Effects of Dietary Interventions on Serum and Macrophage Atherogenicity

Sponsor

Rambam Health Care Campus (Other)

Overall Status

Unknown status

CT.gov ID

NCT02894931

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

While previous atherosclerosis-related studies have focused mainly on the atherogenicity of lipids, the proposed study aims to investigate the effects of other dietary factors, i.e. monosaccharides, disaccharides, amino acids, or artificial sweeteners, on the atherogenicity of serum or macrophages. Findings from the current proposed study may shed light on yet unknown mechanisms by which the above dietary factors could affect atherosclerosis development and CVD risk and hence could possibly assist in the future development of anti-atherogenic strategies.

Condition or Disease	Intervention/Treatment	Phase
Dietary Habits Serum; Disease Macrophage Atherogenicity Atherosclerosis	Dietary Supplement: monosaccharides Dietary Supplement: Disaccharides Dietary Supplement: Amino acids Dietary Supplement: Artificial Sweeteners Other: Control- water	N/A

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. CVD and atherosclerosis development are significantly affected by nutritional factors. Although much progress has been made in understanding the role of different lipids (fatty acids, cholesterol, phospholipids or triglycerides) in atherosclerosis development and macrophage foam-cell formation, little is known about the potential impact of other nutrients, i.e. sugars or amino acids. For instance, hyperglycemia is known to enhance atherosclerosis development, and high glucose levels increases macrophage atherogenicity via pro-inflammatory and oxidative stress-related mechanisms. However, the role of monosaccharides other than glucose (fructose, galactose or mannose) and that of various disaccharides (maltose, sucrose or lactose) in macrophage foam-cell formation, the key event during early atherogenesis, is currently unknown. As for amino acids, a specific subgroup - the branched-chain amino acids (BCAAs), has recently been associated with increased CVD risk. The BCAA subgroup, composed of leucine, isoleucine, and valine, is characterized by an aliphatic structure of their side chains and by a common catabolic pathway. Recent reports have demonstrated an association between BCAAs, CVD and coronary artery disease (CAD). Serum BCAA levels have been positively associated with various CAD risk factors and with the development as well as the severity of CAD, even after controlling for other risk factors. Nevertheless, the role of BCAAs in atherosclerosis development and macrophage foam-cell formation is currently unclear. In recent decades, the availability and the consumption of various artificial sweeteners have increased considerably. In the USA for instance, approximately 30% of adults and 15% of children, report consumption of artificial sweeteners. Although the consumption of artificial sweeteners was previously associated with elevated risk for coronary heart disease (CHD), the effects of different artificial sweeteners, e.g. saccharin, aspartame, sucralose, steviol, cyclamate, and mannitol, on atherosclerosis development and their possible impact on macrophage foam-cell formation have not been investigated yet..

Study Design

Study Type:

Interventional

Anticipated Enrollment :

90 participants

Allocation:

Non-Randomized

Intervention Model:

Crossover Assignment

Masking:

None (Open Label)

Official Title:

Effects of Dietary Interventions (Sugars, Amino Acids and Artificial Sweeteners) on Serum and Macrophage Atherogenicity

Study Start Date :

Sep 1, 2016

Anticipated Primary Completion Date :

May 1, 2018

Anticipated Study Completion Date :

Aug 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: Control Dietary Interventions: Control- water, Flavered Chilled water, will be administered once after O.N fasting.	Other: Control- water Chilled water flavored with lemon juice as control
Active Comparator: Glucose Dietary Interventions: Glucose, Monosaccharides, at the dose of 50 g, based on oral loading tests, once.	Dietary Supplement: monosaccharides The monosaccharides; Glucose, Fructose, Galactose and mannose, will be administrated after O.N fasting, 50gr, once.
Experimental: Fructose Dietary Interventions: Fructose, Monosaccharides, at the dose of 50 g, once.	Dietary Supplement: monosaccharides The monosaccharides; Glucose, Fructose, Galactose and mannose, will be administrated after O.N fasting, 50gr, once.
Experimental: Galactose Dietary Interventions: Monosaccharides, at the dose of 50 g, once.	Dietary Supplement: monosaccharides The monosaccharides; Glucose, Fructose, Galactose and mannose, will be administrated after O.N fasting, 50gr, once.
Experimental: Mannose Dietary Interventions: Monosaccharides, at the dose of 50 g, once.	Dietary Supplement: monosaccharides The monosaccharides; Glucose, Fructose, Galactose and mannose, will be administrated after O.N fasting, 50gr, once.
Experimental: Maltose Dietary Interventions: The dose of the disaccharides - 50 g, once.	Dietary Supplement: Disaccharides The Disaccharides; Lactose, Maltose and sucrose, will be administrated after O.N fasting, 50gr, once.
Experimental: Sucrose Dietary Interventions: The dose of the disaccharides - 50 g, once.	Dietary Supplement: Disaccharides The Disaccharides; Lactose, Maltose and sucrose, will be administrated after O.N fasting, 50gr, once.
Experimental: Lactose Dietary Interventions: The dose of the disaccharides - 50 g, once.	Dietary Supplement: Disaccharides The Disaccharides; Lactose, Maltose and sucrose, will be administrated after O.N fasting, 50gr, once.
Experimental: Saccharin Dietary Interventions: The dose of the different artificial sweeteners - 300 mg, is based on an average adult male body weight of 75 kg and is set not to exceed the acceptable daily intakes of saccharin, aspartame, sucralose and steviol that were reported at 15, 50, 5, and 4 mg/kg body weight/day by the USA Food and Drug Administration, once.	Dietary Supplement: Artificial Sweeteners The Artificial sweeteners: Saccharin, Aspartame, Sucralose and Steviol, will be administrated after O.N fasting, 300 mg, once.
Experimental: Aspartame Dietary Interventions: The dose of the different artificial sweeteners - 300 mg, is based on an average adult male body weight of 75 kg and is set not to exceed the acceptable daily intakes of saccharin, aspartame, sucralose and steviol that were reported at 15, 50, 5, and 4 mg/kg body weight/day by the USA Food and Drug Administration, once.	Dietary Supplement: Artificial Sweeteners The Artificial sweeteners: Saccharin, Aspartame, Sucralose and Steviol, will be administrated after O.N fasting, 300 mg, once.
Experimental: Sucralose Dietary Interventions: The dose of the different artificial sweeteners - 300 mg, is based on an average adult male body weight of 75 kg and is set not to exceed the acceptable daily intakes of saccharin, aspartame, sucralose and steviol that were reported at 15, 50, 5, and 4 mg/kg body weight/day by the USA Food and Drug Administration, once.	Dietary Supplement: Artificial Sweeteners The Artificial sweeteners: Saccharin, Aspartame, Sucralose and Steviol, will be administrated after O.N fasting, 300 mg, once.
Experimental: Steviol Dietary Interventions: The dose of the different artificial sweeteners - 300 mg, is based on an average adult male body weight of 75 kg and is set not to exceed the acceptable daily intakes of saccharin, aspartame, sucralose and steviol that were reported at 15, 50, 5, and 4 mg/kg body weight/day by the USA Food and Drug Administration, once.	Dietary Supplement: Artificial Sweeteners The Artificial sweeteners: Saccharin, Aspartame, Sucralose and Steviol, will be administrated after O.N fasting, 300 mg, once.
Experimental: Leucine Dietary Interventions: The dose of the different BCAAs Amino acids- 5 g, is set not to exceed the mean daily intakes of leucine, isoleucine and valine for adult males that were reported at 8.64, 5.01 and 5.63 g/day, respectively, once.	Dietary Supplement: Amino acids The Amino acids; Leucine, Isoleucine, and Valine, will be administrated after O.N fasting, 5g, once.
Experimental: Isoleucine Dietary Interventions: The dose of the different BCAAs Amino acids - 5 g, is set not to exceed the mean daily intakes of leucine, isoleucine and valine for adult males that were reported at 8.64, 5.01 and 5.63 g/day, respectively, once.	Dietary Supplement: Amino acids The Amino acids; Leucine, Isoleucine, and Valine, will be administrated after O.N fasting, 5g, once.
Experimental: Valine Dietary Interventions: The dose of the different BCAAs Amino acids- 5 g, is set not to exceed the mean daily intakes of leucine, isoleucine and valine for adult males that were reported at 8.64, 5.01 and 5.63 g/day, respectively, once.	Dietary Supplement: Amino acids The Amino acids; Leucine, Isoleucine, and Valine, will be administrated after O.N fasting, 5g, once.

Outcome Measures

Primary Outcome Measures

serum Oxidation dietary factors, i.e. monosaccharides, disaccharides, amino acids, or artificial atherogenicity of serum [2 years]
serum oxidation level; TBARS (nmol MDA /ml)
macrophages cellular Oxidation. [2 years]
oxidation level; TBARS (nmol MDA /mg protein)

Secondary Outcome Measures

Serum lipids- Cholesterol [2 years]
Cholesterol concentration (mg/dl)
Serum lipids- Triglycerides [2 years]
Triglyceride concentration (mg/dl)
macrophages cellular lipids- Cholesterol [2 years]
macrophage Cholesterol mass (mg/mg protein)
macrophages cellular lipids -Triglycerides [2 years]
macrophage Triglyceride mass (mg/mg protein)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Inclusion criteria will include healthy adult males between the ages of 18-50 after signing informed consent.

Exclusion Criteria:

Exclusion criteria will include cardiovascular or pulmonary diseases, diabetes, cancer, morbid obesity (body mass index > 40 kg/m2), heavy smoking (> 20 cigarettes/day), or consumption of more than two alcoholic drinks per day.