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.

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.

Inclusion Criteria:

• 18 - 45 years old, male and female
• Healthy by medical assessment
• Normal weight: BMI 18 - 25
• Sign of a written informed consent

Exclusion Criteria:

• Age > 18 and < 45 years old
• Pregnancy or breastfeeding
• Intestinal or metabolic diseases/disorders such as diabetic, renal, hepatic, hypertension, pancreatic or ulcer, including lactose-intolerance
• Previous abdominal/gastrointestinal surgery
• Regular consumption of medication
• Antibiotic therapy within 2 months previous the study
• Food allergies and intolerances (celiac disease, lactose intolerance, nut allergy etc)
• Unwilling to consume experimental foods
• Concurrent participation or having participated to another clinical trial during the last 3 weeks