

Iliyan D Iliev, PhD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for healthy volunteers interested in how a dietary supplement, L-Phenylalanine, might affect their gut health. Specific eligibility criteria are not provided, but typically participants should be free from the conditions being studied and meet any additional requirements set by the researchers.

Inclusion Criteria

I am over 18 years old.

Exclusion Criteria

I have not taken antibiotics in the last two weeks.

Allergy to L-Phenylalanine or individuals with phenylketonuria (PKU)

Pregnant or nursing women

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive L-Phenylalanine supplements for 14 days

2 weeks

1 visit (in-person) at Day 0

Follow-up

Participants are monitored for changes in phenylpropionic acid levels and fungal populations

2 weeks

1 visit (in-person) at Week 4

What Are the Treatments Tested in This Trial?

Interventions

• L-Phenylalanine

Trial Overview The study is testing the effects of a 500 mg L-Phenylalanine capsule on gut fungal populations and production of phenylpropionic acid (PPA) in healthy individuals to understand its potential benefits for gut microbiome health.

How Is the Trial Designed?

Group I: Healthy Experimental Treatment 1 Intervention

Participants will receive one bottle of L-Phenylalanine 500 mg Veg Capsule product on Day 0. All subjects will be asked to start taking the supplement on Day 1 continuing until Day 14. They will be asked to take 2x 500 mg capsules in the morning and 1x 500 mg capsule in the evening daily for 14 days.

L-Phenylalanine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as L-Phenylalanine for:

• Dietary supplement
• Medical food for phenylketonuria management

Approved in European Union as L-Phenylalanine for:

• Dietary supplement
• Medical food for phenylketonuria management

Approved in Canada as L-Phenylalanine for:

• Dietary supplement
• Medical food for phenylketonuria management

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Published Research Related to This Trial

The new amino acid mixture for treating hyperphenylalaninemia has been found to be safe and well tolerated after over a year of clinical testing as a beverage.

While the mixture can be easily incorporated into various foods without altering taste, it does not provide better control of plasma phenylalanine levels compared to other existing products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A new amino acid mixture permits new approaches to the treatment of phenylketonuria. Buist, NR., Prince, AP., Huntington, KL., et al.[2019]

The increasing use of amino acids from various sources necessitates thorough safety assessments due to the potential for high intake levels that exceed normal dietary amounts.

Establishing reliable Tolerable Upper Intake Levels (ULs) for amino acids is challenging due to insufficient toxicity studies and lack of clinical data, highlighting the need for comprehensive safety evaluations that include quality specifications and potential interactions with medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Importance of Quality Specifications in Safety Assessments of Amino Acids: The Cases of l-Tryptophan and l-Citrulline. Oketch-Rabah, HA., Roe, AL., Gurley, BJ., et al.[2023]

The Phenylalanine Content of Foods system, revised to include 372 food items, provides essential dietary guidance for managing phenylketonuria (PKU) by detailing serving sizes and phenylalanine equivalents.

This system has been adapted to create a low protein equivalency system, which can also assist in designing low protein diets for other inherited metabolic disorders, enhancing dietary management options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revision of the Ontario phenylalanine equivalency system and development of a low protein equivalency system. Chan, L., Bell, L., Hanley, WB.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12554740/

Impact of gut probiotic metabolites on phenylketonuria - PMC The primary treatment for phenylketonuria disease is the restriction of Phenylalanine from the patient's diet, augmented with L-AA. Trillions of ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1043661825002191

Gut microbiota-derived metabolite phenylacetylglutamine ... Research has demonstrated that PAGln is associated with many diseases, such as cardiovascular diseases, gastrointestinal diseases, infectious diseases, and ...

3. nature.com nature.com/articles/s43587-025-00864-8

Gut microbiota-dependent increase in phenylacetic acid ... We demonstrate that colonization of young mice with Clos increases blood PAA levels and induces endothelial senescence and angiogenic incompetence.

4. clinicaltrials.eu clinicaltrials.eu/inn/l-phenylalanine/

L-Phenylalanine: Understanding Its Effects on Gut Mycobiota A recent clinical trial examined how L-Phenylalanine supplements might influence the gut microbiome, particularly focusing on fungal populations. This amino ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11899578/

Disrupted microbial cross-feeding and altered L ... The flux of L-phenylalanine consumption was significantly lower in HIV-infected individuals compared with healthy controls, correlating with a ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5678004/

l-phenylalanine modulates gut hormone release and glucose ... Conclusions: l-Phe reduced food intake, stimulated GLP-1 and PYY release, and reduced plasma ghrelin in rodents. Our data provide evidence ...

7. webmd.com webmd.com/vitamins/ai/ingredientmono-653/phenylalanine

Phenylalanine - Uses, Side Effects, and More L-phenylalanine, D-phenylalanine, and DL-phenylalanine are possibly safe when used as medicine, short-term. Side effects might include anxiety, headache, and ...

8. mayoclinic.org mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/expert-answers/phenylalanine/faq-20058361

Phenylalanine in diet soda: Is it harmful? Phenylalanine is an amino acid, a building block of protein. Most people don't need to worry about it. But it is an issue for people who have a genetic ...

9. withpower.com withpower.com/trial/l-phenylalanine-for-gut-health-a01eb

L-Phenylalanine for Gut Health L-Phenylalanine has been used in medical foods for over a year and is considered safe and well tolerated in humans, although it may not control blood levels of ...