The Role of Betaine in Patients With Chronic Kidney Disease: a Narrative Review

Overview

Journal Curr Nutr Rep

Specialty Nutritional Sciences

Date 2022 Jul 6

PMID 35792998

Authors

Livia Alvarenga

Maira S Ferreira

Julie A Kemp

Denise Mafra

Affiliations

Soon will be listed here.

Abstract

Purpose Of Review: This narrative review aimed to explore the functions of betaine and discuss its role in patients with chronic kidney disease (CKD).

Recent Findings: Some studies on CKD animal models have shown the benefits of betaine supplementation, including decreased kidney damage, antioxidant recovery status, and decreased inflammation. Betaine (N-trimethylglycine) is an N-trimethylated amino acid with an essential regulatory osmotic function. Moreover, it is a methyl donor and has anti-inflammatory and antioxidant properties. Additionally, betaine has positive effects on intestinal health by regulating the osmolality and gut microbiota. Due to these crucial functions, betaine has been studied in several diseases, including CKD, in which betaine plasma levels decline with the progression of the disease. Low betaine levels are linked to increased kidney damage, inflammation, oxidative stress, and intestinal dysbiosis. Furthermore, betaine is considered an essential metabolite for identifying CKD stages.

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References

Kim S, Kim Y . Effects of betaine supplementation on hepatic metabolism of sulfur-containing amino acids in mice. J Hepatol. 2005; 42(6):907-13. DOI: 10.1016/j.jhep.2005.01.017. View

Lever M, Slow S . The clinical significance of betaine, an osmolyte with a key role in methyl group metabolism. Clin Biochem. 2010; 43(9):732-44. DOI: 10.1016/j.clinbiochem.2010.03.009. View

Pourmehdi A, Sakhaei Z, Alirezaei M, Dezfoulian O . Betaine effects against asthma-induced oxidative stress in the liver and kidney of mice. Mol Biol Rep. 2020; 47(8):5729-5735. DOI: 10.1007/s11033-020-05620-2. View

Ueland P . Choline and betaine in health and disease. J Inherit Metab Dis. 2010; 34(1):3-15. DOI: 10.1007/s10545-010-9088-4. View

Dibaba D, Johnson K, Kucharska-Newton A, Meyer K, Zeisel S, Bidulescu A . The Association of Dietary Choline and Betaine With the Risk of Type 2 Diabetes: The Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care. 2020; 43(11):2840-2846. PMC: 7576425. DOI: 10.2337/dc20-0733. View

Mafra D, Esgalhado M, Borges N, Cardozo L, Stockler-Pinto M, Craven H . Methyl Donor Nutrients in Chronic Kidney Disease: Impact on the Epigenetic Landscape. J Nutr. 2019; 149(3):372-380. DOI: 10.1093/jn/nxy289. View

Guo F, Dai Q, Zeng X, Liu Y, Tan Z, Zhang H . Renal function is associated with plasma trimethylamine-N-oxide, choline, L-carnitine and betaine: a pilot study. Int Urol Nephrol. 2020; 53(3):539-551. DOI: 10.1007/s11255-020-02632-6. View

Alirezaei M, Jelodar G, Niknam P, Ghayemi Z, Nazifi S . Betaine prevents ethanol-induced oxidative stress and reduces total homocysteine in the rat cerebellum. J Physiol Biochem. 2011; 67(4):605-12. DOI: 10.1007/s13105-011-0107-1. View

Hagar H, Medany A, Salam R, Medany G, Nayal O . Betaine supplementation mitigates cisplatin-induced nephrotoxicity by abrogation of oxidative/nitrosative stress and suppression of inflammation and apoptosis in rats. Exp Toxicol Pathol. 2014; 67(2):133-41. DOI: 10.1016/j.etp.2014.11.001. View

10.

Zeisel S, Mar M, Howe J, Holden J . Concentrations of choline-containing compounds and betaine in common foods. J Nutr. 2003; 133(5):1302-7. DOI: 10.1093/jn/133.5.1302. View

11.

Ross A, Zangger A, Guiraud S . Cereal foods are the major source of betaine in the Western diet--analysis of betaine and free choline in cereal foods and updated assessments of betaine intake. Food Chem. 2013; 145:859-65. DOI: 10.1016/j.foodchem.2013.08.122. View

12.

Figueroa-Soto C, Valenzuela-Soto E . Glycine betaine rather than acting only as an osmolyte also plays a role as regulator in cellular metabolism. Biochimie. 2018; 147:89-97. DOI: 10.1016/j.biochi.2018.01.002. View

13.

Olthof M, Verhoef P . Effects of betaine intake on plasma homocysteine concentrations and consequences for health. Curr Drug Metab. 2005; 6(1):15-22. DOI: 10.2174/1389200052997366. View

14.

Courtenay E, Capp M, Anderson C, Record Jr M . Vapor pressure osmometry studies of osmolyte-protein interactions: implications for the action of osmoprotectants in vivo and for the interpretation of "osmotic stress" experiments in vitro. Biochemistry. 2000; 39(15):4455-71. DOI: 10.1021/bi992887l. View

15.

Alfieri R, Cavazzoni A, Petronini P, Bonelli M, Caccamo A, Borghetti A . Compatible osmolytes modulate the response of porcine endothelial cells to hypertonicity and protect them from apoptosis. J Physiol. 2002; 540(Pt 2):499-508. PMC: 2290260. DOI: 10.1113/jphysiol.2001.013395. View

16.

Hundahl C, Fago A, Malte H, Weber R . Allosteric effect of water in fish and human hemoglobins. J Biol Chem. 2003; 278(44):42769-73. DOI: 10.1074/jbc.M307515200. View

17.

Horio M, Ito A, Matsuoka Y, Moriyama T, Orita Y, Takenaka M . Apoptosis induced by hypertonicity in Madin Darley canine kidney cells: protective effect of betaine. Nephrol Dial Transplant. 2001; 16(3):483-90. DOI: 10.1093/ndt/16.3.483. View

18.

Li C, Wang Y, Li L, Han Z, Mao S, Wang G . Betaine protects against heat exposure-induced oxidative stress and apoptosis in bovine mammary epithelial cells via regulation of ROS production. Cell Stress Chaperones. 2019; 24(2):453-460. PMC: 6439124. DOI: 10.1007/s12192-019-00982-4. View

19.

Lee E, Jang E, Jung K, Kim D, Yu B, Young Chung H . Betaine attenuates lysophosphatidylcholine-mediated adhesion molecules in aged rat aorta: modulation of the nuclear factor-κB pathway. Exp Gerontol. 2013; 48(5):517-24. DOI: 10.1016/j.exger.2013.02.024. View

20.

Je J, Lee J, Jung K, Sung B, Go E, Yu B . NF-kappaB activation mechanism of 4-hydroxyhexenal via NIK/IKK and p38 MAPK pathway. FEBS Lett. 2004; 566(1-3):183-9. DOI: 10.1016/j.febslet.2004.04.037. View