Central European Journal of Biology

, Volume 6, Issue 1, pp 32–40 | Cite as

An antioxidant probiotic reduces postprandial lipemia and oxidative stress

  • Tiiu KullisaarEmail author
  • Jelena Shepetova
  • Kersti Zilmer
  • Epp Songisepp
  • Aune Rehema
  • Marika Mikelsaar
  • Mihkel Zilmer
Research Article


Reducing postprandial oxidative stress (OxS), decreasing postprandial blood triglyceride level (TG) and improving lipoprotein status is likely to have a preventive impact on the development of cardiovascular disease (CVD). Previously we have shown that the antioxidant probiotic Lactobacillus fermentum ME-3 (DSM14241) is characterized by antiatherogenic effects. This randomized double-blind placebo-controlled study evaluated the influence of kefir enriched with an antioxidative probiotic L. fermentum ME-3 (LfKef) on postprandial OxS, blood TG response and lipoprotein status. 100 clinically healthy subjects were recruited into the study. Blood parameters of postprandial OxS, TG and lipoprotein status were determined by oxidized LDL, baseline diene conjugation in LDL (BDC-LDL), oxidized LDL complex with beta-2 glycoprotein (Beta2-GPI-oxLDL), paraoxonase (PON) activity, LDL-Chol, HDL-Chol and TG. To evaluate general body postprandial OxS-load we measured 8-isoprostanes (8-EPI) in the urine. Consumption of LfKef significantly reduced the postprandial level of oxidized LDL, BDC-LDL, Beta2-GPI-oxLDL, urinary 8-isoprostanes and postprandial TG and caused a significant increase in HDL-Chol and PON activity. This is the first evidence that kefir enriched with an antioxidant probiotic may have a positive effect on both postprandial OxS and TG response as well as on lipoprotein status.


Postprandial period Oxidative stress Postprandial lipemic response Probiotics Lactobacillus fermentum Oxidized low-density lipoprotein Paraoxonase, isoprostanes 


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  1. [1]
    Kullisaar T., Songisepp E., Mikelsaar M., Zilmer K., Vihalemm T., Zilmer M., Antioxidative probiotic fermented goats’ milk decreases oxidative stress-mediated atherogenicity in human subjects, Br. J. Nutr., 2003, 90, 449–456CrossRefPubMedGoogle Scholar
  2. [2]
    Mikelsaar M., Zilmer M., Lactobacillus fermentum ME-3 an antimicrobial and antioxidative probiotic, Microb. Ecol. Health Dis., 2009, 21, 1–27CrossRefPubMedGoogle Scholar
  3. [3]
    Bae J.-H., Bassenge E., Kim K.-B., Kim Y.- N., Kim K.-S., Lee H.-J., et al., Postprandial hypertriglyceridemia impairs endothelial function by enhanced oxidative stress, Atherosclerosis, 2001, 155, 517–523CrossRefPubMedGoogle Scholar
  4. [4]
    Hopps E., Noto D., Caimi G., Averna M.R., A novel component of the metabolic syndrome: The oxidative stress, Nutr. Metab. Cardiovasc. Dis., 2010, 20, 72–77CrossRefPubMedGoogle Scholar
  5. [5]
    Jackson K.G., Armah C.K., Minihane A.M., Meal fatty acids and postprandial vascular reactivity, Biochem. Soc. Trans., 2007, 35, 451–453CrossRefPubMedGoogle Scholar
  6. [6]
    Perez-Martinez P., Ordovas J.M., Garcia-Rios A., Delgado-Lista J., Delgado-Casado N., Cruz-Teno C., et al., Consumption of diets with different type of fat influences triacylglycerols-rich lipoprotein particle number and size during the postprandial state, Nutr. Metab. Cardiovasc. Dis., In press, DOI: 10.1016/j.numecd.2009.07.008Google Scholar
  7. [7]
    Salminen S., Bouley C., Boutron-Ruault M.C., Cummings J.H., Franck A., Gibson G.R., et al., Functional food science and gastrointestinal physiology and function, Br. J. Nutr., 1998, 80, S147–S171CrossRefPubMedGoogle Scholar
  8. [8]
    Salminen S., Human studies on probiotics. Aspects of scientific documentation, Scand. J. Nutr., 2001, 45, 8–12Google Scholar
  9. [9]
    Sepp E., Julge K., Vasar M., Naaber P., Björksten B., Mikelsaar M., Intestinal microflora of Estonian and Swedish infants, Acta Pediatr., 1997, 86, 956–961CrossRefGoogle Scholar
  10. [10]
    Kullisaar T., Zilmer M., Mikelsaar M., Vihalemm T., Annuk H., Kairane C., et al., Two antioxidative lactobacilli strains as promising probiotics, Int. J. Food Microbiol., 2002, 72, 215–224CrossRefPubMedGoogle Scholar
  11. [11]
    Songisepp E., Kals J., Kullisaar T., Mändar R., Hütt P., Zilmer M., et al., Evaluation of the functional efficacy of an antioxidative probiotic in healthy volunteers, Nutr. J., 2005, 20, 4–22Google Scholar
  12. [12]
    Järvenpää S., Tahvonen R.L., Ouwehand A.C., Sandell M., Järvenpää E., Salminen S., A probiotic, Lactobacillus fermentum ME-3, has antioxidative capacity in soft cheese with different fats, J. Dairy Sci., 2007, 90, 3171–3177CrossRefPubMedGoogle Scholar
  13. [13]
    Kals J., Kampus P., Zilmer K., Impact of oxidative stress on arterial elasticity in patients with atherosclerosis, Am. J. Hypertens., 2006, 19, 902–908CrossRefPubMedGoogle Scholar
  14. [14]
    Kaur S., Kullisaar T., Mikelsaar M., Eisen M., Rehema A., Vihalemm T., et al., Successful management of mild atopic dermatitis in adults with probiotics and emollients, Cent. Eur. J. Med., 2008, 3, 215–220CrossRefGoogle Scholar
  15. [15]
    Kullisaar T., Mikelsaar M., Kaur S., Songisepp E., Zilmer K., Hütt P., et al., Probiotics, oxidative stress inflammation and diseases, In: Curic D., (Ed.), Proceedings of the Joint Central European Congress (15-17 May 2008 Cavtat, Croatia), Croatian Chamber of Economy, 2008, 1, 367–373Google Scholar
  16. [16]
    Stsepetova J., Kullisaar T., Songisepp E., Zilmer M., Mikelsaar M., Design of L. fermentum ME-3 strain-specific primers for detecting the cell number in human feces by real-time PCR., Gastroenterol. Sankt-Peterburg, 2009, 4, A26–A27, (in Russian)Google Scholar
  17. [17]
    Ahotupa M., Marniemi J., Lehtimäki T., Talvinen K., Raitakari O.T., Vasankari T., et al., Baseline diene conjugation in LDL lipids as a direct measure of in vivo LDL oxidation, Clin. Biochem., 1998, 31, 257–261CrossRefPubMedGoogle Scholar
  18. [18]
    Schiavon R., Battaglia P., De Fanti E., FasolinA., Biasioli S., Targa L., et al., HDL3-related decreased serum paraoxonase (PON) activity in uremic patients: comparison with the PON allele polymorphism, Clin Chim Acta, 2002, 324, 39–44CrossRefPubMedGoogle Scholar
  19. [19]
    Castillo M., Martin-Orue M.S., Manzanilla E.G., Badiola I., Martin M., Gasa J., Quantification of total bacteria, enterobacteria and lactobacilli populations in pig digesta by real-time PCR, Vet. Microbiol., 2006, 114, 165–170CrossRefPubMedGoogle Scholar
  20. [20]
    Byun R., Nadkarni M.A., Chhour K.L., Martin, F.E., Jacques N.A., Hunter N., Quantitative analysis of diverse lactobacillus species present in advanced caries, J. Clin. Microbiol., 2004, 42, 3128–3136CrossRefPubMedGoogle Scholar
  21. [21]
    Klaenhammer T., Altermann E., Arigoni F., Bolotin A., Breidt F., Broadbent J., et al., Discovering lactic acid bacteria by genomics, Antonie van Leeuwenhoek, 2002, 82, 29–58CrossRefPubMedGoogle Scholar
  22. [22]
    Fisher-Wellman K., Bloomer R.J., Macronutrient specific postprandial oxidative stress: relevance to the development of insulin resistance, Curr. Diabetes Rev., 2009, 5, 228–238CrossRefPubMedGoogle Scholar
  23. [23]
    Lopez-Miranda J., Perez-Martinez P., Marin C., Moreno J.A., Gomez P., Perez-Jimenez F., Postprandial lipoprotein metabolism, genes and risk of cardiovascular disease, Curr. Opin. Lipidol., 2006, 17, 132–138CrossRefPubMedGoogle Scholar
  24. [24]
    Dzau V.J., Antman E.M., Black H.R., Hayes D.L., Manson J.E., Plutzky J., et al., The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part I: Pathophysiology and clinical trial evidence (risk factors through stable coronary artery disease), Circulation, 2006, 114, 2850–2870CrossRefPubMedGoogle Scholar
  25. [25]
    Holvoet P., Lee D.H., Steffes M., Gross M., Jacobs D.R. Jr., Association between circulating oxidized low-density lipoprotein and incidence of the metabolic syndrome, JAMA, 2008, 299, 2287–2293CrossRefPubMedGoogle Scholar
  26. [26]
    Kampus P., Kals J., Ristimäe T., Muda P., Ulst K., Zilmer K., et al.. Augmentation index and carotenoid intima-media thickness are differently related to age, C-reactive protein and oxidized low-density lipoprotein, J. Hypertens., 2007, 25, 132–138CrossRefGoogle Scholar
  27. [27]
    George J., Mechanisms of disease: the evolving role of regulatory T cells in atherosclerosis, Nat. Clin. Pract. Cardiovasc. Med., 2008, 5, 531–540CrossRefPubMedGoogle Scholar
  28. [28]
    Halliwell B., Gutteridge J.M.C., (Eds.), Free radicals in biology and medicine, 3rd Ed., Oxford University Press, New York, 1999Google Scholar
  29. [29]
    Truusalu K., Naaber P., Kullisaar T., Tamm H., Mikelsaar R.-H., Zilmer K., et al., The influence of antibacterial and antioxidative probiotic lactobacilli on gut mucosa in a mouse model of Salmonella infection, Microb. Ecol. Health Dis., 2004, 16, 180–187CrossRefGoogle Scholar
  30. [30]
    Truusalu K., Mikelsaar R.-H., Naaber P., Karki T., Kullisaar T., Zilmer M., et al., Eradication of salmonella Typhimurium infection in a murine mudel of tophoid fever with the combination of probiotic Lactobacillus fermentum ME-3 and ofloxacin, BMC Microbiol., 2008, 8, 132–136CrossRefPubMedGoogle Scholar
  31. [31]
    Chui M.H., Greenwood C.E., Antioxidant vitamins reduce acute meal-induced memory deficits in adults with type 2 diabetes, Nutr. Res., 2008, 28, 423–429CrossRefPubMedGoogle Scholar
  32. [32]
    Kullisaar T., Songisepp E., Aunapuu M., Kilk K., Arend A, Mikelsaar M., et al., Complete glutathione system in probiotic L. fermentum ME-3, Appl. Biochem. Microbiol., 2010, 46, 481–486CrossRefGoogle Scholar
  33. [33]
    Bruckert E., Hansel B., HDL-c is a powerful lipid predictor of cardiovascular diseases, Int. J. Clin. Pract., 2009, 61, 1905–1913CrossRefGoogle Scholar
  34. [34]
    Sutherland W.H., Walker R.J., de Jong S.A., van Rij A.M., Phillips V., Walker H.L., Reduced postprandial serum paraoxonase activity after a meal rich in used cooking fat, Arterioscler. Thromb. Vasc. Biol., 1999, 19, 1340–1347PubMedGoogle Scholar
  35. [35]
    Navab M., Anantharamaiah G.M., Reddy S.T., Van Lenten B.J., Ansell B.J., Fogelman A.M., Mechanisms of disease: proatherogenic HDL - an evolving field, Nat. Clin. Pract. Endocrin. Met., 2006, 2, 504–511CrossRefGoogle Scholar
  36. [36]
    Hansel B., Giral P, Nobecourt E., Clantepie S., Bruckert E., Chapman M.J., et al., Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense high-density lipoprotein particles displaying impaired antioxidative activity, J. Clin. Endocrin. Met., 2006, 89, 4963–4971CrossRefGoogle Scholar
  37. [37]
    Beltowski J., Wojcicka G., Jamroz A., Leptin decreases plasma paraoxonase 1 (PON1) activity and induces oxidative stress: the possible novel mechanism for proatherogenic effect of chronic hyperleptinemia, Atherosclerosis, 2003, 170, 21–29CrossRefPubMedGoogle Scholar
  38. [38]
    Durrington P.N., Mackness B., Mackness M.I., Paraoxonase and atherosclerosis, Arterioscler. Thromb. Vasc. Biol., 2005, 21, 473–480Google Scholar

Copyright information

© © Versita Warsaw and Springer-Verlag Wien 2010

Authors and Affiliations

  • Tiiu Kullisaar
    • 1
    • 3
    • 4
    Email author
  • Jelena Shepetova
    • 2
  • Kersti Zilmer
    • 1
    • 4
  • Epp Songisepp
    • 3
  • Aune Rehema
    • 1
    • 4
  • Marika Mikelsaar
    • 2
  • Mihkel Zilmer
    • 1
    • 4
  1. 1.Department of Biochemistry of Faculty of MedicineTartu UniversityTartuEstonia
  2. 2.Department of Microbiology of Faculty of MedicineTartu UniversityTartuEstonia
  3. 3.Bio-Competence Centre of Healthy Dairy ProductsTartuEstonia
  4. 4.The Centre of Excellence for Translational MedicineTartuEstonia

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