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Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease
Open accessAbstract
Objectives In patients with coronary artery disease (CAD) medically managed according to currently accepted guidelines, we tested whether a 1-month dietary intervention with flavanol-containing cocoa leads to an improvement of endothelial dysfunction and whether this is associated with an enhanced number and function of circulating angiogenic cells (CACs).Background Dietary flavanols can improve endothelial dysfunction. The CACs, also termed endothelial progenitor cells, are critical for vascular repair and maintenance of endothelial function.Methods In a randomized, controlled, double-masked, cross-over trial, 16 CAD patients (64+/-3 years of age) received a dietary high-flavanol intervention (HiFI [375 mg]) and a macronutrient- and micronutrient-matched low-flavanol intervention (LoFI [9 mg]) twice daily in random order over 30 days.Results Endothelium-dependent vasomotor function, as measured by flow-mediated vasodilation of the brachial artery, improved by 47% in the HiFI period compared with the LoFI period. After HiFI, the number of CD34+/KDR+-CACs, as measured by flow cytometry, increased 2.2-fold as compared with after LoFI. The CAC functions, as measured by the capacity to survive, differentiate, proliferate, and to migrate were not different between the groups. The HiFI led to a decrease in systolic blood pressure (mean change over LoFI: -4.2+/-2.7 mm Hg), and increase in plasma nitrite level (mean change over LoFI: 74+/-32 nM). Applying a mixed-effects linear regression model, the results demonstrated a significant increase in flow-mediated vasodilation and a decrease in systolic blood pressure with increasing levels of CD34+/KDR+-CACs.Conclusions Sustained improvements in endothelial dysfunction by regular dietary intake of flavanols are associated with mobilization of functional CACs. (Effect of Cocoa Flavanols on Vascular Function in Optimally Treated Coronary Artery Disease Patients: Interaction Between Endothelial Progenitor Cells, Reactivity of Micro- and Macrocirculation; NCT00553774).
Verified 2026-10-06 · 4 references not checked yet
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Written from the paper’s full text.
TL;DR
In a 30-day randomized crossover trial in 16 medically managed coronary artery disease patients, high-flavanol cocoa improved endothelial function and increased circulating angiogenic cells compared with low-flavanol cocoa. The improvement in flow-mediated dilation and systolic blood pressure tracked with CD34+/KDR+ circulating angiogenic cell mobilization.
Key findings
- Flow-mediated dilation improved by 47% during the high-flavanol period compared with the low-flavanol period; baseline values were 4.4 ± 0.5% and 4.6 ± 0.5% before the low- and high-flavanol regimens, respectively.
- CD34+/KDR+ circulating angiogenic cells increased 2.2-fold after high-flavanol intake versus low-flavanol intake, while assays of survival, differentiation, proliferation, and migration did not differ between groups.
- Systolic blood pressure decreased with high-flavanol intake, reported as a mean change over low-flavanol of −4.2 ± 2.7 mm Hg in the abstract and as a 4.2 ± 0.3 mm Hg decrease in the results; plasma nitrite increased by a mean change over low-flavanol of 74 ± 32 nM.
- In mixed-effects linear regression, each 1% increase in CD34+/KDR+ circulating angiogenic cells was associated with a 4.6% increase in flow-mediated dilation, a 0.52 decrease in brachial artery diameter, and a 4.44 mm Hg decrease in systolic blood pressure.
Methods
- Randomized, controlled, double-masked crossover design: 16 CAD patients (64 ± 3 years; 13 male/3 female) completed the study, receiving high-flavanol cocoa (375 mg) or matched low-flavanol cocoa (9 mg) twice daily for 30 days, with a 1-week washout between interventions.
- Primary and secondary outcomes were brachial artery flow-mediated dilation and circulating angiogenic cell number/function; cells were measured by flow cytometry for CD34/KDR and CD133/KDR and functionally assessed after ex vivo expansion. Tertiary outcomes included plasma nitrite/nitrate, blood pressure, heart rate, and cytokines involved in cell mobilization (VEGF, SDF-1α, SCF).
- Analysis used two-way repeated-measures ANOVA with Holm-Sidak post hoc tests, plus random-effects linear regression to test associations between CD34+/KDR+ circulating angiogenic cells and outcomes.
Limitations
- The paper states that the mechanisms underlying the blood pressure effect cannot be determined from this study and that long-term intervention trials are needed; it also notes that small increases after the low-flavanol regimen may reflect non-flavanol bioactives such as methylxanthines or regression to the mean.
- Evident from the text: the sample was small (16 completers, mostly male), the intervention periods were short (30 days), and no clinical event outcomes were assessed, limiting generalizability and inference about long-term cardiovascular benefit.
- Evident from the text: the study received an unrestricted research grant from Mars, Inc., a coauthor was employed by Mars, Inc., and the company supplied the cocoa beverage powders, indicating a potential conflict of interest.
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14 Own result · 13 Not checked yet · 9 Own method · 6 Own interpretation · 1 Partly supported · accuracy not yet measured
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For each 1% increase in CD34 ϩ /KDR ϩ -CAC numbers, there was a significant increase in FMD of 4.6%, and significant decrease in BA diameter and SBP by 0.52 and 4.44 mm Hg, respectively.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Composition of Matched Flavanol-Containing Test Materials Ingested Twice Daily
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The HiFI led to a decrease in systolic blood pressure (mean change over LoFI: Ϫ4.2 Ϯ 2.7 mm Hg)”
- Also stated in: § Composition of Matched Flavanol-Containing Test Materials Ingested Twice Daily · plain
“corresponding to a 4.2 Ϯ 0.3 mm Hg decrease as compared with LoFI.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Results
plaindirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Composition of Matched Flavanol-Containing Test Materials Ingested Twice Daily · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“After HiFI, the number of CD34 ϩ /KDR ϩ -CACs, as measured by flow cytometry, increased 2.2-fold as compared with after LoFI.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Results
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The CAC functions, as measured by the capacity to survive, differentiate, proliferate, and to migrate were not different between the groups.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Results
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Endothelium-dependent vasomotor function, as measured by flow-mediated vasodilation of the brachial artery, improved by 47% in the HiFI period compared with the LoFI period.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Results
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For each 1% increase in CD34 ϩ /KDR ϩ -CAC numbers, there was a significant increase in FMD of 4.6%, and significant decrease in BA diameter and SBP by 0.52 and 4.44 mm Hg, respectively.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Composition of Matched Flavanol-Containing Test Materials Ingested Twice Daily
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“For each 1% increase in CD34 ϩ /KDR ϩ -CAC numbers, there was a significant increase in FMD of 4.6%, and significant decrease in BA diameter and SBP by 0.52 and 4.44 mm Hg, respectively.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Composition of Matched Flavanol-Containing Test Materials Ingested Twice Daily
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These outcomes demonstrate that a randomized, controlled dietary flavanol intervention results in improvements in endothelial dysfunction and BP, and that this is associated with the mobilization of functional CACs in patients with CAD.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Discussion
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Our data demonstrate that a further increase of endothelial function can be achieved by complementing standard treatments with a flavanol-based dietary intervention.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“The average baseline FMD values were 4.4 Ϯ 0.5% and 4.6 Ϯ 0.5% (p ϭ 0.125) before starting the LoFI or HiFI regimen, respectively (Fig. 2).”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Improvement of FMD.
plain- Asserted: passes — The authors put it forward as true.
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- Probably not a substantial claim. 13
- It may state two separate claims as one. 18
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Brachial artery (BA) FMD was measured by ultrasonography (13-MHz transducer, Sonosite Micromax, Bothell, Washington) in combination with an automated analysis system (Medical Imaging Applications, Iowa City, Iowa) in a 21°C temperature-controlled room after 30 min of supine rest (7).”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Flavanol-containing test material.
What the sources say
- Partly supportedcites [7] Schroeter, 2006, (−)-epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans, Proc Natl Acad Sci U S A sourceExperimental — accuracy not yet measured
Materials and Methods (page not available) confirms that the study measured brachial-artery FMD and that volunteers fasted overnight. It does not specify ultrasonography, an automated analysis system, or 30 minutes of supine rest—the procedural details for which the citing sentence offers this source. (LLM, conf=0.85)
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
- Partly supported
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Notably, during the course of the present study, our patients did not show any signs of augmented inflammation, or increases in the cytokines analyzed (VEGF, SDF-1␣, and SCF).”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Discussion
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In the paper
“Nitrate levels were not significantly affected by either treatment (average at first visit: 23 Ϯ 5 M).”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Improvement of FMD.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We observed no significant changes in plasma VEGF, SDF-1␣, or SCF and clinical laboratory parameters, including C-reactive protein, erythrocyte sedimentation rate, total cholesterol, LDL, high-density lipoprotein, glucose, triglycerides, and blood cell counts.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Improvement of FMD.
plain- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whereas 30-day LoFI did not significantly change systolic blood pressure (SBP [129 Ϯ 1 mm Hg, p ϭ 0.471 vs. day 0]), HiFI significantly decreased SBP to 125 Ϯ 1 mm Hg (p ϭ 0.013 vs. day 0), corresponding to a 4.2 Ϯ 0.3 mm Hg decrease as compared with LoFI.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Composition of Matched Flavanol-Containing Test Materials Ingested Twice Daily
plaindirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The cocoa drinks were well tolerated, and none of the patients experienced major adverse events, cardiovascular-specific events, or hospitalization during the study period.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Characteristics of study group.
plainn = 16- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Mean heart rate and diastolic BP were not significantly affected by either treatment.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Composition of Matched Flavanol-Containing Test Materials Ingested Twice Daily
plain- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and increase in plasma nitrite level (mean change over LoFI: 74 Ϯ 32 nM).”
- Also stated in: § Improvement of FMD. · plain
“Levels of plasma nitrite significantly increased after HiFI, but remained unaltered after LoFI (Fig. 4).”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Results
plaindirect- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Improvement of FMD. · plain
In the paper
“Differing in part from Balzer et al. (11), we observed small but significant increases in FMD and CD34 ϩ / KDR ϩ -CAC after the LoFI regimen.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Discussion
What the sources say
- Not checked yetcites [11] Balzer, 2008, Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial, J Am Coll Cardiol source
plaindirect- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“All individual medications and treatment paradigms, as well as body mass indexes remained unaltered throughout the study.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Characteristics of study group.
plainn = 16- Asserted: passes — The authors put it forward as true.
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In the paper
“The study protocol was approved by the University of California-San Francisco Committee on Human Research, and subjects gave written informed consent.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Study design.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Physiologically, the mobilization of CACs contributes to the repair response after vascular injury (3,4).”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Discussion
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Cocoa drinks (Mars, Inc., McLean, Virginia) were standardized for flavanol content and profile, and closely matched for macronutrient content, micronutrient content, caloric load, and theobromine and caffeine levels.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Flavanol-containing test material.
plain- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Randomization and cocoa drink dispensations were performed by the Department of Pharmacology, University of California-San Francisco.Patients and investigators were masked throughout the study with regard to flavanol content of the test drinks.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Study design.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Functional CAC characterization was performed after ex vivo expansion (8).”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Cell assays.
What the sources say
- Not checked yetcites [8] Heiss, 2005, Impaired progenitor cell activity in age-related endothelial dysfunction, J Am Coll Cardiol source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Endothelial vasomotor function assessed as flowmediated dilation (FMD), as well as CAC numbers and function were defined as primary and secondary outcomes, respectively.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Study design.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
In the paper
“Several controlled human dietary intervention studies that have utilized flavanol-containing foods and beverages in concert with nutrient-matched, low-flavanol controls have demonstrated flavanol-dependent effects, including the recovery of endothelial function, decreased blood pressure, and reductions in platelet aggregation (2).”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Conclusions
What the sources say
- Not checked yetcites [2] Corti, 2009, Cocoa and cardiovascular health, Circulation source
boosteddirect- Asserted: passes — The authors put it forward as true.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“using a randomized, double-masked, crossover study design (Fig. 1) with 1 week of wash-out between interventions.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Study design.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These outcomes demonstrate that a randomized, controlled dietary flavanol intervention results in improvements in endothelial dysfunction and BP, and that this is associated with the mobilization of functional CACs in patients with CAD.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Rests on an assumption: The 16 CAD patients studied are representative of CAD patients medically managed according to current guidelines.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“From the 20 patients initially included, 16 patients completed the study and were included in data analyses.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Study design.
plainn = 16- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“we observed an increase in plasma nitrite, which represents both a marker of NO bioavailability and a bioactive NO donor (10).”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Discussion
What the sources say
- Not checked yetcites [10] Lundberg, 2009, Nitrate and nitrite in biology, nutrition and therapeutics, Nat Chem Biol source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“The CAC number in whole blood was measured by flow cytometry as CD34/KDR and CD133/KDR doublepositive cells in the lymphomononuclear cell gate (8).”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Cell assays.
What the sources say
- Not checked yetcites [8] Heiss, 2005, Impaired progenitor cell activity in age-related endothelial dysfunction, J Am Coll Cardiol source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on previous data, it seems unlikely that the small flavanol amounts present in LoFI would explain our findings, but the presence in both test drinks of bioactive compounds other than flavanols, for example, methylxanthines, as well as a general regression to the mean may need to be considered in this context.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our data support the concept that dietary flavanols, in addition to improving cardiovascular functions, can facilitate endogenous repair mechanisms that act synergistically with current medical therapy.”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper relies on this without support.
The 30-day intervention period is sufficient to produce sustained improvements in endothelial function and circulating angiogenic cell mobilization.
“Sustained improvements in endothelial dysfunction by regular dietary intake of flavanols are associated with mobilization of functional CACs.”
The paper relies on this without support.
The 16 CAD patients studied are representative of CAD patients medically managed according to current guidelines.
“The study group consisted of 16 CAD patients having achieved treatment goals in accordance with current AHA/ACC guidelines”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The current demonstration of significant reductions in both systolic and diastolic blood pressure levels after regular cocoa flavanol consumption is consistent with previous findings obtained both in normotensives and in hypertensive subjects, as well as medicated individuals.17,18,29,30”
From Benefits in Cognitive Function, Blood Pressure, and Insulin Resistance Through Cocoa Flavanol Consumption in Elderly Subjects With Mild Cognitive Impairment: The Cocoa, Cognition, and Aging (CoCoA) Study (2012) · cites this paper as [30]
Experimental — accuracy not yet measuredIn the citing paper
“The associative relation, increased plasma nitrite levels and an increased mobilization of CD34 ϩ /Flk-1 ϩ cells from the bone marrow, has also been observed in patients with coronary artery disease receiving nutrients that increased NO bioavailability.40”
From Dietary nitrate supplementation improves revascularization in chronic ischemia (2012) · cites this paper as [40]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated major: it would touch a result — a value a result rests on, reported and recomputed p-values on opposite sides of the significance level, two passages that conflict with no sign which is right, or a cited work retracted before this paper was published.
In the paper
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Results
“The HiFI led to a decrease in systolic blood pressure (mean change over LoFI: Ϫ4.2 Ϯ 2.7 mm Hg)”
§ Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease > Composition of Matched Flavanol-Containing Test Materials Ingested Twice Daily
“corresponding to a 4.2 Ϯ 0.3 mm Hg decrease as compared with LoFI.”
Citations
Cites
Smith, S. C., Allen, J. K., Blair, S. N., Bonow, R. O., Brass, L. M., Fonarow, G. C., Grundy, S. M., Hiratzka, L. F., Jones, D. W., Krumholz, H. M., et al. (2006) · Circulation · doi:10.1161/circulationaha.106.174516 · Cited by 2,102
Circulating endothelial progenitor cells and cardiovascular outcomes
Werner, N., Kosiol, S., Schiegl, T., Ahlers, P., Walenta, K., Link, A., Böhm, M., & Nickenig, G. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043814 · Cited by 2,048
Polyphenols and disease risk in epidemiologic studies
Arts, I. C., & Hollman, P. C. (2005) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/81.1.317s · Cited by 1,916 · cited 1×
“Heiss), and an unrestricted research grant from 2 f flavanol-containing foods and coronary artery disease CAD) mortality (1).”
Background(–)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans
Schroeter, H., Heiss, C., Balzer, J., Kleinbongard, P., Keen, C. L., Hollenberg, N. K., Sies, H., Kwik-Uribe, C., Schmitz, H. H., & Kelm, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0510168103 · Cited by 1,052
Self-citationSmith, S. C., Allen, J. K., Blair, S. N., Bonow, R. O., Brass, L. M., Fonarow, G. C., Grundy, S. M., Hiratzka, L. F., Jones, D. W., Krumholz, H. M., et al. (2006) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.04.026 · Cited by 672
Nitrate and nitrite in biology, nutrition and therapeutics
Lundberg, J. O., Gladwin, M. T., Ahluwalia, A., Benjamin, N., Bryan, N. S., Butler, A., Cabrales, P., Fago, A., Feelisch, M., Ford, P. C., et al. (2009) · Nature Chemical Biology · doi:10.1038/nchembio.260 · Cited by 617
Self-citationImpaired progenitor cell activity in age-related endothelial dysfunction
Heiss, C., Keymel, S., Niesler, U., Ziemann, J., Kelm, M., & Kalka, C. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2004.12.074 · Cited by 573
Cocoa and Cardiovascular Health
Corti, R., Flammer, A. J., Hollenberg, N. K., & Lüscher, T. F. (2009) · Circulation · doi:10.1161/circulationaha.108.827022 · Cited by 424 · cited 2×
“In line ith previous studies (2), we observed a flavanol intakessociated decrease in SBP, and our data extend these ndings by showing that SBP-lowering effects of dietary avanols may complement standard medical BP manageent.”
BackgroundResultEndothelial progenitor cells in cardiovascular disorders
Shantsila, E., Watson, T., & Lip, G. Y. H. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.09.050 · Cited by 413
Balzer, J., Rassaf, T., Heiss, C., Kleinbongard, P., Lauer, T., Merx, M., Heussen, N., Gross, H. B., Keen, C. L., Schroeter, H., et al. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.01.059 · Cited by 345
Self-citation
Cited by
Sorted by citations
Del Rio, D., Rodriguez-Mateos, A., Spencer, J. P. E., Tognolini, M., Borges, G., & Crozier, A. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4581 · Cited by 2,601
Hooper, L., Kay, C., Abdelhamid, A., Kroon, P. A., Cohn, J. S., Rimm, E. B., & Cassidy, A. (2012) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.111.023457 · Cited by 610
Tzounis, X., Rodriguez‐Mateos, A., Vulevic, J., Gibson, G. R., Kwik-Uribe, C. L., & Spencer, J. P. E. (2010) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.000075 · Cited by 582
Williams, R. J., & Spencer, J. P. E. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.09.010 · Cited by 448
Cocoa and Chocolate in Human Health and Disease
Katz, D. L., Doughty, K. N., & Ali, A. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3697 · Cited by 475
“However, another study in CAD patients published in July 2010 had different results (94).”
Metadata
- Authors
- Heiss, C., Jahn, S., Taylor, M., Real, W. M., Angeli, F. S., Wong, M. L., Amabile, N., Prasad, M., Rassaf, T., Ottaviani, J. I., Mihardja, S., Keen, C. L., Springer, M. L., Boyle, A., Grossman, W., Glantz, S. A., Schroeter, H., & Yeghiazarians, Y.
- Affiliations
- University of California, San Francisco (US)
- Heinrich Heine University Düsseldorf (DE)
- University of California, Davis (US)
- Mars (United States) (US)
- Corresponding author
- Heiss, Christian
- ORCID
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2010-07
- Volume
- 56
- Issue
- 3
- Pages
- 218-224
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2046356569
- Cited by
- 202
- References
- 12
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 8 · 2023: 13 · 2022: 4 · 2021: 7 · 2020: 6 · 2019: 9 · 2018: 13 · 2017: 9 · 2016: 15 · 2015: 19 · 2014: 10 · 2013: 17 · 2012: 32
- FWCI
- 16.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Mars, Inc.
- Mars Inc.
- N30 Pharmaceuticals
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Keywords
- flavan-3-ols, Theobroma cacao, endothelial dysfunction, circulating angiogenic cells, endothelial progenitor cells, coronary artery disease, flow-mediated dilation, CD34+/KDR+ cells, systolic blood pressure, plasma nitrite, dietary intervention, vascular function
- MeSH terms
- Blood Pressure, Cacao, Coronary Disease, Diet, Double-Blind Method, Endothelium, Vascular, Female, Flavonoids, Humans, Male, Middle Aged, Vasodilation, Neovascularization, Physiologic, Endothelial Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-06, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-06 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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