Macrophage Polarization in Response to Macronutrient Intake in Healthy Humans: A Randomized Clinical Study

Atherosclerosis Clinical Trial

Official title:

Monocyte Differentiation and Macrophage Polarization in Circulation in Response to Macronutrient Intake in Healthy Humans: A Randomized Clinical Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03173677
• Other study ID #: SP15/026
• Status: Completed
• Phase: N/A
• First received: May 28, 2017
• Last updated: May 31, 2017
• Start date: February 2, 2016
• Est. completion date: April 29, 2016

Study information

• Verified date: May 2017
• Source: King Saud Bin Abdulaziz University for Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Macrophages can exhibit distinct phenotypes and functions in response to stimuli and can polarize into one of three distinct phenotypes: a pro-inflammatory (M1), an anti-inflammatory pro-tissue (M2) and metabolically-activated (MMe) macrophage phenotypes. Thirty-six healthy volunteers were recruited and randomized into one of three macronutrient intake groups (glucose, lipids, proteins). This study measured the effects of macronutrient intake on the macrophage differentiation.

Description:

Thirty-six normal healthy adult volunteers of normal weight were recruited into the study. All were normotensive, had a normal lipid profile, normal renal and liver function tests, and were not on any medications. All subjects gave their written, informed consent. Institutional Review Board (IRB) of the Ministry of National Guard Health Affairs (MNGHA) approved the study protocol. The 36 participants were randomly assigned by the primary investigator (PI) following simple randomization procedure (computerized random numbers) to three different groups, each received one type of macronutrient (Glucose, whey proteins or lipids). Following an overnight fast, a baseline blood sample was taken. Subjects were then given either 300 calories of glucose (NERL Trutol 75) or lipids (90 grams whipping cream, 31.5 grams fat, 1.7 grams protein and 2.25 grams carbohydrate) or protein (Isopure unflavored Whey proteins isolate (WPI) powder containing 26 grams per serving of 100% WPI, stripped of fat, carbs, fillers, sugars and lactose) solution over 5 minutes. Cream and protein preparations were diluted with water up to 300 mL solutions. Further blood samples were obtained at 1, 2 and 3 hours after the macronutrient intake. Subjects, either one week before or after the macronutrient challenge, were given 300 mL of water to drink in the fasting state. Blood samples were obtained before and at 1, 2 and 3 h after water intake as well. Each subject served as his/her own control and was randomly given macronutrient or water intake.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: April 29, 2016
• Est. primary completion date: April 24, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Normal weight (BMI 18.5-25)

• Healthy adults evident by: physical examination, normal lipid profile, normal renal and liver function tests.

Exclusion Criteria:

• Renal disease

• Hepatic disease

• Cardiovascular disease

• Using multivitamins

• Using NSAIDS

Related Conditions & MeSH terms

• Atherosclerosis

Intervention

Dietary Supplement:
• Lipid Intake
90 grams whipping cream, 31.5 grams fat, 1.7 grams protein, and 2.25 grams carbohydrate
• Glucose intake
300 calories of glucose
• Protein intake
Isopure unflavored Whey proteins isolate (WPI) powder containing 26 grams per serving of 100% WPI, stripped of fat, carbs, fillers, sugars, and lactose

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
King Saud Bin Abdulaziz University for Health Sciences

References & Publications (12)

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Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab. 1998 Mar;83(3):847-50. Review. — View Citation

Guha M, Mackman N. LPS induction of gene expression in human monocytes. Cell Signal. 2001 Feb;13(2):85-94. Review. — View Citation

Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science. 1993 Jan 1;259(5091):87-91. — View Citation

Italiani P, Boraschi D. From Monocytes to M1/M2 Macrophages: Phenotypical vs. Functional Differentiation. Front Immunol. 2014 Oct 17;5:514. doi: 10.3389/fimmu.2014.00514. eCollection 2014. Review. — View Citation

Martinez FO, Gordon S. The M1 and M2 paradigm of macrophage activation: time for reassessment. F1000Prime Rep. 2014 Mar 3;6:13. doi: 10.12703/P6-13. eCollection 2014. Review. — View Citation

Mohanty P, Ghanim H, Hamouda W, Aljada A, Garg R, Dandona P. Both lipid and protein intakes stimulate increased generation of reactive oxygen species by polymorphonuclear leukocytes and mononuclear cells. Am J Clin Nutr. 2002 Apr;75(4):767-72. — View Citation

Shoelson SE, Lee J, Goldfine AB. Inflammation and insulin resistance. J Clin Invest. 2006 Jul;116(7):1793-801. Review. Erratum in: J Clin Invest. 2006 Aug;116(8):2308. — View Citation

Stein M, Keshav S, Harris N, Gordon S. Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation. J Exp Med. 1992 Jul 1;176(1):287-92. — View Citation

Stöger JL, Gijbels MJ, van der Velden S, Manca M, van der Loos CM, Biessen EA, Daemen MJ, Lutgens E, de Winther MP. Distribution of macrophage polarization markers in human atherosclerosis. Atherosclerosis. 2012 Dec;225(2):461-8. doi: 10.1016/j.atherosclerosis.2012.09.013. Epub 2012 Sep 26. — View Citation

Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Elevated C-reactive protein levels in overweight and obese adults. JAMA. 1999 Dec 8;282(22):2131-5. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Detection of markers of M1 and M2 macrophages	The following markers were used to detect M1 and M2 macrophages (M1:CD86, IL-6, CD11c, and CD169, and M2: CD206, CD163, and CD36)	Subject recruitment, enrollment and sample collection were carried out in a period of 3 months. Baseline blood samples were drawn before the caloric or water intake, and subsequent blood samples were drawn at 1-, 2- and 3-hour intervals post the intake