Skip to main content
Erschienen in: European Journal of Nutrition 3/2013

01.04.2013 | Original Contribution

Fate of dietary phytosteryl/-stanyl esters: analysis of individual intact esters in human feces

verfasst von: Tim Lubinus, Andreas Barnsteiner, Thomas Skurk, Hans Hauner, Karl-Heinz Engel

Erschienen in: European Journal of Nutrition | Ausgabe 3/2013

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The objective was to investigate the metabolic fate of phytosteryl/-stanyl fatty acid and ferulic acid esters upon consumption by healthy humans.

Methods

A capillary gas chromatographic methodology was employed to follow a randomized, single-blind three group crossover clinical trial and to quantify simultaneously individual intact esters, liberated phytosterols/-stanols and their metabolites in feces. Skimmed milk drinking yogurts enriched with complex mixtures of phytosteryl/-stanyl fatty acid esters and ferulates, respectively, were employed as food carriers.

Results

On average, 73 % of total plant stanyl fatty acid esters and 80 % of total plant steryl fatty acid esters were hydrolyzed. Among the individuals, the hydrolysis rates ranged from 40 to 96 %. In addition, there were subject-dependent discrepancies between the amounts of phytosterols/-stanols actually determined in the feces and the calculated hydrolysis rates. On average, 69 % of the amounts of sterols/stanols expected from the amounts of remaining intact esters were found.

Conclusions

The study revealed large interindividual variability regarding the recoveries of dietary phytosteryl/-stanyl esters upon gastrointestinal passage in healthy humans. Nevertheless, there was a significant impact of the acid moiety (oleate = linoleate = linolenate > eicosanoate > palmitate > ferulate) on the hydrolysis rates; the influence of the phytosterol/-stanol moiety was less pronounced.
Literatur
1.
Zurück zum Zitat AbumWeis SS, Barake R, Jones PJH (2008) Plant sterols/stanols as cholesterol lowering agents: a meta-analysis of randomized controlled trials. Food Nutr Res 52. doi:10.3402/fnr.v52i0.1811 AbumWeis SS, Barake R, Jones PJH (2008) Plant sterols/stanols as cholesterol lowering agents: a meta-analysis of randomized controlled trials. Food Nutr Res 52. doi:10.​3402/​fnr.​v52i0.​1811
2.
Zurück zum Zitat Chen JT, Wesley R, Shamburek RD, Pucino F, Csako G (2005) Meta-analysis of natural therapies for hyperlipidemia: plant sterols and stanols versus policosanol. Pharmacotherapy 25:171–183CrossRef Chen JT, Wesley R, Shamburek RD, Pucino F, Csako G (2005) Meta-analysis of natural therapies for hyperlipidemia: plant sterols and stanols versus policosanol. Pharmacotherapy 25:171–183CrossRef
3.
Zurück zum Zitat Demonty I, Ras RT, van der Knaap HCM, Duchateau GSMJE, Meijer L, Zock PL, Geleijnse JM, Trautwein EA (2009) Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake. J Nutr 139:271–284 Demonty I, Ras RT, van der Knaap HCM, Duchateau GSMJE, Meijer L, Zock PL, Geleijnse JM, Trautwein EA (2009) Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake. J Nutr 139:271–284
4.
Zurück zum Zitat Katan MB, Grundy SM, Jones P, Law M, Miettinen TA, Paoletti R (2003) Effiacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc 78:965–978 Katan MB, Grundy SM, Jones P, Law M, Miettinen TA, Paoletti R (2003) Effiacy and safety of plant stanols and sterols in the management of blood cholesterol levels. Mayo Clin Proc 78:965–978
5.
Zurück zum Zitat Law M (2000) Plant sterol and stanol margarines and health. BMJ 320:861–864CrossRef Law M (2000) Plant sterol and stanol margarines and health. BMJ 320:861–864CrossRef
6.
Zurück zum Zitat Talati R, Sobieraj DM, Makanji SS, Phung OJ, Coleman CI (2010) The comparative efficacy of plant sterols and stanols on serum lipids: a systematic review and meta-analysis. J Am Diet Assoc 110:719–726CrossRef Talati R, Sobieraj DM, Makanji SS, Phung OJ, Coleman CI (2010) The comparative efficacy of plant sterols and stanols on serum lipids: a systematic review and meta-analysis. J Am Diet Assoc 110:719–726CrossRef
7.
Zurück zum Zitat Rong N, Ausman LM, Nicolosi RJ (1997) Oryzanol decreases cholesterol absorption and aortic fatty streaks in hamsters. Lipids 32:303–309CrossRef Rong N, Ausman LM, Nicolosi RJ (1997) Oryzanol decreases cholesterol absorption and aortic fatty streaks in hamsters. Lipids 32:303–309CrossRef
8.
Zurück zum Zitat Wilson TA, Nicolosi RJ, Woolfrey B, Kritchevsky D (2007) Rice bran oil and oryzanol reduce plasma lipid and lipoprotein cholesterol concentrations and aortic cholesterol ester accumulation to a greater extent than ferulic acid in hypercholesterolemic hamsters. J Nutr Biochem 18:105–112CrossRef Wilson TA, Nicolosi RJ, Woolfrey B, Kritchevsky D (2007) Rice bran oil and oryzanol reduce plasma lipid and lipoprotein cholesterol concentrations and aortic cholesterol ester accumulation to a greater extent than ferulic acid in hypercholesterolemic hamsters. J Nutr Biochem 18:105–112CrossRef
9.
Zurück zum Zitat Berger A, Rein D, Schäfer A, Monnard I, Gremaud G, Lambelet P, Bertoli C (2005) Similar cholesterol-lowering properties of rice bran oil, with varied γ-oryzanol, in mildly hypercholesterolemic men. Eur J Nutr 44:163–173CrossRef Berger A, Rein D, Schäfer A, Monnard I, Gremaud G, Lambelet P, Bertoli C (2005) Similar cholesterol-lowering properties of rice bran oil, with varied γ-oryzanol, in mildly hypercholesterolemic men. Eur J Nutr 44:163–173CrossRef
10.
Zurück zum Zitat Yoshino G, Kazumi T, Amano M, Tateiwa M, Yamasaki T, Takashima S, Iwai M, Hatanaka H, Baba S (1989) Effects of gamma-oryzanol on hyperlipidemic subjects. Curr Therap Res 45:543–552 Yoshino G, Kazumi T, Amano M, Tateiwa M, Yamasaki T, Takashima S, Iwai M, Hatanaka H, Baba S (1989) Effects of gamma-oryzanol on hyperlipidemic subjects. Curr Therap Res 45:543–552
11.
Zurück zum Zitat EFSA (2008) Consumption of food and beverages with added plant sterols in the European Union. EFSA J 133:1–21 EFSA (2008) Consumption of food and beverages with added plant sterols in the European Union. EFSA J 133:1–21
12.
Zurück zum Zitat Carr TP, Ash MM, Brown AW (2010) Cholesterol-lowering phytosterols: factors affecting their use and efficacy. Nutr Dietary Suppl 2:59–72CrossRef Carr TP, Ash MM, Brown AW (2010) Cholesterol-lowering phytosterols: factors affecting their use and efficacy. Nutr Dietary Suppl 2:59–72CrossRef
13.
Zurück zum Zitat Calpe-Berdiel L, Escolà-Gil JC, Blanco-Vaca F (2009) New insights into the molecular actions of plant sterols and stanols in cholesterol metabolism. Atherosclerosis 203:18–31CrossRef Calpe-Berdiel L, Escolà-Gil JC, Blanco-Vaca F (2009) New insights into the molecular actions of plant sterols and stanols in cholesterol metabolism. Atherosclerosis 203:18–31CrossRef
14.
Zurück zum Zitat Brufau G, Canela MA, Rafecas M (2008) Phytosterols: physiologic and metabolic aspects related to cholesterol-lowering properties. Nutr Res 28:217–225CrossRef Brufau G, Canela MA, Rafecas M (2008) Phytosterols: physiologic and metabolic aspects related to cholesterol-lowering properties. Nutr Res 28:217–225CrossRef
15.
Zurück zum Zitat Brown A, Hang J, Dussault P, Carr T (2010) Phytosterol ester constituents affect micellar cholesterol solubility in model bile. Lipids 45:855–862CrossRef Brown A, Hang J, Dussault P, Carr T (2010) Phytosterol ester constituents affect micellar cholesterol solubility in model bile. Lipids 45:855–862CrossRef
16.
Zurück zum Zitat Jesch ED, Carr TP (2006) Sitosterol reduces micellar cholesterol solubility in model bile. Nutr Res 26:579–584CrossRef Jesch ED, Carr TP (2006) Sitosterol reduces micellar cholesterol solubility in model bile. Nutr Res 26:579–584CrossRef
17.
Zurück zum Zitat Mel’nikov SM, Seijen ten Hoorn JWM, Eijkelenboom APAM (2004) Effect of phytosterols and phytostanols on the solubilization of cholesterol by dietary mixed micelles: an in vitro study. Chem Phys Lipids 127:121–141CrossRef Mel’nikov SM, Seijen ten Hoorn JWM, Eijkelenboom APAM (2004) Effect of phytosterols and phytostanols on the solubilization of cholesterol by dietary mixed micelles: an in vitro study. Chem Phys Lipids 127:121–141CrossRef
18.
Zurück zum Zitat Brown AW, Hang J, Dussault PH, Carr TP (2010) Plant sterol and stanol substrate specificity of pancreatic cholesterol esterase. J Nutr Biochem 21:736–740CrossRef Brown AW, Hang J, Dussault PH, Carr TP (2010) Plant sterol and stanol substrate specificity of pancreatic cholesterol esterase. J Nutr Biochem 21:736–740CrossRef
19.
Zurück zum Zitat Ash MM, Hang J, Dussault PH, Carr TP (2011) Phytosterol stearate esters elicit similar responses on plasma lipids and cholesterol absorption but different responses on fecal neutral sterol excretion and hepatic free cholesterol in male Syrian hamsters. Nutr Res 31:537–543CrossRef Ash MM, Hang J, Dussault PH, Carr TP (2011) Phytosterol stearate esters elicit similar responses on plasma lipids and cholesterol absorption but different responses on fecal neutral sterol excretion and hepatic free cholesterol in male Syrian hamsters. Nutr Res 31:537–543CrossRef
20.
Zurück zum Zitat Kobayashi M, Hamada T, Goto H, Imaizumi K, Ikeda I (2008) Comparison of effects of dietary unesterified and esterified plant sterols on cholesterol absorption in rats. J Nutr Sci Vitaminol 54:210–214CrossRef Kobayashi M, Hamada T, Goto H, Imaizumi K, Ikeda I (2008) Comparison of effects of dietary unesterified and esterified plant sterols on cholesterol absorption in rats. J Nutr Sci Vitaminol 54:210–214CrossRef
21.
Zurück zum Zitat Nyström L, Moreau RM, Lampi A-M, Hicks KB, Pironen V (2008) Enzymatic hydrolysis of steryl ferulates and steryl glycosides. Eur Food Res Technol 227:727–733CrossRef Nyström L, Moreau RM, Lampi A-M, Hicks KB, Pironen V (2008) Enzymatic hydrolysis of steryl ferulates and steryl glycosides. Eur Food Res Technol 227:727–733CrossRef
22.
Zurück zum Zitat Miller A, Majauskaite L, Engel K-H (2004) Enzyme-catalyzed hydrolysis of γ-oryzanol. Eur Food Res Technol 218:349–354CrossRef Miller A, Majauskaite L, Engel K-H (2004) Enzyme-catalyzed hydrolysis of γ-oryzanol. Eur Food Res Technol 218:349–354CrossRef
23.
Zurück zum Zitat Moreau RM, Hicks KB (2004) The in vitro hydrolysis of phytosterol conjugates in food matrices by mammalian enzymes. Lipids 39:769–776 Moreau RM, Hicks KB (2004) The in vitro hydrolysis of phytosterol conjugates in food matrices by mammalian enzymes. Lipids 39:769–776
24.
Zurück zum Zitat Miettinen TA, Gylling H (1999) Serum cholesterol lowering properties pf plant sterol. In: Sandberg A-S, Andersson H, Amado R, Schlemmer U, Serra F (eds) COST 916:2nd workshop 1999: bioactive inositol phopsphates and phytosterols in foods. Office for Official Publications of the European Communities, Luxemburg, pp 85–91 Miettinen TA, Gylling H (1999) Serum cholesterol lowering properties pf plant sterol. In: Sandberg A-S, Andersson H, Amado R, Schlemmer U, Serra F (eds) COST 916:2nd workshop 1999: bioactive inositol phopsphates and phytosterols in foods. Office for Official Publications of the European Communities, Luxemburg, pp 85–91
25.
Zurück zum Zitat Nissinen M, Gylling H, Vuoristo M, Miettinen TA (2002) Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion. Am J Physiol Gastrointest Liver Physiol 282:G1009–G1015 Nissinen M, Gylling H, Vuoristo M, Miettinen TA (2002) Micellar distribution of cholesterol and phytosterols after duodenal plant stanol ester infusion. Am J Physiol Gastrointest Liver Physiol 282:G1009–G1015
26.
Zurück zum Zitat Nissinen MJ, Vuoristo M, Gylling H, Miettinen TA (2007) Respective hydrolysis abd esterification of esterified and free plant stanols occur rapidly in human intestine after their duodenal infusion in triacyl- or diacylglycerol. Lipids 42:603–612CrossRef Nissinen MJ, Vuoristo M, Gylling H, Miettinen TA (2007) Respective hydrolysis abd esterification of esterified and free plant stanols occur rapidly in human intestine after their duodenal infusion in triacyl- or diacylglycerol. Lipids 42:603–612CrossRef
27.
Zurück zum Zitat Miettinen TA, Vuoristo M, Nissinen M, Järvinen HJ, Gylling H (2000) Serum, biliary, and fecal cholesterol and plant sterols in colectomized patients before and during consumption of stanol ester margarine. Am J Clin Nutr 71:1095–1102 Miettinen TA, Vuoristo M, Nissinen M, Järvinen HJ, Gylling H (2000) Serum, biliary, and fecal cholesterol and plant sterols in colectomized patients before and during consumption of stanol ester margarine. Am J Clin Nutr 71:1095–1102
28.
Zurück zum Zitat Nissinen MJ, Gylling H, Miettinen TA (2006) Effects of plant stanol esters supplied in a fat free milieu by pastilles on cholesterol metabolism in colectomized human subjects. Nutr Metab Cardiovasc Dis 16:426–435CrossRef Nissinen MJ, Gylling H, Miettinen TA (2006) Effects of plant stanol esters supplied in a fat free milieu by pastilles on cholesterol metabolism in colectomized human subjects. Nutr Metab Cardiovasc Dis 16:426–435CrossRef
29.
Zurück zum Zitat Normén L, Ellegard L, Janssen H-G, Steenbergen H, Trautwein E, Andersson H (2006) Phytosterol and phytostanol esters are effectively hydrolysed in the gut and do not affect fat digestion in ileostomy subjects. Eur J Nutr 45:165–170CrossRef Normén L, Ellegard L, Janssen H-G, Steenbergen H, Trautwein E, Andersson H (2006) Phytosterol and phytostanol esters are effectively hydrolysed in the gut and do not affect fat digestion in ileostomy subjects. Eur J Nutr 45:165–170CrossRef
30.
Zurück zum Zitat Barnsteiner A, Lubinus T, di Gianvito A, Schmid W, Engel K-H (2011) GC-based analysis of plant stanyl fatty acid esters in enriched foods. J Agric Food Chem 59:5204–5214CrossRef Barnsteiner A, Lubinus T, di Gianvito A, Schmid W, Engel K-H (2011) GC-based analysis of plant stanyl fatty acid esters in enriched foods. J Agric Food Chem 59:5204–5214CrossRef
31.
Zurück zum Zitat Yoshida K, Hirose Y, Imai Y, Kondo T (1989) Conformational analysis of cycloartenol, 24-methylenecycloartanol and their derivatives. Agric Biol Chem 53:1901–1912CrossRef Yoshida K, Hirose Y, Imai Y, Kondo T (1989) Conformational analysis of cycloartenol, 24-methylenecycloartanol and their derivatives. Agric Biol Chem 53:1901–1912CrossRef
33.
Zurück zum Zitat Evershed RP, Spooner N, Prescott MC, Goad LJ (1988) Isolation and characterization of intact steryl ferulates from seeds. J Chromatogr 440:23–35CrossRef Evershed RP, Spooner N, Prescott MC, Goad LJ (1988) Isolation and characterization of intact steryl ferulates from seeds. J Chromatogr 440:23–35CrossRef
34.
Zurück zum Zitat Lusby WR, Thompson MJ, Kochansky J (1984) Analysis of sterol esters by capillary gas chromatography-electron impact and chemical ionization-mass spectrometry. Lipids 19:888–901CrossRef Lusby WR, Thompson MJ, Kochansky J (1984) Analysis of sterol esters by capillary gas chromatography-electron impact and chemical ionization-mass spectrometry. Lipids 19:888–901CrossRef
35.
Zurück zum Zitat Evershed RP, Prescott MC, Spooner N, Goad LJ (1989) Negative ion ammonia chemical ionization and electron impact ionization mass spectrometric analysis of steryl fatty acyl esters. Steroids 53:285–309CrossRef Evershed RP, Prescott MC, Spooner N, Goad LJ (1989) Negative ion ammonia chemical ionization and electron impact ionization mass spectrometric analysis of steryl fatty acyl esters. Steroids 53:285–309CrossRef
36.
Zurück zum Zitat Dyas L, Prescott MC, Evershed RP, Goad LJ (1991) Steryl esters in a cell suspension culture of celery (Apium graveolens). Lipids 26:536–541CrossRef Dyas L, Prescott MC, Evershed RP, Goad LJ (1991) Steryl esters in a cell suspension culture of celery (Apium graveolens). Lipids 26:536–541CrossRef
37.
Zurück zum Zitat Miller LAD, Gordon MH (1996) Use of lipolysis in the isolation of sterol esters. Food Chem 56:55–59CrossRef Miller LAD, Gordon MH (1996) Use of lipolysis in the isolation of sterol esters. Food Chem 56:55–59CrossRef
38.
Zurück zum Zitat Keller S, Jahreis G (2004) Determination of underivatised sterols and bile acid trimethyl silyl ether methyl esters by gas chromatography–mass spectrometry—single ion monitoring in faeces. J Chromatogr B 813:199–207CrossRef Keller S, Jahreis G (2004) Determination of underivatised sterols and bile acid trimethyl silyl ether methyl esters by gas chromatography–mass spectrometry—single ion monitoring in faeces. J Chromatogr B 813:199–207CrossRef
39.
Zurück zum Zitat Lütjohann D, Brzezinka A, Barth E, Abramowski D, Staufenbiel M, von Bergmann K, Beyreuther K, Multhaup G, Bayer TA (2002) Profile of cholesterol-related sterols in aged amyloid precursor protein transgenic mouse brain. J Lipid Res 43:1078–1085CrossRef Lütjohann D, Brzezinka A, Barth E, Abramowski D, Staufenbiel M, von Bergmann K, Beyreuther K, Multhaup G, Bayer TA (2002) Profile of cholesterol-related sterols in aged amyloid precursor protein transgenic mouse brain. J Lipid Res 43:1078–1085CrossRef
40.
Zurück zum Zitat Ahmida HSM, Bertucci P, Franzò L, Massoud R, Cortese C, Lala A, Federici G (2006) Simultaneous determination of plasmatic phytosterols and cholesterol precursors using gas chromatography-mass spectrometry (GC-MS) with selective ion monitoring (SIM). J Chromatogr B 842:43–47CrossRef Ahmida HSM, Bertucci P, Franzò L, Massoud R, Cortese C, Lala A, Federici G (2006) Simultaneous determination of plasmatic phytosterols and cholesterol precursors using gas chromatography-mass spectrometry (GC-MS) with selective ion monitoring (SIM). J Chromatogr B 842:43–47CrossRef
41.
Zurück zum Zitat Eastwood MA, Brydon WG, Baird JD, Elton RA, Helliwell S, Smith JH, Pritchard JL (1984) Fecal weight and composition, serum lipids, and diet among subjects aged 18 to 80 years not seeking health care. Am J Clin Nutr 40:628–634 Eastwood MA, Brydon WG, Baird JD, Elton RA, Helliwell S, Smith JH, Pritchard JL (1984) Fecal weight and composition, serum lipids, and diet among subjects aged 18 to 80 years not seeking health care. Am J Clin Nutr 40:628–634
42.
Zurück zum Zitat Bourlioux P, Koletzko B, Guarner F, Braesco V (2003) The intestine and its microflora are partners for the protection of the host: report on the Danone Symposium “The Intelligent Intestine,” held in Paris, June 14, 2002. Am J Clin Nutr 78:675–683 Bourlioux P, Koletzko B, Guarner F, Braesco V (2003) The intestine and its microflora are partners for the protection of the host: report on the Danone Symposium “The Intelligent Intestine,” held in Paris, June 14, 2002. Am J Clin Nutr 78:675–683
43.
Zurück zum Zitat Probert CSJ, Emmett PM, Heaton KW (1995) Some determinants of whole-gut transit-time—a population-based study. Q J Med 88:311–315 Probert CSJ, Emmett PM, Heaton KW (1995) Some determinants of whole-gut transit-time—a population-based study. Q J Med 88:311–315
44.
Zurück zum Zitat Strandberg TE, Gylling H, Tilvis RS, Miettinen TA (2010) Serum plant and other noncholesterol sterols, cholesterol metabolism and 22-year mortality among middle-aged men. Atherosclerosis 210:282–287CrossRef Strandberg TE, Gylling H, Tilvis RS, Miettinen TA (2010) Serum plant and other noncholesterol sterols, cholesterol metabolism and 22-year mortality among middle-aged men. Atherosclerosis 210:282–287CrossRef
45.
Zurück zum Zitat Sudhop T, Sahin Y, Lindenthal B, Hahn C, Luers C, Berthold HK, von Bergmann K (2002) Comparison of the hepatic clearances of campesterol, sitosterol, and cholesterol in healthy subjects suggests that efflux transporters controlling intestinal sterol absorption also regulate biliary secretion. Gut 51:860–863CrossRef Sudhop T, Sahin Y, Lindenthal B, Hahn C, Luers C, Berthold HK, von Bergmann K (2002) Comparison of the hepatic clearances of campesterol, sitosterol, and cholesterol in healthy subjects suggests that efflux transporters controlling intestinal sterol absorption also regulate biliary secretion. Gut 51:860–863CrossRef
46.
Zurück zum Zitat von Bergmann K, Sudhop T, Lütjohann D (2005) Cholesterol and plant sterol absorption: recent insights. Am J Cardiol 96:10D–14DCrossRef von Bergmann K, Sudhop T, Lütjohann D (2005) Cholesterol and plant sterol absorption: recent insights. Am J Cardiol 96:10D–14DCrossRef
47.
Zurück zum Zitat Fujiwara S, Sakurai S, Sugimoto I, Awata N (1983) Absorption and metabolism of γ-oryzanol in rats. Chem Pharm Bull 31:645–652CrossRef Fujiwara S, Sakurai S, Sugimoto I, Awata N (1983) Absorption and metabolism of γ-oryzanol in rats. Chem Pharm Bull 31:645–652CrossRef
48.
Zurück zum Zitat Kelly ER, Plat J, Mensink RP, Berendschot TTJM (2011) Effects of long term plant sterol and -stanol consumption on the retinal vasculature: a randomized controlled trial in statin users. Atherosclerosis 214:225–230CrossRef Kelly ER, Plat J, Mensink RP, Berendschot TTJM (2011) Effects of long term plant sterol and -stanol consumption on the retinal vasculature: a randomized controlled trial in statin users. Atherosclerosis 214:225–230CrossRef
49.
Zurück zum Zitat DIN (2008–11) Chemical analysis—decision limit, detection limit and determination limit under repeatability conditions—terms, methods, evaluation. DIN 32645 DIN (2008–11) Chemical analysis—decision limit, detection limit and determination limit under repeatability conditions—terms, methods, evaluation. DIN 32645
Metadaten
Titel
Fate of dietary phytosteryl/-stanyl esters: analysis of individual intact esters in human feces
verfasst von
Tim Lubinus
Andreas Barnsteiner
Thomas Skurk
Hans Hauner
Karl-Heinz Engel
Publikationsdatum
01.04.2013
Verlag
Springer-Verlag
Erschienen in
European Journal of Nutrition / Ausgabe 3/2013
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-012-0407-4

Weitere Artikel der Ausgabe 3/2013

European Journal of Nutrition 3/2013 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.