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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


Epidemiological studies have repeatedly found that whole-grain (WG) cereal foods reduce the risk of several lifestyle-related diseases, though consistent clinical outcomes and mechanisms are elusive. To compare the effects of a WG-rich diet with a matched refined-grain (RG) diet on plasma biomarkers and bowel health parameters, seventeen healthy subjects (eleven females and six males) completed an exploratory cross-over study with a 2-week intervention diet based on either WG- or RG-based foods, separated by a washout of at least 5 weeks. Both diets were the same except for the use of WG (150 g/d) or RG foods. Subjects undertook a 4 h postprandial challenge on day 8 of each intervention diet. After 2 weeks, the WG diet tended to decrease plasma total and LDL-cholesterol (both P = 0·09), but did not change plasma HDL-cholesterol, fasting glucose, C-reactive protein or homocysteine compared with the RG diet. Plasma betaine and alkylresorcinol concentrations were elevated after 1 week of the WG diet (P = 0·01 and P < 0·0001, respectively). Clostridium leptum populations in faeces were increased after the WG diet, along with a trend for decreased faecal water pH (P = 0·096) and increased stool frequency (P < 0·0001) compared with the RG diet. A short controlled intervention trial with a variety of commercially available WG-based products tended to improve biomarkers of CVD compared with a RG diet. Changes in faecal microbiota related to increased fibre fermentation and increased plasma betaine concentrations point to both fibre and phytochemical components of WG being important in mediating any potential health effects.

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Corresponding author

*Corresponding author: A. B. Ross, fax +41 21 785 9486, email


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1 McKeown, NM, Meigs, JB, Liu, S, et al. (2002) 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 76, 390398.
2 Mellen, PB, Walsh, TF & Herrington, DM (2008) Whole grain intake and cardiovascular disease: a meta-analysis. Nutr Metab Cardiovasc Dis 18, 283290.
3 De Munter, JSL, Hu, FB, Spiegelman, D, et al. (2007) Whole grain, bran, and germ intake and risk of type 2 diabetes: a prospective cohort study and systematic review. PLoS Med 4, 13851395.
4 Sahyoun, NR, Jacques, PF, Zhang, XL, et al. (2006) Whole-grain intake is inversely associated with the metabolic syndrome and mortality in older adults. Am J Clin Nutr 83, 124131.
5 Larsson, SC, Giovannucci, E, Bergkvist, L, et al. (2005) Whole grain consumption and risk of colorectal cancer: a population-based cohort of 60,000 women. Br J Cancer 92, 18031807.
6 Slavin, JL, Jacobs, D, Marquart, L, et al. (2001) The role of whole grains in disease prevention. J Am Diet Assoc 101, 780785.
7 Fardet, A (2010) New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre? Nutr Res Rev 23, 65134.
8 Leinonen, KS, Poutanen, KS & Mykkanen, HM (2000) Rye bread decreases serum total and LDL cholesterol in men with moderately elevated serum cholesterol. J Nutr 130, 164170.
9 Behall, KM, Scholfield, DJ & Hallfrisch, J (2004) Diets containing barley significantly reduce lipids in mildly hypercholesterolemic men and women. Am J Clin Nutr 80, 11851193.
10 Lundin, EA, Zhang, JX, Lairon, D, et al. (2004) Effects of meal frequency and high-fibre rye-bread diet on glucose and lipid metabolism and ileal excretion of energy and sterols in ileostomy subjects. Eur J Clin Nutr 58, 14101419.
11 Giacco, R, Clemente, G, Cipriano, D, et al. (2010) Effects of the regular consumption of wholemeal wheat foods on cardiovascular risk factors in healthy people. Nutr Metab Cardiovasc Dis 20, 186194.
12 Behall, KM, Scholfield, DJ & Hallfrisch, J (2006) Whole-grain diets reduce blood pressure in mildly hypercholesterolemic men and women. J Am Diet Assoc 106, 14451449.
13 Hallfrisch, J, Scholfield, DJ & Behall, KM (2003) Blood pressure reduced by whole grain diet containing barley or whole wheat and brown rice in moderately hypercholesterolemic men. Nutr Res 23, 16311642.
14 Tighe, P, Duthie, G, Vaughan, N, et al. (2010) Effect of increased consumption of whole-grain foods on blood pressure and other cardiovascular risk markers in healthy middle-aged persons: a randomized controlled trial. Am J Clin Nutr 92, 733740.
15 Leinonen, K, Liukkonen, K, Poutanen, K, et al. (1999) Rye bread decreases postprandial insulin response but does not alter glucose response in healthy Finnish subjects. Eur J Clin Nutr 53, 262267.
16 Juntunen, KS, Laaksonen, DE, Poutanen, KS, et al. (2003) High-fiber rye bread and insulin secretion and sensitivity in healthy postmenopausal women. Am J Clin Nutr 77, 385391.
17 Pereira, MA, Jacobs, J, Pins, JJ, et al. (2002) Effect of whole grains on insulin sensitivity in overweight hyperinsulinemic adults. Am J Clin Nutr 75, 848855.
18 McIntosh, GH, Noakes, M, Royle, PJ, et al. (2003) Whole-grain rye and wheat foods and markers of bowel health in overweight middle-aged men. Am J Clin Nutr 77, 967974.
19 Costabile, A, Klinder, A, Fava, F, et al. (2008) Whole-grain wheat breakfast cereal has a prebiotic effect on the human gut microbiota: a double-blind, placebo-controlled, crossover study. Br J Nutr 99, 110120.
20 Melanson, KJ, Angelopoulos, TJ, Nguyen, VT, et al. (2006) Consumption of whole-grain cereals during weight loss: effects on dietary quality, dietary fiber, magnesium, vitamin B-6, and obesity. J Am Diet Assoc 106, 13801388.
21 Andersson, A, Tengblad, S, Karlstrom, B, et al. (2007) Whole-grain foods do not affect insulin sensitivity or markers of lipid peroxidation and inflammation in healthy, moderately overweight subjects. J Nutr 137, 14011407.
22 Brownlee, IA, Moore, C, Chatfield, M, et al. (2010) Markers of cardiovascular risk are not changed by increased whole-grain intake: the WHOLEheart study, a randomised, controlled dietary intervention. Br J Nutr 104, 125134.
23 McKeown, NM & Jacobs, DR (2010) In defence of phytochemical-rich dietary patterns. Br J Nutr 104, 13.
24 Slavin, J (2003) Why whole grains are protective: biological mechanisms. Proc Nutr Soc 62, 129134.
25 Jacobs, J & Gallaher, DD (2004) Whole grain intake and cardiovascular disease: a review. Curr Atheroscler Rep 6, 415423.
26 Waggle, DH, Lambert, MA, Miller, GD, et al. (1967) Extensive analyses of flours and millfeeds made from nine different wheat mixes. II. Amino acids, minerals, vitamins, and gross energy. Cereal Chem 44, 4860.
27 Bruce, SJ, Guy, PA, Rezzi, S, et al. (2010) Quantitative measurement of betaine and free choline in plasma, cereals and cereal products by isotope dilution LC–MS/MS. J Agric Food Chem 58, 20552061.
28 Vos, E (2000) Whole grains and coronary heart disease. Am J Clin Nutr 71, 1009.
29 Konstantinova, SV, Tell, GS, Vollset, SE, et al. (2008) Divergent associations of plasma choline and betaine with components of metabolic syndrome in middle age and elderly men and women. J Nutr 138, 914920.
30 US Department of Health and Human Services & US Department of Agriculture (2005) Dietary Guidelines for Americans 2005, 6th ed. Washington, DC: US Goverment Printing Office.
31 Ross, AB, Pineau, N, Kochhar, S, et al. (2009) Validation of a FFQ for estimating whole-grain cereal food intake. Br J Nutr 102, 15471551.
32 Ross, AB & Kochhar, S (2009) Rapid and sensitive analysis of alkylresorcinols from cereal grains and products using HPLC-Coularray-based electrochemical detection. J Agric Food Chem 57, 51875193.
33 Barbé, F, Abdelmouttaleb, I, Chango, A, et al. (2001) Detection of moderate hyperhomocysteinemia: comparison of the Abbott fluorescence polarization immunoassay with the Bio-Rad and SBD-F high-performance liquid chromatographic assays. Amino Acids 20, 435440.
34 Landberg, R, Åman, P & Kamal-Eldin, A (2009) A rapid gas chromatography–mass spectrometry method for quantification of alkylresorcinols in human plasma. Anal Biochem 385, 712.
35 Klinder, A, Karlsson, PC, Clune, Y, et al. (2007) Fecal water as a non-invasive biomarker in nutritional intervention: comparison of preparation methods and refinement of different endpoints. Nutr Cancer 57, 158167.
36 Linko-Parvinen, AM, Landberg, R, Tikkanen, MJ, et al. (2007) Alkylresorcinols from whole-grain wheat and rye are transported in human plasma lipoproteins. J Nutr 137, 11371142.
37 Fuldkornspartnerskabet/Fødevarestyrelsen (2010) Hvor meget (fuldkorn) skal jeg have? (How much (wholegrain) should I have?
38 Slow, S, Donaggio, M, Cressey, PJ, et al. (2005) The betaine content of New Zealand foods and estimated intake in the New Zealand diet. J Food Comp Anal 18, 473485.
39 Ross, AB, Becker, W, Chen, Y, et al. (2005) Intake of alkylresorcinols from wheat and rye in the United Kingdom and Sweden. Br J Nutr 94, 496499.
40 Maki, KC, Beiseigel, JM, Jonnalagadda, SS, et al. (2010) Whole-grain ready-to-eat oat cereal, as part of a dietary program for weight loss, reduces low-density lipoprotein cholesterol in adults with overweight and obesity more than a dietary program including low-fiber control foods. J Am Diet Assoc 110, 205214.
41 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.
42 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.
43 Craig, SA (2004) Betaine in human nutrition. Am J Clin Nutr 80, 539549.
44 Olthof, MR, van, VT, Boelsma, E, et al. (2003) Low dose betaine supplementation leads to immediate and long term lowering of plasma homocysteine in healthy men and women. J Nutr 133, 41354138.
45 Chiuve, SE, Giovannucci, EL, Hankinson, SE, et al. (2007) The association between betaine and choline intakes and the plasma concentrations of homocysteine in women. Am J Clin Nutr 86, 10731081.
46 Detopoulou, P, Panagiotakos, DB, Antonopoulou, S, et al. (2008) Dietary choline and betaine intakes in relation to concentrations of inflammatory markers in healthy adults: the ATTICA study. Am J Clin Nutr 87, 424430.
47 Dalmeijer, GW, Olthof, MR, Verhoef, P, et al. (2008) Prospective study on dietary intakes of folate, betaine, and choline and cardiovascular disease risk in women. Eur J Clin Nutr 62, 386394.
48 McNulty, H, Pentieva, K, Hoey, L, et al. (2008) Homocysteine, B-vitamins and CVD. Proc Nutr Soc 67, 232237.
49 Refsum, H, Nurk, E, Smith, AD, et al. (2006) The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease. J Nutr 136, 1731S1740S.
50 Allen, RH, Stabler, SP & Lindenbaum, J (1993) Serum betaine, N, N-dimethylglycine and N-methylglycine levels in patients with cobalamin and folate deficiency and related inborn errors of metabolism. Metab Clin Exp 42, 14481460.
51 Ueland, PM, Holm, PI & Hustad, S (2005) Betaine: a key modulator of one-carbon metabolism and homocysteine status. Clin Chem Lab Med 43, 10691075.
52 Atkinson, W, Elmslie, J, Lever, M, et al. (2008) Dietary and supplementary betaine: acute effects on plasma betaine and homocysteine concentrations under standard and postmethionine load conditions in healthy male subjects. Am J Clin Nutr 87, 577585.
53 Schwab, U, Törrönen, A, Meririnne, E, et al. (2006) Orally administered betaine has an acute and dose-dependent effect on serum betaine and plasma homocysteine concentrations in healthy humans. J Nutr 136, 3438.
54 Ikeda, GJ, Miller, E & Sapienza, PP (1985) Maternal-foetal distribution studies in late pregnancy. 1. Distribution of [N-methyl-14C]betaine in tissues of beagle dogs and miniature pigs. Food Chem Toxicol 23, 609614.
55 Slow, S, Lever, M, Chambers, ST, et al. (2009) Plasma dependent and independent accumulation of betaine in male and female rat tissues. Physiol Res 58, 403410.
56 Olthof, MR, van Vliet, T, Verhoef, P, et al. (2005) Effect of homocysteine-lowering nutrients on blood lipids: results from four randomised, placebo-controlled studies in healthy humans. PLoS Med 2, 04460456.
57 Zeisel, SH (2006) Betaine supplementation and blood lipids: fact or artifact? Nutr Rev 64, 7779.
58 Ross, AB, Kamal-Eldin, A & Åman, P (2004) Dietary alkylresorcinols: absorption, bioactivities, and possible use as biomarkers of whole-grain wheat- and rye-rich foods. Nutr Rev 62, 8195.
59 Landberg, R, Kamal-Eldin, A, Andersson, A, et al. (2008) Alkylresorcinols as biomarkers of whole-grain wheat and rye intake: plasma concentration and intake estimated from dietary records. Am J Clin Nutr 87, 832838.
60 Landberg, R, Linko, AM, Kamal-Eldin, A, et al. (2006) Human plasma kinetics and relative bioavailability of alkylresorcinols after intake of rye bran. J Nutr 136, 27602765.
61 Linko, AM, Ross, AB, Kamal-Eldin, A, et al. (2006) Kinetics of the appearance of cereal alkylresorcinols in pig plasma. Br J Nutr 95, 282287.
62 Harland, JI & Garton, LE (2008) Whole-grain intake as a marker of healthy body weight and adiposity. Public Health Nutr 11, 554563.
63 McKeown, NM, Yoshida, M, Shea, MK, et al. (2009) Whole-grain intake and cereal fiber are associated with lower abdominal adiposity in older adults. J Nutr 139, 19501955.
64 Jacobs, DR, Murtaugh, MA, Pereira, MA, et al. (2004) Commercially available whole grain foods reduce body weight compared to equal servings of refined grain foods. FASEB J (Abstracts 128.1).
65 Holma, R, Hongisto, SM, Saxelin, M, et al. (2010) Constipation is relieved more by rye bread than wheat bread or laxatives without increased adverse gastrointestinal effects. J Nutr 140, 534541.
66 Carvalho-Wells, AL, Helmolz, K, Nodet, C, et al. (2010) Determination of the in vivo prebiotic potential of a maize-based whole grain breakfast cereal: a human feeding study. Br J Nutr 104, 13531356.
67 Shen, J, Zhang, B, Wei, G, et al. (2006) Molecular profiling of the Clostridium leptum subgroup in human fecal microflora by PCR-denaturing gradient gel electrophoresis and clone library analysis. Appl Environ Microbiol 72, 52325238.
68 Abnous, K, Brooks, SPJ, Kwan, J, et al. (2009) Diets enriched in oat bran or wheat bran temporally and differentially alter the composition of the fecal community of rats. J Nutr 139, 20242031.
69 Vitaglione, P, Napolitano, A & Fogliano, V (2008) Cereal dietary fibre: a natural functional ingredient to deliver phenolic compounds into the gut. Trends Food Sci Technol 19, 451463.
70 Selma, MV, Espin, JC & Tomas-Barberan, FA (2009) Interaction between phenolics and gut microbiota: role in human health. J Agric Food Chem 57, 64856501.
71 Cleveland, LE, Moshfegh, AJ, Albertson, AM, et al. (2000) Dietary intake of whole grains. J Am Coll Nutr 19, 331S338S.
72 Maras, JE, Newby, PK, Bakun, PJ, et al. (2009) Whole grain intake: The Baltimore Longitudinal Study of Aging. J Food Compost Anal 22, 5358.
73 Gråsten, SM, Juntunen, KS, Poutanen, KS, et al. (2000) Rye bread improves bowel function and decreases the concentrations of some compounds that are putative colon cancer risk markers in middle-aged women and men. J Nutr 130, 22152221.
74 Pins, JJ, Geleva, D, Keenan, JM, et al. (2002) Do whole-grain oat cereals reduce the need for antihypertensive medications and improve blood pressure control? J Fam Pract 51, 353359.


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


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