Interactions between cocoa flavanols and inorganic nitrate: Additive effects on endothelial function at achievable dietary amounts |
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| Institution: | 1. Division of Cardiology, Pulmonology, and Vascular Medicine, Medical Faculty, and;2. Cardiovascular Research Institute Düsseldorf, University of Düsseldorf, Düsseldorf 40225, Germany;3. Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden;4. Molecular Nutrition Group, School of Chemistry, Food and Pharmacy, University of Reading, Reading, UK;1. Sport and Health Sciences, College of Life and Environmental Sciences, St. Luke''s Campus, University of Exeter, Heavitree, Exeter, EX1 2LU, UK;2. Gatorade Sports Science Institute, PepsiCo Global Nutrition R&D, Barrington, IL, USA;1. Instituto de Química, Universidade Federal do Rio de Janeiro, Avenida Athos da Silveira Ramos 149, 21941-909 Rio de Janeiro, RJ, Brazil;2. Departamento de Clínica Médica, Hospital Universitário Pedro Ernesto, Universidade do Estadodo Rio de Janeiro, Boulevard 28 de Setembro 77, 20551-030 Rio de Janeiro, RJ, Brazil;1. Penn State College of Medicine, Hershey, PA, USA;2. Penn State University, University Park, PA, USA;3. Penn State Harrisburg, Harrisburg, PA, USA;4. Penn State Hershey Family and Community Medicine, University Park, USA;5. Wake Forest University, Winston-Salem, NC, USA;1. Department of Physical Therapy and Rehabilitation Science, Carver College of Medicine, University of Iowa, Iowa City, IA, USA;2. Department of Anesthesia, Carver College of Medicine, University of Iowa, 200 Hawkins Dr, Iowa City, IA, USA;3. Abboud Cardiovascular Research Center, University of Iowa, 285 Newton Rd, Iowa City, IA, USA;4. Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, 169 Newton Rd, IA, USA;1. Penn State University, University Park, PA, USA;2. Penn State College of Medicine, Hershey, PA, USA;3. Auburn University, Auburn, AL, USA;4. Bloomsburg University, Bloomsburg, PA, USA;5. Penn State Health Family and Community Medicine, University Park, PA, USA;6. Wake Forest University, Winston-Salem, NC, USA;7. University Hospitals Cleveland Medical Center, Cleveland, OH, USA |
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| Abstract: | Dietary intervention studies have shown that flavanols and inorganic nitrate can improve vascular function, suggesting that these two bioactives may be responsible for beneficial health effects of diets rich in fruits and vegetables. We aimed to study interactions between cocoa flavanols (CF) and nitrate, focusing on absorption, bioavailability, excretion, and efficacy to increase endothelial function. In a double-blind randomized, dose–response crossover study, flow-mediated dilation (FMD) was measured in 15 healthy subjects before and at 1, 2, 3, and 4 h after consumption of CF (1.4–10.9 mg/kg bw) or nitrate (0.1–10 mg/kg bw). To study flavanol–nitrate interactions, an additional intervention trial was performed with nitrate and CF taken in sequence at low and high amounts. FMD was measured before (0 h) and at 1 h after ingestion of nitrate (3 or 8.5 mg/kg bw) or water. Then subjects received a CF drink (2.7 or 10.9 mg/kg bw) or a micro- and macronutrient-matched CF-free drink. FMD was measured at 1, 2, and 4 h thereafter. Blood and urine samples were collected and assessed for CF and nitric oxide (NO) metabolites with HPLC and gas-phase reductive chemiluminescence. Finally, intragastric formation of NO after CF and nitrate consumption was investigated. Both CF and nitrate induced similar intake-dependent increases in FMD. Maximal values were achieved at 1 h postingestion and gradually decreased to reach baseline values at 4 h. These effects were additive at low intake levels, whereas CF did not further increase FMD after high nitrate intake. Nitrate did not affect flavanol absorption, bioavailability, or excretion, but CF enhanced nitrate-related gastric NO formation and attenuated the increase in plasma nitrite after nitrate intake. Both flavanols and inorganic nitrate can improve endothelial function in healthy subjects at intake amounts that are achievable with a normal diet. Even low dietary intake of these bioactives may exert relevant effects on endothelial function when ingested together. |
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| Keywords: | Cocoa flavanols Nitrate Endothelial function Interactions Bioavailability NO Free radicals |
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