Branched-chain ketoacid co-ingestion with protein lowers amino acid oxidation during hemodialysis: A randomized controlled cross-over trial

Floris K. Hendriks; Jorn Trommelen; Frank M. van der Sande; Janneau M. X. van Kranenburg; Jeffrey H. W. Kuijpers; Dion C. J. Houtvast; Guus H. J. Jetten; Joy P. B. Goessens; Steven J. R. Meex; Jeroen P. Kooman; Luc J. C. van Loon

doi:10.1016/j.clnu.2023.06.034

Branched-chain ketoacid co-ingestion with protein lowers amino acid oxidation during hemodialysis: A randomized controlled cross-over trial

Floris K. Hendriks, Jorn Trommelen, Frank M. van der Sande, Janneau M. X. van Kranenburg, Jeffrey H. W. Kuijpers, Dion C. J. Houtvast, Guus H. J. Jetten, Joy P. B. Goessens, Steven J. R. Meex, Jeroen P. Kooman, Luc J. C. van Loon^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background & aims: Hemodialysis removes amino acids from the circulation, thereby stimulating muscle proteolysis. Protein ingestion during hemodialysis can compensate for amino acid removal but may also increase uremic toxin production. Branched-chain ketoacid (BCKA) co-ingestion may provide an additional anabolic stimulus without adding to uremic toxin accumulation. In the present study we assessed the impact of BCKA co-ingestion with protein on forearm amino acid balance and amino acid oxidation during hemodialysis. Methods: Nine patients (age: 73 ± 10 y) on chronic hemodialysis participated in this crossover trial. During two 4-h hemodialysis sessions, patients ingested 18 g protein with (PRO + BCKA) or without (PRO) 9 g BCKAs in a randomized order. Test beverages were labeled with L-[ring- ¹³C ₆]-phenylalanine and provided throughout the last 3 h of hemodialysis as 18 equal sips consumed with 10-min intervals. Arterial and venous plasma as well as breath samples were collected frequently throughout hemodialysis. Results: Arterial plasma total amino acid (TAA) concentrations during PRO and PRO + BCKA treatments were significantly lower after 1 h of hemodialysis (2.6 ± 0.3 and 2.6 ± 0.3 mmol/L, respectively) when compared to pre-hemodialysis concentrations (4.2 ± 1.0 and 4.0 ± 0.5 mmol/L, respectively; time effect: P < 0.001). Arterial plasma TAA concentrations increased throughout test beverage ingestion (time effect: P = 0.027) without differences between treatments (time∗treatment: P = 0.62). Forearm arteriovenous TAA balance during test beverage ingestion did not differ between timepoints (time effect: P = 0.31) or treatments (time∗treatment: P = 0.34). Whole-body phenylalanine oxidation was 33 ± 16% lower during PRO + BCKA when compared to PRO treatments (P < 0.001). Conclusions: BCKA co-ingestion with protein during hemodialysis does not improve forearm net protein balance but lowers amino acid oxidation.

Original language	English
Pages (from-to)	1436-1444
Number of pages	9
Journal	Clinical Nutrition
Volume	42
Issue number	8
DOIs	https://doi.org/10.1016/j.clnu.2023.06.034
Publication status	Published - 1 Aug 2023

Keywords

Ketoanalogues
End-stage renal disease
Nutrition
Intradialytic
Muscle
NUTRITION IMPROVES PROTEIN
INTERNATIONAL SOCIETY
RENAL NUTRITION
MUSCLE
HOMEOSTASIS
TURNOVER
DIALYSIS
DISEASE
LOSSES

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Hendriks, F. K., Trommelen, J., van der Sande, F. M., van Kranenburg, J. M. X., Kuijpers, J. H. W., Houtvast, D. C. J., Jetten, G. H. J., Goessens, J. P. B., Meex, S. J. R., Kooman, J. P., & van Loon, L. J. C. (2023). Branched-chain ketoacid co-ingestion with protein lowers amino acid oxidation during hemodialysis: A randomized controlled cross-over trial. Clinical Nutrition, 42(8), 1436-1444. https://doi.org/10.1016/j.clnu.2023.06.034

@article{5e966c8b61c148b7b94c2798ae2ad099,

title = "Branched-chain ketoacid co-ingestion with protein lowers amino acid oxidation during hemodialysis: A randomized controlled cross-over trial",

abstract = "Background & aims: Hemodialysis removes amino acids from the circulation, thereby stimulating muscle proteolysis. Protein ingestion during hemodialysis can compensate for amino acid removal but may also increase uremic toxin production. Branched-chain ketoacid (BCKA) co-ingestion may provide an additional anabolic stimulus without adding to uremic toxin accumulation. In the present study we assessed the impact of BCKA co-ingestion with protein on forearm amino acid balance and amino acid oxidation during hemodialysis. Methods: Nine patients (age: 73 ± 10 y) on chronic hemodialysis participated in this crossover trial. During two 4-h hemodialysis sessions, patients ingested 18 g protein with (PRO + BCKA) or without (PRO) 9 g BCKAs in a randomized order. Test beverages were labeled with L-[ring- 13C 6]-phenylalanine and provided throughout the last 3 h of hemodialysis as 18 equal sips consumed with 10-min intervals. Arterial and venous plasma as well as breath samples were collected frequently throughout hemodialysis. Results: Arterial plasma total amino acid (TAA) concentrations during PRO and PRO + BCKA treatments were significantly lower after 1 h of hemodialysis (2.6 ± 0.3 and 2.6 ± 0.3 mmol/L, respectively) when compared to pre-hemodialysis concentrations (4.2 ± 1.0 and 4.0 ± 0.5 mmol/L, respectively; time effect: P < 0.001). Arterial plasma TAA concentrations increased throughout test beverage ingestion (time effect: P = 0.027) without differences between treatments (time∗treatment: P = 0.62). Forearm arteriovenous TAA balance during test beverage ingestion did not differ between timepoints (time effect: P = 0.31) or treatments (time∗treatment: P = 0.34). Whole-body phenylalanine oxidation was 33 ± 16% lower during PRO + BCKA when compared to PRO treatments (P < 0.001). Conclusions: BCKA co-ingestion with protein during hemodialysis does not improve forearm net protein balance but lowers amino acid oxidation.",

keywords = "Ketoanalogues, End-stage renal disease, Nutrition, Intradialytic, Muscle, NUTRITION IMPROVES PROTEIN, INTERNATIONAL SOCIETY, RENAL NUTRITION, MUSCLE, HOMEOSTASIS, TURNOVER, DIALYSIS, DISEASE, LOSSES",

author = "Hendriks, {Floris K.} and Jorn Trommelen and {van der Sande}, {Frank M.} and {van Kranenburg}, {Janneau M. X.} and Kuijpers, {Jeffrey H. W.} and Houtvast, {Dion C. J.} and Jetten, {Guus H. J.} and Goessens, {Joy P. B.} and Meex, {Steven J. R.} and Kooman, {Jeroen P.} and {van Loon}, {Luc J. C.}",

year = "2023",

month = aug,

day = "1",

doi = "10.1016/j.clnu.2023.06.034",

language = "English",

volume = "42",

pages = "1436--1444",

journal = "Clinical Nutrition",

issn = "0261-5614",

publisher = "Churchill Livingstone",

number = "8",

}

Hendriks, FK, Trommelen, J , van der Sande, FM , van Kranenburg, JMX, Kuijpers, JHW, Houtvast, DCJ, Jetten, GHJ, Goessens, JPB, Meex, SJR , Kooman, JP & van Loon, LJC 2023, 'Branched-chain ketoacid co-ingestion with protein lowers amino acid oxidation during hemodialysis: A randomized controlled cross-over trial', Clinical Nutrition, vol. 42, no. 8, pp. 1436-1444. https://doi.org/10.1016/j.clnu.2023.06.034

TY - JOUR

T1 - Branched-chain ketoacid co-ingestion with protein lowers amino acid oxidation during hemodialysis

T2 - A randomized controlled cross-over trial

AU - Hendriks, Floris K.

AU - Trommelen, Jorn

AU - van der Sande, Frank M.

AU - van Kranenburg, Janneau M. X.

AU - Kuijpers, Jeffrey H. W.

AU - Houtvast, Dion C. J.

AU - Jetten, Guus H. J.

AU - Goessens, Joy P. B.

AU - Meex, Steven J. R.

AU - Kooman, Jeroen P.

AU - van Loon, Luc J. C.

PY - 2023/8/1

Y1 - 2023/8/1

N2 - Background & aims: Hemodialysis removes amino acids from the circulation, thereby stimulating muscle proteolysis. Protein ingestion during hemodialysis can compensate for amino acid removal but may also increase uremic toxin production. Branched-chain ketoacid (BCKA) co-ingestion may provide an additional anabolic stimulus without adding to uremic toxin accumulation. In the present study we assessed the impact of BCKA co-ingestion with protein on forearm amino acid balance and amino acid oxidation during hemodialysis. Methods: Nine patients (age: 73 ± 10 y) on chronic hemodialysis participated in this crossover trial. During two 4-h hemodialysis sessions, patients ingested 18 g protein with (PRO + BCKA) or without (PRO) 9 g BCKAs in a randomized order. Test beverages were labeled with L-[ring- 13C 6]-phenylalanine and provided throughout the last 3 h of hemodialysis as 18 equal sips consumed with 10-min intervals. Arterial and venous plasma as well as breath samples were collected frequently throughout hemodialysis. Results: Arterial plasma total amino acid (TAA) concentrations during PRO and PRO + BCKA treatments were significantly lower after 1 h of hemodialysis (2.6 ± 0.3 and 2.6 ± 0.3 mmol/L, respectively) when compared to pre-hemodialysis concentrations (4.2 ± 1.0 and 4.0 ± 0.5 mmol/L, respectively; time effect: P < 0.001). Arterial plasma TAA concentrations increased throughout test beverage ingestion (time effect: P = 0.027) without differences between treatments (time∗treatment: P = 0.62). Forearm arteriovenous TAA balance during test beverage ingestion did not differ between timepoints (time effect: P = 0.31) or treatments (time∗treatment: P = 0.34). Whole-body phenylalanine oxidation was 33 ± 16% lower during PRO + BCKA when compared to PRO treatments (P < 0.001). Conclusions: BCKA co-ingestion with protein during hemodialysis does not improve forearm net protein balance but lowers amino acid oxidation.

AB - Background & aims: Hemodialysis removes amino acids from the circulation, thereby stimulating muscle proteolysis. Protein ingestion during hemodialysis can compensate for amino acid removal but may also increase uremic toxin production. Branched-chain ketoacid (BCKA) co-ingestion may provide an additional anabolic stimulus without adding to uremic toxin accumulation. In the present study we assessed the impact of BCKA co-ingestion with protein on forearm amino acid balance and amino acid oxidation during hemodialysis. Methods: Nine patients (age: 73 ± 10 y) on chronic hemodialysis participated in this crossover trial. During two 4-h hemodialysis sessions, patients ingested 18 g protein with (PRO + BCKA) or without (PRO) 9 g BCKAs in a randomized order. Test beverages were labeled with L-[ring- 13C 6]-phenylalanine and provided throughout the last 3 h of hemodialysis as 18 equal sips consumed with 10-min intervals. Arterial and venous plasma as well as breath samples were collected frequently throughout hemodialysis. Results: Arterial plasma total amino acid (TAA) concentrations during PRO and PRO + BCKA treatments were significantly lower after 1 h of hemodialysis (2.6 ± 0.3 and 2.6 ± 0.3 mmol/L, respectively) when compared to pre-hemodialysis concentrations (4.2 ± 1.0 and 4.0 ± 0.5 mmol/L, respectively; time effect: P < 0.001). Arterial plasma TAA concentrations increased throughout test beverage ingestion (time effect: P = 0.027) without differences between treatments (time∗treatment: P = 0.62). Forearm arteriovenous TAA balance during test beverage ingestion did not differ between timepoints (time effect: P = 0.31) or treatments (time∗treatment: P = 0.34). Whole-body phenylalanine oxidation was 33 ± 16% lower during PRO + BCKA when compared to PRO treatments (P < 0.001). Conclusions: BCKA co-ingestion with protein during hemodialysis does not improve forearm net protein balance but lowers amino acid oxidation.

KW - Ketoanalogues

KW - End-stage renal disease

KW - Nutrition

KW - Intradialytic

KW - Muscle

KW - NUTRITION IMPROVES PROTEIN

KW - INTERNATIONAL SOCIETY

KW - RENAL NUTRITION

KW - MUSCLE

KW - HOMEOSTASIS

KW - TURNOVER

KW - DIALYSIS

KW - DISEASE

KW - LOSSES

U2 - 10.1016/j.clnu.2023.06.034

DO - 10.1016/j.clnu.2023.06.034

M3 - Article

C2 - 37441814

SN - 0261-5614

VL - 42

SP - 1436

EP - 1444

JO - Clinical Nutrition

JF - Clinical Nutrition

IS - 8

ER -