Effects of Dietary Amino Acids on Serum and Macrophage Atherogenicity

NCT ID: NCT03180775

Last Updated: 2017-06-08

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 110 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-01
• Study Completion Date: 2018-05-01

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.

Detailed Description

Atherosclerosis is the underlying cause of cardiovascular diseases (CVD), the major cause of death worldwide. Atherosclerosis is an inflammatory disease of the arteries in which activated macrophages are abundant in the atherosclerotic lesions. Macrophages play key roles during early atherogenesis. After differentiating from peripheral blood monocytes, the formed intimal macrophages take up oxidized/modified lipoproteins and are transformed into lipid-rich foam cells, the hallmark feature of early atherogenesis. In addition to lipoprotein uptake, lipid accumulation in macrophages can also result from alterations in cellular lipid metabolism, e.g. attenuated reverse lipid transport or enhanced rates of lipid biosynthesis. Although much progress has been made in understanding the role of different lipids (fatty acids, cholesterol, phospholipids or triglycerides) in macrophage foam-cell formation and atherosclerosis development, little is known about the potential impact of other nutrients, such as amino acids (AAs).

Previous studies have demonstrated an association between specific AAs and increased CVD risk or higher prevalence of coronary artery disease (CAD). For instance, the role of the branched chain AAs (BCAAs; valine, leucine, and isoleucine) in atherogenesis and CVD has been recently studied. Association studies showed that the plasma levels of BCAAs significantly and independently correlated with dyslipidemia and CAD. However, BCAAs were found to possess cardio-protective effects in a heart failure rat model. Specifically, leucine was reported to attenuate atherosclerosis development in the atherosclerotic apoE-deficient (apoE-/-) mice model, by improving the plasma lipid profile and by reducing systemic inflammation. Other studies have indicated the ability of some AAs to exert anti-atherogenic effects. Glycine, the simplest AA, was inversely associated with the risk of acute myocardial infarction (AMI) in patients with high apolipoprotein B (apoB) and LDL-cholesterol levels. Cysteine is an essential AA in the biosynthesis of glutathione, a key endogenous anti-oxidant known for its anti-atherogenic properties in macrophage lipid metabolism leading to the attenuation of atherosclerosis development. Cysteine analogues such as N-acetyl cysteine (NAC) or ribose cysteine were shown to be anti-atherogenic. Arginine, a basic AA, is the main precursor for nitric oxide production in the vascular endothelium. Arginine was shown to protect endothelial cells from lipid peroxidation, and to delay or reduce atheroma formation. Arginine anti-atherogenicity includes its anti-oxidant properties and its ability to improve endothelial function in CVD or overweight patients.

The aim of the proposed study is to investigate the effects of one month of supplementation with specific AAs on changes in the macrophage atherogenicity and lipid metabolism together with other risk markers of atherosclerosis development, such as serum oxidative status and lipid levels, on healthy subjects. Findings from the current proposed study may shed light on yet unknown mechanisms by which specific AAs affect atherosclerosis development and CVD risk and hence could possibly assist in the future development of anti-atherogenic strategies

Conditions

Atherosclerosis; Diet Modification; Serum; Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Control

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

Group Type: SHAM_COMPARATOR

Cellulose (control)

Intervention Type: 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.

Glycine (Trade name: Glycine)

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

Group Type: EXPERIMENTAL

Glycine

Intervention Type: 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).

Alanine (Trade name: L-Alanine)

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

Group Type: EXPERIMENTAL

Alanine

Intervention Type: 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).

Leucine (Trade name: L-Leucine)

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

Group Type: EXPERIMENTAL

Leucine

Intervention Type: 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).

Isoleucine (Trade name: L-Isoleucine)

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

Group Type: EXPERIMENTAL

Isoleucine

Intervention Type: 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).

Valine (Trade name: L-Valine)

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

Group Type: EXPERIMENTAL

Valine

Intervention Type: 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).

Cysteine (Trade name: L-Cysteine)

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

Group Type: EXPERIMENTAL

Cysteine

Intervention Type: 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).

Arginine (Trade name: L-Arginine)

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

Group Type: EXPERIMENTAL

Arginine

Intervention Type: 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).

Methionine (Trade name: DL-Methionine)

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

Group Type: EXPERIMENTAL

Methionine

Intervention Type: 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).

Glutamate (Trade name: L-Glutamic acid)

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

Group Type: EXPERIMENTAL

Glutamate

Intervention Type: 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).

Glutamine (Trade name: L-Glutamine)

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

Group Type: EXPERIMENTAL

Glutamine

Intervention Type: 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).

Interventions

Cellulose (control)

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.

Intervention Type: OTHER

Glycine

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).

Intervention Type: DIETARY_SUPPLEMENT

Alanine

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).

Intervention Type: DIETARY_SUPPLEMENT

Leucine

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).

Intervention Type: DIETARY_SUPPLEMENT

Isoleucine

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).

Intervention Type: DIETARY_SUPPLEMENT

Valine

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).

Intervention Type: DIETARY_SUPPLEMENT

Cysteine

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).

Intervention Type: DIETARY_SUPPLEMENT

Arginine

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).

Intervention Type: DIETARY_SUPPLEMENT

Methionine

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).

Intervention Type: DIETARY_SUPPLEMENT

Glutamate

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).

Intervention Type: DIETARY_SUPPLEMENT

Glutamine

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).

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Trade name: Glycine (Manufacturer Fagron Inc); Trade name: L-Alanine (Manufacturer Fagron Inc); Trade name: L-Leucine (Manufacturer Fagron Inc); Trade name: L-Isoleucine (Manufacturer Fagron Inc); Trade name: L-Valine (Manufacturer Fagron Inc); Trade name: L-Cysteine (Manufacturer Fagron Inc); Trade name: L-Arginine (Manufacturer Fagron Inc); Trade name: DL-Methionine (Manufacturer Fagron Inc); Trade name: L-Glutamic acid (Manufacturer Fagron Inc); Trade name: L-Glutamine (Manufacturer Fagron Inc)

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Rambam Health Care Campus

OTHER

Sponsor Role: lead

Responsible Party

Prof. Tony hayek MD

Director, Department of Internal Medicine E

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tony Hayek, Prof

Role: PRINCIPAL_INVESTIGATOR

Rambam Health Care Center

Central Contacts

Claudia Grajeda Iglesias, PhD

Role: CONTACT

claugrajeda@technion.ac.il

972-4-8295278

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Reference Type: RESULT

PMID: 24401239 (View on PubMed)

Trumbo P, Schlicker S, Yates AA, Poos M; Food and Nutrition Board of the Institute of Medicine, The National Academies. Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein and amino acids. J Am Diet Assoc. 2002 Nov;102(11):1621-30. doi: 10.1016/s0002-8223(02)90346-9. No abstract available.

Reference Type: RESULT

PMID: 12449285 (View on PubMed)

Other Identifiers

0566-16-RMB CTIL

Identifier Type: -

Identifier Source: org_study_id