Effects of Probiotic Supplementation on Trimethylamine-N-Oxide Plasma Levels in Hemodialysis Patients: a Pilot Study

  • Natália A. Borges
  • P. Stenvinkel
  • P. Bergman
  • A. R. Qureshi
  • B. Lindholm
  • C. Moraes
  • M. B. Stockler-Pinto
  • D. Mafra


Components present in the diet, l-carnitine, choline, and betaine are metabolized by gut microbiota to produce metabolites such as trimethylamine-N-oxide (TMAO) that appear to promote cardiovascular disease in chronic kidney disease (CKD) patients. The objective of this pilot study was to evaluate the effects of probiotic supplementation for 3 months on plasma TMAO levels in CKD patients on hemodialysis (HD). A randomized, double-blind trial was performed in 21 patients [54.8 ± 10.4 years, nine men, BMI 26.1 ± 4.8 kg/m2, dialysis vintage 68.5 (34.2–120.7) months]. Ten patients were randomly allocated to the placebo group and 11 to the probiotic group [three capsules, totaling 9 × 1013 colony-forming units per day of Streptococcus thermophilus (KB19), Lactobacillus acidophilus (KB27), and Bifidobacteria longum (KB31). Plasma TMAO, choline, and betaine levels were measured by LC-MS/MS at baseline and after 3 months. While TMAO did not change after probiotic supplementation, there was a significant increase in betaine plasma levels. In contrast, the placebo group showed a significant decrease in plasma choline levels. Short-term probiotic supplementation does not appear to influence plasma TMAO levels in HD patients. Long-term studies are needed to determine whether probiotics may affect TMAO production in CKD patients.


Chronic kidney disease Hemodialysis Probiotic Inflammation Trimethylamine-N-oxide 



The Heart and Lung Foundation and “Njurfonden” support Peter Stenvinkel’s research. Conselho Nacional de Pesquisa (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ) support Denise Mafra’s research. Baxter Novum is the result of a grant from Baxter Healthcare to Karolinska Institutet.

Compliance with Ethical Standards

Conflict of Interest

Bengt Lindholm is employed by Baxter Healthcare. The other authors do not declare any potential conflicts of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Natália A. Borges
    • 1
    • 2
  • P. Stenvinkel
    • 3
  • P. Bergman
    • 4
  • A. R. Qureshi
    • 3
  • B. Lindholm
    • 3
  • C. Moraes
    • 1
  • M. B. Stockler-Pinto
    • 1
    • 2
  • D. Mafra
    • 1
    • 2
    • 5
  1. 1.Graduate Program in Cardiovascular SciencesFluminense Federal University (UFF)NiteróiBrazil
  2. 2.Unidade de Pesquisa ClínicaNiteróiBrazil
  3. 3.Department of Clinical Science Intervention and Technology, Division of Renal Medicine and Baxter NovumKarolinska InstitutetStockholmSweden
  4. 4.Department of Laboratory Medicine, Division of Clinical MicrobiologyKarolinska University HospitalStockholmSweden
  5. 5.Graduate Program in Medical SciencesFluminense Federal University (UFF)NiteróiBrazil

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