Effects of Short-term Curcumin and Multi-polyphenol Supplementation on the Anti-inflammatory Properties of HDL
Condition: Inflammation; Atherosclerosis; Cardiovascular Disease
MeSH terms: Cardiovascular Diseases; Atherosclerosis; Inflammation
Study type: Interventional

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.
    

Detailed 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.
    

Intervention name(s): PolyResveratrol Supplementation; Curcumin Supplementation
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): 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).
Intervention MeSH terms: Curcumin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: Inflammation; HDL; Anti-inflammatory; Supplementation; Curcumin; polyphenol; V-cam; I-cam; atherosclerosis; cardiovascular disease; atherogenesis; antioxidant; resveratrol; quercetin