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

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

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.

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.

Inflammation, HDL, Anti-inflammatory, Supplementation, Curcumin, polyphenol, V-cam, I-cam, atherosclerosis, cardiovascular disease, atherogenesis, antioxidant, resveratrol, quercetin

Participants take 500 mg of PolyResveratrol (100 mg curcumin phytosome, 100 mg quercetin phytosome, 100 mg green tea phytosome, 100 mg trans-resveratrol, 100 mg trans-pterostilbene; Thorne Research) twice daily for one week. Two blood Draws are taken on both the first and last days of the week. One blood draw is done fasted just before consumption of one supplement dose, and one blood draw is done after consumption of one supplement dose.

Participants take 500 mg of Curcumin phytosome twice daily for one week. Two blood draws are taken on both the first and last days of the week. One blood draw is done fasted just before consumption of one supplement dose, and one blood draw is done after consumption of one supplement dose.

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).

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).

VCAM-1 and ICAM-1 expression in whole plasma will be measured at baseline, and one hour after a single dose of each supplement using flow cytometry. Differences in one-hour changes in inflammation between each supplement will be compared.

VCAM-1 and ICAM-1 expression in whole plasma will be measured at baseline, and after one week of supplementation for each supplement using flow cytometry. Differences in one-week changes in inflammation between each supplement will be compared.

VCAM-1 and ICAM-1 expression in HDL plasma will be measured at baseline, and one hour after a single dose of each supplement using flow cytometry. Differences in one-hour changes in inflammation between each supplement will be compared.

VCAM-1 and ICAM-1 expression in HDL plasma will be measured at baseline, and after one week of supplementation for each supplement using flow cytometry. Differences in one-week changes in inflammation between each supplement will be compared.

HDL cholesterol efflux capacity will be measured at baseline, one hour after a single dose, and after a week of supplementation in non-apolipoprotein B containing plasma.

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

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