Effects of Dietary Amino Acids on Serum and Macrophage Atherogenicity

NCT03180775 | Unknown DMC

• 1 other identifier: 0566-16-RMB CTIL
• Study Type: interventional
• Target: 110
• Locations: 0 countries
• Sites: N/A

Brief Summary

Recently, the investigators have been screening for anti-atherogenic or pro-atherogenic amino acids (AAs) in the macrophage model system to better understand their role in atherogenesis. The findings so far suggest that specific AAs induce selective anti-atherogenic effects (glycine, alanine, leucine and cysteine) or pro-atherogenic effects (glutamate and glutamine) in macrophages. Taking together the above previous reports with the mechanisms behind macrophage foam cell formation and atherogenesis, it is possible that AAs could be anti-atherogenic or pro-atherogenic via their mechanism of action on macrophage foam cell formation. This paradigm may serve as a basis for the development of novel cardio-protective, anti-atherogenic nutritional, or therapeutic approaches, that should be studied in human trials.

Conditions

Atherosclerosis; Diet Modification; Serum; Disease

Keywords

Amino acids; Macrophage atherogenicity; Triglycerides; Cholesterol; Lipoproteins

Outcome Measures

Primary Outcomes (1)

• Serum atherogenicity

  Macrophage lipids (triglycerides and cholesterol) content (μg/mg cell protein) following incubation with serum derived from the subjects.

  1 year

Secondary Outcomes (3)

• Serum triglyceride concentration

  1 year

• Macrophage cholesterol content

  1 year

• Serum oxidation

  1 year

Study Arms (11)

Control

SHAM COMPARATOR

Other: Cellulose (control): cellulose, water soluble powder, 2 g in one daily dose, during 30 days

Other: Cellulose (control)

Glycine (Trade name: Glycine)

EXPERIMENTAL

Dietary Supplement: Glycine, water soluble powder, 7.8 g daily in one dose, during 30 days.

Dietary Supplement: Glycine

Alanine (Trade name: L-Alanine)

EXPERIMENTAL

Dietary Supplement: Alanine, water soluble powder, 8.5 g daily in one dose, during 30 days.

Dietary Supplement: Alanine

Leucine (Trade name: L-Leucine)

EXPERIMENTAL

Dietary Supplement: Leucine, water soluble powder, 14 g daily in one dose, during 30 days.

Dietary Supplement: Leucine

Isoleucine (Trade name: L-Isoleucine)

EXPERIMENTAL

Dietary Supplement: Isoleucine, water soluble powder, 8.2 g daily in one dose, during 30 days.

Dietary Supplement: Isoleucine

Valine (Trade name: L-Valine)

EXPERIMENTAL

Dietary Supplement: Valine, water soluble powder, 9 g daily in one dose, during 30 days.

Dietary Supplement: Valine

Cysteine (Trade name: L-Cysteine)

EXPERIMENTAL

Dietary Supplement: Cysteine, water soluble powder, 2.2 g daily in one dose, during 30 days.

Dietary Supplement: Cysteine

Arginine (Trade name: L-Arginine)

EXPERIMENTAL

Dietary Supplement: Arginine, water soluble powder, 10 g daily in one dose, during 30 days.

Dietary Supplement: Arginine

Methionine (Trade name: DL-Methionine)

EXPERIMENTAL

Dietary Supplement: Methionine, water soluble powder, 4 g daily in one dose, during 30 days.

Dietary Supplement: Methionine

Glutamate (Trade name: L-Glutamic acid)

EXPERIMENTAL

Dietary Supplement: Glutamate, water soluble powder, 33 g daily in one dose, during 30 days.

Dietary Supplement: Glutamate

Glutamine (Trade name: L-Glutamine)

EXPERIMENTAL

Dietary Supplement: Glutamine, water soluble powder, 30 g daily in one dose, during 30 days.

Dietary Supplement: Glutamine

Interventions

Cellulose (control) OTHER

Cellulose (a vegetal product, in powder form, used as dietary fiber, that is not digested or absorbed in the intestines), will be supplemented in the form of water soluble powder.

Control

Glycine DIETARY_SUPPLEMENT

Amino acids are the building blocks of proteins, they are essential organic compounds in the normal diet, and are also individually administered as nutritional supplements. Glycine will be supplied in the form of water soluble powder (the commercial form), for one daily dose. The corresponding amino acid doses were established based on the highest intakes at the 99th percentile in adult men (Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, D.C.: The National Academies Press. doi.org/10.17226/10490).

Also known as: Trade name: Glycine (Manufacturer Fagron Inc)

Glycine (Trade name: Glycine)

Alanine DIETARY_SUPPLEMENT

Amino acids are the building blocks of proteins, they are essential organic compounds in the normal diet, and are also individually administered as nutritional supplements. Alanine will be supplied in the form of water soluble powder (the commercial form), for one daily dose. The corresponding amino acid doses were established based on the highest intakes at the 99th percentile in adult men (Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, D.C.: The National Academies Press. doi.org/10.17226/10490).

Also known as: Trade name: L-Alanine (Manufacturer Fagron Inc)

Alanine (Trade name: L-Alanine)

Leucine DIETARY_SUPPLEMENT

Amino acids are the building blocks of proteins, they are essential organic compounds in the normal diet, and are also individually administered as nutritional supplements. Leucine will be supplied in the form of water soluble powder (the commercial form), for one daily dose. The corresponding amino acid doses were established based on the highest intakes at the 99th percentile in adult men (Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, D.C.: The National Academies Press. doi.org/10.17226/10490).

Also known as: Trade name: L-Leucine (Manufacturer Fagron Inc)

Leucine (Trade name: L-Leucine)

Isoleucine DIETARY_SUPPLEMENT

Amino acids are the building blocks of proteins, they are essential organic compounds in the normal diet, and are also individually administered as nutritional supplements. Isoleucine will be supplied in the form of water soluble powder (the commercial form), for one daily dose. The corresponding amino acid doses were established based on the highest intakes at the 99th percentile in adult men (Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, D.C.: The National Academies Press. doi.org/10.17226/10490).

Also known as: Trade name: L-Isoleucine (Manufacturer Fagron Inc)

Isoleucine (Trade name: L-Isoleucine)

Valine DIETARY_SUPPLEMENT

Amino acids are the building blocks of proteins, they are essential organic compounds in the normal diet, and are also individually administered as nutritional supplements. Valine will be supplied in the form of water soluble powder (the commercial form), for one daily dose. The corresponding amino acid doses were established based on the highest intakes at the 99th percentile in adult men (Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, D.C.: The National Academies Press. doi.org/10.17226/10490).

Also known as: Trade name: L-Valine (Manufacturer Fagron Inc)

Valine (Trade name: L-Valine)

Cysteine DIETARY_SUPPLEMENT

Amino acids are the building blocks of proteins, they are essential organic compounds in the normal diet, and are also individually administered as nutritional supplements. Cysteine will be supplied in the form of water soluble powder (the commercial form), for one daily dose. The corresponding amino acid doses were established based on the highest intakes at the 99th percentile in adult men (Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, D.C.: The National Academies Press. doi.org/10.17226/10490).

Also known as: Trade name: L-Cysteine (Manufacturer Fagron Inc)

Cysteine (Trade name: L-Cysteine)

Arginine DIETARY_SUPPLEMENT

Amino acids are the building blocks of proteins, they are essential organic compounds in the normal diet, and are also individually administered as nutritional supplements. Arginine will be supplied in the form of water soluble powder (the commercial form), for one daily dose. The corresponding amino acid doses were established based on the highest intakes at the 99th percentile in adult men (Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, D.C.: The National Academies Press. doi.org/10.17226/10490).

Also known as: Trade name: L-Arginine (Manufacturer Fagron Inc)

Arginine (Trade name: L-Arginine)

Methionine DIETARY_SUPPLEMENT

Amino acids are the building blocks of proteins, they are essential organic compounds in the normal diet, and are also individually administered as nutritional supplements. Methionine will be supplied in the form of water soluble powder (the commercial form), for one daily dose. The corresponding amino acid doses were established based on the highest intakes at the 99th percentile in adult men (Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, D.C.: The National Academies Press. doi.org/10.17226/10490).

Also known as: Trade name: DL-Methionine (Manufacturer Fagron Inc)

Methionine (Trade name: DL-Methionine)

Glutamate DIETARY_SUPPLEMENT

Amino acids are the building blocks of proteins, they are essential organic compounds in the normal diet, and are also individually administered as nutritional supplements. Glutamate will be supplied in the form of water soluble powder (the commercial form), for one daily dose. The corresponding amino acid doses were established based on the highest intakes at the 99th percentile in adult men (Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, D.C.: The National Academies Press. doi.org/10.17226/10490).

Also known as: Trade name: L-Glutamic acid (Manufacturer Fagron Inc)

Glutamate (Trade name: L-Glutamic acid)

Glutamine DIETARY_SUPPLEMENT

Amino acids are the building blocks of proteins, they are essential organic compounds in the normal diet, and are also individually administered as nutritional supplements. Glutamine will be supplied in the form of water soluble powder (the commercial form), for one daily dose. The corresponding amino acid doses were established based on the highest intakes at the 99th percentile in adult men (Institute of Medicine. 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, D.C.: The National Academies Press. doi.org/10.17226/10490).

Also known as: Trade name: L-Glutamine (Manufacturer Fagron Inc)

Glutamine (Trade name: L-Glutamine)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• healthy adult males between the ages of 18-50 after signing informed consent

You may not qualify if:

• pregnancy, renal, pulmonary, cardiovascular or endocrinal diseases, diabetes, cancer, morbid obesity (body mass index, BMI \> 40 kg/m2), heavy smoking (\> 20 cigarettes/day), or consumption of more than two alcoholic drinks per day. Subjects from the same hospital unit or from the laboratory where this study is conducted are also excluded

Sponsors & Collaborators

• Rambam Health Care Campus: lead

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MeSH Terms

Conditions

Atherosclerosis; Disease

Interventions

Cellulose; Glycine; Alanine; Leucine; Isoleucine; Valine; Cysteine; Arginine; Methionine; Glutamic Acid; Glutamine

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glucans; Biopolymers; Polymers; Macromolecular Substances; Polysaccharides; Carbohydrates; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Branched-Chain; Amino Acids, Essential; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Sulfhydryl Compounds; Amino Acids, Neutral; Amino Acids, Basic; Amino Acids, Diamino; Glutamates; Amino Acids, Acidic; Amino Acids, Dicarboxylic; Excitatory Amino Acids

Study Officials

• Tony Hayek, Prof

  Rambam Health Care Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Claudia Grajeda Iglesias, PhD

CONTACT

972-4-8295278; claugrajeda@technion.ac.il

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Department of Internal Medicine E

Study Record Dates

• First Submitted: May 25, 2017
• First Posted: June 8, 2017
• Study Start: July 1, 2017
• Primary Completion: December 15, 2017
• Study Completion: May 1, 2018
• Last Updated: June 8, 2017

Record last verified: 2017-06