Abstract
Purpose
Limited robust randomised controlled trials investigating fruit and vegetable (F&V) intake in people at risk of cardiovascular disease (CVD) exist. We aimed to design and validate a dietary strategy of increasing flavonoid-rich versus flavonoid-poor F&V consumption on nutrient biomarker profile.
Methods
A parallel, randomised, controlled, dose–response dietary intervention study. Participants with a CVD relative risk of 1.5 assessed by risk scores were randomly assigned to one of the 3 groups: habitual (control, CT), high-flavonoid (HF) or low-flavonoid (LF) diets. While the CT group (n = 57) consumed their habitual diet throughout, the HF (n = 58) and LF (n = 59) groups sequentially increased their daily F&V intake by an additional 2, 4 and 6 portions for 6-week periods during the 18-week study.
Results
Compliance to target numbers and types of F&V was broadly met and verified by dietary records, and plasma and urinary biomarkers. Mean (±SEM) number of F&V portions/day consumed by the HF and LF groups at baseline (3.8 ± 0.3 and 3.4 ± 0.3), 6 weeks (6.3 ± 0.4 and 5.8 ± 0.3), 12 weeks (7.0 ± 0.3 and 6.8 ± 0.3) and 18 weeks (7.6 ± 0.4 and 8.1 ± 0.4), respectively, was similar at baseline yet higher than the CT group (3.9 ± 0.3, 4.3 ± 0.3, 4.6 ± 0.4, 4.5 ± 0.3) (P = 0.015). There was a dose-dependent increase in dietary and urinary flavonoids in the HF group, with no change in other groups (P = 0.0001). Significantly higher dietary intakes of folate (P = 0.035), non-starch polysaccharides (P = 0.001), vitamin C (P = 0.0001) and carotenoids (P = 0.0001) were observed in both intervention groups compared with CT, which were broadly supported by nutrient biomarker analysis.
Conclusions
The success of improving nutrient profile by active encouragement of F&V intake in an intervention study implies the need for a more hands-on public health approach.
Similar content being viewed by others
Abbreviations
- CVD:
-
Cardiovascular disease
- CT:
-
Control
- HF:
-
High-flavonoid
- LF:
-
Low-flavonoid
- NSP:
-
Non-starch polysaccharide
- F&V:
-
Fruits and vegetables
References
Bazzano LA, He J, Ogden LG, Loria CM, Whelton PK (2003) Dietary fiber intake and reduced risk of coronary heart disease in US men and women—The national health and nutrition examination survey I epidemiologic follow-up study. Arch Internal Med 163(16):1897–1904
Joshipura KJ, Hu FB, Manson JE, Stampfer MJ, Rimm EB, Speizer FE, Colditz G, Ascherio A, Rosner B, Spiegelman D, Willett WC (2001) The effect of fruit and vegetable intake on risk for coronary heart disease. Ann Internal Med 134(12):1106–1114
Law MR, Morris JK (1998) By how much does fruit and vegetable consumption reduce the risk of ischaemic heart disease? Eur J Clin Nutr 52(8):549–556
WHO (2003) Food based dietary guidelines in the WHO European region, Eur/03/5045414. WHO, Copenhagen
Hughes DA (1999) Effects of carotenoids on human immune function. Proc Nutr Soc 58(3):713–718
Klipstein-Grobusch K, Geleijnse JM, den Breeijen JH, Boeing H, Hofman A, Grobbee DE, Witteman JCM (1999) Dietary antioxidants and risk of myocardial infarction in the elderly: the Rotterdam Study. Am J Clin Nutr 69(2):261–266
Carluccio MA, Siculella L, Ancora MA, Massaro M, Scoditti E, Storelli C, Visioli F, Distante A, De Caterina R (2003) Olive oil and red wine antioxidant polyphenols inhibit endothelial activation - Antiatherogenic properties of Mediterranean diet phytochemicals. Arteriosclerosis Thrombosis Vasc Biol 23(4):622–629. doi:10.1161/01.atv.0000062884.69432.a0
Schroeter H, Heiss C, Balzer J, Kleinbongard P, Keen CL, Hollenberg NK, Sies H, Kwik-Uribe C, Schmitz HH, Kelm M (2006) (−)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc Natl Acad Sci USA 103(4):1024–1029. doi:10.1073/pnas.0510168103
Hertog MGL, Feskens EJM, Hollman PCH, Katan MB, Kromhout D (1993) Dietary antioxidant flavonoids and risk of coronary heart-disease—the Zutphen elderly study. Lancet 342(8878):1007–1011
Grassi D, Desideri G, Necozione S, Lippi C, Casale R, Properzi G, Blumberg JB, Ferri C (2008) Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate. J Nutr 138(9):1671–1676
Egert S, Bosy-Westphal A, Seiberl J, Kurbitz C, Settler U, Plachta-Danielzik S, Wagner AE, Frank J, Schrezenmeir J, Rimbach G, Wolffram S, Muller MJ (2009) Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study. Br J Nutr 102(7):1065–1074. doi:10.1017/s0007114509359127
Hubbard GP, Wolffram S, de Vos R, Bovy A, Gibbins JM, Lovegrove JA (2006) Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man: a pilot study. Br J Nutr 96(3):482–488. doi:10.1079/bjn20061831
Bates B, Lennox A, Swan G (2010) National Diet and Nutrition Survey: headline results from year 1 of the Rolling Programme (2008/09). [Online]: Available from: http://www.food.gov.uk/science/dietarysurveys/ndnsdocuments/ndns0809year0801
Wilson PWF, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97(18):1837–1847
Grundy SM, Balady GJ, Criqui MH, Fletcher G, Greenland P, Hiratzka LF, Houston-Miller N, Kris-Etherton P, Krumholz HM, LaRosa J, Ockene IS, Pearson TA, Reed J, Washington R, Smith SC Jr (1998) Primary prevention of coronary heart disease: guidance from Framingham: a statement for healthcare professionals from the AHA task force on risk reduction. American heart association. Circulation 97(18):1876–1887
Wilson PW, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97(18):1837–1847
Lewington S, Clarke R, Qizilbash N, Peto R, Collins R (2002) Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 360(9349):1903–1913
Doll R, Peto R (1976) Mortality in relation to smoking: 20 years’ observations on male British doctors. Br Med J 2(6051):1525–1536
Lean ME (2000) Pathophysiology of obesity. Proc Nutr Soc 59(3):331–336
Treasure T, MacRae KD (1998) Minimisation: the platinum standard for trials? Randomisation doesn’t guarantee similarity of groups; minimisation does. Br Med J 317(7155):362–363
Pocock SJ, Simon R (1975) Sequential treatment assignment with balancing for prognostic factors in controlled clinical trial. Biometrics 31(1):103–115
USDA (2007) USDA Database for the Flavonoid Content of Selected Foods (Release 2.1). http://www.nal.usda.gov/fnic/foodcomp/Data/Flav/Flav02-1.pdf
Nelson M, Atkinson M, Meyer J (1997) Food portion sizes: a photographic atlas. MAFF Publications
White BL, Howard LR, Prior RL (2011) Impact of different stages of juice processing on the anthocyanin, flavonol, and procyanidin contents of cranberries. J Agric Food Chem 59(9):4692–4698. doi:10.1021/jf200149a
Lee SU, Lee JH, Choi SH, Lee JS, Ohnisi-Kameyama M, Kozukue N, Levin CE, Friedman M (2008) Flavonoid content in fresh, home-processed, and light-exposed onions and in dehydrated commercial onion products. J Agric Food Chem 56(18):8541–8548. doi:10.1021/jf801009p
Thurnham DI, Smith E, Flora PS (1988) Concurrent liquid-chromatographic assay of retinol, alpha-tocopherol, beta-carotene, alpha-carotene, lycopene and beta-cryptoxanthin in plasma, with tocopherol acetate as internal standard. Clin Chem 34(2):377–381
Liau LS, Lee BL, New AL, Ong CN (1993) Determination of plasma ascorbic acid by high-performance liquid chromatography with ultraviolet and electrochemical detection. J Chromatogr Biomed Appl 612(1):63–70
O’Broin S, Kelleher B (1992) Microbiological assay on microtitre plates of folate in serum and red cells. J Clin Pathol 45(4):344–347
Hald PM (1946) The flame photometer for the measurement of sodium and potassium in biological materials. J Clin Chem 163:429
Nielsen SE, Sandstrom B (2003) Simultaneous determination of hydroxycinnamates and catechins in human urine samples by column switching liquid chromatography coupled to atmospheric pressure chemical ionization mass spectrometry. J Chromatogr B 787(2):369–379
El Mohsen MA, Marks J, Kuhnle G, Moore K, Debnam E, Kaila Srai S, Rice-Evans C, Spencer JP (2006) Absorption, tissue distribution and excretion of pelargonidin and its metabolites following oral administration to rats. Br J Nutr 95(1):51–58
Benzie IFF, Strain JJ (1999) Ferric reducing antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Oxid Antioxid Pt A 299:15–27
Bub A, Watzl B, Abrahamse L, Delincee H, Adam S, Wever J, Muller H, Rechkemmer G (2000) Moderate intervention with carotenoid-rich vegetable products reduces lipid peroxidation in men. J Nutr 130(9):2200–2206
Brown H, Prescott R (2006) Applied mixed models in medicine, 2nd edn. John Wiley & Sons, New York
Kenward M, Roger J (1997) Small sample inference for fixed effects from restricted maximum likelihood. Biometrics 53(3):983
Smirnov N (1948) Table for estimating the goodness of fit of empirical distributions. Ann Math Stat 19(2):279–281
Paterson E, Gordon MH, Niwat C, George TW, Parr L, Waroonphan S, Lovegrove JA (2006) Supplementation with fruit and vegetable soups and beverages increases plasma carotenoid concentrations but does not alter markers of oxidative stress or cardiovascular risk factors. J Nutr 136(11):2849–2855
McCall DO, McGartland CP, McKinley MC, Sharpe P, McCance DR, Young IS, Woodside JV (2010) The effect of increased dietary fruit and vegetable consumption on endothelial activation, inflammation and oxidative stress in hypertensive volunteers. Nutrition, Metabolism and Cardiovascular Diseases [online] 1–7
Zino S, Skeaff M, Williams S, Mann J (1997) Randomised controlled trial of effect of fruit and vegetable consumption on plasma concentrations of lipids and antioxidants. Br Med J 314(7097):1787–1791
Levine M, ConryCantilena C, Wang YH, Welch RW, Washko PW, Dhariwal KR, Park JB, Lazarev A, Graumlich JF, King J, Cantilena LR (1996) Vitamin C pharmacokinetics in healthy volunteers: evidence for a recommended dietary allowance. Proc Natl Acad Sci USA 93(8):3704–3709
Vioque J, Weinbrenner T, Asensio L, Castello A, Young IS, Fletcher A (2007) Plasma concentrations of carotenoids and vitamin C are better correlated with dietary intake in normal weight than overweight and obese elderly subjects. Br J Nutr 97(5):977–986. doi:10.1017/s0007114507659017
Appel LJ, Moore TJ, Obarzanek E, Vollmer WM, Svetkey LP, Sacks FM, Bray GA, Vogt TM, Cutler JA, Windhauser MM, Lin PH, Karanja N (1997) A clinical trial of the effects of dietary patterns on blood pressure. N Engl J Med 336(16):1117–1124
Troyer JL, Racine EF, Ngugi GW, McAuley WJ (2010) The effect of home-delivered Dietary Approach to Stop Hypertension (DASH) meals on the diets of older adults with cardiovascular disease. Am J Clin Nutr 91(5):1204–1212. doi:10.3945/ajcn.2009.28780
Berry SE, Mulla UZ, Chowienczyk PJ, Sanders TAB (2010) Increased potassium intake from fruit and vegetables or supplements does not lower blood pressure or improve vascular function in UK men and women with early hypertension: a randomised controlled trial. Br J Nutr 104:1839–1847
Wayner D, Burton G, Ingold K, Barclay L, Locke S (1987) The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical trapping antioxidant activity of human blood plasma. Biochim Biophys Acta 924:408–419
Mulder TP, Rietveld AG, van Amelsvoort JM (2005) Consumption of both black tea and green tea results in an increase in the excretion of hippuric acid into urine. Am J Clin Nutr 81(1 Suppl):256S–260S
Vauzour D, Houseman EJ, George TW, Corona G, Garnotel R, Jackson KG, Sellier C, Gillery P, Kennedy OB, Lovegrove JA, Spencer JPE (2010) Moderate Champagne consumption promotes an acute improvement in acute endothelial-independent vascular function in healthy human volunteers. Br J Nutr 103(8):1168–1178. doi:10.1017/s0007114509992959
Jin Y, Alimbetov D, George T, Gordon MH, Lovegrove JA (2011) A randomised trial to investigate the effects of acute consumption of a blackcurrant juice drink on markers of vascular reactivity and bioavailability of anthocyanins in human subjects. Eur J Clin Nutr 65(7):849–856. doi:10.1038/ejcn.2011.55
Hollands W, Brett GM, Radreau P, Saha S, Teucher B, Bennett RN, Kroon PA (2008) Processing blackcurrants dramatically reduces the content and does not enhance the urinary yield of anthocyanins in human subjects. Food Chem 108(3):869–878. doi:10.1016/j.foodchem.2007.11.052
Acknowledgments
FLAVURS trial was supported by the Food Standards Agency, UK, Project no.: N02039/F5234012; Clinical trial registration number: ISRCTN47748735. The FLAVURS team would like to thank the FLAVURS participants for their time and dedication, without whom this study would not have been possible, and to Sainsbury’s for their advice on F&V storage and delivery. In addition, Anna Macready deserves thanks for her help with editing the manuscript, for designing the bespoke food ordering system used in the study and for delivering the fruit and vegetables. We would also like to acknowledge the invaluable help from the following individuals: Recruitment—Jan Luff, Melissa Knight-Adams; Sample analysis—Saran Waroonphan, Paulina Garcia-Macias; Delivery drivers—Franscesca Fava, Fisseha Tesfay Welderufael, Mohammed Al Khusaibi, Nasser Al-Habsi, Ben Cruickshank, Stacey Lockyer, Heather Ferris, Xenofon Tzounis; Advice on F&V storage- Emma Schofield; Dietary analysis —Melissa Knight-Adams, Claire Hester, Anna David, Jana Majdoub, Niloofar Hadizadeh Yazdi, Xenofon Tzounis; Statistical analysis—Alberto Vidal.
Conflict of interest
MF Chong, TW George, D Alimbetov, Y Jin, M Weech and AL Macready have no conflicts of interest. MH Gordon has received in kind donations of foods and research funding for previous studies from GSK. JA Lovegrove sits on Government advisory committees which have members of the food industry as members. She has received in kind donations of foods and has had previous research studies and PhD studentships sponsored by Unilever Bestfoods, Jordans and Ryvita Company Ltd, GSK and Nutricia. AM Minihane has ongoing PhD studentships sponsored by Unilever Bestfoods. JP Spencer has ongoing studies sponsored by Mars and Pepsico.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Chong, M.F., George, T.W., Alimbetov, D. et al. Impact of the quantity and flavonoid content of fruits and vegetables on markers of intake in adults with an increased risk of cardiovascular disease: the FLAVURS trial. Eur J Nutr 52, 361–378 (2013). https://doi.org/10.1007/s00394-012-0343-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00394-012-0343-3