A Systematic Review and Meta-Analysis of the Effects of Flavanol-Containing Tea, Cocoa and Apple Products on Body Composition and Blood Lipids: Exploring the Factors Responsible for Variability in Their Efficacy

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Abstract

Several randomized controlled trials (RCTs) and meta-analyses support the benefits of flavanols on cardiometabolic health, but the factors affecting variability in the responses to these compounds have not been properly assessed. The objectives of this meta-analysis were to systematically collect the RCTs-based-evidence of the effects of flavanol-containing tea, cocoa and apple products on selected biomarkers of cardiometabolic risk and to explore the influence of various factors on the variability in the responses to the consumption of these products. A total of 120 RCTs were selected. Despite a high heterogeneity, the intake of the flavanol-containing products was associated using a random model with changes (reported as standardized difference in means (SDM)) in body mass index (−0.15, p < 0.001), waist circumference (−0.29, p < 0.001), total-cholesterol (−0.21, p < 0.001), LDL-cholesterol (−0.23, p < 0.001), and triacylglycerides (−0.11, p = 0.027), and with an increase of HDL-cholesterol (0.15, p = 0.005). Through subgroup analyses, we showed the influence of baseline-BMI, sex, source/form of administration, medication and country of investigation on some of the outcome measures and suggest that flavanols may be more effective in specific subgroups such as those with a BMI ≥ 25.0 kg/m ², non-medicated individuals or by specifically using tea products. This meta-analysis provides the first robust evidence of the effects induced by the consumption of flavanol-containing tea, cocoa and apple products on weight and lipid biomarkers and shows the influence of various factors that can affect their bioefficacy in humans. Of note, some of these effects are quantitatively comparable to those produced by drugs, life-style changes or other natural products. Further, RCTs in well-characterized populations are required to fully comprehend the factors affecting inter-individual responses to flavanol and thereby improve flavanols efficacy in the prevention of cardiometabolic disorders.

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Most cited references 147

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Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies.

Claudine Manach, C Rémésy, Gary Williamson … (2004)

Polyphenols are abundant micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases is emerging. Bioavailability differs greatly from one polyphenol to another, so that the most abundant polyphenols in our diet are not necessarily those leading to the highest concentrations of active metabolites in target tissues. Mean values for the maximal plasma concentration, the time to reach the maximal plasma concentration, the area under the plasma concentration-time curve, the elimination half-life, and the relative urinary excretion were calculated for 18 major polyphenols. We used data from 97 studies that investigated the kinetics and extent of polyphenol absorption among adults, after ingestion of a single dose of polyphenol provided as pure compound, plant extract, or whole food/beverage. The metabolites present in blood, resulting from digestive and hepatic activity, usually differ from the native compounds. The nature of the known metabolites is described when data are available. The plasma concentrations of total metabolites ranged from 0 to 4 mumol/L with an intake of 50 mg aglycone equivalents, and the relative urinary excretion ranged from 0.3% to 43% of the ingested dose, depending on the polyphenol. Gallic acid and isoflavones are the most well-absorbed polyphenols, followed by catechins, flavanones, and quercetin glucosides, but with different kinetics. The least well-absorbed polyphenols are the proanthocyanidins, the galloylated tea catechins, and the anthocyanins. Data are still too limited for assessment of hydroxycinnamic acids and other polyphenols. These data may be useful for the design and interpretation of intervention studies investigating the health effects of polyphenols.

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Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials.

Lee Hooper, Colin Kay, Asmaa Abdelhamid … (2012)

There is substantial interest in chocolate and flavan-3-ols for the prevention of cardiovascular disease (CVD). The objective was to systematically review the effects of chocolate, cocoa, and flavan-3-ols on major CVD risk factors. We searched Medline, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) of chocolate, cocoa, or flavan-3-ols. We contacted authors for additional data and conducted duplicate assessment of study inclusion, data extraction, validity, and random-effects meta-analyses. We included 42 acute or short-term chronic (≤18 wk) RCTs that comprised 1297 participants. Insulin resistance (HOMA-IR: -0.67; 95% CI: -0.98, -0.36) was improved by chocolate or cocoa due to significant reductions in serum insulin. Flow-mediated dilatation (FMD) improved after chronic (1.34%; 95% CI: 1.00%, 1.68%) and acute (3.19%; 95% CI: 2.04%, 4.33%) intakes. Effects on HOMA-IR and FMD remained stable to sensitivity analyses. We observed reductions in diastolic blood pressure (BP; -1.60 mm Hg; 95% CI: -2.77, -0.43 mm Hg) and mean arterial pressure (-1.64 mm Hg; 95% CI: -3.27, -0.01 mm Hg) and marginally significant effects on LDL (-0.07 mmol/L; 95% CI: -0.13, 0.00 mmol/L) and HDL (0.03 mmol/L; 95% CI: 0.00, 0.06 mmol/L) cholesterol. Chocolate or cocoa improved FMD regardless of the dose consumed, whereas doses >50 mg epicatechin/d resulted in greater effects on systolic and diastolic BP. GRADE (Grading of Recommendations, Assessment, Development and Evaluation, a tool to assess quality of evidence and strength of recommendations) suggested low- to moderate-quality evidence of beneficial effects, with no suggestion of negative effects. The strength of evidence was lowered due to unclear reporting for allocation concealment, dropouts, missing data on outcomes, and heterogeneity in biomarker results in some studies. We found consistent acute and chronic benefits of chocolate or cocoa on FMD and previously unreported promising effects on insulin and HOMA-IR. Larger, longer-duration, and independently funded trials are required to confirm the potential cardiovascular benefits of cocoa flavan-3-ols.

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Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study.

Jelena Vulevic, Catherine Kwik-Uribe, Xenofon Tzounis … (2010)

The absorption of cocoa flavanols in the small intestine is limited, and the majority of the flavanols reach the large intestine where they may be metabolized by resident microbiota. We assessed the prebiotic potential of cocoa flavanols in a randomized, double-blind, crossover, controlled intervention study. Twenty-two healthy human volunteers were randomly assigned to either a high-cocoa flavanol (HCF) group (494 mg cocoa flavanols/d) or a low-cocoa flavanol (LCF) group (23 mg cocoa flavanols/d) for 4 wk. This was followed by a 4-wk washout period before volunteers crossed to the alternant arm. Fecal samples were recovered before and after each intervention, and bacterial numbers were measured by fluorescence in situ hybridization. A number of other biochemical and physiologic markers were measured. Compared with the consumption of the LCF drink, the daily consumption of the HCF drink for 4 wk significantly increased the bifidobacterial (P < 0.01) and lactobacilli (P < 0.001) populations but significantly decreased clostridia counts (P < 0.001). These microbial changes were paralleled by significant reductions in plasma triacylglycerol (P < 0.05) and C-reactive protein (P < 0.05) concentrations. Furthermore, changes in C-reactive protein concentrations were linked to changes in lactobacilli counts (P < 0.05, R(2) = -0.33 for the model). These in vivo changes were closely paralleled by cocoa flavanol-induced bacterial changes in mixed-batch culture experiments. This study shows, for the first time to our knowledge, that consumption of cocoa flavanols can significantly affect the growth of select gut microflora in humans, which suggests the potential prebiotic benefits associated with the dietary inclusion of flavanol-rich foods. This trial was registered at clinicaltrials.gov as NCT01091922.

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Author and article information

Journal

Journal ID (nlm-ta): Nutrients

Journal ID (iso-abbrev): Nutrients

Journal ID (publisher-id): nutrients

Title: Nutrients

Publisher: MDPI

ISSN (Electronic): 2072-6643

Publication date (Electronic): 13 July 2017

Publication date Collection: July 2017

Volume: 9

Issue: 7

Electronic Location Identifier: 746

Affiliations

[1 ]Research Group on Quality, Safety and Bioactivity of Plant Foods, Campus de Espinardo, Centro de Edafologia y Biologia Aplicada del Segura-Consejo Superior de Investigaciones Científicas (CEBAS-CSIC), P.O. Box 164, 30100 Murcia, Spain

[2 ]Human Nutrition, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G31 2ER, UK; Emilie.CombetAspray@ 123456glasgow.ac.uk

[3 ]Polytechnic Institute of Santarem, Escola Superior Agrária (ESA), Department of Food Technology, Biotechnology and Nutrition, 2001-904 Santarém, Portugal; paula.pinto@ 123456esa.ipsantarem.pt

[4 ]Human Nutrition Unit, Department of Food & Drug, University of Parma, 43125 Parma, Italy; pedromiguel.menaparreno@ 123456unipr.it (P.M.); margherita.dallasta@ 123456unipr.it (M.D.)

[5 ]Biomarkers and Nutrimetabolomic Laboratory, Department of Nutrition, Food Sciences and Gastronomy, University of Barcelona, 08028 Barcelona, Spain; margarcia@ 123456ub.edu

[6 ]CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 08028 Barcelona, Spain

[7 ]Division of Diabetes and Nutritional Sciences, King’s College London, London SE1 9NH, UK; ana.rodriguez-mateos@ 123456kcl.ac.uk

[8 ]Institute of Food and Health, School of Agriculture and Food Science, University College Dublin (UCD), Belfield, Dublin 4, Ireland; eileen.gibney@ 123456ucd.ie

[9 ]U1167-RID-AGE-Facteurs de risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, University Lille, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire (CHU) Lille, Institut Pasteur de Lille, F-59000 Lille, France; julie.dumont@ 123456pasteur-lille.fr

[10 ]National Research Council (CNR), Institute of Clinical Physiology, 73100 Lecce, Italy; marika@ 123456ifc.cnr.it

[11 ]Department of Basic Psychology & Methodology, Faculty of Psychology, University of Murcia, 30100 Murcia, Spain; jsmeca@ 123456um.es

[12 ]Institut National de la Recherche Agronomique (INRA), Human Nutrition Unit, Université Clermont Auvergne (UCA), Centre de Recherches en Nutrition Humaine (CRNH) Auvergne, F-63000 Clermont-Ferrand, France; christine.morand@ 123456inra.fr

Author notes

[* ]Correspondence: agsarrias@ 123456cebas.csic.es (A.G.-S.); mtconesa@ 123456cebas.csic.es (M.-T.G.-C.); Tel.: +34-968-396276 (A.G.-S. & M.-T.G.-C.); Fax: +34-968-396213(A.G.-S. & M.-T.G.-C.)

Author information

Emilie Combet https://orcid.org/0000-0002-9302-8971

Pedro Mena https://orcid.org/0000-0003-2150-2977

Mar Garcia-Aloy https://orcid.org/0000-0002-1330-6610

Eileen R. Gibney https://orcid.org/0000-0001-9465-052X

María-Teresa García-Conesa https://orcid.org/0000-0002-4125-853X

Article

Publisher ID: nutrients-09-00746

DOI: 10.3390/nu9070746

PMC ID: 5537860

SO-VID: d6147bec-830c-48e8-9f92-e73c9badfec1

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

History

Date received : 26 June 2017

Date accepted : 10 July 2017

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A Systematic Review and Meta-Analysis of the Effects of Flavanol-Containing Tea, Cocoa and Apple Products on Body Composition and Blood Lipids: Exploring the Factors Responsible for Variability in Their Efficacy

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Most cited references 147

Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies.

Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials.

Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study.

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