Effects of Dietary Interventions on Serum and Macrophage Atherogenicity

NCT ID: NCT02894931

Last Updated: 2016-09-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

90 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-09-30

Study Completion Date

2018-08-31

Brief Summary

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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.

Detailed Description

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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..

Conditions

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Dietary Habits Serum; Disease Macrophage Atherogenicity Atherosclerosis

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

CROSSOVER

Blinding Strategy

NONE

Study Groups

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Control

Dietary Interventions: Control- water, Flavered Chilled water, will be administered once after O.N fasting.

Group Type SHAM_COMPARATOR

Control- water

Intervention Type OTHER

Chilled water flavored with lemon juice as control

Glucose

Dietary Interventions: Glucose, Monosaccharides, at the dose of 50 g, based on oral loading tests, once.

Group Type ACTIVE_COMPARATOR

monosaccharides

Intervention Type DIETARY_SUPPLEMENT

The monosaccharides; Glucose, Fructose, Galactose and mannose, will be administrated after O.N fasting, 50gr, once.

Fructose

Dietary Interventions: Fructose, Monosaccharides, at the dose of 50 g, once.

Group Type EXPERIMENTAL

monosaccharides

Intervention Type DIETARY_SUPPLEMENT

The monosaccharides; Glucose, Fructose, Galactose and mannose, will be administrated after O.N fasting, 50gr, once.

Galactose

Dietary Interventions: Monosaccharides, at the dose of 50 g, once.

Group Type EXPERIMENTAL

monosaccharides

Intervention Type DIETARY_SUPPLEMENT

The monosaccharides; Glucose, Fructose, Galactose and mannose, will be administrated after O.N fasting, 50gr, once.

Mannose

Dietary Interventions: Monosaccharides, at the dose of 50 g, once.

Group Type EXPERIMENTAL

monosaccharides

Intervention Type DIETARY_SUPPLEMENT

The monosaccharides; Glucose, Fructose, Galactose and mannose, will be administrated after O.N fasting, 50gr, once.

Maltose

Dietary Interventions: The dose of the disaccharides - 50 g, once.

Group Type EXPERIMENTAL

Disaccharides

Intervention Type DIETARY_SUPPLEMENT

The Disaccharides; Lactose, Maltose and sucrose, will be administrated after O.N fasting, 50gr, once.

Sucrose

Dietary Interventions: The dose of the disaccharides - 50 g, once.

Group Type EXPERIMENTAL

Disaccharides

Intervention Type DIETARY_SUPPLEMENT

The Disaccharides; Lactose, Maltose and sucrose, will be administrated after O.N fasting, 50gr, once.

Lactose

Dietary Interventions: The dose of the disaccharides - 50 g, once.

Group Type EXPERIMENTAL

Disaccharides

Intervention Type DIETARY_SUPPLEMENT

The Disaccharides; Lactose, Maltose and sucrose, will be administrated after O.N fasting, 50gr, once.

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.

Group Type EXPERIMENTAL

Artificial Sweeteners

Intervention Type DIETARY_SUPPLEMENT

The Artificial sweeteners: Saccharin, Aspartame, Sucralose and Steviol, will be administrated after O.N fasting, 300 mg, once.

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.

Group Type EXPERIMENTAL

Artificial Sweeteners

Intervention Type DIETARY_SUPPLEMENT

The Artificial sweeteners: Saccharin, Aspartame, Sucralose and Steviol, will be administrated after O.N fasting, 300 mg, once.

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.

Group Type EXPERIMENTAL

Artificial Sweeteners

Intervention Type DIETARY_SUPPLEMENT

The Artificial sweeteners: Saccharin, Aspartame, Sucralose and Steviol, will be administrated after O.N fasting, 300 mg, once.

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.

Group Type EXPERIMENTAL

Artificial Sweeteners

Intervention Type DIETARY_SUPPLEMENT

The Artificial sweeteners: Saccharin, Aspartame, Sucralose and Steviol, will be administrated after O.N fasting, 300 mg, once.

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.

Group Type EXPERIMENTAL

Amino acids

Intervention Type DIETARY_SUPPLEMENT

The Amino acids; Leucine, Isoleucine, and Valine, will be administrated after O.N fasting, 5g, once.

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.

Group Type EXPERIMENTAL

Amino acids

Intervention Type DIETARY_SUPPLEMENT

The Amino acids; Leucine, Isoleucine, and Valine, will be administrated after O.N fasting, 5g, once.

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.

Group Type EXPERIMENTAL

Amino acids

Intervention Type DIETARY_SUPPLEMENT

The Amino acids; Leucine, Isoleucine, and Valine, will be administrated after O.N fasting, 5g, once.

Interventions

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monosaccharides

The monosaccharides; Glucose, Fructose, Galactose and mannose, will be administrated after O.N fasting, 50gr, once.

Intervention Type DIETARY_SUPPLEMENT

Disaccharides

The Disaccharides; Lactose, Maltose and sucrose, will be administrated after O.N fasting, 50gr, once.

Intervention Type DIETARY_SUPPLEMENT

Amino acids

The Amino acids; Leucine, Isoleucine, and Valine, will be administrated after O.N fasting, 5g, once.

Intervention Type DIETARY_SUPPLEMENT

Artificial Sweeteners

The Artificial sweeteners: Saccharin, Aspartame, Sucralose and Steviol, will be administrated after O.N fasting, 300 mg, once.

Intervention Type DIETARY_SUPPLEMENT

Control- water

Chilled water flavored with lemon juice as control

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Rambam Health Care Campus

OTHER

Sponsor Role lead

Responsible Party

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Prof. Tony hayek MD

Director, Department of Internal Medicine E

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Tony Hayek, Prof.

Role: PRINCIPAL_INVESTIGATOR

Rambam Health care center

Locations

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Rambam Health care center

Haifa, Haifa District, Israel

Site Status RECRUITING

Countries

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Israel

Central Contacts

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Niroz Abu-Saleh Zoabi, PhD

Role: CONTACT

+972-50-4728858

Facility Contacts

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Niroz Abu-Saleh, PhD

Role: primary

972504278858

References

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Michas G, Micha R, Zampelas A. Dietary fats and cardiovascular disease: putting together the pieces of a complicated puzzle. Atherosclerosis. 2014 Jun;234(2):320-8. doi: 10.1016/j.atherosclerosis.2014.03.013. Epub 2014 Mar 27.

Reference Type BACKGROUND
PMID: 24727233 (View on PubMed)

Dickhout JG, Basseri S, Austin RC. Macrophage function and its impact on atherosclerotic lesion composition, progression, and stability: the good, the bad, and the ugly. Arterioscler Thromb Vasc Biol. 2008 Aug;28(8):1413-5. doi: 10.1161/ATVBAHA.108.169144. No abstract available.

Reference Type BACKGROUND
PMID: 18650503 (View on PubMed)

Bornfeldt KE, Tabas I. Insulin resistance, hyperglycemia, and atherosclerosis. Cell Metab. 2011 Nov 2;14(5):575-85. doi: 10.1016/j.cmet.2011.07.015.

Reference Type BACKGROUND
PMID: 22055501 (View on PubMed)

Huang Y, Zhou M, Sun H, Wang Y. Branched-chain amino acid metabolism in heart disease: an epiphenomenon or a real culprit? Cardiovasc Res. 2011 May 1;90(2):220-3. doi: 10.1093/cvr/cvr070.

Reference Type BACKGROUND
PMID: 21502372 (View on PubMed)

Shah SH, Bain JR, Muehlbauer MJ, Stevens RD, Crosslin DR, Haynes C, Dungan J, Newby LK, Hauser ER, Ginsburg GS, Newgard CB, Kraus WE. Association of a peripheral blood metabolic profile with coronary artery disease and risk of subsequent cardiovascular events. Circ Cardiovasc Genet. 2010 Apr;3(2):207-14. doi: 10.1161/CIRCGENETICS.109.852814. Epub 2010 Feb 19.

Reference Type BACKGROUND
PMID: 20173117 (View on PubMed)

Bhattacharya S, Granger CB, Craig D, Haynes C, Bain J, Stevens RD, Hauser ER, Newgard CB, Kraus WE, Newby LK, Shah SH. Validation of the association between a branched chain amino acid metabolite profile and extremes of coronary artery disease in patients referred for cardiac catheterization. Atherosclerosis. 2014 Jan;232(1):191-6. doi: 10.1016/j.atherosclerosis.2013.10.036. Epub 2013 Nov 12.

Reference Type BACKGROUND
PMID: 24401236 (View on PubMed)

Yang RY, Wang SM, Sun L, Liu JM, Li HX, Sui XF, Wang M, Xiu HL, Wang S, He Q, Dong J, Chen WX. Association of branched-chain amino acids with coronary artery disease: A matched-pair case-control study. Nutr Metab Cardiovasc Dis. 2015 Oct;25(10):937-42. doi: 10.1016/j.numecd.2015.06.003. Epub 2015 Jun 14.

Reference Type BACKGROUND
PMID: 26231617 (View on PubMed)

Yang R, Dong J, Zhao H, Li H, Guo H, Wang S, Zhang C, Wang S, Wang M, Yu S, Chen W. Association of branched-chain amino acids with carotid intima-media thickness and coronary artery disease risk factors. PLoS One. 2014 Jun 9;9(6):e99598. doi: 10.1371/journal.pone.0099598. eCollection 2014.

Reference Type BACKGROUND
PMID: 24910999 (View on PubMed)

Swithers SE. Artificial sweeteners produce the counterintuitive effect of inducing metabolic derangements. Trends Endocrinol Metab. 2013 Sep;24(9):431-41. doi: 10.1016/j.tem.2013.05.005. Epub 2013 Jul 10.

Reference Type BACKGROUND
PMID: 23850261 (View on PubMed)

Fung TT, Malik V, Rexrode KM, Manson JE, Willett WC, Hu FB. Sweetened beverage consumption and risk of coronary heart disease in women. Am J Clin Nutr. 2009 Apr;89(4):1037-42. doi: 10.3945/ajcn.2008.27140. Epub 2009 Feb 11.

Reference Type BACKGROUND
PMID: 19211821 (View on PubMed)

Rom O, Aviram M. Endogenous or exogenous antioxidants vs. pro-oxidants in macrophage atherogenicity. Curr Opin Lipidol. 2016 Apr;27(2):204-6. doi: 10.1097/MOL.0000000000000287. No abstract available.

Reference Type RESULT
PMID: 26959710 (View on PubMed)

Other Identifiers

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0285-16-RMB CTIL

Identifier Type: -

Identifier Source: org_study_id

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