Amino Acid Supplements for Protein Metabolism

Recruiting in Palo Alto (17 mi)

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Texas A&M University

Must not be taking: Oral corticosteroids

Disqualifiers: Malignancy, Metabolic diseases, Pregnancy, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

Previous studies suggest that changes in metabolism due to the effects of aging might serve as a potential for therapeutic agents. The investigating lab developed a pulse method combining multiple stable isotopes to study multiple metabolic pathways in the same individual simultaneously. By measuring whole-body metabolism in a large group of older adults, the investigators may be able to unravel age-related deterioration in protein turnover (synthesis and breakdown) that contributes to impaired functional capacity. Metabolic profiles could explain differences in pathways in the aging process with special interest in metabolism of amino acids as they have been associated with aging-related disorders.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are using oral corticosteroids, you must not have taken them within 4 weeks before the study.

What data supports the effectiveness of this treatment?

Research shows that essential amino acid (EAA) supplements can help improve muscle protein synthesis, especially in older adults and those with chronic conditions like COPD. EAAs are more effective than complete protein supplements in stimulating muscle growth and improving nutritional status. ^{1 2 3 4 5}

Is it safe to take essential amino acid supplements?

Research suggests that essential amino acids are generally well tolerated in healthy adults, with specific upper intake levels identified for some amino acids. Studies have shown that combinations like HMB with amino acids are also considered safe, although the safety of each mixture should be evaluated individually. ^{2 6 7 8 9}

How does the amino acid supplement treatment differ from other treatments for protein metabolism?

This treatment is unique because it combines essential amino acids with specific compounds like leucine and HMB, which may enhance muscle protein synthesis (the process of building muscle) more effectively than standard amino acid supplements, especially during exercise or energy deficit. ^{2 7 10 11 12}

Research Team

Eligibility Criteria

This trial is for healthy adults aged 60-80 who have maintained a stable body weight and can move around independently. They must be able to lie down for up to 7 hours and follow the study's procedures. People with acute illnesses, unstable chronic conditions, current cancer, untreated metabolic diseases like liver or kidney disorders, recent fever, steroid use within the last month, or those who are pregnant cannot participate.

Inclusion Criteria

Stable body-weight (± 5%) for the past 3 months

Subject is judged to be in satisfactory health based on medical history, physical examination, and laboratory screening evaluations

I can lie on my back or slightly raised for up to 7 hours.

Exclusion Criteria

I have been diagnosed with cancer.

I do not have any severe or unstable illnesses right now.

Possible pregnancy

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 hours

1 visit (in-person)

Study Days

Participants undergo metabolic testing with stable isotopes and nutritional supplements

6 days

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Essential Amino Acids (Dietary Supplement)
• Essential Amino Acids High (Dietary Supplement)
• Essential Amino Acids + Hydroxy-methylbutyric acid (HMB) (Dietary Supplement)
• Essential Amino Acids + Leucine (Dietary Supplement)
• Placebo Water (Behavioural Intervention)
• Total Amino Acids (Dietary Supplement)

Trial Overview The study tests how different combinations of amino acids affect protein metabolism in older adults. Participants will receive either Essential Amino Acids with HMB (a muscle health supplement), Essential Amino Acids with Leucine (an important nutrient for muscle), regular Essential Amino Acids, Total Amino Acids mixtures at high levels or placebo water to compare effects on aging-related changes in metabolism.

Participant Groups

Group I: Healthy male older adults Experimental Treatment 6 Interventions

Healthy male older adults

Group II: Healthy female older adults Experimental Treatment 6 Interventions

Healthy female older adults

Essential Amino Acids is already approved in Canada, Japan for the following indications:

Approved in Canada as Essential Amino Acids for:

• Nutritional deficiencies
• Malnutrition
• Wound healing

Approved in Japan as Essential Amino Acids for:

• Nutritional deficiencies
• Malnutrition
• Wound healing

Who Is Running the Clinical Trial?

Texas A&M University

Lead Sponsor

Trials

156

Recruited

28,900+

Jeremy Gibson

Texas A&M University

Chief Medical Officer

MD

William “BJ” Jones

Texas A&M University

Chief Executive Officer

M.S. in Industrial Engineering from Texas A&M University

Findings from Research

In a comparison of essential amino acid (EAA) supplementation and keto-analogues (KA) in patients with chronic uremia, KA supplementation after EAA led to a reduction in urea levels and improved nitrogen balance across 9 studies.

Long-term KA treatment (3-9 months) in 7 patients resulted in notable improvements in renal function for some, with 5 patients remaining asymptomatic for periods of 3-8 months, suggesting potential benefits of KA in managing chronic kidney conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketoacids in the treatment of uremia. Walser, M.[2013]

In a study involving rats with uremia, essential amino acids (EAA) improved nutritional status and reduced blood urea nitrogen (BUN) levels compared to standard amino acids (SAA), indicating better efficacy for managing renal failure.

However, administering EAA requires a higher calorie and lower nitrogen ratio (Cal/N 600) to avoid complications, while SAA can be safely used at Cal/N 300, although it presents issues with nitrogen availability and plasma amino acid balance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Amino acid supplementation to hyperalimentation in uremic rats: effects of amount and composition of amino acids on nutrition and uremia. Kikuchi, T., Tanaka, H., Kokuba, Y., et al.[2019]

A leucine-enriched whey protein supplement with lower calories significantly increases serum levels of total amino acids (TAA), essential amino acids (EAA), and leucine in healthy older adults compared to casein protein or higher calorie options.

The differences in amino acid absorption are influenced by the gastrointestinal behavior of the protein sources, with whey protein showing better digestion and absorption than casein.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protein type and caloric density of protein supplements modulate postprandial amino acid profile through changes in gastrointestinal behaviour: A randomized trial. Luiking, YC., Abrahamse, E., Ludwig, T., et al.[2022]

In a study of 32 patients with severe COPD and sarcopenia, oral supplementation of essential amino acids (EAAs) for three months led to significant improvements in body weight (increased by 6 kg) and fat-free mass (increased by 3.6 kg), indicating enhanced nutritional status and muscle metabolism.

The EAA supplementation also resulted in improved physical activity (increased by 80%) and cognitive function (MMSE score improved from 19.1 to 20.8), suggesting that EAAs may positively impact overall health and quality of life in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive effects of supplemented essential amino acids in patients with severe COPD and sarcopenia. Dal Negro, RW., Aquilani, R., Bertacco, S., et al.[2016]

There has been a significant rise in the use of individual amino acids as dietary supplements, driven by their perceived health benefits and effects on physical and psychological performance.

Current reviews indicate that while there is some evidence regarding the safety of amino acids, most studies focus on animal research, and more comprehensive human safety data is needed, especially concerning the effects of excessive intake compared to dietary protein sources.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The nature of human hazards associated with excessive intake of amino acids. Garlick, PJ.[2023]

In a study involving 19 young males, consuming high doses of essential amino acids (0.3 g/kg) significantly improved whole-body protein synthesis and breakdown during energy deficits compared to standard doses (0.1 g/kg), indicating better overall protein status.

Despite the enhanced protein turnover with high EAA intake, both high and standard EAA consumption resulted in similar rates of muscle protein synthesis, suggesting that there is a threshold for maximizing muscle protein synthesis even during energy deficits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of high versus standard essential amino acid intakes on whole-body protein turnover and mixed muscle protein synthesis during energy deficit: A randomized, crossover study. Gwin, JA., Church, DD., Hatch-McChesney, A., et al.[2021]

A comprehensive review of clinical studies has established the first tolerable upper intake levels (ULs) for several essential and nonessential amino acids, indicating that they are generally well tolerated in healthy adults.

Specific ULs were determined for amino acids such as leucine (35 g/d for young adults), tryptophan (4.5 g/d), and arginine (30 g/d), which can guide safety standards for amino acid supplementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerable Upper Intake Level for Individual Amino Acids in Humans: A Narrative Review of Recent Clinical Studies. Elango, R.[2023]

The combination of HMB, arginine, and glutamine is safe for use in treating muscle wasting in patients with AIDS and cancer, as shown in three double-blind studies involving a total of 109 participants.

Supplementation with these amino acids led to positive health outcomes, including improved emotional well-being and increased red blood cell counts, without any significant adverse health effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supplementation with a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters. Rathmacher, JA., Nissen, S., Panton, L., et al.[2022]

In a study involving 12 older adults, an egg-based breakfast led to a greater net protein balance compared to a cereal-based breakfast, primarily by reducing protein breakdown.

Despite differences in plasma essential amino acid levels after the meals, muscle protein synthesis rates were similar between the egg and cereal breakfasts, indicating that the quality of protein influences protein turnover rather than directly enhancing muscle protein synthesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quality of meal protein determines anabolic response in older adults. Kim, IY., Shin, YA., Schutzler, SE., et al.[2023]

Supplementing with a higher concentration of leucine (3.5 g) during moderate endurance exercise significantly increased muscle protein synthesis (MPS) by 33% compared to a lower concentration (1.87 g), indicating that leucine plays a crucial role in muscle recovery.

The study also found that whole-body protein breakdown and synthesis were lower after consuming the leucine-enriched supplement, suggesting improved protein metabolism during recovery, while key signaling pathways related to muscle growth were activated regardless of leucine concentration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Leucine-enriched essential amino acid supplementation during moderate steady state exercise enhances postexercise muscle protein synthesis. Pasiakos, SM., McClung, HL., McClung, JP., et al.[2023]

In a study involving 10 maintenance dialysis patients and 6 healthy individuals, it was found that dialysis patients had significantly lower total body clearance of certain essential amino acids (EAAs) like threonine, phenylalanine, valine, leucine, and isoleucine, indicating potential metabolic disorders in EAA processing.

The decreased clearance of branched-chain amino acids in dialysis patients suggests a defect in muscle metabolism, which could impact their overall amino acid utilization and nutritional status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of essential amino acids in chronic dialysis-patients. Chami, J., Reidenberg, MM., Wellner, D., et al.[2018]

References

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

Effectiveness of essential amino acid supplementation in stimulating whole body net protein anabolism is comparable between COPD patients and healthy older adults. [2019]

2. Germany pubmed.ncbi.nlm.nih.gov

Ketoacids in the treatment of uremia. [2013]

3. England pubmed.ncbi.nlm.nih.gov

Amino acid supplementation to hyperalimentation in uremic rats: effects of amount and composition of amino acids on nutrition and uremia. [2019]

4. England pubmed.ncbi.nlm.nih.gov

Protein type and caloric density of protein supplements modulate postprandial amino acid profile through changes in gastrointestinal behaviour: A randomized trial. [2022]

5. Italy pubmed.ncbi.nlm.nih.gov

Comprehensive effects of supplemented essential amino acids in patients with severe COPD and sarcopenia. [2016]

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

The nature of human hazards associated with excessive intake of amino acids. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Effects of high versus standard essential amino acid intakes on whole-body protein turnover and mixed muscle protein synthesis during energy deficit: A randomized, crossover study. [2021]

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

Tolerable Upper Intake Level for Individual Amino Acids in Humans: A Narrative Review of Recent Clinical Studies. [2023]

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

Supplementation with a combination of beta-hydroxy-beta-methylbutyrate (HMB), arginine, and glutamine is safe and could improve hematological parameters. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Quality of meal protein determines anabolic response in older adults. [2023]

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

Leucine-enriched essential amino acid supplementation during moderate steady state exercise enhances postexercise muscle protein synthesis. [2023]

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

Pharmacokinetics of essential amino acids in chronic dialysis-patients. [2018]