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Dark chocolate is one of the richest sources of polyphenols though it has been hypothesised that the bioavailability and therefore probably the bioefficacy of epicatechin from milk chocolate was reduced compared to dark. This study is designed to compare milk and dark chocolate as a source of polyphenols with a control "chocolate" for improving a risk biomarker for vascular disease.
Dark chocolate is one of the richest sources of polyphenols, for example, a standard 40g portion of dark chocolate contains 400-800 mg of polyphenols, compared to red wine (170 mg /100ml) or an apple (200 mg/piece). Cocoa polyphenols, most notably the catechins, can exist in both lipid and water-based environments (amphipathic), meaning they can spare both lipophilic and hydrophilic vitamins. There have been a number of human trials conducted using chocolate or cocoa and measuring various endpoints. Most have been conducted with dark chocolate. An article in Nature found that the bioavailability of epicatechin from milk chocolate was substantially reduced compared to dark, and even dark taken with a glass of milk (Serafini et al 2003). The hypothesis was that the milk proteins bind to polyphenols, making them unavailable. Subsequent studies have not been able to reproduce this, but none have been conducted using solid chocolate as the first study, all have been done using a drink matrix, which may completely alter the binding interactions of the polyphenols and protein. To this end, this study is designed to compare solid chocolates as a source of polyphenols for improving a risk biomarker for vascular disease.
This study is designed as a blinded, three arm crossover trial. The primary outcome measure is to compare endothelial function after consumption of 3 chocolates (1 milk, 1 dark, 1 polyphenol-free control) with a secondary outcome of arterial stiffness. All volunteers will take all chocolate types in a crossover design. Subjects will undergo medical screening, anthropometry, physical activity and dietary assessments before randomization for the order of consumption.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| dark chocolate containing polyphenols | Experimental | dark chocolate |
|
| Milk chocolate containing polyphenols | Experimental | Bespoke milk chocolate |
|
| Control chocolate with no polyphenols | Active Comparator | cocoa-free chocolate |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dark Chocolate | Dietary Supplement | 1 portion |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Reactive Hyperemia Index (RHI) From Baseline (20 Min Before Product Intake) to 2 Hours Following Product Intake | Value of RHI at 2 hours minus value at baseline. RHI reflects the endothelial function of a vessel at the distal phalanx of a finger, i.e. the capacity of the vessel to dilate after an ischemia. RHI is the increase of blood flow following the occlusion of the brachial artery during 5 minutes by the inflation of an armcuff. RHI was measured by peripheral arterial tonometry using a fingerprobe connected to an EndoPat analyser. | Baseline and 2 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Arterial Stiffness From Baseline (20 Min Before Product Intake) to Two Hours Following Product Intake | Value of arterial stiffness at 2 hours minus value at baseline. Arterial stiffness is also automatically calculated by peripheral arterial tonometry which consists in measuring the peripheral vessel endothelial response to an ischemia provoked by a 5-min occlusion of the humeral artery using an armcuff. An increase in arterial stiffness means an increase in the resistance of the vessel wall which reflects an impaired endothelial response to ischemia. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Karen A Cooper, PhD | Société des Produits Nestlé (SPN) | Principal Investigator |
| Gary Williamson, PhD | Société des Produits Nestlé (SPN) | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nestle Research Center | Lausanne | Canton of Vaud | 1000 | Switzerland |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17312446 | Background | Heiss C, Finis D, Kleinbongard P, Hoffmann A, Rassaf T, Kelm M, Sies H. Sustained increase in flow-mediated dilation after daily intake of high-flavanol cocoa drink over 1 week. J Cardiovasc Pharmacol. 2007 Feb;49(2):74-80. doi: 10.1097/FJC.0b013e31802d0001. | |
| 16877960 | Background | Fisher ND, Hollenberg NK. Aging and vascular responses to flavanol-rich cocoa. J Hypertens. 2006 Aug;24(8):1575-80. doi: 10.1097/01.hjh.0000239293.40507.2a. |
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From 3 days before the first test session no foods containing epicatechin or catechin or procyanidins should be ingested. The subjects received a single dose of the 3 products in a randomised order with a minimum of 3 days washout in between (crossover design). The duration of the study was a minimum of 15 days.
5 healthy subjects, 2 females and 3 males, were recruited within the staff of the Nestlé Research Center in June-July 2008.
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| ID | Title | Description |
|---|---|---|
| FG000 | Each Subject Tested the Three Products Randomly Following | Before the 1st intervention, no food with polyphenols was admitted Each subject was administered the three products randomly(one product per one-day intervention) according to the six possible sequencies:
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| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Diet Restriction (3 Days) |
| |||||||||||||
| 1st Intervention 1 Day |
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| Washout Period 3 Days |
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| 2nd Intervention 1 Day |
| |||||||||||||
| Washout Period 3 Days |
| |||||||||||||
| 3rd Intervention 1 Day |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Entire Study Population | Includes groups randomized to receive control first, milk chocolate first, and dark chocolate first |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Reactive Hyperemia Index (RHI) From Baseline (20 Min Before Product Intake) to 2 Hours Following Product Intake | Value of RHI at 2 hours minus value at baseline. RHI reflects the endothelial function of a vessel at the distal phalanx of a finger, i.e. the capacity of the vessel to dilate after an ischemia. RHI is the increase of blood flow following the occlusion of the brachial artery during 5 minutes by the inflation of an armcuff. RHI was measured by peripheral arterial tonometry using a fingerprobe connected to an EndoPat analyser. | Taking into account the fact that there is no background data and that we need to have accurate evaluation of central tendency and dispersion, a minimum of five complete subjects are needed. Data from all randomized subjects were considered in the intention to treat model (for the primary outcome). | Posted | Mean | Standard Error | percentage of the pulse wave amplitude | Baseline and 2 hours |
|
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Adverse Events Not Collected
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Dark Chocolate |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Maurice Beaumont, Principal Investigator | Clinical Development Unit / Metabolic Unit | +41217858054 | maurice.beaumont@rdls.nestle.com |
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| ID | Term |
|---|---|
| D000069956 | Chocolate |
| ID | Term |
|---|---|
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D019602 | Food and Beverages |
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| Milk Chocolate |
| Dietary Supplement |
1 portion |
|
| Control (polyphenol-free) "Chocolate" | Dietary Supplement | one portion |
|
| baseline and 2 hours |
| years |
|
| Age, Customized | Number | participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
cocoa-free chocolate Control (polyphenol-free) |
| OG001 | Milk Chocolate Containing Polyphenols | Bespoke milk chocolate Milk Chocolate : 1 portion |
| OG002 | Dark Chocolate Containing Polyphenols | dark chocolate Dark Chocolate : 1 portion |
|
|
| Secondary | Change in Arterial Stiffness From Baseline (20 Min Before Product Intake) to Two Hours Following Product Intake | Value of arterial stiffness at 2 hours minus value at baseline. Arterial stiffness is also automatically calculated by peripheral arterial tonometry which consists in measuring the peripheral vessel endothelial response to an ischemia provoked by a 5-min occlusion of the humeral artery using an armcuff. An increase in arterial stiffness means an increase in the resistance of the vessel wall which reflects an impaired endothelial response to ischemia. | Posted | Mean | Standard Deviation | percentage of baseline | baseline and 2 hours |
|
|
|
| 0 |
| 0 |
| 0 |
| 0 |
| EG001 | Milk Chocolate | 0 | 0 | 0 | 0 |
| EG002 | Control | 0 | 0 | 0 | 0 |
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