Skip to main content Accessibility help

Whole grains beyond fibre: what can metabolomics tell us about mechanisms?

  • Alastair B. Ross (a1)


Dietary fibre alone does not fully explain the frequent association between greater intake of whole grains and reduced risk of disease in observational studies, and other phytochemicals or food structure may also play an important role. For all the observational evidence for the benefits of a whole-grain-rich diet, we have only limited knowledge of the mechanisms behind this reduction in disease risk, aside from the action of specific cereal fibres on reduction of blood cholesterol and the post-prandial glucose peak. Nutritional metabolomics, the global measurement and interpretation of metabolic profiles, assesses the interaction of food with the endogenous gene–protein cascade and the gut microbiome. This approach allows the generation of new hypotheses which account for systemic effects, rather than just focusing on one or two mechanisms or metabolic pathways. To date, animal and human trials using metabolomics to investigate mechanistic changes to metabolism on eating whole grains and cereal fractions have led to new hypotheses around mechanistic effects of whole grains. These include the role of cereals as a major source of dietary glycine betaine, a possible effect on phospholipid synthesis or metabolism, the role of branched-chain amino acids and improvements in insulin sensitivity, and the possibility that whole grains may have an effect on protein metabolism. These hypotheses help explain some of the observed effects of whole grains, although mechanistic studies using stable isotopes and fully quantitative measures are required to confirm these potential mechanisms.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Whole grains beyond fibre: what can metabolomics tell us about mechanisms?
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Whole grains beyond fibre: what can metabolomics tell us about mechanisms?
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Whole grains beyond fibre: what can metabolomics tell us about mechanisms?
      Available formats


Corresponding author

Corresponding author: A. B. Ross, email


Hide All
1. Ye, EQ, Chacko, SA, Chou, EL et al. (2012) Greater whole-grain intake is associated with lower risk of type 2 diabetes, cardiovascular disease, and weight gain. J Nutr 142, 13041313.
2. Frølich, W, Åman, P & Tetens, I (2013) Whole grain foods and health – A Scandinavian perspective. Food Nutr Res 57; Epublication 12 February 2012. Available at
3. Satija, A & Hu, FB (2012) Cardiovascular benefits of dietary fiber. Curr Atheroscl Rep 14, 505514.
4. Smith, CE & Tucker, KL (2011) Health benefits of cereal fibre: a review of clinical trials. Nutr Res Rev 24, 118131.
5. Lattimer, JM & Haub, MD (2010) Effects of dietary fiber and its components on metabolic health. Nutrients 2, 12661289.
6. Andersson, AAM, Dimberg, L, Åman, P et al. (2014) Recent findings on certain bioactive components in whole grain wheat and rye. J Cereal Sci 59, 294311.
7. Slavin, J (2003) Why whole grains are protective: biological mechanisms. Proc Nutr Soc 62, 129134.
8. Myung, SK, Ju, W, Cho, B et al. (2013) Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: systematic review and meta-analysis of randomised controlled trials. BMJ 346. Available at
9. Zulyniak, MA & Mutch, DM (2011) Harnessing metabolomics for nutrition research. Curr Pharm Biotechnol 12, 10051015.
10. Bertram, HC, Bach Knudsen, KE, Serena, A et al. (2006) NMR-based metabonomic studies reveal changes in the biochemical profile of plasma and urine from pigs fed high-fibre rye bread. Br J Nutr 95, 955962.
11. Ross, AB, Pere-Trepat, E, Montoliu, I et al. (2013) A whole-grain-rich diet reduces urinary excretion of markers of protein catabolism and gut microbiota metabolism in healthy men after one week. J Nutr 143, 766773.
12. Lees, HJ, Swann, JR, Wilson, ID et al. (2013) Hippurate: the natural history of a mammalian-microbial cometabolite. J Proteome Res 12, 15271546.
13. Bertram, HC, Duarte, IF, Gil, AM et al. (2007) Metabolic profiling of liver from hypercholesterolemic pigs fed rye or wheat fiber and from normal pigs. High-resolution magic angle spinning 1H NMR spectroscopic study. Anal Chem 79, 168175.
14. Bertram, HC, Malmendal, A, Nielsen, NC et al. (2009) NMR-based metabonomics reveals that plasma betaine increases upon intake of high-fiber rye buns in hypercholesterolemic pigs. Mol Nutr Food Res 53, 10551062.
15. Norskov, NP, Hedemann, MS, Laerke, HN et al. (2013) Multicompartmental Nontargeted LC-MS Metabolomics: explorative study on the metabolic responses of rye fiber versus refined wheat fiber intake in plasma and urine of hypercholesterolemic pigs. J Proteome Res 12, 28182832.
16. Laerke, HN, Mortensen, MA, Hedemann, MS et al. (2009) Quantitative aspects of the metabolism of lignans in pigs fed fibre-enriched rye and wheat bread. Br J Nutr 102, 985994.
17. Nielsen, KL, Hartvigsen, ML, Hedemann, MS et al. (2014) Similar metabolic responses in pigs and humans to breads with different contents and compositions of dietary fibers: a metabolomics study. Am J Clin Nutr 99, 941949.
18. Fardet, A, Canlet, C, Gottardi, G et al. (2007) Whole-grain and refined wheat flours show distinct metabolic profiles in rats as assessed by a 1H NMR-based metabonomic approach. J Nutr 137, 923929.
19. Pekkinen, J, Rosa, NN, Savolainen, OI et al. (2014) Disintegration of wheat aleurone structure has an impact on the bioavailability of phenolic compounds and other phytochemicals as evidenced by altered urinary metabolite profile of diet-induced obese mice. Nutr Metab (Lond) 11, 1.
20. Lankinen, M, Schwab, U, Seppänen-Laakso, T et al. (2011) Metabolomic analysis of plasma metabolites that may mediate effects of rye bread on satiety and weight maintenance in postmenopausal women1,2. J Nutr 141, 3136.
21. Forsberg, T, Åman, P & Landberg, R (2014) Effects of whole grain rye crisp bread for breakfast on appetite and energy intake in a subsequent meal: two randomised controlled trails with different amounts of test foods and breakfast energy content. Nutr J 13. Avalable at
22. Isaksson, H, Tillander, I, Andersson, R et al. (2012) Whole grain rye breakfast – Sustained satiety during three weeks of regular consumption. Physiol Behav 105, 877884.
23. Moazzami, AA, Zhang, JX, Kamal-Eldin, A et al. (2011) Nuclear magnetic resonance-based metabolomics enable detection of the effects of a whole grain rye and rye bran diet on the metabolic profile of plasma in prostate cancer patients. J Nutr 141, 21262132.
24. Landberg, R, Andersson, SO, Zhang, JX et al. (2010) Rye whole grain and bran intake compared with refined wheat decreases urinary C-peptide, plasma insulin, and prostate specific antigen in men with prostate cancer. J Nutr 140, 21802186.
25. Price, RK, Keaveney, EM, Hamill, LL et al. (2010) Consumption of wheat aleurone-rich foods increases fasting plasma betaine and modestly decreases fasting homocysteine and LDL-cholesterol in adults. J Nutr 140, 21532157.
26. Ross, AB, Bruce, SJ, Blondel-Lubrano, A et al. (2011) A whole-grain cereal-rich diet increases plasma betaine, and tends to decrease total and LDL-cholesterol compared with a refined-grain diet in healthy subjects. Br J Nutr 105, 14921502.
27. Moazzami, AA, Bondia-Pons, I, Hanhineva, K et al. (2012) Metabolomics reveals the metabolic shifts following an intervention with rye bread in postmenopausal women – a randomized control trial. Nutr J 11, 88.
28. Moazzami, AA, Shrestha, A, Morrison, DA et al. (2014) Metabolomics reveals differences in postprandial responses to breads and fasting metabolic characteristics associated with postprandial insulin demand in postmenopausal women. J Nutr 144, 807814.
29. Bondia-Pons, I, Nordlund, E, Mattila, I et al. (2011) Postprandial differences in the plasma metabolome of healthy Finnish subjects after intake of a sourdough fermented endosperm rye bread versus white wheat bread. Nutr J 10, 116.
30. Lankinen, M, Schwab, U, Kolehmainen, M et al. (2011) Whole grain products, fish and bilberries alter glucose and lipid metabolism in a randomized, controlled trial: the sysdimet study. PLoS ONE 6.
31. Zeisel, SH (2006) Betaine supplementation and blood lipids: fact or artifact? Nutr Rev 64, 7779.
32. Floegel, A, von Ruesten, A, Drogan, D et al. (2013) Variation of serum metabolites related to habitual diet: a targeted metabolomic approach in EPIC-Potsdam. Eur J Clin Nutr 67, 11001108.
33. Parks, JS, Huggins, KW, Gebre, AK et al. (2000) Phosphatidylcholine fluidity and structure affect lecithin:cholesterol acyltransferase activity. J Lipid Res 41, 546553.
34. Pekkinen, J, Olli, K, Huotari, A et al. (2013) Betaine supplementation causes increase in carnitine metabolites in the muscle and liver of mice fed a high-fat diet as studied by nontargeted LC-MS metabolomics approach. Mol Nutr Food Res 57, 19591968.
35. Medici, V, Schroeder, DI, Woods, R et al. (2014) Methylation and gene expression responses to ethanol feeding and betaine supplementation in the cystathionine beta synthase-deficient mouse. Alc Clin Exp Res 38, 15401549.
36. Cordero, P, Campion, J, Milagro, FI et al. (2013) Transcriptomic and epigenetic changes in early liver steatosis associated to obesity: effect of dietary methyl donor supplementation. Mol Genet Metab 110, 388395.
37. Ross, AB, Zangger, A, Guiraud, SP (2014) Cereal foods are the major source of betaine in the Western diet - Analysis of betaine and free choline in cereal foods and updated assessments of betaine intake. Food Chem 145, 859865.
38. Harris Jackson, K, West, SG, Vanden Heuvel, JP et al. (2014) Effects of whole and refined grains in a weight-loss diet on markers of metabolic syndrome in individuals with increased waist circumference: a randomized controlled-feeding trial. Am J Clin Nutr 100, 577586.
39. Malin, SK, Kullman, EL, Scelsi, AR et al. (2014) Whole Grain Diet Improves Glucose Tolerance, Insulin Sensitivity, and Beta-Cell Function in Overweight Prediabetic Adults. American Diabetes Association. San Francisco.
40. Newgard, CB (2012) Interplay between lipids and branched-chain amino acids in development of insulin resistance. Cell Metab 15, 606614.
41. Ross, AB, Pere-Trepat, E, Montoliu, I et al. (2013) A whole-grain-rich diet reduces urinary excretion of markers of protein catabolism and gut microbiota metabolism in healthy men after one week. J Nutr 143, 766773.
42. McKeown, NM, Troy, LM, Jacques, PF et al. (2010) Whole- and refined-grain intakes are differentially associated with abdominal visceral and subcutaneous adiposity in healthy adults: the Framingham Heart Study. Am J Clin Nutr 92, 11651171.
43. Katcher, HI, Legro, RS, Kunselman, AR et al. (2008) The effects of a whole grain-enriched hypocaloric diet on cardiovascular disease risk factors in men and women with metabolic syndrome. Am J Clin Nutr 87, 7990.
44. Kristensen, M, Toubro, S, Jensen, MG et al. (2012) Whole grain compared to refined wheat decreases the percentage body fat following a 12-week energy restricted dietary intervention in postmenopausal women. J Nutr 142, 710716.
45. Ostler, JE, Maurya, SK, Dials, J et al. (2014) Effects of insulin resistance on skeletal muscle growth and exercise capacity in type 2 diabetic mouse models. Am J Physiol Endocrinol Metab 306, E592605.
46. Priebe, MG, Wang, H, Weening, D et al. (2010) Factors related to colonic fermentation of nondigestible carbohydrates of a previous evening meal increase tissue glucose uptake and moderate glucose-associated inflammation. Am J Clin Nutr 91, 9097.
47. Wurtz, P, Makinen, VP, Soininen, P et al. (2012) Metabolic signatures of insulin resistance in 7,098 young adults. Diabetes 61, 13721380.
48. Wurtz, P, Soininen, P, Kangas, AJ et al. (2013) Branched-chain and aromatic amino acids are predictors of insulin resistance in young adults. Diab Care 36, 648655.
49. Walford, GA, Davis, J, Warner, AS et al. (2013) Branched chain and aromatic amino acids change acutely following two medical therapies for type 2 diabetes mellitus. Metabolism 62, 17721778.
50. Wang, Z, Klipfell, E, Bennett, BJ et al. (2011) Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472, 5763.
51. Ridaura, VK, Faith, JJ, Rey, FE et al. (2013) Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science 341, 1241214.
52. Beckmann, M, Lloyd, AJ, Haldar, S et al. (2013) Hydroxylated phenylacetamides derived from bioactive benzoxazinoids are bioavailable in humans after habitual consumption of whole grain sourdough rye bread. Mol Nutr Food Res 57, 18591873.
53. Bondia-Pons, I, Barri, T, Hanhineva, K et al. (2013) UPLC-QTOF/MS metabolic profiling unveils urinary changes in humans after a whole grain rye versus refined wheat bread intervention. Mol Nutr Food Res 57, 412422.
54. Hanhineva, K, Keski-Rahkonen, P, Lappi, J et al. (2014) The postprandial plasma rye fingerprint includes benzoxazinoid-derived phenylacetamide sulfates. J Nutr 144, 10161022.
55. Primrose, S, Draper, J, Elsom, R et al. (2011) Workshop report: metabolomics and human nutrition. Br J Nutr 105, 12771283.
56. Hopton, RP, Turner, E, Burley, VJ et al. (2010) Urine metabolite analysis as a function of deoxynivalenol exposure: an NMR-based metabolomics investigation. Food addit Contam A 27, 255261.


Whole grains beyond fibre: what can metabolomics tell us about mechanisms?

  • Alastair B. Ross (a1)


Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed