Exercise + Amino Acid Infusion for Obesity

Overseen By Lori R Roust

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Must not be taking: Prescription drugs, OTC drugs

Disqualifiers: Diabetes, Heart disease, Liver disease, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 month

35 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Maintenance of protein homeostasis is impaired in skeletal muscle of humans with obesity. A hallmark of this defect is distorted expression of isoforms of the myosin heavy chain (MHC) protein, and this defect is linked to obesity-associated adverse health outcomes. By employing exercise and increase in plasma amino acids as investigational tools the investigators intend to modulate the metabolism of muscle MHC isoforms in order to unravel the biological mechanisms that sustain distorted MHC protein metabolism in muscle of humans with obesity.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any prescription or over-the-counter medications, as well as supplements that affect protein metabolism, to participate in this trial.

Is the combination of exercise and amino acid infusion safe for humans?

Amino acid infusions have been linked to side effects like acidosis (too much acid in the body), hyperammonemia (high ammonia levels), and possible bone and liver issues. Exercise combined with amino acid infusion in studies has shown increased amino acid turnover in muscles, but no specific safety concerns were noted in the context of exercise. ^{1 2 3 4 5}

How does the treatment of exercise combined with amino acid infusion for obesity differ from other treatments?

This treatment is unique because it combines physical activity with the infusion of amino acids, which may enhance fat burning and energy expenditure. The amino acids, particularly branched-chain amino acids, can increase protein synthesis and muscle function, potentially leading to better weight management compared to traditional diet and exercise alone. ^{1 2 3 6 7}

What data supports the effectiveness of the treatment Exercise + Amino Acid Infusion for Obesity?

Research suggests that combining exercise with amino acid supplementation can help increase fat burning and improve muscle protein metabolism. Specifically, amino acids like phenylalanine may enhance fat oxidation (the process of breaking down fat for energy) when paired with exercise, and exercise itself can improve amino acid turnover in muscles, which is beneficial for weight management. ^{1 2 6 8 9}

Who Is on the Research Team?

Christos S Katsanos, PhD

Principal Investigator

Arizona State University

Lori R Roust, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults with obesity, having a BMI of 32-50 kg/m2. They must be able to consent to the study and should not have acute illnesses, liver or severe heart disease, low blood counts, recent steroid use, extreme diets like veganism, or be on weight-loss regimens. Smokers and pregnant individuals are excluded.

Inclusion Criteria

Body mass index (BMI), 18-26 kg/m2 (lean subjects), 32-50 kg/m2 (subjects with obesity)

Ability to sign informed consent form

Exclusion Criteria

I do not have any uncontrolled metabolic or kidney diseases.

I have not used anabolic steroids or corticosteroids in the last 3 months.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo exercise and/or amino acid infusion to evaluate changes in muscle protein metabolism

1 month

2 visits (in-person)

Follow-up

Participants are monitored for changes in muscle protein synthesis and breakdown after interventions

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Exercise
• Infusion of Amino Acids

Trial Overview The trial investigates how exercise combined with amino acid infusions affects muscle protein regulation in obese individuals. It aims to understand how these interventions can correct protein imbalances linked to poor health outcomes in obesity.

How Is the Trial Designed?

Group I: Exercise, Infusion of Amino Acids Experimental Treatment 2 Interventions

Exercise followed by infusion of amino acids, or infusion of amino acids alone.

Group II: Exercise Active Control 1 Intervention

Exercise with no infusion of amino acids

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study involving obese prediabetic ZDF rats, swimming exercise significantly reduced elevated plasma concentrations of essential amino acids and altered protein metabolism without affecting food intake or weight gain.

The exercise improved hyperglycemia independently of body weight changes, suggesting that it may help regulate blood sugar levels by modulating muscle AKT activation and systemic amino acid metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise in ZDF rats does not attenuate weight gain, but prevents hyperglycemia concurrent with modulation of amino acid metabolism and AKT/mTOR activation in skeletal muscle. Adegoke, OA., Bates, HE., Kiraly, MA., et al.[2021]

In a study involving six healthy male volunteers, supplementation with L-phenylalanine before exercise significantly increased plasma glycerol and glucagon levels, indicating enhanced fat mobilization during physical activity.

The results suggest that taking L-phenylalanine prior to exercise may promote fat oxidation without any serious side effects, making it a potentially effective strategy for improving fat loss during workouts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of phenylalanine on exercise-induced fat oxidation: a preliminary, double-blind, placebo-controlled, crossover trial. Ueda, K., Sanbongi, C., Yamaguchi, M., et al.[2022]

In a study involving 20 male Sprague-Dawley rats, exercise as an adjunct to parenteral nutrition did not significantly affect nitrogen balance or body weight compared to nonexercised rats, indicating that exercise alone may not enhance overall recovery in this context.

However, exercised rats showed a 15% decrease in plasma amino acids but a 66% increase in muscle amino acids, suggesting that exercise stimulates amino acid turnover in muscle, which may support energy metabolism and protein synthesis without altering nitrogen balance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of exercise on postoperative nitrogen balance. Freund, H., Yoshimura, N., Fischer, JE.[2017]

In a 12-week study involving 35 overweight adults, both medium (1,500 mg/d) and low (750 mg/d) doses of an amino acid mixture showed potential in reducing abdominal fat compared to a placebo, with the medium dose resulting in a notable average reduction of -25.3 cm² in total abdominal fat area.

No adverse events were reported during the trial, indicating that the amino acid mixture is safe for use in conjunction with physical activity promotion, but further research with a larger sample size is needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-ranging pilot randomized trial of amino acid mixture combined with physical activity promotion for reducing abdominal fat in overweight adults. Sasai, H., Ueda, K., Tsujimoto, T., et al.[2022]

Branched-chain amino acid (BCAA) solutions may help normalize amino acid levels in patients with hepatic encephalopathy, but controlled trials show little impact on clinical outcomes, especially in acute liver failure or liver transplantation.

Amino acid infusions can enhance ventilatory drive, but they also carry risks of side effects like acidosis and hyperammonemia, highlighting the need for careful use and further research into their effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

General and specialized parenteral amino acid formulations for nutrition support. Heyman, MB.[2006]

Amino acids, particularly leucine and its metabolite HMB, play a crucial role in activating mTORC1, which enhances protein synthesis in skeletal muscle, highlighting their importance in muscle health and recovery.

Supplementation with β-alanine has been shown to improve physical performance and cognitive function in middle-aged individuals, suggesting potential benefits for aging populations and athletes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulation of Skeletal Muscle Function by Amino Acids, Especially Non-Proteinogenic Amino Acids. Sugimoto, T., Kamei, Y.[2022]

Consuming an essential amino acid-carbohydrate supplement (EAC) immediately before resistance exercise leads to a significantly greater increase in muscle protein synthesis compared to taking it after exercise, as shown in a study with six healthy participants.

The study found that amino acid delivery to the muscles was higher during and immediately after exercise when the EAC was consumed before the workout, resulting in a total net phenylalanine uptake of 209 mg compared to 81 mg when taken after exercise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Timing of amino acid-carbohydrate ingestion alters anabolic response of muscle to resistance exercise. Tipton, KD., Rasmussen, BB., Miller, SL., et al.[2022]

In a study involving 20 postoperative coronary bypass patients and 6 healthy volunteers, both balanced amino acid and BCAA-enriched solutions increased resting energy expenditure (REE), with the BCAA solution showing a significantly higher thermogenic response in patients (46.9% vs. 28.5%).

Healthy volunteers only experienced an increase in REE with the balanced amino acid solution, indicating that BCAAs may have a lower energy cost for metabolism and less thermogenic effect compared to balanced amino acids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Branched-chain and mixed amino acid solutions and thermogenesis in postoperative patients. Pitkänen, O., Takala, J., Pöyhönen, M., et al.[2004]

In a study involving 26 brain-dead patients, the infusion of amino acid solutions did not lead to an increase in energy expenditure or thermogenesis, suggesting that these effects may be absent in this population.

The findings indicate a potential central pathway that regulates energy expenditure and thermogenesis, as predicted energy expenditure was higher than resting energy expenditure, but no significant metabolic changes were observed during the amino acid infusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thermogenic and metabolic response to amino acid solution in brain-dead patients. Cankayali, I., Demirağ, K., Kocabaş, S., et al.[2015]

Citations

1. Germany pubmed.ncbi.nlm.nih.gov

Exercise in ZDF rats does not attenuate weight gain, but prevents hyperglycemia concurrent with modulation of amino acid metabolism and AKT/mTOR activation in skeletal muscle. [2021]

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

The effects of phenylalanine on exercise-induced fat oxidation: a preliminary, double-blind, placebo-controlled, crossover trial. [2022]

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

Effect of exercise on postoperative nitrogen balance. [2017]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Dose-ranging pilot randomized trial of amino acid mixture combined with physical activity promotion for reducing abdominal fat in overweight adults. [2022]

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

General and specialized parenteral amino acid formulations for nutrition support. [2006]

6. Japan pubmed.ncbi.nlm.nih.gov

Regulation of Skeletal Muscle Function by Amino Acids, Especially Non-Proteinogenic Amino Acids. [2022]

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

Timing of amino acid-carbohydrate ingestion alters anabolic response of muscle to resistance exercise. [2022]

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

Branched-chain and mixed amino acid solutions and thermogenesis in postoperative patients. [2004]

9. Turkey pubmed.ncbi.nlm.nih.gov

Thermogenic and metabolic response to amino acid solution in brain-dead patients. [2015]