Physiological Effects of New Polyphenol-enriched Foods in Humans
Condition: Healthy
Study type: Interventional

Summary: 
      Polyphenolic compounds exert several health benefits depending on bioavailability.
      Encapsulation may improve bioavailability of these compounds.This study will evaluate
      bioavailability of some polyphenols (curcumin and cocoa polyphenols) from new enriched-foods.
      In particular bread and nut based creams will be used as food matrices to include free or
      encapsulated polyphenols.
    

Detailed description: 
      Polyphenolic compounds are abundant in foods and have been suggested to exert several health
      benefits including prevention of cancer, cardiovascular disease, suppressing inflammation,
      diabetes, etc. These properties are mediated by bioavailability of individual polyphenols
      that is, in turn, influenced by food properties (food matrix, technological processing,
      etc.), interaction with other compounds, and host related factors. Some well-studied dietary
      polyphenols include catechins from tea, curcumin from turmeric, procyanidins and
      anthocyanidins in grapes, berries, and dark chocolate. These compounds have strong
      antioxidative activities in vitro and have been suggested to have several beneficial health
      effects.

      Curcumin, a phenolic compound deriving from turmeric spice, shows many biological and
      pharmacological effects, and clinical studies in humans proved that it's extremely safe and
      well tolerated even at very high doses (8-12 g/day). However, curcumin has not yet been
      approved as a therapeutic agent, because of its very low bioavailability depending on a poor
      absorption, rapid metabolism and rapid systemic clearance. Different approaches have been
      investigated to improve curcumin bioavailability. Among them, the use of adjuvants that
      interferes with metabolic pathways of curcumin, like piperine, represents one of the main
      strategies used to enhance its bioavailability. A further approach consists on manufacturing
      of curcumin containing liposomes, phospholipids complexes or nanoparticles. For polymer-based
      nanoparticles, maintenance of biological activity, increased absorption and delayed delivery
      was reported.

      Cocoa based products are widely consumed in many countries, and indications of health
      benefits by some cocoa constituents, mainly polyphenols, have also been reported. Cocoa
      contains very high levels of polyphenols, in particular flavanols and among these, mainly
      epicatechins. The bioavailability of cocoa polyphenols has been measured in several human
      studies from acute consumption of cocoa rich beverages or chocolate. Monomeric flavonoids as
      well as dimeric and trimeric procyanidins were detected in human plasma over 2-3 hours from
      consumption. Plasma concentration of cocoa polyphenols were often in the nanomolar or low
      micromolar range. Donovan and coworkers demonstrated that commercial available chocolate
      samples contain a predominance of the less bioavailable (-)-catechin enantiomer as compared
      to the (+)-catechin which is present in most other plant derived foods. This may explain the
      relatively low bioavailability of catechins from chocolate and cocoa-containing products. The
      food matrix seems to be an important factor that may affect the bioavailability of cocoa
      polyphenols. For instance, proteins in the food matrix are supposed to form highly
      polymerized complexes with procyanidins, which can reduce bioaccessibility of these phenolic
      compounds. However, the potential negative effect of protein content in foods was not
      confirmed in a study that evaluated the cocoa polyphenols bioavailability after the intake of
      a milk-powder cocoa beverage. However, concurrent carbohydrates consumption seems to increase
      significantly the uptake of flavonols in humans. Little is known whether and to what extent
      oligomeric procyanidins from cocoa are absorbed. However, the biological activity of
      procyanidins with high polymerization degree may be partly attributed to their colonic
      breakdown products, including phenolic acids.

      Actually there is also a growing interest in other biological properties of phenolic
      compounds in addition to their antioxidant effects; particularly, some evidences suggest that
      certain dietary phenols may modulate metabolic homeostasis. This is the case of chlorogenic
      acids, that are reported to play a potential role in modifying the pattern of intestinal
      glucose uptake and of other flavonoids (quercetin, catechins) that may modulate activation of
      GLP-1 receptor, involved in modulation of insulin and glucagon secretion, gastric emptying,
      and appetite.

      In this randomized, crossover trial, serum, urine and fecal concentrations of curcumin and
      cocoa polyphenols, their parental compounds, metabolites and phenolic acids, following a two
      day multi-dose administration with six food sources, will be measured. All volunteers will
      undergo to six interventions - bread enriched with three different forms of curcumin (free,
      encapsulated, and encapsulated plus piperine) and nut based creams enriched with cocoa
      polyphenols (free or encapsulated one) or control cream (without enrichment). A one-week
      wash-out period will be included between two sequential treatments. Blood, urine and feces
      will be collected at time 0 (baseline), 24, and 48 hours; further blood samples at 0.5, 1, 2,
      4, 6 hours after consumption of the first meal, and urine samples at 2 hours time intervals
      up to 10 hours, will be collected too. In particular, area under the curve (AUC) of serum and
      urine concentrations of parental compounds and metabolites in the time interval 0-24 hours
      will be calculated as primary outcomes. In addition the amount of total polyphenols in fecal
      samples will be measured.
    

Intervention name(s): free curcumin; encapsulated curcumin; encapsulated curcumin + PQG; free cocoa polyphenol; encapsulated cocoa polyphenols; control nut cream
Intervention type(s): Other; Other; Other; Other; Other; Other
Intervention description(s): free curcumin in bread, dosage 1g/100g, 200g/day per 1 day; encapsulated curcumin-enriched bread, 1g/100g bread, 200g bread/day; bread enriched with encapsulated curcumin plus piperine, quercetin and genistein, 1g/100g bread, 200g bread/day; nut cream enriched with free cocoa polyphenols, 1,5 g/100g cream, 100g/day per 1 day; nut cream enriched with encapsulated cocoa polyphenols, 1,5 g/100g cream, 100g/day per 1 day; nut cream, cocoa polyphenols 0g/100g cream, 100 g/day per 1 day
Intervention MeSH terms: Curcumin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: polyphenols; curcumin; bioavailability; cocoa