L-Phenylalanine for Gut Health

Overseen By Aidan A Conroy, BA

Age: 18+

Sex: Any

Trial Phase: Phase < 1

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)

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

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to explore how the dietary supplement L-Phenylalanine affects the production of the metabolite phenylpropionic acid (PPA) and changes fungal populations of the gut microbiome.

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.

Is L-Phenylalanine safe for human consumption?

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 phenylalanine better than other products. ^{1 2 3 4 5}

How does the drug L-Phenylalanine differ from other treatments for gut health?

L-Phenylalanine is unique because it helps improve gut health by remodeling the gut microbiota (the community of microorganisms in the intestines) and altering metabolite levels, which enhances intestinal motility and reduces inflammation, unlike other treatments that may focus on probiotics or neurotransmitter regulation. ^{6 7 8 9 10}

Research Team

Iliyan D Iliev, PhD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Special Low Protein Foods in the UK: An Examination of Their Macronutrient Composition in Comparison to Regular Foods. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

The Importance of Quality Specifications in Safety Assessments of Amino Acids: The Cases of l-Tryptophan and l-Citrulline. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Phenylketonuric diet negatively impacts on butyrate production. [2019]

4. Norway pubmed.ncbi.nlm.nih.gov

A new amino acid mixture permits new approaches to the treatment of phenylketonuria. [2019]

5. Canada pubmed.ncbi.nlm.nih.gov

Revision of the Ontario phenylalanine equivalency system and development of a low protein equivalency system. [2013]

6. England pubmed.ncbi.nlm.nih.gov

An investigation into the effect of a probiotic on gut immune function in surgical patients. [2006]

7. United States pubmed.ncbi.nlm.nih.gov

Lactobacillus plantarum PS128 Promotes Intestinal Motility, Mucin Production, and Serotonin Signaling in Mice. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Lactiplantibacillus plantarum GUANKE on Diphenoxylate-Induced Slow Transit Constipation and Gut Microbiota in Mice. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Integrated metagenomics and targeted-metabolomics analysis of the effects of phenylalanine on loperamide-induced constipation in rats. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Soluble proteins produced by probiotic bacteria regulate intestinal epithelial cell survival and growth. [2022]