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Physiological Effects of New Polyphenol-enriched Foods in Humans

Physiological Effects of New Polyphenol-enriched Foods in Healthy Humans

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01288859
Enrollment
10
Registered
2011-02-03
Start date
2010-12-31
Completion date
2011-07-31
Last updated
2012-08-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy

Keywords

polyphenols, curcumin, bioavailability, cocoa

Brief 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.

Interventions

OTHERfree curcumin

free curcumin in bread, dosage 1g/100g, 200g/day per 1 day

OTHERencapsulated curcumin

encapsulated curcumin-enriched bread, 1g/100g bread, 200g bread/day

OTHERencapsulated curcumin + PQG

bread enriched with encapsulated curcumin plus piperine, quercetin and genistein, 1g/100g bread, 200g bread/day

OTHERfree cocoa polyphenol

nut cream enriched with free cocoa polyphenols, 1,5 g/100g cream, 100g/day per 1 day

OTHERencapsulated cocoa polyphenols

nut cream enriched with encapsulated cocoa polyphenols, 1,5 g/100g cream, 100g/day per 1 day

OTHERcontrol nut cream

nut cream, cocoa polyphenols 0g/100g cream, 100 g/day per 1 day

Sponsors

Federico II University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)

Eligibility

Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes

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

Design outcomes

Primary

MeasureTime frameDescription
Serum Polyphenol Concentrations Over 24h From Food Consumption0, 0.5, 1, 2, 4, 6, and 24 hours post-doseArea Under the Curves (AUC) from 0 to 24h of parent polyphenols was calculated using a trapezoidal rule applied to the concentration-time curves of compounds.
Urinary Excretion of Total PolyphenolsTime intervals: 0-2, 2-4, 4-6, 6-8, 10-24 hours post-dose.Area Under the Curve (AUC) from 0 to 24h of total polyphenols (sum of parent polyphenols and metabolites)was calculated using a trapezoidal rule applied to the urinary concentration-time curves of compounds.
Amount of Total Fecal Polyphenols0 and 24 hours post-dose.Amount of parent polyphenols and metabolites in feces was calculated by multiplying net concentrations by the amount of feces.

Countries

Italy

Participant flow

Recruitment details

The recruitment was performed at the ambulatory of Department of Food Science (University of Naples) among students of Agriculture Faculty. It began on December 2010 up to February 2011.

Pre-assignment details

Subjects were enrolled after signing a Consent Form and were randomized to the treatments. All subjects enrolled completed the study.

Participants by arm

ArmCount
All Study Participants
All participants followed all the periods
10
Total10

Baseline characteristics

CharacteristicAll Study Participants
Age, Categorical
<=18 years
0 Participants
Age, Categorical
>=65 years
0 Participants
Age, Categorical
Between 18 and 65 years
10 Participants
Age Continuous31 years
STANDARD_DEVIATION 2
Region of Enrollment
Italy
10 participants
Sex: Female, Male
Female
5 Participants
Sex: Female, Male
Male
5 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
deaths
Total, all-cause mortality
— / —— / —— / —— / —— / —— / —
other
Total, other adverse events
0 / 100 / 100 / 100 / 100 / 100 / 10
serious
Total, serious adverse events
0 / 100 / 100 / 100 / 100 / 100 / 10

Outcome results

Primary

Amount of Total Fecal Polyphenols

Amount of parent polyphenols and metabolites in feces was calculated by multiplying net concentrations by the amount of feces.

Time frame: 0 and 24 hours post-dose.

ArmMeasureValue (MEAN)Dispersion
Free CurcuminAmount of Total Fecal Polyphenols3.49 nmolStandard Error 2.13
Encapsulated CurcuminAmount of Total Fecal Polyphenols0.49 nmolStandard Error 0.01
Encapsulated Curcumin + PQGAmount of Total Fecal Polyphenols27.98 nmolStandard Error 13.97
Control CreamAmount of Total Fecal Polyphenols4.27 nmolStandard Error 4.52
Free Cocoa PolyphenolsAmount of Total Fecal Polyphenols150.97 nmolStandard Error 54.65
Encapsulated Cocoa PolyphenolsAmount of Total Fecal Polyphenols0.59 nmolStandard Error 0.38
p-value: 0.04ANOVA
Primary

Serum Polyphenol Concentrations Over 24h From Food Consumption

Area Under the Curves (AUC) from 0 to 24h of parent polyphenols was calculated using a trapezoidal rule applied to the concentration-time curves of compounds.

Time frame: 0, 0.5, 1, 2, 4, 6, and 24 hours post-dose

Population: The number of subjects was based on power calculations derived from our previous study. We calculated that, at α = 0.05 with a power of 80%, 8 subjects would allow us to detect a 20% difference in serum and urinary concentrations of parental compounds, glucuronides and phenolic acids.

ArmMeasureValue (MEAN)Dispersion
Free CurcuminSerum Polyphenol Concentrations Over 24h From Food Consumption1.7 nmol*h/LStandard Error 0.1
Encapsulated CurcuminSerum Polyphenol Concentrations Over 24h From Food Consumption12.1 nmol*h/LStandard Error 1.1
Encapsulated Curcumin + PQGSerum Polyphenol Concentrations Over 24h From Food Consumption7.7 nmol*h/LStandard Error 1.8
Control CreamSerum Polyphenol Concentrations Over 24h From Food Consumption0.01 nmol*h/LStandard Error 0
Free Cocoa PolyphenolsSerum Polyphenol Concentrations Over 24h From Food Consumption7.3 nmol*h/LStandard Error 0.9
Encapsulated Cocoa PolyphenolsSerum Polyphenol Concentrations Over 24h From Food Consumption0.5 nmol*h/LStandard Error 0.1
p-value: 0.02ANOVA
Primary

Urinary Excretion of Total Polyphenols

Area Under the Curve (AUC) from 0 to 24h of total polyphenols (sum of parent polyphenols and metabolites)was calculated using a trapezoidal rule applied to the urinary concentration-time curves of compounds.

Time frame: Time intervals: 0-2, 2-4, 4-6, 6-8, 10-24 hours post-dose.

Population: Basing on power analysis calculation on a previous work

ArmMeasureValue (MEAN)Dispersion
Free CurcuminUrinary Excretion of Total Polyphenols2.0 nmol•h/LStandard Error 0.8
Encapsulated CurcuminUrinary Excretion of Total Polyphenols2.21 nmol•h/LStandard Error 1.27
Encapsulated Curcumin + PQGUrinary Excretion of Total Polyphenols9.67 nmol•h/LStandard Error 6.7
Control CreamUrinary Excretion of Total Polyphenols19.1 nmol•h/LStandard Error 12.3
Free Cocoa PolyphenolsUrinary Excretion of Total Polyphenols4.92 nmol•h/LStandard Error 3.36
Encapsulated Cocoa PolyphenolsUrinary Excretion of Total Polyphenols1.31 nmol•h/LStandard Error 0.81
Comparison: Statistical analysis was performed using the statistical package SPSS for Windows (version15). By the analysis of variance (ANOVA) for repeated measures the subjective time curves for all measured compounds were compared and tested for the effect of treatment and of time as factors. For all tests, following a significant main effect in the ANOVA, individual means were compared using the Bonferroni test (p \< 0.05). Results were considered significant at p \< 0.05.p-value: 0.01ANOVA

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026