Effects of Short-term Curcumin and Multi-polyphenol Supplementation on the Anti-inflammatory Properties of HDL

Inflammation Clinical Trial

— PSI  

Official title:

Effects of Short-term Curcumin and Multi-polyphenol Supplementation on the Anti-inflammatory Properties of HDL

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02998918
• Other study ID #: Pro00055882
• Status: Completed
• Phase: N/A
• Start date: September 2016
• Est. completion date: June 2020

Study information

• Verified date: November 2023
• Source: University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Polyphenol supplements, including curcumin and resveratrol, are known to decrease inflammation, but previous polyphenol supplements were poorly absorbed and thus their effects were reduced. A new phytosome formulation coats the supplements and allows them to be better absorbed. The purpose of this study is to examine the acute (1-hr) and short-term (1-week) effects of two different phytosome-formulated polyphenol supplements on inflammation. The two supplements that will be used are: 1) PolyResveratrol and 2) Curcumin.

Description:

Atherosclerosis is a chronic inflammatory disease underlying coronary artery disease, driven in part by the innate immune system, particularly macrophages. The adhesion of leukocytes to the vascular endothelium, mediated by endothelial cellular adhesion molecules including vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), is one of the crucial initial steps in atherogenesis. Elevated levels of high-density lipoprotein cholesterol (HDL-C) are associated with reduced risk for cardiovascular disease (CVD); however, interventions designed to increase HDL-C concentration in humans have yet to lead to reductions in cardiovascular events. A possible explanation for the failure of recent clinical trials is the structural and functional complexity of HDL particles, which have multiple cardioprotective properties, including anti-inflammatory, antioxidative, and reverse cholesterol transport activities. The anti-inflammatory effects of HDL include reduction of inflammatory cytokines and vascular leukocyte adhesion molecules. A recent study showed that dietary composition can affect HDL's anti-inflammatory properties, namely the ability to inhibit the expression of ICAM-1 and VCAM-1.

Numerous studies have shown that polyphenols, including curcumin, quercetin, and resveratrol, exhibit multiple health benefits, including anti-inflammatory properties. Curcumin is a flavonoid polyphenol that is the active ingredient in the spice turmeric. Quercetin is one of the most abundant dietary flavonoids and is found in many fruits, vegetables, and beverages. Resveratrol is a non-flavonoid polyphenol present in a limited number of plant-derived foods, including grapes and peanuts. In vitro studies show these three polyphenols independently decrease VCAM-1 and ICAM-1 expression induced by tumor necrosis factor alpha (TNFα) in human endothelial cells, as well as increase cholesterol efflux to apolipoprotein A-I (apoA-I) and HDL in macrophages. However, previous in vitro models used direct incubation with each polyphenol (i.e., HDL was directly exposed to the polyphenol in the cell culture, as opposed to incubation with plasma after consumption of the polyphenol), with doses much higher than found in typical human diets or supplements.

The health effects of polyphenols in humans are limited by their poor bioavailability, as they are rapidly metabolized and excreted. Recent studies have found that formulating poorly-absorbed molecules with phosphatidylcholine via phytosomes increases their bioavailability. For example, recent studies comparing curcumin phytosome (Meriva®) and standard curcumin formulations in humans found that the curcumin phytosome formulation increased curcuminoid bioavailability between 8- to 29-fold. To our knowledge, no study has examined the effects of polyphenol supplementation, particularly phytosome-formulated polyphenols, in humans on the ability of circulating plasma to inhibit the expression of cellular adhesion molecules or enhance cholesterol efflux capacity in vitro. Furthermore, it is unknown whether polyphenol supplementation modulates the ability of HDL particles to perform these same functions.

Therefore, the purpose of this study is to examine whether acute and short-term (1-week) polyphenol supplementation in humans affects inflammation measured at the whole plasma level, as well as the inflammatory and cholesterol efflux properties of HDL particles. The investigators will test the effects of two supplements in a cross-over design: a curcumin phytosome and a multi-polyphenol supplement (containing curcumin phytosome, quercetin phytosome, and trans-resveratrol). The investigators hypothesize that one of the mechanisms by which polyphenols exert a beneficial effect on inflammation and atherosclerosis is through its modulation of HDL particles.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: June 2020
• Est. primary completion date: July 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• General good health

• Between 18 and 60 years old

• Non-smoker

• Not taking any medications or dietary supplements

Exclusion Criteria:

• Taking prescription anti-inflammatory drugs or supplements/drugs that may affect inflammation

Related Conditions & MeSH terms

• Atherosclerosis
• Cardiovascular Disease
• Cardiovascular Diseases
• Inflammation

Intervention

Dietary Supplement:
• PolyResveratrol Supplementation
Participants will take 1 mg of a polyresveratrol phytosome supplement each day for one week. The acute effect (1 hr) of one 500 mg dose of the polyresveratrol phytosome supplement on inflammation will be examined along with the short-term effect (1 week).
• Curcumin Supplementation
Participants will take 1 mg of a curcumin phytosome supplement each day for one week. The acute effect (1 hr) of one 500 mg dose of the curcumin phytosome supplement on inflammation will be examined along with the short-term effect (1 week).

Locations

Country	Name	City	State
United States	Clinical Exercise Research Center	Columbia	South Carolina

Sponsors (1)

Lead Sponsor	Collaborator
University of South Carolina

Country where clinical trial is conducted

United States, 

References & Publications (24)

Barter PJ, Nicholls S, Rye KA, Anantharamaiah GM, Navab M, Fogelman AM. Antiinflammatory properties of HDL. Circ Res. 2004 Oct 15;95(8):764-72. doi: 10.1161/01.RES.0000146094.59640.13. — View Citation

Berrougui H, Grenier G, Loued S, Drouin G, Khalil A. A new insight into resveratrol as an atheroprotective compound: inhibition of lipid peroxidation and enhancement of cholesterol efflux. Atherosclerosis. 2009 Dec;207(2):420-7. doi: 10.1016/j.atherosclerosis.2009.05.017. Epub 2009 May 22. — View Citation

Binion DG, Heidemann J, Li MS, Nelson VM, Otterson MF, Rafiee P. Vascular cell adhesion molecule-1 expression in human intestinal microvascular endothelial cells is regulated by PI 3-kinase/Akt/MAPK/NF-kappaB: inhibitory role of curcumin. Am J Physiol Gastrointest Liver Physiol. 2009 Aug;297(2):G259-68. doi: 10.1152/ajpgi.00087.2009. Epub 2009 Jun 11. — View Citation

Bisht K, Wagner KH, Bulmer AC. Curcumin, resveratrol and flavonoids as anti-inflammatory, cyto- and DNA-protective dietary compounds. Toxicology. 2010 Nov 28;278(1):88-100. doi: 10.1016/j.tox.2009.11.008. Epub 2009 Nov 10. — View Citation

Boots AW, Haenen GR, Bast A. Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol. 2008 May 13;585(2-3):325-37. doi: 10.1016/j.ejphar.2008.03.008. Epub 2008 Mar 18. — View Citation

Chang YC, Lee TS, Chiang AN. Quercetin enhances ABCA1 expression and cholesterol efflux through a p38-dependent pathway in macrophages. J Lipid Res. 2012 Sep;53(9):1840-50. doi: 10.1194/jlr.M024471. Epub 2012 Jun 18. — View Citation

Chen FY, Zhou J, Guo N, Ma WG, Huang X, Wang H, Yuan ZY. Curcumin retunes cholesterol transport homeostasis and inflammation response in M1 macrophage to prevent atherosclerosis. Biochem Biophys Res Commun. 2015 Nov 27;467(4):872-8. doi: 10.1016/j.bbrc.2015.10.051. Epub 2015 Oct 19. — View Citation

Cockerill GW, Rye KA, Gamble JR, Vadas MA, Barter PJ. High-density lipoproteins inhibit cytokine-induced expression of endothelial cell adhesion molecules. Arterioscler Thromb Vasc Biol. 1995 Nov;15(11):1987-94. doi: 10.1161/01.atv.15.11.1987. — View Citation

Cuomo J, Appendino G, Dern AS, Schneider E, McKinnon TP, Brown MJ, Togni S, Dixon BM. Comparative absorption of a standardized curcuminoid mixture and its lecithin formulation. J Nat Prod. 2011 Apr 25;74(4):664-9. doi: 10.1021/np1007262. Epub 2011 Mar 17. — View Citation

Emerging Risk Factors Collaboration; Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, Wood AM, Lewington S, Sattar N, Packard CJ, Collins R, Thompson SG, Danesh J. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009 Nov 11;302(18):1993-2000. doi: 10.1001/jama.2009.1619. — View Citation

Ferrero ME, Bertelli AE, Fulgenzi A, Pellegatta F, Corsi MM, Bonfrate M, Ferrara F, De Caterina R, Giovannini L, Bertelli A. Activity in vitro of resveratrol on granulocyte and monocyte adhesion to endothelium. Am J Clin Nutr. 1998 Dec;68(6):1208-14. doi: 10.1093/ajcn/68.6.1208. — View Citation

Gordon SM, Deng J, Lu LJ, Davidson WS. Proteomic characterization of human plasma high density lipoprotein fractionated by gel filtration chromatography. J Proteome Res. 2010 Oct 1;9(10):5239-49. doi: 10.1021/pr100520x. — View Citation

Hatcher H, Planalp R, Cho J, Torti FM, Torti SV. Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci. 2008 Jun;65(11):1631-52. doi: 10.1007/s00018-008-7452-4. — View Citation

Jager R, Lowery RP, Calvanese AV, Joy JM, Purpura M, Wilson JM. Comparative absorption of curcumin formulations. Nutr J. 2014 Jan 24;13:11. doi: 10.1186/1475-2891-13-11. — View Citation

Kleemann R, Verschuren L, Morrison M, Zadelaar S, van Erk MJ, Wielinga PY, Kooistra T. Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models. Atherosclerosis. 2011 Sep;218(1):44-52. doi: 10.1016/j.atherosclerosis.2011.04.023. Epub 2011 May 5. — View Citation

Nicholls SJ, Lundman P, Harmer JA, Cutri B, Griffiths KA, Rye KA, Barter PJ, Celermajer DS. Consumption of saturated fat impairs the anti-inflammatory properties of high-density lipoproteins and endothelial function. J Am Coll Cardiol. 2006 Aug 15;48(4):715-20. doi: 10.1016/j.jacc.2006.04.080. Epub 2006 Jul 24. — View Citation

Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999 Jan 14;340(2):115-26. doi: 10.1056/NEJM199901143400207. No abstract available. — View Citation

Russo M, Spagnuolo C, Tedesco I, Bilotto S, Russo GL. The flavonoid quercetin in disease prevention and therapy: facts and fancies. Biochem Pharmacol. 2012 Jan 1;83(1):6-15. doi: 10.1016/j.bcp.2011.08.010. Epub 2011 Aug 16. — View Citation

Seneviratne AN, Sivagurunathan B, Monaco C. Toll-like receptors and macrophage activation in atherosclerosis. Clin Chim Acta. 2012 Jan 18;413(1-2):3-14. doi: 10.1016/j.cca.2011.08.021. Epub 2011 Aug 22. — View Citation

Smoliga JM, Baur JA, Hausenblas HA. Resveratrol and health--a comprehensive review of human clinical trials. Mol Nutr Food Res. 2011 Aug;55(8):1129-41. doi: 10.1002/mnfr.201100143. Epub 2011 Jun 20. — View Citation

Strimpakos AS, Sharma RA. Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials. Antioxid Redox Signal. 2008 Mar;10(3):511-45. doi: 10.1089/ars.2007.1769. — View Citation

Tome-Carneiro J, Larrosa M, Gonzalez-Sarrias A, Tomas-Barberan FA, Garcia-Conesa MT, Espin JC. Resveratrol and clinical trials: the crossroad from in vitro studies to human evidence. Curr Pharm Des. 2013;19(34):6064-93. doi: 10.2174/13816128113199990407. — View Citation

Toth PP, Barter PJ, Rosenson RS, Boden WE, Chapman MJ, Cuchel M, D'Agostino RB Sr, Davidson MH, Davidson WS, Heinecke JW, Karas RH, Kontush A, Krauss RM, Miller M, Rader DJ. High-density lipoproteins: a consensus statement from the National Lipid Association. J Clin Lipidol. 2013 Sep-Oct;7(5):484-525. doi: 10.1016/j.jacl.2013.08.001. Epub 2013 Aug 11. — View Citation

Voloshyna I, Hai O, Littlefield MJ, Carsons S, Reiss AB. Resveratrol mediates anti-atherogenic effects on cholesterol flux in human macrophages and endothelium via PPARgamma and adenosine. Eur J Pharmacol. 2013 Jan 5;698(1-3):299-309. doi: 10.1016/j.ejphar.2012.08.024. Epub 2012 Oct 4. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Inflammation Change: HDL Plasma	VCAM-1 expression in HDL plasma will be measured at baseline, and after one week of supplementation for each supplement. Differences in one-week changes in inflammation between each supplement will be compared.	One week