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Carbohydrates, glycemic index and diabetes mellitus

Alkylresorcinols in adipose tissue biopsies as biomarkers of whole-grain intake: an exploratory study of responsiveness to advised intake over 12 weeks

Abstract

Background/Objectives:

Alkylresorcinols (ARs) have been suggested as biomarkers of whole-grain wheat and rye intake. Plasma AR concentrations have a short half-life; hence, long-term biomarkers are needed. This study evaluated the responsiveness of ARs in adipose tissue biopsies as biomarkers after a whole-grain intake intervention.

Subjects/Methods:

Samples and data of 27 participants from a 12-week randomized parallel-group dietary intervention were available. The participants were replacing their habitual diet with a whole-grain-enriched diet (WGDG) or a refined grain diet (RDG) during the intervention. Blood samples and adipose tissue biopsies were collected at baseline and after 12 weeks, and AR concentrations in the plasma and adipose tissues from the participants were compared against estimated whole-grain intake.

Results:

AR concentrations in the adipose tissue and plasma did not change after 12 weeks in the WGDG group, as no significant increase in whole-grain intake was observed, but was significantly lower than baseline in the RDG group (P<0.05), owing to decreased whole-grain intake in this group. Plasma and adipose tissue AR concentrations were significantly higher in the WGDG group than in the RDG group (P<0.05), and were highly correlated with average whole-grain intake estimated by food records (Spearman’s r=0.60–0.72 (P<0.05, n=16) for total and individual AR homolog concentrations in the plasma; r=0.60–-0.84, (P<0.05, n=16) for total and individual AR homolog concentrations in the adipose tissue).

Conclusions:

In this small pilot study, AR concentrations in adipose tissue responded to reduced intake of whole grain over 12 weeks. Although not significantly different from plasma AR, adipose tissue AR concentrations were highly correlated with whole-grain intake after a 12-week intervention. These results show that adipose tissue AR concentrations have promise as biomarkers of whole-grain wheat and rye intake. Larger studies are needed to evaluate whether they are better long-term biomarkers than AR in the plasma.

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References

  1. McKeown NM, Meigs JB, Liu S, Wilson PW, Jacques PF . Whole-grain intake is favorably associated with metabolic risk factors for type 2 diabetes and cardiovascular disease in the Framingham Offspring Study. Am J Clin Nutr 2002; 76: 390–398.

    Article  CAS  Google Scholar 

  2. Ye EQ, Chacko SA, Chou EL, Kugizaki M, Liu S . Greater whole-grain intake is associated with lower risk of type 2 diabetes, cardiovascular disease, and weight gain. J Nutr 2012; 142: 1304–1313.

    Article  CAS  Google Scholar 

  3. von Ruesten A, Feller S, Bergmann M, Boeing H . Diet and risk of chronic diseases: results from the first 8 years of follow-up in the EPIC-Potsdam study. Eur J Clin Nutr 2013; 67: 412–419.

    Article  CAS  Google Scholar 

  4. Kristensen M, Toubro S, Jensen MG, Ross AB, Riboldi G, Petronio M et al. Whole grain compared with refined wheat decreases the percentage of body fat following a 12-week, energy-restricted dietary intervention in postmenopausal women. J Nutr 2012; 142: 710–716.

    Article  CAS  Google Scholar 

  5. Aune D, Chan DSM, Lau R, Vieira R, Greenwood DC, Kampman E et al. Dietary fibre, whole grains, and risk of colorectal cancer: systematic review and dose-response meta-analysis of prospective studies. BMJ 2011; 343: d6617.

    Article  Google Scholar 

  6. Andersson AAM, Dimberg L, Åman P, Landberg R . Recent findings on certain bioactive components in whole grain wheat and rye. J Cereal Sci 2014; 59: 294–311.

    Article  CAS  Google Scholar 

  7. Fardet A . New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre? Nutr Res Rev 2010; 23: 65–134.

    Article  CAS  Google Scholar 

  8. Liu S, Manson JE, Stampfer MJ, Rexrode KM, Hu FB, Rimm EB et al. Whole grain consumption and risk of ischemic stroke in women. JAMA 2000; 284: 1534–1540.

    Article  CAS  Google Scholar 

  9. Brownlee IA, Kuznesof SA, Moore C, Jebb SA, Seal CJ . The impact of a 16-week dietary intervention with prescribed amounts of whole-grain foods on subsequent, elective whole grain consumption. Br J Nutr 2013; 110: 943–948.

    Article  CAS  Google Scholar 

  10. Esmaillzadeh A, Kimiagar M, Mehrabi Y, Azadbakht L, Hu FB, Willett WC . Dietary patterns and markers of systemic inflammation among Iranian women. J Nutr 2007; 137: 992–998.

    Article  CAS  Google Scholar 

  11. Kipnis V, Subar AF, Midthune D, Freedman LS, Ballard-Barbash R, Troiano RP et al. Structure of dietary measurement error: results of the OPEN Biomarker Study. Am J Epidemiol 2003; 158: 14–21.

    Article  Google Scholar 

  12. Kipnis V, Midthune D, Freedman L, Bingham S, Day NE, Riboli E et al. Bias in dietary-report instruments and its implications for nutritional epidemiology. Public Health Nutr 2002; 5: 915–923.

    Article  Google Scholar 

  13. Kristal AR, Peters U, Potter JD . Is it time to abandon the food frequency questionnaire? Cancer Epidemiol Biomarkers Prev 2005; 14: 2826–2828.

    Article  Google Scholar 

  14. Thompson FE, Subar AF . Dietary Assessment Methodology. In: Coulston AM, Boushey CJ, Ferruzzi MG (eds). Nutrition in the Prevention and Treatment of Disease, 3rd edn. Academic Press: New York, NY, USA, 2013, pp 5–46.

    Book  Google Scholar 

  15. van der Kamp JW, Poutanen K, Seal CJ, Richardson DP . The HEALTHGRAIN definition of ‘whole grain’. Food Nutr Res 2014; 58; doi:10.3402/fnr.v58.22100.

  16. Kantor LS, Variyam JN, Allshouse JE, Putnam JJ, Lin BH . Choose a variety of grains daily, especially whole grains: a challenge for consumers. J Nutr 2001; 131: 473S–486S.

    Article  CAS  Google Scholar 

  17. Landberg R, Marklund M, Kamal-Eldin A, Åman P . An update on alkylresorcinols – occurrence, bioavailability, bioactivity and utility as biomarkers. J Funct Foods 2014; 7: 77–89.

    Article  CAS  Google Scholar 

  18. Ma J, Ross AB, Shea MK, Bruce SJ, Jacques PF, Saltzman E et al. Plasma alkylresorcinols, biomarkers of whole-grain intake, are related to lower bmi in older adults. J Nutr 2012; 142: 1859–1864.

    Article  CAS  Google Scholar 

  19. Magnusdottir OK, Landberg R, Gunnarsdottir I, Cloetens L, Akesson B, Onning G et al. Plasma alkylresorcinols reflect important whole-grain components of a healthy Nordic diet. J Nutr 2013; 143: 1383–1390.

    Article  CAS  Google Scholar 

  20. Landberg R, Kamal-Eldin A, Salmenkallio-Marttila M, Rouau X, Åman P . Localization of alkylresorcinols in wheat, rye and barley kernels. J Cereal Sci 2008; 48: 401–406.

    Article  CAS  Google Scholar 

  21. Ross AB, Kamal-Eldin A, Jung C, Shepherd MJ, Åman P . Gas chromatographic analysis of alkylresorcinols in rye (Secale cereale L) grains. J Sci Food Agriculture 2001; 81: 1405–1411.

    Article  CAS  Google Scholar 

  22. Chen Y, Ross AB, Åman P, Kamal-Eldin A . Alkylresorcinols as markers of whole grain wheat and rye in cereal products. J Agric Food Chem 2004; 52: 8242–8246.

    Article  CAS  Google Scholar 

  23. Landberg R, Kamal-Eldin A, Andersson R, Åman P . Alkylresorcinol content and homologue composition in durum wheat (Triticum durum kernels and pasta products. J Agric Food Chem 2006; 54: 3012–3014.

    Article  CAS  Google Scholar 

  24. Ross AB, Kamal-Eldin A, Lundin EA, Zhang J-X, Hallmans G, Åman P . Cereal alkylresorcinols are absorbed by humans. J Nutr 2003; 133: 2222–2224.

    Article  CAS  Google Scholar 

  25. Linko A-M, Parikka K, Wähälä K, Adlercreutz H . Gas chromatographic–mass spectrometric method for the determination of alkylresorcinols in human plasma. Anal Biochem 2002; 308: 307–313.

    Article  CAS  Google Scholar 

  26. Ross AB, Chen Y, Frank J, Swanson JE, Parker RS, Kozubek A et al. Cereal alkylresorcinols elevate γ-tocopherol levels in rats and inhibit γ-tocopherol metabolism in vitro. J Nutr 2004; 134: 506–510.

    Article  CAS  Google Scholar 

  27. Jansson E, Landberg R, Kamal-Eldin A, Wolk A, Vessby B, Åman P . Presence of alkylresorcinols, potential whole grain biomarkers, in human adipose tissue. Br J Nutr 2010; 104: 633.

    Article  CAS  Google Scholar 

  28. Landberg R, Aman P, Hallmans G, Johansson I . Long-term reproducibility of plasma alkylresorcinols as biomarkers of whole-grain wheat and rye intake within Northern Sweden Health and Disease Study Cohort. Eur J Clin Nutr 2013; 67: 259–263.

    Article  CAS  Google Scholar 

  29. Knudsen MD, Kyrø C, Olsen A, Dragsted LO, Skeie G, Lund E et al. Self-reported whole-grain intake and plasma alkylresorcinol concentrations in combination in relation to the incidence of colorectal cancer. Am J Epidemiol 2014; 179: 1188–1196.

    Article  Google Scholar 

  30. Kyrø C, Olsen A, Landberg R, Skeie G, Loft S, Åman P et al. Plasma alkylresorcinols, biomarkers of whole-grain wheat and rye intake, and incidence of colorectal cancer. J Natl Cancer Inst 2013; 106: djt352.

    PubMed  PubMed Central  Google Scholar 

  31. Arab L . Biomarkers of fat and fatty acid intake. J Nutr 2003; 133: 925S–932S.

    Article  CAS  Google Scholar 

  32. de Mello VD, Schwab U, Kolehmainen M, Koenig W, Siloaho M, Poutanen K et al. A diet high in fatty fish, bilberries and wholegrain products improves markers of endothelial function and inflammation in individuals with impaired glucose metabolism in a randomised controlled trial: the Sysdimet study. Diabetologia 2011; 54: 2755–2767.

    Article  CAS  Google Scholar 

  33. Lankinen M, Schwab U, Kolehmainen M, Paananen J, Poutanen K, Mykkanen H et al. Whole grain products, fish and bilberries alter glucose and lipid metabolism in a randomized, controlled trial: the Sysdimet study. PLoS One 2011; 6: e22646.

    Article  CAS  Google Scholar 

  34. Landberg R, Åman P, Kamal-Eldin A . A rapid gas chromatography–mass spectrometry method for quantification of alkylresorcinols in human plasma. Anal Biochem 2009; 385: 7–12.

    Article  CAS  Google Scholar 

  35. Aubertin-Leheudre M, Koskela A, Marjamaa A, Adlercreutz H . Plasma alkylresorcinols and urinary alkylresorcinol metabolites as biomarkers of cereal fiber intake in Finnish women. Cancer Epidemiol Biomarkers Prev 2008; 17: 2244–2248.

    Article  CAS  Google Scholar 

  36. Landberg R, Kamal-Eldin A, Aman P, Christensen J, Overvad K, Tjonneland A et al. Determinants of plasma alkylresorcinol concentration in Danish post-menopausal women. Eur J Clin Nutr 2011; 65: 94–101.

    Article  CAS  Google Scholar 

  37. Kyrø C, Olsen A, Bueno-de-Mesquita HB, Skeie G, Loft S, Åman P et al. Plasma alkylresorcinol concentrations, biomarkers of whole-grain wheat and rye intake, in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Br J Nutr 2014; 111: 1881–1890.

    Article  Google Scholar 

  38. Helldán A, Raulio S, Kosola M, Tapanainen H, Ovaskainen M-L, Virtanen S, Finravinto 2012-tutkimus-The National FINDIET 2012 Survey. Raportti: 2013_016 2013.

  39. Rebro SM, Patterson RE, Kristal AR, Cheney CL . The effect of keeping food records on eating patterns. J Am Diet Assoc 1998; 98: 1163–1165.

    Article  CAS  Google Scholar 

  40. Landberg R, Kamal-Eldin A, Andersson A, Vessby B, Åman P . Alkylresorcinols as biomarkers of whole-grain wheat and rye intake: plasma concentration and intake estimated from dietary records. Am J Clin Nutr 2008; 87: 832–838.

    Article  CAS  Google Scholar 

  41. Linko A-M, Juntunen KS, Mykkänen HM, Adlercreutz H . Whole-grain rye bread consumption by women correlates with plasma alkylresorcinols and increases their concentration compared with low-fiber wheat bread. J Nutr 2005; 135: 580–583.

    Article  CAS  Google Scholar 

  42. Marklund M, Landberg R, Andersson A, Åman P, Kamal-Eldin A . Alkylresorcinol metabolites in urine correlate with the intake of whole grains and cereal fibre in free-living Swedish adults. Br J Nutr 2013; 109: 129–136.

    Article  CAS  Google Scholar 

  43. Strawford A, Antelo F, Christiansen M, Hellerstein MK . Adipose tissue triglyceride turnover, de novo lipogenesis, and cell proliferation in humans measured with 2H2O. Am J Physiol Endocrinol Metab 2004; 286: E577–E588.

    Article  CAS  Google Scholar 

  44. Beynen AC, Hermus RJ, Hautvast JG . A mathematical relationship between the fatty acid composition of the diet and that of the adipose tissue in man. Am J Clin Nutr 1980; 33: 81–85.

    Article  CAS  Google Scholar 

  45. Handelman GJ, Epstein WL, Peerson J, Spiegelman D, Machlin LJ, Dratz EA . Human adipose alpha-tocopherol and gamma-tocopherol kinetics during and after 1 y of alpha-tocopherol supplementation. Am JClin Nutr 1994; 59: 1025–1032.

    Article  CAS  Google Scholar 

  46. Linko AM, Adlercreutz H . Whole-grain rye and wheat alkylresorcinols are incorporated into human erythrocyte membranes. Br J Nutr 2005; 93: 11–13.

    Article  CAS  Google Scholar 

  47. Simon E, Gariepy J, Cogny A, Moatti N, Simon A, Paul J-L . Erythrocyte, but not plasma, vitamin E concentration is associated with carotid intima–media thickening in asymptomatic men at risk for cardiovascular disease. Atherosclerosis 2001; 159: 193–200.

    Article  CAS  Google Scholar 

  48. Asghar A, Gray JI, Booren AM, Gomaa EA, Abouzied MM, Miller ER et al. Effects of supranutritional dietary vitamin E levels on subcellular deposition of α-tocopherol in the muscle and on pork quality. J Sci Food Agriculture 1991; 57: 31–41.

    Article  CAS  Google Scholar 

  49. Brasaemle DL . Thematic review series: Adipocyte Biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis. J Lipid Res 2007; 48: 2547–2559.

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Dr Jenni Lappi for assistance in calculating whole-grain intake. The Swedish Research Council Formas and the Academy of Finland are acknowledged for financial support.

Author contributions

HW conducted the data analysis, interpreted the data and drafted the manuscript. MK, HM, KP, MU and US contributed to the design and execution of the SYSDIMET study in Finland, and provided samples and data for the present study. RL conceived the study and supervised sample and data analysis and manuscript preparation. AW supervised manuscript preparation. All authors contributed to interpretation of the data and have approved the final content.

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Correspondence to H Wu.

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Wu, H., Kolehmainen, M., Mykkänen, H. et al. Alkylresorcinols in adipose tissue biopsies as biomarkers of whole-grain intake: an exploratory study of responsiveness to advised intake over 12 weeks. Eur J Clin Nutr 69, 1244–1248 (2015). https://doi.org/10.1038/ejcn.2015.138

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