Effects of Dietary Interventions on Serum and Macrophage Atherogenicity

Atherosclerosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02894931
• Other study ID #: 0285-16-RMB CTIL
• Status: Recruiting
• Phase: N/A
• First received: August 22, 2016
• Last updated: September 26, 2016
• Start date: September 2016
• Est. completion date: August 2018

Study information

• Verified date: September 2016
• Source: Rambam Health Care Campus
• Contact: Niroz Abu-Saleh Zoabi, PhD
• Phone: +972-50-4728858
• Email: asniroz[@]gmail.com
• Is FDA regulated: No
• Health authority: Israel: Ethics Commission
• Study type: Interventional

Clinical Trial 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.

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..

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: August 2018
• Est. primary completion date: May 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 50 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Intervention Model: Crossover Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Atherosclerosis
• Dietary Habits
• Macrophage Atherogenicity
• Serum; Disease

Intervention

Dietary Supplement:
• monosaccharides
The monosaccharides; Glucose, Fructose, Galactose and mannose, will be administrated after O.N fasting, 50gr, once.
• Disaccharides
The Disaccharides; Lactose, Maltose and sucrose, will be administrated after O.N fasting, 50gr, once.
• Amino acids
The Amino acids; Leucine, Isoleucine, and Valine, will be administrated after O.N fasting, 5g, once.
• Artificial Sweeteners
The Artificial sweeteners: Saccharin, Aspartame, Sucralose and Steviol, will be administrated after O.N fasting, 300 mg, once.

Other:
• Control- water
Chilled water flavored with lemon juice as control

Locations

Country	Name	City	State
Israel	Rambam Health care center	Haifa

Sponsors (1)

Lead Sponsor	Collaborator
Rambam Health Care Campus

Country where clinical trial is conducted

Israel, 

References & Publications (11)

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. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	serum Oxidation dietary factors, i.e. monosaccharides, disaccharides, amino acids, or artificial atherogenicity of serum	serum oxidation level; TBARS (nmol MDA /ml)	2 years	No
Primary	macrophages cellular Oxidation.	oxidation level; TBARS (nmol MDA /mg protein)	2 years	No
Secondary	Serum lipids- Cholesterol	Cholesterol concentration (mg/dl)	2 years	No
Secondary	Serum lipids- Triglycerides	Triglyceride concentration (mg/dl)	2 years	No
Secondary	macrophages cellular lipids- Cholesterol	macrophage Cholesterol mass (mg/mg protein)	2 years	No
Secondary	macrophages cellular lipids -Triglycerides	macrophage Triglyceride mass (mg/mg protein)	2 years	No