Flavanol Supplementation Research Articles

Cocoa flavanol supplementation and incident atrial fibrillation in the COSMOS trial.

Cocoa flavanol supplementation and incident atrial fibrillation in the COSMOS trial.

Effects of short-term, high-dose cocoa-derived flavanol supplementation on gut microbiota composition: secondary findings from a randomized, double-blind, placebo-controlled crossover study

Abstract Cocoa-derived flavanols (CDF) may act as prebiotics. However, evidence is inconsistent, and the duration and dose of CDF intake needed to elicit any prebiotic effect are undefined. This randomized, double-blind, crossover study determined the effects of short-term, high-dose dietary supplementation with CDF versus matched placebo on gut microbiota composition in 8 healthy adults. A single faecal sample was collected 8 d after supplementation with 900 mg/d CDF or placebo. Gut microbiota composition and Bifidobacterium spp. and Lactobacillus spp. abundance were measured as secondary outcomes by 16S ribosomal ribonucleic acid (rRNA) amplicon sequencing and quantitative polymerase chain reaction, respectively. No between-treatment differences in the relative or absolute abundance of Bifidobacterium spp. (Cohen’s d = 0.89, P = 0.22) or Lactobacillus spp. (Cohen’s d = 0.42, P = 0.65) were detected. Shannon diversity (Cohen’s d = 0.38, P = 0.04) and overall community richness (Cohen’s d = 0.34, P = 0.06) were lower following CDF supplementation versus placebo, but no between-treatment differences in β-diversity or taxa relative abundances were observed. Findings are not consistent with a clear prebiotic effect of this short-term, high-dose CDF supplementation strategy relative to placebo.

Short-term cocoa bioflavanol supplementation does not improve cold-induced vasodilation in young healthy adults.

Cold-induced vasodilation (CIVD) is an oscillatory rise in blood flow to glabrous skin that occurs in cold-exposed extremities. Dietary flavanols increase bioavailable nitric oxide, a proposed mediator of CIVD through active vasodilation and/or withdrawal of sympathetic vascular smooth muscle tone. However, no studies have examined the effects of flavanol intake on extremity skin perfusion during cold exposure. We tested the hypothesis that acute and 8-day flavanol supplementation would augment CIVD during single-digit cold water immersion (CWI). Eleven healthy adults (24 ± 6years; 10M/1F) ingested cocoa flavanols (900mg/day) or caffeine- and theobromine-matched placebo for 8days in a double-blind, randomized, crossover design. On Days 1 and 8, CIVD was assessed 2h post-treatment. Subjects immersed their 3rd finger in warm water (42°C) for 15min before CWI (4°C) for 30min, during which nail bed and finger pad skin temperature were measured. Flavanol ingestion had no effect on CIVD frequency (Day 1, Flavanol: 3 ± 2 vs. Placebo: 3 ± 2; Day 8, Flavanol: 3 ± 2 vs. Placebo: 3 ± 1) or amplitude (Day 1, Flavanol: 4.3 ± 1.7 vs. Placebo: 4.9 ± 2.6°C; Day 8, Flavanol: 3.9 ± 1.9 vs. Placebo: 3.9 ± 2.0°C) in the finger pad following acute or 8-day supplementation (P > 0.05). Furthermore, average, nadir, and apex finger pad temperatures during CWI were not different between treatments on Days 1 or 8 of supplementation (P > 0.05). Similarly, no differences in CIVD parameters were observed in the nail bed following supplementation (P > 0.05). These data suggest that cocoa flavanol ingestion does not alter finger CIVD. Clinical Trial Registration Clinicaltrials.gov Identifier: NCT04359082. April 24, 2020.

Cocoa Flavanol Supplementation Protects Neurocognitive Function During Hypoxia

Cocoa Flavanol Supplementation Protects Neurocognitive Function During Hypoxia

Bioavailable Microbial Metabolites of Flavanols Demonstrate Highly Individualized Bioactivity on In Vitro β-Cell Functions Critical for Metabolic Health.

Dietary flavanols are known for disease preventative properties but are often poorly absorbed. Gut microbiome flavanol metabolites are more bioavailable and may exert protective activities. Using metabolite mixtures extracted from the urine of rats supplemented with flavanols and treated with or without antibiotics, we investigated their effects on INS-1 832/13 β-cell glucose stimulated insulin secretion (GSIS) capacity. We measured insulin secretion under non-stimulatory (low) and stimulatory (high) glucose levels, insulin secretion fold induction, and total insulin content. We conducted treatment-level comparisons, individual-level dose responses, and a responder vs. non-responder predictive analysis of metabolite composition. While the first two analyses did not elucidate treatment effects, metabolites from 9 of the 28 animals demonstrated significant dose responses, regardless of treatment. Differentiation of responders vs. non-responder revealed that levels of native flavanols and valerolactones approached significance for predicting enhanced GSIS, regardless of treatment. Although treatment-level patterns were not discernable, we conclude that the high inter-individual variability shows that metabolite bioactivity on GSIS capacity is less related to flavanol supplementation or antibiotic treatment and may be more associated with the unique microbiome or metabolome of each animal. These findings suggest flavanol metabolite activities are individualized and point to the need for personalized nutrition practices.

(-)-Epicatechin and its colonic metabolite hippuric acid protect against dexamethasone-induced atrophy in skeletal muscle cells

Cocoa flavanols have been shown to improve muscle function and may offer a novel approach to protect against muscle atrophy. Hippuric acid (HA) is a colonic metabolite of (-)-epicatechin (EPI), the primary bioactive compound of cocoa, and may be responsible for the associations between cocoa supplementation and muscle metabolic alterations. Accordingly, we investigated the effects of EPI and HA upon skeletal muscle morphology and metabolism within an in vitro model of muscle atrophy. Under atrophy-like conditions (24h 100μM dexamethasone (DEX)), C2C12 myotube diameter was significantly greater following co-incubation with either 25μM HA (11.19±0.39μm) or 25μM EPI (11.01±0.21μm) compared to the vehicle control (VC; 7.61±0.16μm, both P < .001). In basal and leucine-stimulated states, there was a significant reduction in myotube protein synthesis (MPS) rates following DEX treatment in VC (P=.024). Interestingly, co-incubation with EPI or HA abrogated the DEX-induced reductions in MPS rates, whereas no significant differences versus control treated myotubes (CTL) were noted. Furthermore, co-incubation with EPI or HA partially attenuated the increase in proteolysis seen in DEX-treated cells, preserving LC3 α/β II:I and caspase-3 protein expression in atrophy-like conditions. The protein content of PGC1α, ACC, and TFAM (regulators of mitochondrial function) were significantly lower in DEX-treated versus. CTL cells (all P < .050). However, co-incubation with EPI or HA was unable to prevent these DEX-induced alterations. For the first time we demonstrate that EPI and HA exert anti-atrophic effects on C2C12 myotubes, providing novel insight into the association between flavanol supplementation and favourable effects on muscle health.

Effect of FLAVAnols on bone turnover markers in type 2 diabetes mellitus–post hoc analysis from a 3-month randomized placebo-controlled trial

BACKGROUND: Individuals with type 2 diabetes mellitus (T2DM) have increased fracture risk with high bone mineral density, possibly related to advanced glycation end products (AGEs) accumulation in bone. Flavanol supplementation in postmenopausal women reduced AGEs formation and decreased bone resorption markers. However, to date, these effects have not been investigated in T2DM. OBJECTIVE: We used a post hoc secondary analysis to determine the effect of monomeric and oligomeric flavanols supplementation on bone turnover markers (BTMs) in individuals with T2DM. METHODS: Eighty-three individuals with T2DM, aged 40–85 years, with microalbuminuria were enrolled from 4 trial centers in Rotterdam, the Netherlands, into a randomized, double-blind, placebo-controlled trial with renal vascular health as the primary outcome. Participants were randomized (1:1) to receive either a placebo or 200 mg of monomeric and oligomeric flavanols as intervention for three months. Serum alkaline phosphatase (ALP), type I collagen crosslinked beta C-telopeptide (β-CTx), and type I procollagen-N-propeptide (P1NP) were measured at baseline and three months. ANCOVA was performed on rank transformed BTMs at three months as the outcome, adjusting for baseline BTMs, group, age, sex, and BMI. RESULTS: Baseline characteristics did not differ between the two arms. The adjusted mean change in BTMs at three months was not different between the placebo vs. intervention arm: ALP –0.059 (–0.262–0.145) vs. 0.060 (–0.135–0.356), p = 0.41; β-CTx 0.013 (–0.205–0.231) vs. 0.100 (–0.109–0.310), p = 0.53 and P1NP 0.091 (–0.080–0.262) vs. 0.030 (–0.134–0.195), p = 0.61. There was no significant within-group change in BTMs after three months in both study arms. CONCLUSION: Supplementation with daily 200 mg of flavanols during three months, on top of usual care in individuals with T2DM, did not result in changes in BTMs compared to placebo. Future studies are needed to show whether long-term supplementation in higher dosages may positively affect BTMs in individuals with T2DM.

Effect of cocoa flavanol supplementation for the prevention of cardiovascular disease events: the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial

ABSTRACTBackgroundCocoa extract is a source of flavanols that favorably influence vascular risk factors in small and short-term trials, yet effects on clinical cardiovascular events are untested.ObjectivesWe examined whether cocoa extract supplementation decreases total cardiovascular disease (CVD) among older adults.MethodsWe conducted a randomized, double-blind, placebo-controlled, 2-by-2 factorial trial of cocoa extract supplementation and multivitamins for prevention of CVD and cancer among 21,442 US adults (12,666 women aged ≥65 y and 8776 men aged ≥60 y), free of major CVD and recently diagnosed cancer. The intervention phase was June 2015 through December 2020. This article reports on the cocoa extract intervention. Participants were randomly assigned to a cocoa extract supplement [500 mg flavanols/d, including 80 mg (–)-epicatechin] or placebo. The primary outcome was a composite of confirmed incident total cardiovascular events, including myocardial infarction (MI), stroke, coronary revascularization, cardiovascular death, carotid artery disease, peripheral artery surgery, and unstable angina.ResultsDuring a median follow-up of 3.6 y, 410 participants taking cocoa extract and 456 taking placebo had confirmed total cardiovascular events (HR: 0.90; 95% CI: 0.78, 1.02; P = 0.11). For secondary endpoints, HRs were 0.73 (95% CI: 0.54, 0.98) for CVD death, 0.87 (95% CI: 0.66, 1.16) for MI, 0.91 (95% CI: 0.70, 1.17) for stroke, 0.95 (95% CI: 0.77, 1.17) for coronary revascularization, neutral for other individual cardiovascular endpoints, and 0.89 (95% CI: 0.77, 1.03) for all-cause mortality. Per-protocol analyses censoring follow-up at nonadherence supported a lower risk of total cardiovascular events (HR: 0.85; 95% CI: 0.72, 0.99). There were no safety concerns.ConclusionsCocoa extract supplementation did not significantly reduce total cardiovascular events among older adults but reduced CVD death by 27%. Potential reductions in total cardiovascular events were supported in per-protocol analyses. Additional research is warranted to clarify whether cocoa extract may reduce clinical cardiovascular events. This trial is registered at www.clinicaltrials.gov as NCT02422745.

Dietary Bioflavanol Supplementation Does Not Improve Cold‐Induced Vasodilation in Healthy Adults

BackgroundCold‐induced vasodilation (CIVD) is a cyclical rise in blood flow to glabrous skin that occurs during cold exposure of the extremities. Nitric oxide (NO) is a proposed mediator of the CIVD response through active vasodilation and/or withdrawal of sympathetic vascular smooth muscle tone. Dietary flavanols augment bioavailable NO by upregulating NO synthase, the main source of NO in the vasculature, and by enhancing removal of reactive oxygen species that are known to breakdown NO. Although acute dietary flavanol intake has been shown to augment skin blood flow, at least in part through increased NO, no studies have examined the impact of flavanol intake on skin perfusion during cold exposure. Improving skin blood flow to the extremities may enhance manual dexterity and reduce the risk of peripheral cold injury, benefits pertinent to warfighters or other populations that spend time in cold environments.PurposeTo examine the effect of high‐dose flavanol supplementation on CIVD. We hypothesized that acute and 8‐day flavanol supplementation would augment CIVD during single‐digit cold water immersion.MethodsEleven healthy adults (24±6 yrs; 10M/1F) ingested cocoa‐based flavanols (FLV; 900 mg/d) or caffeine and theobromine‐matched placebo (PLA) for 8 days in a double‐blind, randomized, crossover design. On Days 1 and 8, CIVD was assessed 2 hours after treatment ingestion. Subjects immersed their middle finger in warm water (42°C) for 15 minutes before cold water immersion (4°C) for 30 min, during which nail bed and finger pad skin temperature were measured continuously.ResultsFlavanol ingestion had no effect (all P &gt; 0.05) on CIVD event frequency (Day 1, FLV: 3±2 vs. PLA: 3±2; Day 8, FLV: 3±2 vs. PLA: 3±1) or amplitude (Day 1, FLV: 4.3±1.7 vs. PLA: 4.9±2.6 °C; Day 8, FLV: 3.9±1.9 vs. PLA: 3.9±2.0 °C) in the finger pad following acute or 8‐day supplementation. Furthermore, average (Day 1, FLV: 9.2±1.5 vs. PLA: 9.2±1.8 °C; Day 8, FLV: 8.3±1.7 vs. PLA: 8.9±1.9 °C), maximum (Day 1, FLV: 11.9±3.0 vs. PLA: 11.2±2.3 °C; Day 8, FLV: 10.1±1.9 vs. PLA: 10.6±2.3 °C), and minimum (Day 1, FLV: 6.2±1.3 vs. PLA: 6.0±1.5 °C; Day 8, FLV: 5.8±1.8 vs. PLA: 6.2±1.7 °C) finger pad temperatures during cold water immersion were not different (all P &gt; 0.05) between treatments on Day 1 or Day 8 of supplementation. Similarly, no differences (all P &gt; 0.05) in CIVD parameters were observed in the nail bed following acute or 8‐day supplementation.ConclusionDietary ingestion of cocoa‐based flavanols does not improve the CIVD response to single‐digit cold water immersion.

Combination of Aerobic Training and Cocoa Flavanols as Effective Therapies to Reduce Metabolic and Inflammatory Disruptions in Insulin-Resistant Rats: The Exercise, Cocoa, and Diabetes Study.

We aimed to investigate the combined effects of aerobic exercise (EXE) and cocoa flavanol (COCOA) supplementation on performance, metabolic parameters, and inflammatory and lipid profiles in obese insulin-resistant rats. Therefore, 32 male Wistar rats (230-250g) were fed a high-fat diet and a fructose-rich beverage for 30days to induce insulin resistance. Next, the rats were randomized into four groups, orally administered placebo solution or COCOA supplementation (45mg·kg-1), and either remained sedentary or were subjected to EXE on a treadmill at 60% peak velocity for 30min, for 8 weeks. Blood samples and peripheral tissues were collected and processed to analyze metabolic and inflammatory parameters, lipid profiles, and morphological parameters. Supplementation with COCOA and EXE improved physical performance and attenuated body mass gain, adipose index, and adipocyte area. When analyzed as individual interventions, supplementation with COCOA and EXE improved glucose intolerance and the lipid profile reduced the concentrations of leptin, glucose, and insulin, and reduced homeostasis assessment index (all effects were p < .001 for both interventions), while ameliorated some inflammatory mediators in examined tissues. In skeletal muscles, both COCOA supplementation and EXE increased the expression of glucose transporter (p < .001 and p < .001), and combined intervention showed additive effects (p < .001 vs. COCOA alone or EXE alone). Thus, combining COCOA with EXE represents an effective nonpharmacological strategy to treat insulin resistance; it could prevent Type 2 diabetes mellitus by improving physical performance, glucose metabolism, neuroendocrine control, and lipid and inflammatory mediators in the liver, pancreas, adipose tissue, and skeletal muscle in obese male insulin-resistant rats.

Cocoa Flavanols Adjuvant to an Oral Nutritional Supplement Acutely Enhances Nutritive Flow in Skeletal Muscle without Altering Leg Glucose Uptake Kinetics in Older Adults.

Ageing is associated with postprandial muscle vascular and metabolic dysfunction, suggesting vascular modifying interventions may be of benefit. Reflecting this, we investigated the impact of acute cocoa flavanol (450–500 mg) intake (versus placebo control) on vascular (via ultrasound) and glucose/insulin metabolic responses (via arterialised/venous blood samples and ELISA) to an oral nutritional supplement (ONS) in twelve healthy older adults (50% male, 72 ± 4 years), in a crossover design study. The cocoa condition displayed significant increases in m. vastus lateralis microvascular blood volume (MBV) in response to feeding at 180 and 240-min after ONS consumption (baseline: 1.00 vs. 180 min: 1.09 ± 0.03, p = 0.05; 240 min: 1.13 ± 0.04, p = 0.002), with MBV at these timepoints significantly higher than in the control condition (p < 0.05). In addition, there was a trend (p = 0.058) for MBV in m. tibialis anterior to increase in response to ONS in the cocoa condition only. Leg blood flow and vascular conductance increased, and vascular resistance decreased in response to ONS (p < 0.05), but these responses were not different between conditions (p > 0.05). Similarly, glucose uptake and insulin increased in response to ONS (p < 0.05) comparably between conditions (p > 0.05). Thus, acute cocoa flavanol supplementation can potentiate oral feeding-induced increases in MBV in older adults, but this improvement does not relay to muscle glucose uptake.

The influence of different concentrations of flavanol chocolate bars under acute supplement conditions on exercise and performance.

The purpose of this study was to assess the effects and acute dosage of different flavanol concentrations in a dark chocolate bar on physiological parameters during steady state (SS) and incremental exercise. In a double-blind, randomised, crossover study, 15 healthy participants with a mean ± SD age of 30 ± 7years; stature 176.8 ± 8.6cm and body mass 80.3 ± 8.4kg supplemented with high flavanol (HF) (1060mg), moderate flavanol (MF) (746mg), low flavanol (LF) (406mg), or a control (CON) (88mg) chocolate bar (~ 34g), 2h prior to 40min of SS cycling (80% gas-exchange threshold) followed by an incremental test to volitional fatigue. During the SS cycle oxygen consumption ([Formula: see text]), respiratory exchange ratio (RER) and heart rate (HR) were continuously monitored. Plasma samples were collected prior to commencing exercise to determine nitrate (NO3-) and nitrite (NO2-) levels under each condition. There was no observed effect between flavanol concentrations on [Formula: see text], RER, and HR during SS cycling (P > 0.05). [Formula: see text], peak power, HR peak, and RER peak also did not significantly differ between conditions (P > 0.05). There was a small trend for higher plasma NO2- levels following higher flavanol concentration; however, this did not reach statistical significance (P > 0.05). Acute supplementation with cocoa of differing flavanol concentrations does not appear to have any effect on exercise and performance. It is plausible that longer flavanol supplementation periods might have greater accumulative effects and thus may potentially elicit a larger effect.

P3581Periinterventional cocoa flavanol supplementation prevents functional and structural damage to the arterial wall after transradial catheter intervention

Abstract Background The transradial approach is commonly preferred over the femoral approach for coronary angiography to reduce vascular complications like bleeding, aneurysm formation and all-cause mortality ensuring early ambulation after coronary procedures. However, there is growing evidence that damage to the radial artery endothelium elicits intimal hyperplasia, vascular remodeling and might ultimately lead to total vessel occlusion. Objective Our study aimed to investigate the effects of dietary flavanol intervention on (a) early endothelial functional recovery and (b) late structural changes i.e. intimal hyperplasia after mechanical vascular wall injury in the human forearm model during coronary angiography. Methods Radial artery flow-mediated vasodilation (RA-FMD), local stiffness (fractional diameter change, Fdc), intima-media thickness (IMT), luminal and external arterial diameter at the site of intervention and the contralateral control artery were measured in 38 male patients (19 flavanol intervention, 19 placebo control) undergoing transradial coronary angiography (TCA) at baseline, after 7 days of 450mg flavanol supplementation BID, directly after TCA and 6 months after TCA. Circulating levels of endothelial microparticle (EMP) subpopulations CD31+/41-, CD62e+and CD144+were analyzed simultaneously as a surrogate for endothelial functional integrity and activation. Results One week of flavanol supplementation, not placebo, significantly increased RA-FMD (8.88±2.03% vs. 11.17±2.89%, p&lt;0.01 in flavanol and 8.64±1.87% vs. 8.32±1.63%, p=n.s. in placebo). RA-FMD significantly decreased in the intervention artery directly after TCA, which was partly mitigated by flavanol supplementation (delta to baseline: −2.61±0.82% in flavanol vs. −4.91±0.63% in placebo, p=0.034). TCA induced significant intimal hyperplasia in the radial artery (0.36±0.02mm vs. 0.44±0.04mm, p&lt;0.01) in placebo, but not in the flavanol group (0.36±0.02mm vs. 0.37±0.02mm, p=n.s.) after 6 month. One week of flavanol supplementation increased Fdc (1.94±0.99 vs. 3.07±1.31, p&lt;0.01). No changes occurred in the placebo group (1.99±1.29 vs. 1.96±1.17, p=n.s.). On the contralateral arm, the decrease in RA-FMD was blunted by flavanols (delta to baseline: +0.42±1.05% in flavanol vs. −0.61±1.55% in placebo) along with decreased circulating levels of EMPs. Conclusions TCA impairs endothelial function (RA-FMD), vascular physicomechanics (Fdc) and induces intimal hyperplasia (IMT). Periinterventional flavanol supplementation blunts the acute decreases in endothelial function and physicomechanics and prevents chronic negative vascular remodeling.

Gene-based analysis of angiogenesis, mitochondrial and insulin-related pathways in skeletal muscle of older individuals following nutraceutical supplementation.

Cocoa flavanols and fish oil omega-3 fatty acids are two bio-active nutrients that may improve muscle microvascular function, insulin sensitivity and mitochondrial function in older adults. We assessed changes in gene expression of these pathways in muscle from two nutritional intervention studies in older healthy volunteers: (i) 6-weeks daily fish oil supplementation in older females (3.4 g/d; age: 64.4 ± 0.8 y, BMI: 26.2 ± 0.7 kg/m2), and (ii) 7-day daily cocoa flavanol supplementation in older males (1050 mg/d; age: 70.1 ± 0.9 y, BMI: 25.7 ± 0.6 kg/m2). There was a main effect of 6-weeks fish oil supplementation on angiogenesis gene expression, with no overall changes in mitochondrial or insulin signaling genes. 7-day cocoa supplementation elicited changes in extracellular matrix (ECM) related genes. Thus, the effects of fish oil supplementation on vascular remodeling in skeletal muscle, and ECM remodeling with cocoa supplementation have emerged as areas for future study.

Flavanol supplementation protects against obesity-associated increases in systemic interleukin-6 levels without inhibiting body mass gain in mice fed a high-fat diet

Weight gain and obesity are associated with increased levels of proinflammatory cytokines. Studies have demonstrated the ability of dietary flavanols to reduce the severity of metabolic derangements due to high-fat (HF) feeding. The degree of polymerization of the flavanols appears to play a role in determining the extent of these protective effects. This study evaluated the preventative effects of grape seed and pine bark flavanol supplementation, with significantly different flavanol degree of polymerization, in the context of an HF diet. For 13 weeks, mice were given 35 mg/kg body weight per day grape seed or pine bark as part of an HF diet and compared to mice fed a low-fat diet and control HF diet. All flavanol-supplemented groups and the HF control incurred significantly higher weight gain compared to the lean control, and the grape seed group gained significantly more weight than the HF control. Increased weight gain of treatment groups was likely caused by hyperphagia. Despite lack of improvements to weight gain and glycemic control, it was observed that all flavanol treatment groups were able to significantly reduce interleukin-6 compared to HF control. The grape seed group, which gained the most weight overall, also exhibited the lowest levels of interleukin-6 compared to other groups. Overall, low-dose flavanol extract supplementation, regardless of mean degrees of polymerization, blunted cytokine production despite increased weight gain. This obesity-independent effect suggests flavanols may be used as complementary interventions to ameliorate increased inflammatory tone in the contexts of obesity and diabetes. Furthermore, flavanol-induced hyperphagia may have use for attenuation of cachexia.

Cocoa Flavanol Supplementation and Exercise: A Systematic Review.

Cocoa flavanols (CFs) have antioxidant and anti-inflammatory capacities and can improve vascular function. It has recently been suggested that CF intake may improve exercise performance and recovery. This systematic review aimed to evaluate the literature on the effects of CF intake on exercise performance and recovery and exercise-induced changes in vascular function, cognitive function, oxidative stress, inflammation, and metabolic parameters. Two electronic databases (Pubmed and Web of Science) were searched for studies examining the combination of CF intake and exercise in humans (up to 28 March 2017). Articles were included if the exact amount of CFs was mentioned. The methodological quality and level of bias of the 13 included studies was assessed according to the checklist for randomized controlled trials from the Dutch Cochrane center. Acute, sub-chronic (2weeks) and chronic (3months) CF intake reduced exercise-induced oxidative stress. Evidence on the effect of CF on exercise-induced inflammation and platelet activation was scarce. Acute CF intake reduced and tempered the exercise-induced increase in blood pressure in obese participants. Acute and sub-chronic CF intake altered fat and carbohydrate metabolism during exercise. Acute and sub-chronic CF intake did not have ergogenic effects in athletes, while chronic CF intake improved mitochondrial efficiency in untrained participants. While combining sub-chronic CF intake and exercise training improved cardiovascular risk factors and vascular function, evidence on the synergistic effects of CF and exercise training on oxidative stress, inflammation, and fat and glucose metabolism was lacking. CF intake may improve vascular function, reduce exercise-induced oxidative stress, and alter fat and carbohydrate utilization during exercise, but without affecting exercise performance. There is a strong need for future studies examining the synergetic effect of chronic CF intake and exercise training.

Impact of short-term flavanol supplementation on fasting plasma trimethylamine N-oxide concentrations in obese adults.

The gut microbiome metabolizes choline and carnitine to release trimethylamine (TMA), which subsequently undergoes hepatic conversion to trimethylamine N-oxide (TMAO). Elevated TMAO levels are associated with cardiovascular disease and all-cause mortality risk. Dietary flavanols modulate the composition and function of the gut microbiome. Therefore, the possibility exists that these compounds could reduce intestinal TMA production and lower circulating TMAO. However, this hypothesis has never been tested in humans. A secondary analysis was performed on blood samples from a clinical study in which obese subjects at risk for insulin resistance consumed tea or cocoa flavanols in a randomized crossover design while consuming a controlled diet. These subjects generally had elevated TMAO levels (∼5 μM) compared to levels previously measured in healthy subjects (∼1 μM). None of the interventions significantly altered TMAO levels. Individual variability for choline and carnitine was relatively low. However, TMAO exhibited somewhat greater inter-individual variability. No differences in mean TMAO concentrations observed across interventions were seen based on separating subjects by glycemic status, body mass index (BMI), race, age, or gender. However, subject minimum and maximum values observed across the interventions appeared to be more strongly associated with glycemic status and age than mean values across interventions, suggesting that average TMAO values over time may be less useful than maximum or minimum values as markers of disease risk. Traditional physiological characteristics do not appear to predict TMAO responsiveness to flavanol interventions. However, African-American subjects appeared less responsive compared to non-Hispanic white subjects for both green tea and high cocoa treatments, and female subjects appeared less responsive than males for the high cocoa treatment. The present results suggest that a short-term flavanol intervention does not generally reduce fasting TMAO levels in subjects with elevated circulating TMAO.

Cocoa flavanol supplementation improves photoaged skin in women: A 24-week double-blind, randomized, controlled trial

Cocoa flavanol supplementation improves photoaged skin in women: A 24-week double-blind, randomized, controlled trial

Acute Flavanol Intake Does Not Restore Attenuated Cutaneous Microvascular Function in Healthy, Young African-Americans

African Americans (AA) have increased risk for cardiovascular diseases relative to Caucasians (CA) and the underlying impairments manifest as early as the second generation prior to any overt signs of risk. We have recently demonstrated that nitric oxide dependent microvascular function in response to local heating of skin is attenuated in healthy young AA relative to CA. PURPOSE: To test the hypothesis that acute flavanol consumption restores reduced cutaneous microvascular responses to local heating in AA. METHODS: This was a double-blind crossover study To date full data sets have been collected in 7 AA and 7 CA (age: CA: 22 ± 4.0 vs. AA: 22 ± 3.6 years; BMI: CA: 23.9 ± 1.6 vs. AA: 23.7 ± 2.4 kg/m2, P>0.05 for both comparisons). Data was collected on 2 separate days (each occurred at the same time of day) separated by a minimum of 1 week. An intradermal microdialysis membrane was inserted in the forearm and skin blood flow was indexed via a laser Doppler flow probe housed within a local heater over the membrane site. After instrumentation, participants were randomly assigned to consume either a placebo or flavanol containing beverage. After recovery from the insertion trauma, the local heater was clamped at 32 °C for 45 min of baseline data collection after which the temperature was increased to 39 °C for 30 min. During 32 °C and 39 °C local heating the membrane was infused with Lactated Ringer’s Solution. Finally, maximal cutaneous vasodilation was achieved by a combination of infusion of 28 mM sodium nitroprusside and 43 °C local heating. Cutaneous vascular conductance (CVC) was calculated as cutaneous blood flux/mean arterial pressure and normalized as % maximal CVC (%CVCmax). RESULTS: CVC was similar between groups at 32 °C (Placebo: AA, 8 ± 4 vs. CA, 10 ± 3 % max, P=0.40; Flavanol: AA: 8 ± 5 vs. 11 ± 4 % max, P=0.26). CVC at 39 °C was reduced in AA (Placebo: AA, 40 ± 11 vs. CA: 59 ± 14 % max; P=0.01; Flavanol: AA, 33 ± 16 vs. 53 ± 12 % max; P=0.02); however, there was no effect between treatments (P>0.05 for interaction). CONCLUSION: These data suggest that AA have reduced cutaneous vascular responses to local heating; however this response is not effected by acute flavanol supplementation. This project was supported by institutional start-up funds provided to R. Matthew Brothers from The University of Texas at Austin.

Acute cocoa flavanol supplementation improves muscle macro- and microvascular but not anabolic responses to amino acids in older men.

The anabolic effects of nutrition on skeletal muscle may depend on adequate skeletal muscle perfusion, which is impaired in older people. Cocoa flavanols have been shown to improve flow-mediated dilation, an established measure of endothelial function. However, their effect on muscle microvascular blood flow is currently unknown. Therefore, the objective of this study was to explore links between the consumption of cocoa flavanols, muscle microvascular blood flow, and muscle protein synthesis (MPS) in response to nutrition in older men. To achieve this objective, leg blood flow (LBF), muscle microvascular blood volume (MBV), and MPS were measured under postabsorptive and postprandial (intravenous Glamin (Fresenius Kabi, Germany), dextrose to sustain glucose ∼7.5 mmol·L(-1)) conditions in 20 older men. Ten of these men were studied with no cocoa flavanol intervention and a further 10 were studied with the addition of 350 mg of cocoa flavanols at the same time that nutrition began. Leg (femoral artery) blood flow was measured by Doppler ultrasound, muscle MBV by contrast-enhanced ultrasound using Definity (Lantheus Medical Imaging, Mass., USA) perflutren contrast agent and MPS using [1, 2-(13)C2]leucine tracer techniques. Our results show that although older individuals do not show an increase in LBF or MBV in response to feeding, these absent responses are apparent when cocoa flavanols are given acutely with nutrition. However, this restoration in vascular responsiveness is not associated with improved MPS responses to nutrition. We conclude that acute cocoa flavanol supplementation improves muscle macro- and microvascular responses to nutrition, independently of modifying muscle protein anabolism.