Dark Chocolate and Platelet Function in Humans
Information source: University of Aberdeen
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cardiovascular Disease
Intervention: Dark chocolate enriched in flavan-3-ols and procyanidins (Dietary Supplement); Standard dark chocolate (Dietary Supplement); White chocolate (Dietary Supplement)
Phase: N/A
Status: Completed
Sponsored by: University of Aberdeen Official(s) and/or principal investigator(s): Baukje de Roos, MSc PhD, Principal Investigator, Affiliation: University of Aberdeen Rowett Institute of Nutrition and Health
Summary
Cardiovascular disease is a major cause of mortality worldwide and responsible for one out
of three global deaths. A main characteristic of cardiovascular disease is impaired blood
flow and formation of blood clots. Platelets are clot-forming cells responsible for the
prevention of bleeding. However, in disease conditions they may be overly activated,
promoting blood clots and blockage of blood vessels.
Consumption of diets rich in fruits and vegetables decreases mortality from cardiovascular
disease through a number of mechanisms, including the prevention of platelet clotting and
aggregation. There is some evidence suggesting that platelet aggregation may be modulated
through a group of compounds known as flavan-3-ols, which are found in various foods, and
especially in cocoa. However, the mechanisms by which those compounds affect platelet
function are not yet fully understood. We designed a human study assessing the mechanisms by
which flavan-3-ols from cocoa beneficially affect platelet function and the platelet
proteome.
Clinical Details
Official title: Acute Effects of the Consumption of Dark Chocolate Enriched in Flavan-3-ols on Platelet Function and the Platelet Proteome
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Single Blind (Investigator), Primary Purpose: Prevention
Primary outcome: Change in light transmission aggregometry of platelet-rich plasma
Secondary outcome: Change in ex vivo bleeding time using the Platelet Function Analyzer-100 (PFA-100)Change in P-selectin expression and activation of the fibrinogen receptor by flow cytometry Levels of flavan-3-ols and their metabolites in plasma and urine Changes in the platelet proteome Changes in thromboxane A2 production induced by ADP and TRAP Levels of prostacyclin and/ or leukotrienes in plasma Total phenolics in urine Total catechins in urine Urinary creatinine Analysis of flavan-3-ol and procyanidin contents in study chocolates Non-targeted 1H-NMR of plasma and urine samples Non-targeted LC-MS of urine samples Markers of oxidative stress in plasma Fatty acid analysis of study chocolates
Detailed description:
Cardiovascular disease (CVD) is a primary cause of premature deaths worldwide, with
incidence rates in the United Kingdom, particularly in Scotland, being amongst the highest
worldwide. Thus identification of dietary components that most effectively prevent CVD is
potentially of wide public health benefit.
Consumption of diets rich in plant-based products protects against the development of CVD.
Such effects have been ascribed in part to polyphenols, which are non-nutritive but,
potentially bioactive secondary metabolites ubiquitous found in fruits, vegetables, herbs,
spices, teas and wines. The beneficial effects of polyphenols on CVD is believed to be
mediated, at least in part, though improving platelet function. At least 10 human
intervention studies found a consistent and robust beneficial effect of cocoa products on
platelet function, but unfortunately all of these studies used only one or two methods to
assess platelet function, therefore only getting limited insights into the complex
physiological behavior of platelets. In addition, none of these studies assessed potential
mechanisms by which flavan-3-ols may inhibit platelet function. Schramm et al. have shown
that consumption of chocolate rich in flavan-3-ols and their oligomers (procyanidins) lead
to increased production of prostacyclin, a strong platelet inhibitor. This finding has also
been observed when aortic endothelial cells are treated with procyanidins in vitro. Thus the
stimulation of prostacyclin production in endothelial cells may reflect one pathway by which
flavan-3-ols indirectly inhibit platelet activation. Many other potential mechanisms are
discussed in the literature but so far the evidence for such mechanisms is limited or
non-existing.
In this study we assess effects of consumption of chocolate enriched in flavan-3-ols on
platelet function by measuring not only platelet aggregation, but also in vitro coagulation
and platelet activation in healthy humans. In addition, we examine the effects of
consumption of flavan-3-ols on the regulation of the platelet proteome to elucidate pathways
by which these bioactive cocoa compounds affect platelet function.
HYPOTHESIS
Acute consumption of a moderate amount of dark chocolate enriched in flavan-3-ols results in
decreased platelet activation and aggregation by decreasing the levels of thromboxane A2
produced by endothelial cells.
OBJECTIVES
The main objective of the proposed study is to determine whether consumption of 60 g dark
chocolate enriched in flavan-3-ols results in decreased platelet activation and aggregation
by decreasing levels of thromboxane A2, as well as assessing what other mechanisms could be
involved.
The specific objectives of the proposed study are to determine:
1. whether acute intake of 60 g dark chocolate enriched in flavan-3-ols, as compared with
standard dark chocolate low in flavan-3-ols and white chocolate containing no
flavan-3-ols, affects platelet aggregation, thromboxane A2 formation upon aggregation,
in vitro bleeding time, P-selectin expression, and activation of the fibrinogen
receptor;
2. whether and how acute intake of 60 g dark chocolate enriched in flavan-3-ols, as
compared with standard dark chocolate and white chocolate, affects the platelet
proteome, and thereby potential new biomarkers of platelet function, as well as protein
levels of anti-oxidant enzymes;
3. identities and concentrations of flavan-3-ols and their metabolites in plasma and/ or
urine 2 and 6 h after acute intake of 60 g dark chocolate enriched in flavan-3-ols, as
compared with standard dark chocolate and white chocolate.
Eligibility
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Healthy male and/or female volunteers, aged between 18 and 70 years
Exclusion Criteria:
Subjects are excluded if:
- they are taking aspirin or aspirin-containing drugs, other anti-inflammatory drugs,
or any drugs or herbal medicines known to alter platelet function or the haemostatic
system in general (without a minimum washout period of one month)
- they are taking fish oils or evening primrose oil, or fat soluble vitamin supplements
within the last 4 weeks
- they are taking any medicine known to affect lipid and/or glucose metabolism
- they are taking hormone replacement therapy
- they have any known clinical signs of diabetes, hypertension, renal, hepatic,
hematological disease, gastrointestinal disorders, endocrine disorders, coronary
heart disease, infection or cancer
- they are suffering from alcohol or any other substance abuse or are having eating
disorders
- they are usually consuming a vegetarian diet
- they have a BMI below 18 or above 35 kg/ sqm
- they are undertaking more than 6 hours of vigorous exercise per week
- they are having an abnormal menstrual cycle
- they are pregnant
- they suffer from an allergy to cocoa or any of the ingredients contained within
either of the chocolate bars
- they have been giving a pint of blood for transfusion purposes within the last month
- they have a low platelet count (< 170 x 10E09/ L)
- they have unsuitable veins for blood sampling and/ or cannulation
- their hematocrit is below 40 % for males and 35 % for females
- their haemoglobin is below 130 g/ L for males and 115 g/ L for females
- they are not able to travel on their own to the Rowett Institute of Nutrition and
Health, Aberdeen for each of the interventions
Locations and Contacts
University of Aberdeen Rowett Institute of Nutrition and Health, Aberdeen, Aberdeenshire AB21 9SB, United Kingdom
Additional Information
Press release about study to recruit volunteers, 2009-04-23
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Starting date: March 2009
Last updated: April 15, 2012
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