Journal of Nutrition OpenSOurce Diets- www.ResearchDiets.com

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Linko-Parvinen, A.-M.
Right arrow Articles by Peñalvo, J. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Linko-Parvinen, A.-M.
Right arrow Articles by Peñalvo, J. L.
© 2007 American Society for Nutrition J. Nutr. 137:1137-1142, May 2007

Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Alkylresorcinols from Whole-Grain Wheat and Rye Are Transported in Human Plasma Lipoproteins1,2

Anna-Maria Linko-Parvinen3,*, Rikard Landberg4, Matti J. Tikkanen3,5, Herman Adlercreutz3 and José L. Peñalvo3

3 Institute for Preventive Medicine, Nutrition and Cancer, Folkhälsan Research Center and Division of Clinical Chemistry, University of Helsinki, FIN-00014 Helsinki, Finland; 4 Department of Food Science, Swedish University of Agricultural Science (SLU), S-750 07 Uppsala, Sweden; and 5 Department of Medicine, University of Helsinki, FIN-00014 Helsinki, Finland

* To whom correspondence should be addressed. E-mail: anna.linko{at}helsinki.fi.


   ABSTRACT
TOP
 ABSTRACT
Introduction
 Subjects and Methods
 Results
 Discussion
 LITERATURE CITED
 
Alkylresorcinols with alkyl chains C17:0-C25:0 are abundant in whole-grain wheat and rye. Concentrations in human plasma have been suggested to be biomarkers of dietary whole-grain intake. We measured human plasma, erythrocyte, and lipoprotein alkylresorcinol concentrations and alkylresorcinol homolog distribution, and evaluated the use of plasma alkylresorcinol concentration as a dietary biomarker of whole-grain intake compared with serum enterolactone. A total of 15 subjects (8 women) consumed whole-grain wheat or whole-grain rye crisp bread (~100 g/d) in a crossover design for 1 wk. The test bread periods were preceded by 1-wk periods of consuming refined wheat bread. Plasma, erythrocyte, lipoprotein alkylresorcinol, and serum enterolactone concentrations were measured before and after each period, and plasma alkylresorcinols and serum enterolactone were measured after habitual diet intake before and 1 wk after the trial. Plasma alkylresorcinols are transported in lipoproteins with VLDL and HDL being the main carriers. AR concentrations in plasma, erythrocytes, and lipoproteins were increased (P < 0.05) by whole-grain wheat bread and even more so with rye crisp bread, although interindividual variation was high. The alkylresorcinol homolog C17:0 to C21:0 ratio in plasma was higher after the whole-grain rye diet period compared with the whole-grain wheat diet period (P < 0.05). Serum enterolactone concentrations were increased significantly by whole-grain rye intake only in men. This is the first report to show that alkylresorcinols in human plasma are mainly transported in lipoproteins. The plasma alkylresorcinol C17:0 to C21:0 ratio reflects intake of whole-grain wheat and rye, and the plasma total alkylresorcinol concentration appears to be a useful biomarker of whole-grain cereal intake.


   Introduction
TOP
 ABSTRACT
 Introduction
Subjects and Methods
 Results
 Discussion
 LITERATURE CITED
 
Increasing attention has been paid to the role of human nutrition in health promotion and the prevention of chronic diseases, such as certain cancers, type II diabetes, and cardiovascular diseases (1,2). Partly due to lack of a reliable biomarker for whole-grain intake, with consequent difficulties in defining dietary intake, the disease preventing mechanism of whole-grains in humans remains to be clarified (3,4).

Alkylresorcinols (AR)6 are phenolic lipids with an odd-numbered alkyl chain attached to position 5 of the 1,3-dihydroxybenzene ring. They are abundant in the outer layers of rye and wheat grains and are absent in highly refined white flour and in other foods used for human nutrition (5,6). In grains they exist mainly with alkyl chain lengths C15:0-C25:0 (7). The AR homolog composition is different in rye and wheat grains, and the AR C17:0 to C21:0 ratio has been proposed to indicate the source of grains in foods (8) and, hypothetically, in human blood samples (6). Preliminary data suggests that AR could function as a biomarker for human whole-grain intake (6). AR are absorbed from the small intestine via the lymphatic system (9,10) and are incorporated into human erythrocyte membranes (11). They have also been detected in the adipose tissue of rats (12). In vitro studies suggest that AR affect the properties and functions of biological membranes (13–16). AR seem to be rather weak antioxidants per se (17), but recent studies have shown that AR can inhibit LDL oxidation in vitro (18) and might provide antioxidant protection when present in biological membranes (19).

Whole grains, in particular rye, and other foods, such as berries, certain fruits and vegetables, and seeds, constitute the main sources of plant lignans in the human diet (20–23). The mammalian lignan enterolactone (ENL) is formed as the main end-product from plant lignans by intestinal microflora (24–26). The consumption of rye products has been shown to increase serum ENL concentrations and to correlate positively with these concentrations in men and in some studies in women (27–30), but because ENL is derived from several dietary sources, it does not seem to function as a specific marker of whole-grain intake (31–33).

To our knowledge, this is the first study to determine AR concentrations and their homolog distribution in human plasma, erythrocytes, and lipoproteins in a whole-grain feeding trial. The plasma AR and serum ENL concentrations were compared after the consumption of whole-grain rye and wheat breads and after the consumption of the diet based on refined grains.


   Subjects and Methods
TOP
 ABSTRACT
 Introduction
 Subjects and Methods
Results
 Discussion
 LITERATURE CITED
 
    Subjects and study design. Eight women and 7 men, aged 21–36 y with a BMI of 24.4 ± 0.99 kg/m2 (mean ± SEM), participated in the study. The exclusion criteria were diseases or medications affecting bowel function or plasma lipoproteins, antibiotics taken within 3 mo before the study, serious chronic illnesses, and alcohol abuse. Hemoglobin had to be >125 g/L for women and 135 g/L for men to avoid anemia due to sample taking. The trial was a 2 x 1 wk randomized crossover study with whole-grain wheat and rye crisp breads as the test breads and with 1-wk refined bread periods, baseline (RF I) and washout (RF II), before the test bread weeks. Subjects were instructed to eat 8 pieces (12.5 g per piece of bread, a total of 100 g/d) of whole-grain wheat (wheat diet, WD) or whole-grain rye crisp bread (rye diet, RD) per day. During RF I and RF II subjects consumed soft refined wheat bread. All breads were provided by Vaasan and Vaasan Oy (Table 1). Subjects were allowed to eat 1 additional portion of white refined cereal product daily, such as pasta, but no bread or any other whole-grain products other than the study breads during the follow-up. Otherwise their dietary habits were not changed. Study participants used food diaries to record their daily intake of breads (as pieces per day) and their consumption of cereal products 1 wk before the study and during the whole trial. They were also asked to record their entire habitual diet for 1 d prior to the study. Blood samples were taken after the habitual diet and before the first refined bread week as well as after the refined-bread and whole-grain test periods and 1 wk after the trial. Plasma, erythrocyte, and lipoprotein AR concentrations, and serum ENL concentrations were analyzed in the samples taken after RF I, RF II, wheat diet (WD), and rye diet (RD). In addition, plasma AR and serum ENL concentrations after habitual diets were analyzed before the study and 1 wk after the study. Hemoglobin, blood cells, and lipoprotein fractions were measured in all samples. The Ethics Committee for the Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland, approved the study. All study participants gave permission to publish the results.


View this table:
[in this window]
[in a new window]

  		TABLE 1 Nutrient and alkylresorcinols composition of the whole-grain wheat and rye crisp breads and refined wheat bread1

 
    Blood samples. Spot blood samples after overnight fasting were collected into 10 mL EDTA-containing tubes and serum tubes. Plasma and lipoprotein cholesterol and plasma triacylglycerols were measured by Konelab 60i (Thermo Electron). Hemoglobin, erythrocyte mean corpuscular volume, and blood cells were measured from whole blood in EDTA-tubes by Sysmex KX-21 (TOA Medical Electronics). Blood samples were centrifuged at 3500 x g for 10 min at 10°C and plasma and serum were separated and stored at –20°C until analysis.

    Isolation of lipoproteins. Lipoproteins [VLDL (density 1.006 kg/L), LDL (1.019–1.063 kg/L), and total HDL (1.063–1.21 kg/L)] were isolated from 3 mL of plasma by sequential ultracentrifugation as previously described (34,35). Lipoprotein fractions (sample volume 2 mL) were purified, and unbound AR and other small-molecular weight compounds, including EDTA, that protected the samples from oxidation prior to analysis, were removed by size exclusion gel filtration on Sephadex G-25 (Pharmacia Biotech; column dimensions 1 x 20 cm). PBS (pH 7.4) was used as eluting solvent (36). Samples were stored at –80°C until further analysis.

    Analysis of alkylresorcinols and enterolactone. Bread AR were analyzed in triplicate using a gas chromatographic method for cereal products (5). Plasma AR were analyzed by GC-MS as previously reported (37). AR in VLDL, LDL, and HDL fractions were analyzed using the plasma method and modified by extracting 4 times with 4 mL diethyl ether for better analyte recovery. After the 4th extraction, only traces of AR were detectable in the remaining solution, which suggests that the extraction was adequate. Erythrocyte alkylresorcinols were analyzed with a modified method for the analysis of vitamin E (11,38,39). In short, erythrocytes were separated from plasma by centrifugation (3500 x g for 10 min) and washed 3 times with 0.9% NaCl solution. Following the removal of the washing solution, 1 mL of cells was pipetted and combined with 1 mL of 2 mmol/L EDTA. The cells were stored at –80°C until analysis. Prior to analysis, an internal standard AR C20:0 that does not exist naturally in grains (kindly provided by Prof. K. Wähälä, Department of Chemistry, University of Helsinki, Finland) was added and proteins were denaturated by adding 5 mL of methanol and shaking for 2 min. AR were extracted 3 times with 7 mL of n-heptane. The combined organic phase was completely evaporated, and the samples were purified with anion exchange chromatography DEAE-Sephadex A-25 (Pharmacia Biotech AB; column dimensions 0.5 x 1.5 cm) in a free base form and analyzed by the GC-MS (Fisons Instruments) as described earlier (37). All plasma and erythrocyte samples were analyzed in duplicate, but lipoprotein samples were analyzed once due to scarcity of the sample material. A control sample and a blank were included in all assays. Interseries CV was 12% for the plasma method, 11% for erythrocytes, and 20% for lipoproteins. The results are expressed as the total amount of AR homologs (AR C17:0–C25:0), unless otherwise stated.

Serum ENL concentrations were measured by a time-resolved fluoroimmunoassay with AutoDELFIA 1235 Automatic Immunoassay System (Wallac Oy) (40,41). Control samples with 3 different concentrations and a blank were included in every batch. Interseries CV was <10%.

    Statistical analysis. Normality of the data were tested with Shapiro-Wilk's test. Spearman's rho was used to test associations between AR and bread intake and plasma, erythrocyte, and lipoprotein AR concentrations, and to test associations between plasma, erythrocyte, and lipoprotein AR concentrations after different diets. Differences in AR and ENL concentrations after the test periods and between women and men, and AR homolog distribution as well as AR C17:0 to C21:0 ratio between the diets were tested with Friedman's test followed by Wilcoxon's signed rank test. We performed all statistical analyses with SPSS 11.0.1. Differences were considered significant at the 95% CI (P < 0.05). The results are expressed as means ± SEM.


   Results
TOP
 ABSTRACT
 Introduction
 Subjects and Methods
 Results
Discussion
 LITERATURE CITED
 
Plasma, erythrocyte, and lipoprotein AR concentrations did not differ between women (n = 8) and men (n = 7) so their data were combined (n = 15). Serum ENL concentrations differed between women and men and were analyzed separately. The sequence of the feeding periods did not affect either variable so the and the data from the 2 RD periods and those from the WD periods were combined.

Dietary compliance throughout the study was good. Bread consumption was 95.5 ± 2.1 g/d (7.6 ± 0.17 pieces/d) during WD and 97.5 ± 0.97 g/d (7.8 ± 0.08 pieces/d) during RD of the recommended 100 g/d (8 pieces/d), and no intake of additional breads was recorded. Calculated intake of AR was 29.4 ± 0.65 mg/d (75.0 ± 1.6 µmol/d) during WD and 67.3 ± 0.67 mg/d (174.6 ± 1.7 µmol/d) during RD. RF diets did not contain AR.

When subjects consumed their habitual diet before the study, the plasma AR concentration was 127 ± 33.9 nmol/L (range 7.5–434 nmol/L). Refined bread periods effectively decreased AR concentrations in plasma, erythrocytes, and lipoproteins. AR concentrations significantly rose in all studied matrices after both WD and RD and were significantly higher after RD compared with WD (Table 2). One week after the study, the plasma AR concentration was 74.6 ± 17.3 nmol/L (11.5–263 nmol/L). Although individual intakes of the breads or AR did not correlate with the AR concentrations in plasma, erythrocytes, or lipoproteins, the plasma AR concentration was greater when the subjects consumed more AR; concentrations were higher after the RD period than after the WD period and both were greater than after the RF periods. To eliminate variations in AR carriers, plasma AR also are expressed relative to plasma cholesterol and triacylglycerol concentrations (Table 2).


View this table:
[in this window]
[in a new window]

  		TABLE 2 Circulating lipids and AR in subjects after WD, RD, RFl, and RFII periods1

 
The AR C17:0 to C21:0 ratio was 0.12 ± 0.002 in whole-grain wheat crisp bread and 1.02 ± 0.01 in whole-grain rye crisp bread. The AR homolog pattern in plasma, erythrocytes, and lipoproteins differed significantly between the WD and RD periods (Fig. 1). After WD and RD, the AR C17:0 to C21:0 ratios in plasma were 0.10 ± 0.01 and 0.60 ± 0.06, respectively, and in erythrocytes 0.06 ± 0.01 and 0.33 ± 0.03, respectively (Fig. 1). These ratios differed after the subjects consumed WD and RD compared with RF I (0.05 ± 0.03) and RF II (0.01 ± 0.01) (P < 0.05). The corresponding ratios in plasma were 0.28 ± 0.05 and 0.52 ± 0.09 after subjects consumed their habitual diets before and 1 wk after the trial, respectively. The ratio of total AR in plasma (nmol/L) to that in erythrocytes (nmol/L packed cells) was 0.53 ± 0.1 after WD and 0.71 ± 0.1 after RD. Erythrocyte mean corpuscular volume and hemoglobin did not change during the study.


Figure 1
View larger version (31K):
[in this window]
[in a new window]

  		FIGURE 1  AR homolog (C17:0–C25:0) composition of plasma, erythrocytes, and lipoproteins, and in the test bread after subjects consumed the WD (A) and RD (B) for 1 wk. Values are means ± SEM, n = 15 except diet, n = 3. *Different from RD, P < 0.05.

 
AR concentrations measured in the combined lipoprotein fractions were 69 ± 2.5% after WD and 72 ± 3.9% after RD of the corresponding plasma total AR concentrations (Table 2). Plasma AR (nmol/L) and total lipoprotein AR (nmol/L of plasma) were correlated after RD (r2 = 0.839, P < 0.05) and after WD (r2 = 0.939, P < 0.05). The AR contents of lipoprotein classes did not differ between women and men. VLDL contained 46 ± 2.1%; LDL, 20 ± 1.3%; and HDL, 33 ± 1.5% of the lipoprotein AR (Table 2). Lipoprotein-deficient plasma after ultracentrifugation did not contain detectable amounts of AR. Lipoprotein concentrations did not change during the study (Table 2).

Plasma (nmol/L) and erythrocyte (nmol/L packed cells) AR concentrations were correlated after the RD period (r2 = 0.854, P < 0.05) and tended to be correlated after the WD period (r2 = 0.421 P = 0.12), but the correlations were stronger when plasma AR were expressed relative to plasma cholesterol and triacylglycerols (r2 = 0.925, P < 0.05 after RD and r2 = 0.668, P < 0.05 after WD).

Serum ENL concentrations were affected by the intake of RD only in men (Table 3). Serum ENL concentrations after the habitual diet periods were 21.7 ± 4.4 and 19.5 ± 2.7 nmol/L in women and 10.5 ± 2.2 and 11.9 ± 2.3 nmol/L in men. Serum ENL concentrations in men were lower than in women throughout the study, but the differences were significant only during the RF periods. Bread intake did not correlate with serum ENL concentrations. There were 2 men whose ENL concentrations did not increase and 1 female whose ENL concentration decreased after intake of RD, whereas no intake of antibiotics was recorded. Serum ENL and plasma AR concentrations were not correlated.


View this table:
[in this window]
[in a new window]

  		TABLE 3 Serum enterolactone (ENL) concentrations in subjects after WD, RD, RFl, and RFII periods1

 

   Discussion
TOP
 ABSTRACT
 Introduction
 Subjects and Methods
 Results
 Discussion
LITERATURE CITED
 
To our knowledge, this is the first study to show that AR are carried by human lipoprotein particles in the circulation. Also, the increased concentrations were increased by the intake of whole-grain products, and more so with whole-grain rye than with whole-grain wheat.

In a previous study we found a significant correlation between an 8-wk intake of whole-grain rye bread and plasma AR concentrations (42). In the present study, after 1 wk of whole-grain consumption, plasma AR concentrations (n = 15) increased significantly with intake of whole-grain wheat crisp and whole-grain rye crisp bread (Table 2). However, AR concentrations did not correlate with individual bread intake, which can be explained by the study's shorter intervention period. AR concentrations were 50–100% higher after whole-grain rye intake than after the habitual diet, which agrees with our previous study (42). AR plasma concentrations were significantly higher after consumption of the habitual diet both before and after the feeding study than after the baseline (RF I) or washout (RF II) periods (P < 0.05), which indicates the habitual intake of whole-grain breads and agrees with dietary food records. AR in plasma, erythrocytes, and in lipoproteins after the AR-free RF I and RF II periods can perhaps be explained by their storage in tissues and their liberation during minimal AR intake. Erythrocyte AR may function as long-term biomarkers of whole-grain intake insofar as AR appear to be retained in erythrocyte membranes during low whole-grain intake. High extracellullar AR concentrations have caused haemolysis in vitro (13,14). Erythrocyte cell size remained the same throughout the present study, indicating that AR incorporation into the cells did not cause swelling or shrinkage of the cells in vivo. In this study, erythrocyte AR concentrations immediately after whole-grain intake were not analyzed, and therefore we cannot draw any conclusions about the possible effects of extreme AR concentrations in vivo on erythrocyte cell size. Human plasma AR concentrations up to 3365 nmol/L have been reached after intake of rye bran (43).

AR homolog composition differed after WD and RD in all measured samples. The plasma AR C17:0 to C21:0 ratio seemed to best distinguish between the 2 test breads. The ratio was significantly higher after RD, compared with WD, although it was lower after 1 wk of RD (0.60) in the present study compared with 8 wk of whole-grain rye bread intake in our previous study (0.84) (42). There are data of increasing relative bioavailability with increasing AR chain length, which may affect homolog distribution in the body (43). A high variation of AR concentrations between subjects after intake of the same amounts of AR was probably caused by individual differences in metabolism or absorption from the intestine. The amount of fiber in the test breads might also affect the absorption. The amount of fat consumed, which was not monitored in the present study, is another possible factor affecting AR absorption.

We found quantifiable amounts of AR in all major lipoprotein fractions. The amount of AR measured in the combined lipoprotein fractions constituted 70–80% of that measured in total plasma. Taking into account the procedural losses during quantitative measurement, this indicates that AR are almost exclusively transported in lipoproteins in plasma. Plasma AR concentrations can be expressed in relation to cholesterol and triacylglycerol concentrations, as recommended for tocopherols (44–46), to adjust for variations in the concentrations of carrier lipoproteins. Although LDL is the main cholesterol carrier in human subjects, VLDL, followed by HDL, are the main carriers of AR. The samples in the present study were taken after an overnight fast, which can affect the AR distribution in the lipoproteins. AR are probably absorbed and transported in chylomicrons via the lymphatic system to the circulation and to the liver and thereafter incorporated into VLDL or into HDL in a similar way as tocopherols. Tocopherols have a similar structure and log P (octanol-water partition coefficient) to alkylresorcinols (45,47). HDL could also receive AR directly from chylomicrons and VLDL during lipolysis, which could partly explain higher AR concentrations compared with LDL.

Intake of whole-grain cereals, especially rye, has been linked to increased serum ENL concentrations, although no consistent correlation with intake has been reported (27,28,48). In this study, serum ENL concentrations increased significantly during 1 wk of whole-grain rye intake in men but not in women. In some study participants, serum ENL concentrations did not increase at all, although increased AR concentrations indicated dietary compliance. This is likely due to inefficient conversion of plant lignans to enterolactone by intestinal microflora. Minimal changes in serum ENL concentrations during plant lignan intake have also been seen in previous studies (31). Our results indicate that women may consume more plant lignans derived from other sources than whole-grain bread, resulting in greater ENL production. Accordingly, ENL is not a useful biomarker of whole-grain intake, although it may reflect a healthy diet with high intake of lignan-rich foods, or an effective individual gut microflora activity, as previously suggested (27,31–33).

In conclusion, the plasma AR C17:0 to C21:0 ratio reflects the relative contents of whole-grain wheat and rye in the diet; high values, 0.60 in this study, indicating a predominance of rye. The plasma total AR concentration and the homolog C17:0 to C21:0 ratio could be used as specific dietary biomarkers to determine the amount and the type of whole-grain product intake, although there appears to be a large amount of interindividual variation. Expressing plasma AR relative to plasma cholesterol and triacylglycerols might provide a more accurate estimate of the individual AR status by eliminating the effects in variation of carrier lipoprotein concentrations. To our knowledge, this is the first study to show that AR are transported in human lipoproteins in vivo.


   ACKNOWLEDGMENTS
 
We thank Anja Koskela, Adile Samaletdin, Inga Wiik, and Terhi Hakala for excellent technical assistance.


   FOOTNOTES
 
1 Supported by Ida Montin Foundation, Maud Kuistila Memorial Foundation, and Finska Läkaresällskapet and Sigrid Jusélius Foundation. Vaasan and Vaasan Oy of Finland provided the test breads used in the study. Back

2 Author disclosures: A.-M. Linko-Parvinen, no conflicts of interest; R. Landberg, no conflicts of interest; M. J. Tikkanen, no conflicts of interest; H. Aldercreutz, no conflicts of interest; and José L. Peñalvo, no conflicts of interest. Back

6 Abbreviations used: AR, alkylresorcinol(s); ENL, enterolactone; RD, whole-grain rye bread diet; RF, refined bread diet; WD, whole-grain wheat bread diet. Back

Manuscript received 15 November 2006. Initial review completed 20 December 2006. Revision accepted 5 February 2007.


   LITERATURE CITED
TOP
 ABSTRACT
 Introduction
 Subjects and Methods
 Results
 Discussion
 LITERATURE CITED
 

1. Slavin J. Whole grains and human health. Nutr Res Rev. 2004;17:99–110.

2. Marquart L, Wiemer KL, Jones JM, Jacob B. Whole grains health claims in the USA and other efforts to increase whole-grain consumption. Proc Nutr Soc. 2003;62:151–60.[Medline]

3. Kantor LS, Variyam JN, Allshouse JE, Putnam JJ, Lin B-H. Choose a variety of grains daily, especially whole grains: a challenge for consumers. J Nutr. 2001;131:473S–86S.[Abstract/Free Full Text]

4. Lang R, Jebb SA. Who consumes whole grains, and how much? Proc Nutr Soc. 2003;62:123–7.[Medline]

5. Ross AB, Shepherd MJ, Schüpphaus M, Sinclair V, Alfaro B, Kamal-Eldin A, Åman P. Alkylresorcinols in cereals and cereal products. J Agric Food Chem. 2003;51:4111–8.[Medline]

6. Ross AB, Kamal-Eldin A, Åman P. Dietary alkylresorcinols: absorption, bioactivities, and possible use as biomarkers of whole-grain wheat- and rye-rich foods. Nutr Rev. 2004;62:81–95.[Medline]

7. 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 Agric. 2001;81:1405–11.

8. 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;52:8242–6.[Medline]

9. Linko A-M, Ross AB, Kamal-Eldin A, Serena A, Bjørnbak Kjaer AK, Jørgensen H, Peñalvo JL, Adlercreutz H, Åman P, Bach Knudsen KE. Kinetics of the appearance of cereal alkylresorcinols in pig plasma. Br J Nutr. 2006;95:282–7.[Medline]

10. Ross AB, Kamal-Eldin A, Lundin EA, Zhang JX, Hallmans G, Åman P. Cereal alkylresorcinols are absorbed by humans. J Nutr. 2003;133:2222–4.[Abstract/Free Full Text]

11. Linko A-M, Adlercreutz H. Whole grain rye and wheat alkylresorcinols are incorporated into human erythrocyte membranes. Br J Nutr. 2005;93:11–3.[Medline]

12. Ross AB, Chen Y, Frank J, Swanson JE, Parker RS, Kozubek A, Lundh T, Vessby B, Åman P, Kamal-Eldin A. Cereal alkylresorcinols elevate {gamma}-tocopherol levels in rats and inhibit {gamma}-tocopherol metabolism in vitro. J Nutr. 2004;134:506–10.[Abstract/Free Full Text]

13. Kozubek A. The effect of 5-(n-alk(en)yl)resorcinols on membranes. I. Characterization of the permeability increase induced by 5-(n-heptadecenyl)resorcinol. Acta Biochim Pol. 1987;34:357–67.[Medline]

14. Kozubek A. The effect of 5-(n-alk(en)yl)resorcinols on membranes. II. Dependence of the aliphatic chain length and unsaturation. Acta Biochim Pol. 1987;34:387–94.[Medline]

15. Kozubek A, Nietubyc M, Sikorski AF. Modulation of the activities of membrane enzymes by cereal grain resorcinolic lipids. Z Naturforsch Sect C J Biosci. 1992;47:41–6.

16. Kozubek A, Tyman JHP. Resorcinolic lipids, the natural non-isoprenoid phenolic amphiphiles and their biological activity. Chem Rev. 1999;99:1–25.[Medline]

17. Kamal-Eldin A, Pouru A, Eliasson C, Åman P. Alkylresorcinols as antioxidants: hydrogen donation and peroxyl radical-scavenging effects. J Sci Food Agric. 2001;81:353–6.

18. Parikka K, Rowland IR, Welch RW, Wähälä K. In Vitro Antioxidant Activity and Antigenotoxicity of 5-n-Alkylresorcinols. J Agric Food Chem. 2006;54:1646–50.[Medline]

19. Kozubek A, Nienartowich B. Cereal grain resorcinolic lipids inhibit H2O2-induced peroxidation of biological membranes. Acta Biochim Pol. 1995;42:309–15.[Medline]

20. Mazur W, Adlercreutz H. Naturally occurring oestrogens in food. Pure Appl Chem. 1998;70:1759–76.

21. Nilsson M, Åman P, Härkönen H, Hallmans G, Bach Knudsen KE, Mazur W, Adlercreutz H. Content of nutrients and lignans in roller milled fractions of rye. J Sci Food Agric. 1997;73:143–8.

22. Heinonen S, Nurmi T, Liukkonen K, Poutanen K, Wähälä K, Deyama T, Nishibe S, Adlercreutz H. In vitro metabolism of plant lignans: new precursors of mammalian lignans enterolactone and enterodiol. J Agric Food Chem. 2001;49:3178–86.[Medline]

23. Peñalvo JL, Heinonen S-M, Aura A-M, Adlercreutz H. Dietary sesamin is converted to enterolactone in humans. J Nutr. 2005;135:1056–62.[Abstract/Free Full Text]

24. Setchell KDR, Lawson AM, Mitchell FL, Adlercreutz H, Kirk DN, Axelson M. Lignans in man and in animal species. Nature. 1980;288:740–2.[Medline]

25. Setchell KDR, Lawson AM, Borriello SP, Harkness R, Gordon H, Morgan DM, Kirk DN, Adlercreutz H, Anderson LC, Axelson M. Lignan formation in man-microbal involvement and possible roles in relation to cancer. Lancet. 1981;2:4–7.[Medline]

26. Borriello SP, Setchell KDR, Axelsson M, Lawson AM. Production and metabolism of lignans by the human faecal flora. J Appl Bacteriol. 1985;58:37–43.[Medline]

27. Kilkkinen A, Valsta LM, Virtamo J, Stumpf K, Adlercreutz H, Pietinen P. Intake of lignans is associated with serum enterolactone concentration in Finnish men and women. J Nutr. 2003;133:1830–3.[Abstract/Free Full Text]

28. Juntunen KS, Mazur W, Liukkonen KH, Uehara M, Poutanen KS, Adlercreutz HCT, Mykkänen HM. Consumption of wholemeal rye bread increases serum concentrations and urinary excretion of enterolactone compared with consumption of white wheat bread in healthy Finnish men and women. Br J Nutr. 2000;84:839–46.[Medline]

29. Jacobs DRJ, Pereira MA, Stumpf K, Pins JJ, Adlercreutz H. Whole grain food intake elevates serum enterolactone. Br J Nutr. 2002;88:111–6.[Medline]

30. Pietinen P, Stumpf K, Männistö S, Kataja V, Uusitupa M, Adlercreutz H. Serum enterolactone and risk of breast cancer: a case-control study in eastern Finland. Cancer Epidemiol Biomarkers Prev. 2001;10:339–44.[Abstract/Free Full Text]

31. Stumpf K, Pietinen P, Puska P, Adlercreutz H. Changes in serum enterolactone, genistein, and daidzein in a dietary intervention study in Finland. Cancer Epidemiol Biomarkers Prev. 2000;9:1369–72.[Abstract/Free Full Text]

32. Horner NK, Kristal AR, Prunty J, Skor HE, Potter JD, Lampe JW. Dietary determinants of plasma enterolactone. Cancer Epidemiol Biomarkers Prev. 2002;11:121–6.[Abstract/Free Full Text]

33. Johnsen NF, Hausner H, Olsen A, Tetens I, Christensen J, Bach Knudsen KE, Overvad K, Tjonneland A. Intake of whole grains and vegetables determines the plasma enterolactone concentration of Danish women. J Nutr. 2004;134:2691–7.[Abstract/Free Full Text]

34. Havel RJ, Eder HA, Bragdon JH. The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest. 1955;34:1345–53.[Medline]

35. Höckerstedt A, Tikkanen MJ, Jauhiainen M. LCAT facilitates transacylation of 17 beta-estradiol in the presence of HDL3 subfraction. J Lipid Res. 2002;43:392–7.[Abstract/Free Full Text]

36. Helisten H, Höckerstedt A, Wähälä K, Tiitinen A, Adlercreutz H, Jauhiainen M, Tikkanen MJ. Accumulation of high-density lipoprotein-derived estradiol-17beta fatty acid esters in low-density lipoprotein particles. J Clin Endocrinol Metab. 2001;86:1294–300.[Abstract/Free Full Text]

37. 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;308:307–13.[Medline]

38. Bieri JG, Tolliver TJ, Caliguani BS. Simultaneous determination of {alpha}-tocopherol and retinol in plasma and red cells by high performance liquid chromatography. Am J Clin Nutr. 1979;32:2143–9.[Abstract/Free Full Text]

39. Simon E, Gariepy J, Cogn 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.[Medline]

40. Adlercreutz H, Wang GJ, Lapcik O, Hampl R, Wähälä K, Mäkelä T, Lusa K, Talme M, Mikola H. Time-resolved fluoroimmunoassay for plasma enterolactone. Anal Biochem. 1998;265:208–15.[Medline]

41. Stumpf K, Uehara M, Nurmi T, Adlercreutz H. Changes in the time-resolved fluoroimmunoassay of plasma enterolactone. Anal Biochem. 2000;284:153–7.[Medline]

42. 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;135:580–3.[Abstract/Free Full Text]

43. Landberg R, Linko-Parvinen A-M, Kamal-Eldin A, Vessby B, Adlercreutz H, Åman P. Human plasma kinetics and relative bioavailability of alkylresorcinols after intake of rye bran. J Nutr. 2006;136:2760–5.[Abstract/Free Full Text]

44. Behrens WA, Thompson JN, Madère R. Distribution of {alpha}-tocopherol in human plasma lipoproteins. Am J Clin Nutr. 1982;35:691–6.[Abstract/Free Full Text]

45. Bjørneboe A, Bjørneboe GE, Drevon CA. Absorption, transport and distribution of vitamin E. J Nutr. 1990;120:233–42.[Abstract/Free Full Text]

46. Horwitt MK, Harvey CC, Dahm CHJ, Searcy MT. Relationship between tocopherol and serum lipid levels for determination of nutritional adequacy. Ann N Y Acad Sci. 1972;203:223–36.[Medline]

47. Frank J. Beyond vitamin E supplementation: an alternative strategy to improve vitamin E status. J Plant Physiol. 2005;162:834–43.[Medline]

48. Kilkkinen A, Stumpf K, Pietinen P, Valsta LM, Tapanainen H, Adlercreutz H. Determinants of serum enterolactone concentration. Am J Clin Nutr. 2001;73:1094–100.[Abstract/Free Full Text]




This article has been cited by other articles:


Home page
 Am. J. Clin. Nutr.Home page
R. M van Dam and F. B Hu
Are alkylresorcinols accurate biomarkers for whole grain intake?
Am. J. Clinical Nutrition, April 1, 2008; 87(4): 797 - 798.
[Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
R. Landberg, A. Kamal-Eldin, A. Andersson, B. Vessby, and P. Aman
Alkylresorcinols as biomarkers of whole-grain wheat and rye intake: plasma concentration and intake estimated from dietary records
Am. J. Clinical Nutrition, April 1, 2008; 87(4): 832 - 838.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Linko-Parvinen, A.-M.
Right arrow Articles by Peñalvo, J. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Linko-Parvinen, A.-M.
Right arrow Articles by Peñalvo, J. L.

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]