This study will be the first in the literature to evaluate the relationship between aerobic and resistance exercises, plasma amino acid levels, metabolic control of patients, and the metabolic response to exercise with different types of meals in patients with Phenylketonuria (PKU). In patients with phenylketonuria, the aim is to determine which pre-exercise dietary recommendations are more physiologically appropriate and ideal for achieving good metabolic control.

In the literature, there are very few studies examining the effects of exercise on plasma amino acid levels and metabolic parameters in PKU patients.

With this study, it is aimed to determine the effects of amino acid mixtures and carbohydrates on the plasma amino acid (phenylalanine, tyrosine, branched-chain aa, etc.) concentrations of patients with Classical Phenylketonuria (PKU) during different types of exercise and to investigate the hormonal responses to exercise. Adults (≥18 years) with classical phenylketonuria (PKU), who are on a phenylalanine-restricted diet and using amino acid substitutes, followed at the Hacettepe University Faculty of Medicine, Department of Pediatric Metabolism (outpatient clinic), will be assessed using the International Physical Activity Questionnaire (IPAQ) and dietary intake records. Based on these assessments and evaluation by sports medicine specialists, 10 participants deemed physically suitable will be allocated to the intervention group. The study, planned as a single-center, randomised, meal-based trial, will include 10 individuals with Classic Phenylketonuria (PKU) aged 18 and above, who are on a phenylalanine (PA) restricted diet and use an amino acid mixture.

All participants will be invited to the hospital on different days with a one-week interval for a total of 6 days. After a standard breakfast, they will perform 30 minutes of exercise before the amino acid mixture, amino acid+carbohydrate mixture, carbohydrate only, and water only, in two different types (3 aerobic + 3 resistance exercises) for a total of 6 exercises over 6 different weeks. On the first day of the study, the patients included will undergo blood FA level control, pre-exercise EKG measurement, and evaluation of exercise conditioning status. The daily protein requirement of the patients will be provided in the remaining meals, taking into account the amount consumed in their individual diets, using amino acid mixtures.

In the study, each patient will undergo both aerobic and resistance exercises separately in two different types of exercise (aerobic and resistance). Prior to these exercises, three different test diets (water only, carbohydrate only, carbohydrate+protein test diets) will be administered to monitor the patients' blood amino acid levels and some metabolic control parameters. Therefore, patients will have their blood profiles monitored for 2 hours each time they receive one type of exercise and one test diet once a week for 6 weeks (the washout period is 1 week). Before the exercise, 3 test diets will be administered with 2 types of exercise on 6 different days, and the analyses of plasma amino acid concentration, glucose, insulin, lactate, BUN, and creatinine levels will be evaluated. The content of the given test diets will be prepared.

Before exercise, 3 test diets will be administered on 6 different days with 2 types of exercise, and the analyses of plasma amino acid concentration, glucose, insulin, lactate, BUN, and creatinine levels will be evaluated. The content of the provided test diets will be prepared to include only water, only carbohydrates, and a mixture of amino acids + carbohydrates. The prepared test diets will be presented to the patient both before resistance and aerobic exercise, resulting in a total of 6 different measurements.

The plasma aa levels of the patients will be examined before breakfast (120 minutes before exercise), at the start of exercise (0 minutes of exercise), and in venous blood at 30-minute intervals over a 2-hour period. Two hours before exercise, blood samples will be taken at 0, 30, 60, 90, and 120 minutes to investigate plasma amino acid, glucose, insulin, and lactate levels. It is aimed to investigate the levels of essential amino acids such as blood FA, Tyrosine (Tyr), and Branched-Chain Amino Acids (BCAA), as well as plasma glucose, insulin, lactate, BUN, and creatinine levels in patients with aerobic exercise. The obtained data will be evaluated using appropriate statistical analysis methods.

All participants will be invited to the hospital on different days with a one-week interval, and two hours after a standard breakfast (different test diets 10 minutes before exercise), they will receive 1 g/kg/hour of carbohydrates, 0.4 g/kg/hour of protein equivalent amino acids (aa) + 1 g/kg/hour of carbohydrates, and fasting (only hydration with 200 ml of water) to determine their role in post-exercise blood metabolic parameters. At the same time, these test diets will also be applied before aerobic and resistance exercises to examine the changes according to the type of exercise. In the literature, there are very few studies examining the effects of exercise on plasma amino acid levels and metabolic parameters in PKU patients. Determining which dietary recommendations before exercise are more physiologically appropriate and ideal for achieving good metabolic control in patients with phenylketonuria will be guiding.

Inclusion Criteria:

• Be over 18 years old,
• Having a classic FKU diagnosis,
• Not being actively engaged in sports,
• Not having any other existing diseases,
• Not having an active infection,
• Have a BMI in the range of 20-28 kg/m2 within the last 3 months,
• Agreeing to consume test meals and provide blood samples for parameters that will evaluate plasma amino acid levels as part of the research
• Being willing to participate in this study

Exclusion Criteria:

• Presence of a chronic disease accompanying FKU disease (endocrine, etc.)
• The individual with FKU has mental retardation or is deemed unfit for work based on psychomotor assessment,
• Recent weight loss, history of hospitalisation, a past infection, or a diagnosed illness
• Use of drugs or alcohol that alter protein and energy metabolism (e.g., corticosteroids, etc.)
• Pregnancy status
• Smoking habits The considerations to be taken into account when planning the day/date of the test are as follows.
• Having engaged in heavy exercise or sports within 24 hours before the application of test diets,
• Being in the menstrual period for female patients.

The data can be obtained by contacting the author upon a reasonable request.