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Combining vitamin C and carotenoid biomarkers better predicts fruit and vegetable intake than individual biomarkers in dietary intervention studies

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Abstract

Purpose

The aim of this study was to determine whether combining potential biomarkers of fruit and vegetables is better at predicting FV intake within FV intervention studies than single biomarkers.

Design

Data from a tightly controlled randomised FV intervention study (BIOFAV; all food provided and two meals/day on weekdays consumed under supervision) were used. A total of 30 participants were randomised to either 2, 5 or 8 portions FV/day for 4 weeks, and blood samples were collected at baseline and 4 weeks for plasma vitamin C and serum carotenoid analysis. The combined biomarker approach was also tested in three further FV intervention studies conducted by the same research team, with less strict dietary control (FV provided and no supervised meals).

Results

The combined model containing all carotenoids and vitamin C was a better fit than either the vitamin C only (P < 0.001) model or the lutein only (P = 0.006) model in the BIOFAV study. The C-statistic was slightly lower in the lutein only model (0.85) and in the model based upon factor analysis (0.88), and much lower in the vitamin C model (0.68) compared with the full model (0.95). Results for the other studies were similar, although the differences between the models were less marked.

Conclusions

Although there was some variation between studies, which may relate to the level of dietary control or participant characteristics, a combined biomarker approach to assess overall FV consumption may more accurately predict FV intake within intervention studies than the use of a single biomarker. The generalisability of these findings to other populations and study designs remains to be tested.

Clinical trial Registration Number NCT01591057 (www.clinicaltrials.gov).

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Abbreviations

FV:

Fruit and vegetables

References

  1. Boeing H, Bechthold A, Bub A, Ellinger S, Haller D, Kroke A, Leschik-Bonnet E, Müller MJ, Oberritter H, Schulze M et al (2012) Critical review: vegetables and fruit in the prevention of chronic diseases. Eur J Nutr 51:637–663

    Article  CAS  Google Scholar 

  2. He FJ, Nowson CA, Lucas M, MacGregor GA (2007) Increased consumption of fruit and vegetables is related to a reduced risk of coronary heart disease: meta-analysis of cohort studies. J Hum Hypertens 21:717–728

    Article  CAS  Google Scholar 

  3. He FJ, Nowson CA, MacGregor GA (2006) Fruit and vegetable consumption and stroke: meta-analysis of cohort studies. Lancet 367:320–326

    Article  Google Scholar 

  4. Macready AL, George TW, Chong MF, Alimbetov DS, Jin Y, Vidal A, Spencer JP, Kennedy OB, Tuohy KM, Minihane AM et al: FLAVURS Study Group (2014) Flavonoid-rich fruit and vegetables improve microvascular reactivity and inflammatory status in men at risk of cardiovascular disease–FLAVURS: a randomized controlled trial. Am J Clin Nutr 99:479–489

    Article  Google Scholar 

  5. Wallace IR, McEvoy CT, Hunter SJ, Hamill LL, Ennis CN, Bell PM, Patterson CC, Woodside JV, Young IS, McKinley MC (2013) Dose-response effect of fruit and vegetables on insulin resistance in people at high risk of cardiovascular disease: a randomized controlled trial. Diabetes Care 36:3888–3896

    Article  CAS  Google Scholar 

  6. Neville CE, Young IS, Gilchrist SE, McKinley MC, Gibson A, Edgar JD, Woodside JV (2014) Effect of increased fruit and vegetable consumption on bone turnover in older adults: a randomised controlled trial. Osteoporos Int 25:223–233

    Article  CAS  Google Scholar 

  7. Gibson A, Edgar JD, Neville CE, Gilchrist SE, McKinley MC, Patterson CC, Young IS, Woodside JV (2012) Effect of fruit and vegetable consumption on immune function in older people: a randomized controlled trial. Am J Clin Nutr 96:1429–1436

    Article  CAS  Google Scholar 

  8. McCall DO, McGartland C, McKinley MC, Patterson CC, Sharpe P, McCance D, Young IS, Woodside JV (2009) Dietary intake of fruits and vegetables improves microvascular function in hypertensive subjects in a dose dependent manner. Circulation 119:2153–2160

    Article  CAS  Google Scholar 

  9. Bingham SA (2001) Biomarkers in nutritional epidemiology. Public Health Nutr 5:821–827

    Article  Google Scholar 

  10. Lee RD, Nieman DC (2003) Nutritional assessments, 3rd edn. McGraw-Hill, New York

    Google Scholar 

  11. Livingstone MBE, Black AE (2003) Markers of the validity of reported energy intake. J Nutr 133:895S–920S

    CAS  Google Scholar 

  12. Woodside JV, Young IS, McKinley MC (2013) Fruits and vegetables: measuring intake and encouraging increased consumption. Proc Nutr Soc 72:236–245

    Article  Google Scholar 

  13. Hunter D (1990) Biochemical indicators of dietary intake. In: Willett W (ed) Nutritional epidemiology. Oxford University Press, New York, pp 143–216

    Google Scholar 

  14. Crews H, Alink G, Anderson R, Braesco V, Holst B, Maiani G, Ovesen L, Scotter M, Solfrizzo M, van den Berg R et al (2001) A critical assessment of some biomarker approaches linked with dietary intake. Br J Nutr 86:S5–S35

    Article  CAS  Google Scholar 

  15. Baldrick FR, Woodside JV, Elborn JS, Young IS, McKinley MC (2011) Biomarkers of fruit and vegetable intake in human intervention studies: a systematic review. Crit Rev Food Sci Nutr 51:795–815

    Article  CAS  Google Scholar 

  16. Block G, Norkus E, Hudes M, Mandel S, Helzlsouer K (2001) Which plasma antioxidants are most related to fruit and vegetable consumption? Am J Epidemiol 154:1113–1118

    Article  CAS  Google Scholar 

  17. Al-Delaimy WK, Ferrari P, Slimani N, Pala V, Johansson I, Nilsson S, Mattisson I, Wirfalt E, Galasso R, Palli D et al (2005) Plasma carotenoids as biomarkers of intake of fruits and vegetables: individual-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC). Eur J Clin Nutr 59:1387–1396

    Article  CAS  Google Scholar 

  18. Al-Delaimy WK, Slimani N, Ferrari P, Key T, Spencer E, Johansson I, Johansson G, Mattisson I, Wirfalt E, Sieri S et al (2005) Plasma carotenoids as biomarkers of intake of fruits and vegetables: ecological-level correlations in the European Prospective Investigation into Cancer and Nutrition (EPIC). Eur J Clin Nutr 59:1397–1408

    Article  CAS  Google Scholar 

  19. Padayatty SJ, Levine M (2008) Fruit and vegetables: think variety, go ahead, eat! Am J Clin Nutr 87:5–7

    CAS  Google Scholar 

  20. 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. BMJ 314:1787

    Article  CAS  Google Scholar 

  21. Riso P, Visioli F, Erba D, Testolin G, Porrini M (2004) Lycopene and vitamin C concentrations increase in plasma and lymphocytes after tomato intake. Effects on cellular antioxidant protection. Eur J Clin Nutr 58:1350–1358

    Article  CAS  Google Scholar 

  22. Bingham SA, Gill C, Welch A, Cassidy A, Runswick SA, Oakes S, Lubin R, Thurnham DI, Key TJ, Roe L et al (1997) Validation of dietary assessment methods in the UK arm of EPIC using weighed records, and 24-hour urinary nitrogen and potassium and vitamin C and carotenoids as biomarkers. Int J Epidemiol 26:S137–S151

    Article  Google Scholar 

  23. Jansen MC, van Kappel AL, Ocké MC, Van’t Veer P, Boshuizen HC, Riboli R, Bueno-de-Mesquita HB (2004) Plasma carotenoid levels in Dutch men and women, and the relation with vegetable and fruit consumption. Eur J Clin Nutr 58:1386–1395

    Article  CAS  Google Scholar 

  24. Drewnowski A, Rock CL, Henderson SA, Shore AB, Fischler C, Galan P, Preziosi P, Hercberg S (1997) Serum beta-carotene and vitamin C as biomarkers of vegetable and fruit intakes in a community-based sample of French adults. Am J Clin Nutr 65:1796–1802

    CAS  Google Scholar 

  25. Ferrari P, Al-Delaimy WK, Slimani N, Boshuizen HC, Roddam A, Orfanos P, Skeie G, Rodríguez-Barranco M, Thiebaut A, Johansson G et al (2005) An approach to estimate between- and within-group correlation coefficients in multicenter studies: plasma carotenoids as biomarkers of intake of fruits and vegetables. Am J Epidemiol 162:591–598

    Article  Google Scholar 

  26. Campbell DR, Gross MD, Martini MC, Grandits GA, Slavin JL, Potter JD (1994) Plasma carotenoids as biomarkers of vegetable and fruit intake. Cancer Epidemiol Biomark Prev 3:493–500

    CAS  Google Scholar 

  27. National Health Service. Rough guide—fruit and vegetable portion sizes. Internet: http://www.nhs.uk/Livewell/5ADAY/Documents/Downloads/5ADAY_portion_guide.pdf. Accessed 25 July 2014

  28. Vuilleumier JP, Keck E (1989) Fluorometric assay of vitamin C in biological materials using a centrifugal analyser with fluorescence attachment. J Micronut Anal 5:25–34

    CAS  Google Scholar 

  29. Craft NE, Wise SA, Soares JH (1992) Optimisation of an isocratic high performance liquid chromatography separation of carotenoids. J Chromatogr 589:171–176

    Article  CAS  Google Scholar 

  30. Newson R (2006) Confidence intervals for rank statistics: Somers’ D and extensions. Stata J 6:309–334

    Google Scholar 

  31. Steyerberg EW (2010) Clinical prediction models: a practical approach to development, validation, and updating. Springer, Berlin

    Google Scholar 

  32. Le Marchand L, Hankin JH, Carter FS, Essling C, Luffey D, Franke AA, Wilkens LR, Cooney RV, Kolonel LN (1994) A pilot study on the use of plasma carotenoids and ascorbic acid as markers of compliance to a high fruit and vegetable dietary intervention. Cancer Epidemiol Biomark Prev 3:245–251

    Google Scholar 

  33. Tucker KL, Chen H, Vogel S, Wilson PW, Schaefer EJ, Lammi-Keefe C (1999) Carotenoid intakes, assessed by dietary questionnaire, are associated with plasma carotenoid concentrations in an elderly population. J Nutr 129:438–445

    CAS  Google Scholar 

  34. Chong MF, George TW, Alimbetov D, Jin Y, Weech M, Macready AL, Spencer JP, Kennedy OB, Minihane AM, Gordon MH, Lovegrove JA (2013) 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

    Article  CAS  Google Scholar 

  35. Szeto YT, Tomlinson B, Benzie IF (2002) Total antioxidant and ascorbic acid content of fresh fruits and vegetables: implications for dietary planning and food preservation. Br J Nutr 87:55–59

    Article  CAS  Google Scholar 

  36. Heinonen MI (1990) Carotenoids and provitamin A activity of carrot (Daucus carota L.) cultivars. J Agric Food Chem 38:609–612

    Article  CAS  Google Scholar 

  37. Kurilich AC, Juvik JA (1999) Quantification of carotenoids and tocopherol antioxidants in Zea mays. J Agric Food Chem 47:1948–1955

    Article  CAS  Google Scholar 

  38. Kalt W (2005) Effects of production and processing factors on major fruit and vegetable antioxidants. J Food Sci 70:R11–R19

    Article  CAS  Google Scholar 

  39. Vioque J, Weinbrenner T, Asensio L, Castelló 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 97:977–986

    Article  CAS  Google Scholar 

  40. Alberg A (2002) The influence of cigarette smoking on circulating concentrations of antioxidant micronutrients. Toxicology 180:121–137

    Article  CAS  Google Scholar 

  41. Jacques PF, Hartz SC, McGandy RB, Jacob RA, Russell RM (1987) Ascorbic acid, HDL, and total plasma cholesterol in the elderly. J Am Coll Nutr 6:169–174

    Article  CAS  Google Scholar 

  42. Sanchez-Moreno C, Cano MP, de Ancos B, Plaza L, Olmedilla B, Granado F, Martin A (2003) Effect of orange juice intake on vitamin C concentrations and biomarkers of antioxidant status in humans. Am J Clin Nutr 78:454–460

    CAS  Google Scholar 

  43. Brown MJ, Ferruzzi MG, Nguyen ML, Cooper DA, Eldridge AL, Schwartz SJ, White WS (2004) Carotenoid bioavailability is higher from salads ingested with full-fat than with fat-reduced salad dressings as measured with electrochemical detection. Am J Clin Nutr 80:396–403

    CAS  Google Scholar 

  44. Unlu NZ, Bohn T, Clinton SK, Schwartz SJ (2005) Carotenoid absorption from salad and salsa by humans is enhanced by the addition of avocado or avocado oil. J Nutr 135:431–436

    CAS  Google Scholar 

  45. Hussein L, El-Tohamy M (1990) Vitamin A potency of carrot and spinach carotenes in human metabolic studies. Int J Vit Nutr Res 60:229–235

    CAS  Google Scholar 

  46. Castenmiller JJM, West CE, Linssen JPH, van het Hof KH, Voragen AGJ (1999) The food matrix of spinach is a limiting factor in determining the bioavailability of β-carotene and to a lesser extent of lutein in humans. J Nutr 129:349–355

    CAS  Google Scholar 

  47. Dehghan M, Akhtar-Danesh N, McMillan CR, Thabane L (2007) Is plasma vitamin C an appropriate biomarker of vitamin C intake? A systematic review and meta-analysis. Nutr J 6:41–53

    Article  Google Scholar 

  48. Woodside JV, Young IS, Gilchrist SE, Vioque J, Chakravarthy U, de Jong PT, Rahu M, Seland J, Soubrane G, Tomazzoli L et al (2013) Factors associated with serum/plasma concentrations of vitamins A, C, E and carotenoids in older people throughout Europe: the EUREYE study. Eur J Nutr 52:1493–1501

    Article  CAS  Google Scholar 

  49. Krogholm KS, Haraldsdottir J, Knuthsen P, Rasmussen SE (2004) Urinary total flavonoid excretion but not 4-pyridoxic acid or potassium can be used as a biomarker for the intake of fruits and vegetables. J Nutr 134:445–451

    CAS  Google Scholar 

  50. Nielsen SE, Freese R, Kleemola P, Mutanen M (2002) Flavonoids in human urine as biomarkers for intake of fruits and vegetables. Cancer Epidemiol Biomark Prev 11:459–466

    CAS  Google Scholar 

  51. Mennen LI, Sapinho D, Ito H, Bertrais S, Galan P, Hercberg S, Scalbert A (2006) Urinary flavonoids and phenolic acids as biomarkers of intake for polyphenol-rich foods. Br J Nutr 96:191–198

    Article  CAS  Google Scholar 

  52. Yannan J, Gordon MH, Alimbetov D, Chong MF, George TW, Spencer JPE, Kennedy OB, Tuohy K, Minihane AM, Lovegrove JA, for the FLAVURS Study Group (2014) A novel combined biomarker including plasma carotenoids, vitamin C, and ferric reducing antioxidant power is more strongly associated with fruit and vegetable intake than the individual components. J Nutr [Epub ahead of print]. doi:10.3945/jn.114.192856

  53. Freedman LS, Midthune D, Carroll RJ, Tasevska N, Schatzkin A, Mares J, Tinker L, Potischman N, Kipnis V (2011) Using regression calibration equations that combine self-reported intake and biomarker measures to obtain unbiased estimates and more powerful tests of dietary associations. Am J Epidemiol 174:1238–1245

    Article  Google Scholar 

  54. Freedman LS, Kipnis V, Schatzkin A, Tasevska N, Potischman N (2010) Can we use biomarkers in combination with self-reports to strengthen the analysis of nutritional epidemiologic studies? Epidemiol Perspect Innov 7:2

    Article  Google Scholar 

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Acknowledgments

Supported by the Medical Research Council as part of Grant G0901793. Grateful thanks to the technical assistance of Shrobona Bhattacharya in terms of food preparation and delivery and Sarah Gilchrist in terms of biomarker analysis.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Centre for Public Health, First Floor, Institute of Clinical Science B, Queen’s University Belfast, Grosvenor Road, Belfast, BT12 6BJ, UK

    Alanna J. McGrath, Lesley L. Hamill, Chris R. Cardwell, Claire R. Draffin, Charlotte E. Neville, Jane McEneny, Michelle C. McKinley, Ian S. Young & Jayne V. Woodside

  2. Department of Psychology, Bournemouth University, Bournemouth, UK

    Katherine M. Appleton

Authors
  1. Alanna J. McGrath
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  2. Lesley L. Hamill
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  3. Chris R. Cardwell
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  4. Claire R. Draffin
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  5. Charlotte E. Neville
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  6. Katherine M. Appleton
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  7. Jane McEneny
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  9. Ian S. Young
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  10. Jayne V. Woodside
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Correspondence to Jayne V. Woodside.

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McGrath, A.J., Hamill, L.L., Cardwell, C.R. et al. Combining vitamin C and carotenoid biomarkers better predicts fruit and vegetable intake than individual biomarkers in dietary intervention studies. Eur J Nutr 55, 1377–1388 (2016). https://doi.org/10.1007/s00394-015-0953-7

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  • DOI: https://doi.org/10.1007/s00394-015-0953-7

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