Phe for Me? The Effects of L-Phe on PKU Carriers and Non-carriers (Phe for Me)

Phe for Me? A Precision Nutrition Clinical Trial of Metabolic, Cardiovascular, and Neurocognitive Responses to Phenylalanine Among Carriers and Non-carriers of PKU

This is a clinical intervention study of PKU carriers (cases) and non-carriers (controls). Upon completing the informed consent process, participants will complete baseline measures of chronic mental health prior to the intervention (PHQ-9, GAD-7, BIS-11). Participants will attend the Human Nutraceutical Research Unit (HNRU) at the University of Guelph, fasted, and first undergo baseline measures of cognition and acute mental health (mood) and provide samples or saliva, urine and dried blood spots to evaluate phenylalanine (Phe), tyrosine (Tyr) and their metabolites (PAH pathway functioning) as well as for genetic testing of the PAH gene. Participants will also complete a brief questionnaire which will include age, sex, ethnicity, income, weight and height (measured using a stadiometer and calibrated weigh scale), and confirmation that participants arrived to the lab fasted (i.e. have only had water to drink and no other foods/ beverages prior to analyses). Blood pressure and heart rate will also be measured at baseline.

Following baseline tests, participants will consume a pure L-Phe supplement dosed at 100 mg/kg mixed with 125 mL of water and 125mL of orange juice. Blood pressure and heart rate will be repeated at 1-hour post-L-Phe consumption. Two-hours postprandial, participants will repeat the cognitive tests and acute mental health (mood) assessment, blood pressure and heart rate measurement and provide follow-up saliva, urine and dried blood spot samples. Participants will also be asked to report any side effects they experienced with the L-Phe consumption.

Study Overview

• Status: Completed
• Conditions: Autosomal Recessive Disorder (Genetic Carriers of PKU)
• Intervention / Treatment: Dietary supplement: L-Phenylalanine

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Guelph, Ontario, Canada, N1G 2W1
      • University of Guelph

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Carrier or non-carrier of PKU
• At least 18 Years of age
• Comfortable fasting the morning of the study (no food or drink other than water)

Exclusion Criteria:

• Diagnosed with: PKU, severe neurodegenerative conditions affecting cognition (e.g. Alzheimer's, Parkinson's, dementia), melanoma, hypertension, liver disease and/or kidney disease
• Diagnosed with hypertension or hypotension
• Taking a monoamine oxidase inhibitor anti-depressant
• Pregnant or breastfeeding
• Orange/citrus allergy or intolerance
• Body weight 150 kg or greater
• History of fainting during blood sampling

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Genetic Carriers and Non-Carriers of PKU	Dietary supplement: L-Phenylalanine; 100 mg/kg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stop Signal Reaction Time	Response Inhibition	Change from baseline to 2-hours post L-Phe supplementation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Working Memory	N-Back Test Outcome	Change from baseline to 2-hours post L-Phe supplementation
Blood Pressure	Systolic and Diastolic	Change from baseline to 1-hour and 2-hours post L-Phe supplementation
Individual Coefficient of Variance (Variability in Reaction Time)	Stop Signal Task Outcome	Change from baseline to 2-hours post L-Phe supplementation
Phenylalanine Metabolites	e.g. phenylethylamine, tyramine, phenylpyruvate, others	Change from baseline to 2-hours post L-Phe supplementation
Tyrosine Metabolites	e.g. L-DOPA, dopamine, norepinephrine, epinephrine, p-hydroxyphenylpyruvate, homogentisic acid, fumarate, others	Change from baseline to 2-hours post L-Phe supplementation
Mood	Profile of Mood State (POMS) Outcome	Change from baseline to 2-hours post L-Phe supplementation
Side Effects Following L-Phe Consumption	To be monitored throughout the visit to the research unit	0-3 hours post L-Phe consumption
Phenylalanine Levels	Blood, saliva and urine sample analyses	Change from baseline to 2-hours post L-Phe supplementation
Tyrosine Levels	Blood, saliva and urine sample analyses	Change from baseline to 2-hours post L-Phe supplementation
Heart rate	BPM	Change from baseline to 1-hour and 2-hours post L-Phe supplementation

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trial-by-Trial Analysis	to be conducted if there are significant findings from the four main stop signal task outcomes	Change from baseline to 2-hours post L-Phe supplementation
Chronic Anxiety	GAD-7 Outcome (higher scores indicate worse anxiety: range of 0 to >15)	Baseline
Chronic Depression	PHQ-9 Outcome (higher scores indicate worse depression: range of 0 to 27)	Baseline
Impulsivity	BIS-11 Outcome (higher scores indicate more impulsivity: range 30 to 120)	Baseline

Collaborators and Investigators

• Sponsor: University of Guelph
• Collaborators: McMaster University; Laval University

Study record dates

Study Major Dates

• Study Start (Actual): June 18, 2024
• Primary Completion (Actual): October 3, 2025
• Study Completion (Actual): October 3, 2025

Study Registration Dates

• First Submitted: October 31, 2023
• First Submitted That Met QC Criteria: October 31, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): May 4, 2026
• Last Update Submitted That Met QC Criteria: April 28, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Amino Acids; Amino Acids, Essential; Amino Acids, Aromatic; Amino Acids, Cyclic; Phenylalanine
• Other Study ID Numbers: 23-03-017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No