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

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.

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