The Association of the Essential Amino Acids Lysine, Methionine, and Threonine with Clinical Outcomes in Patients at Nutritional Risk: Secondary Analysis of a Randomized Clinical Trial
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design
2.2. Patient Population
2.3. Study Intervention (Randomization/Procedures)
2.4. Analysis of Blood Biomarkers
2.5. Outcomes
2.6. Definition of Low Muscle Mass and Muscle Radiodensity Based on Abdominal CT Scans
2.7. Statistical Analysis
3. Results
3.1. Patient Population
3.2. Association of Lysine, Methionine, and Threonine with Nutritional Parameters
3.3. Association of Lysine, Methionine, and Threonine with Mortality and Further Clinical Outcomes
3.4. Association of Lysine, Methionine, and Threonine with Muscle-Specific Outcomes
3.5. Association of Lysine, Methionine, and Threonine on Responding to Nutritional Support
4. Discussion
Strengths and Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Overall | No 30-Day Mortality | 30-Day Mortality | p-Value | |
---|---|---|---|---|
n = 237 | n = 179 | n = 58 | ||
Sociodemographic | ||||
Male sex, n (%) | 136 (57.4%) | 94 (52.5%) | 42 (72.4%) | 0.008 |
Age, years, mean (SD) | 73.4 (13.6) | 72.5 (13.9) | 76.1 (12.4) | 0.083 |
Nutritional assessment, mean (SD) | ||||
BMI, kg/m2 | 24.3 (5.0) | 24.4 (5.2) | 24.0 (4.0) | 0.60 |
Weight, kg | 68.7 (14.9) | 68.7 (15.4) | 68.8 (13.7) | 0.96 |
Height, cm | 168.1 (8.6) | 167.8 (8.4) | 169.1 (9.2) | 0.33 |
Admission diagnosis, n (%) | ||||
Infection | 64 (27.0%) | 50 (27.9%) | 14 (24.1%) | 0.57 |
Cancer | 75 (31.6%) | 50 (27.9%) | 25 (43.1%) | 0.031 |
Cardiovascular disease | 24 (10.1%) | 17 (9.5%) | 7 (12.1%) | 0.57 |
Frailty | 13 (5.5%) | 10 (5.6%) | 3 (5.2%) | 0.90 |
Lung disease | 11 (4.6%) | 6 (3.4%) | 5 (8.6%) | 0.097 |
Gastrointestinal disease | 13 (5.5%) | 13 (7.3%) | 0 (0.0%) | 0.035 |
Neurological disease | 4 (1.7%) | 4 (2.2%) | 0 (0.0%) | 0.25 |
Renal disease | 15 (6.3%) | 14 (7.8%) | 1 (1.7%) | 0.097 |
Metabolic disease | 6 (2.5%) | 5 (2.8%) | 1 (1.7%) | 0.65 |
Other | 3 (1.3%) | 2 (1.1%) | 1 (1.7%) | 0.72 |
Comorbidities, n (%) | ||||
Hypertension | 138 (58.2%) | 107 (59.8%) | 31 (53.4%) | 0.40 |
Malignant disease | 113 (47.7%) | 78 (43.6%) | 35 (60.3%) | 0.026 |
Chronic kidney disease | 81 (34.2%) | 63 (35.2%) | 18 (31.0%) | 0.56 |
Coronary heart disease | 54 (22.8%) | 41 (22.9%) | 13 (22.4%) | 0.94 |
Diabetes | 43 (18.1%) | 33 (18.4%) | 10 (17.2%) | 0.84 |
Congestive heart failure | 45 (19.0%) | 30 (16.8%) | 15 (25.9%) | 0.12 |
Chronic obstructive pulmonary disease | 28 (11.8%) | 17 (9.5%) | 11 (19.0%) | 0.052 |
Peripheral arterial disease | 26 (11.0%) | 19 (10.6%) | 7 (12.1%) | 0.76 |
Cerebrovascular disease | 27 (11.4%) | 21 (11.7%) | 6 (10.3%) | 0.77 |
Dementia | 11 (4.6%) | 7 (3.9%) | 4 (6.9%) | 0.35 |
Amino acids | ||||
Low lysine, n (%) | 122 (51.5%) | 97 (54.2%) | 25 (43.1%) | 0.14 |
Low methionine, n (%) | 70 (29.5%) | 46 (25.7%) | 24 (41.4%) | 0.023 |
Low threonine, n (%) | 110 (46.4%) | 86 (48.0%) | 24 (41.4%) | 0.38 |
Lysine | Methionine | Threonine | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Mean | Coef. | p-Value | 95%-CI | Mean | Coef. | p-Value | 95%-CI | Mean | Coef. | p-Value | 95%-CI | |
NRS 2002 score | ||||||||||||
3 | 211.1 | reference | 25.3 | reference | 103.0 | reference | ||||||
4 | 199.1 | −12.0 | 0.23 | −31.4 to 7.4 | 22.5 | −2.8 | 0.08 | −6.0 to 0.4 | 96.8 | −6.2 | 0.34 | −19.0 to 6.6 |
≥5 | 186.7 | −24.4 | 0.01 | −43.0 to −5.8 | 22.6 | −2.7 | 0.09 | −5.7 to 0.4 | 96.4 | −6.6 | 0.29 | −18.9 to 5.7 |
Food intake | ||||||||||||
>75% | 215.9 | reference | 25.8 | reference | 104.2 | reference | ||||||
50–75% | 185.7 | −30.2 | 0.03 | −58.0 to −2.4 | 22.9 | −2.9 | 0.22 | −7.4 to 1.7 | 94.8 | −9.5 | 0.31 | −27.8 to 8.9 |
25–50% | 202.0 | −13.9 | 0.30 | −40.4 to 12.6 | 22.8 | −2.9 | 0.19 | −7.2 to 1.4 | 97.2 | −7.1 | 0.43 | −24.5 to 10.4 |
0–25% | 193.7 | −22.2 | 0.14 | −51.6 to 7.1 | 23.4 | −2.3 | 0.34 | −7.1 to 2.5 | 102.7 | −1.5 | 0.88 | −20.8 to 17.8 |
BMI | ||||||||||||
<18.5 | 178.7 | reference | 23.2 | reference | 91.4 | reference | ||||||
18.5–25 | 200.1 | 21.4 | 0.11 | −4.9 to 47.7 | 22.9 | −0.3 | 0.88 | −4.7 to 4.0 | 98.2 | 6.8 | 0.44 | −10.4 to 24.1 |
25–30 | 195.2 | 16.5 | 0.25 | −11.8 to 44.9 | 22.9 | −0.3 | 0.90 | −4.9 to 4.4 | 95.2 | 3.8 | 0.69 | −14.8 to 22.5 |
>30 | 205.0 | 26.3 | 0.09 | −3.7 to 56.2 | 24.6 | 1.4 | 0.58 | −3.5 to 6.3 | 106.9 | 15.5 | 0.12 | −4.2 to 35.2 |
Weight loss | ||||||||||||
1 (none) | 201.0 | reference | 23.1 | reference | 97.6 | reference | ||||||
2 (>5% in 3 mts) | 197.4 | −3.6 | 0.74 | −24.4 to 17.3 | 23.8 | 0.7 | 0.70 | −2.7 to 4.1 | 100.6 | 3.0 | 0.67 | −10.7 to 16.6 |
3 (>5% in 2 mts) | 201.7 | 0.7 | 0.95 | −20.9 to 22.3 | 24.9 | 1.8 | 0.31 | −1.7 to 5.3 | 104.5 | 6.9 | 0.34 | −7.3 to 21.0 |
4 (>5% in 1 mts) | 184.6 | −16.4 | 0.11 | −36.6 to 3.8 | 21.7 | −1.5 | 0.38 | −4.8 to 1.8 | 92.4 | −5.2 | 0.44 | −18.5 to 8.0 |
Disease severity | ||||||||||||
0 | 182.0 | reference | 27.2 | reference | 132.0 | reference | ||||||
1 | 198.4 | 16.4 | 0.63 | −51.1 to 83.9 | 23.4 | −3.8 | 0.49 | −14.8 to 7.1 | 99.3 | −32.7 | 0.14 | −76.7 to 11.3 |
2 | 194.6 | 12.6 | 0.72 | −55.5 to 80.6 | 23.0 | −4.2 | 0.45 | −15.3 to 6.8 | 95.3 | −36.7 | 0.10 | −81.1 to 7.7 |
3 | 274.0 | 92.0 | 0.18 | −41.6 to 225.6 | 14.0 | −13.2 | 0.23 | −34.9 to 8.5 | 84.3 | −47.7 | 0.28 | −134.8 to 39.5 |
All-Cause Mortality | Low Plasma Levels | High Plasma Levels | HR (95% CI) | p-Value | |
30-day mortality | |||||
Lysine | 25/122 (20.5%) | 33/115 (28.7%) | 0.69 (0.40–1.18) | 0.17 | |
Methionine | 24/70 (34.3%) | 34/167 (20.4%) | 1.98 (1.16–3.36) | 0.01 | |
Threonine | 24/110 (21.8%) | 34/127 (26.8%) | 0.77 (0.45–1.30) | 0.33 | |
180-day mortality | |||||
Lysine | 54/122 (44.3%) | 48/115 (41.7%) | 1.02 (0.68–1.53) | 0.93 | |
Methionine | 35/70 (50.0%) | 67/167 (40.1%) | 1.45 (0.95–2.22) | 0.08 | |
Threonine | 48/110 (43.6%) | 54/127 (42.5%) | 0.85 (0.57–1.27) | 0.43 | |
Other Clinical Outcomes | Low Plasma Levels | High Plasma Levels | OR (95% CI) | p-Value | |
Adverse event 30 days | |||||
Lysine | 44/122 (36.0%) | 48/115 (41.7%) | 0.72 (0.41–1.27) | 0.26 | |
Methionine | 36/70 (51.4%) | 56/167 (33.5%) | 2.21 (1.21–4.05) | 0.01 | |
Threonine | 42/110 (38.2%) | 50/127 (39.4%) | 0.86(0.09–8.49) | 0.60 | |
Barthel Decline > 10 | |||||
Lysine | 31/122 (25.4%) | 34/115 (29.6%) | 0.77 (0.41–1.46) | 0.42 | |
Methionine | 26/70 (37.1%) | 39/167 (23.6%) | 2.06 (1.06–4.01) | 0.03 | |
Threonine | 29/110 (26.4%) | 36/127 (28.4%) | 0.79 (0.42–1.48) | 0.46 | |
Falls 180 days | |||||
Lysine | 14/121 (11.6%) | 9/115 (7.8%) | 1.47 (0.59–3.62) | 0.41 | |
Methionine | 8/70 (11.4%) | 15/166 (9.0%) | 1.26 (0.50–3.20) | 0.62 | |
Threonine | 15/109 (13.8%) | 8/127 (6.3%) | 2.46 (0.98–6.19) | 0.05 | |
Muscle-Specific Outcomes | Low Plasma Levels | High Plasma Levels | OR (95% CI) | p-Value | |
Sarcopenia | |||||
Lysine | 17/72 (23.6%) | 22/81 (27.2%) | 0.37 (0.14–0.95) | 0.04 | |
Methionine | 12/43 (27.9%) | 27/110 (24.5%) | 0.53 (0.19–1.47) | 0.22 | |
Threonine | 23/78 (29.5%) | 16/75 (21.3%) | 0.96 (0.39–2.35) | 0.93 | |
Low skeletal muscle index | |||||
Lysine | 26/33 (78.8%) | 20/28 (71.4%) | 1.46 (0.40–5.27) | 0.57 | |
Methionine | 15/18 (83.3%) | 31/43 (72.1%) | 2.05 (0.46–9.08) | 0.35 | |
Threonine | 28/33 (84.8%) | 18/28 (64.3%) | 3.14 (0.89–11.02) | 0.07 | |
Low muscle radiodensity | |||||
Lysine | 27/33 (81.8%) | 15/28 (53.6%) | 2.48 (0.63–9.85) | 0.20 | |
Methionine | 15/18 (83.3%) | 27/43 (62.8%) | 2.88 (0.48–17.29) | 0.25 | |
Threonine | 26/33 (78.8%) | 16/28 (57.1%) | 2.93 (0.72–12.00) | 0.13 | |
High intramuscular adipose tissue | |||||
Lysine | 11/33 (33.3%) | 4/28 (14.3%) | 2.37 (0.14–10.06) | 0.24 | |
Methionine | 4/18 (22.2%) | 11/43 (25.5%) | 0.54 (0.12–2.34) | 0.41 | |
Threonine | 8/33 (24.2%) | 7/28 (25.0%) | 0.69 (0.19–2.54) | 0.58 |
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Wunderle, C.; Haller, L.; Laager, R.; Bernasconi, L.; Neyer, P.; Stumpf, F.; Tribolet, P.; Stanga, Z.; Mueller, B.; Schuetz, P. The Association of the Essential Amino Acids Lysine, Methionine, and Threonine with Clinical Outcomes in Patients at Nutritional Risk: Secondary Analysis of a Randomized Clinical Trial. Nutrients 2024, 16, 2608. https://doi.org/10.3390/nu16162608
Wunderle C, Haller L, Laager R, Bernasconi L, Neyer P, Stumpf F, Tribolet P, Stanga Z, Mueller B, Schuetz P. The Association of the Essential Amino Acids Lysine, Methionine, and Threonine with Clinical Outcomes in Patients at Nutritional Risk: Secondary Analysis of a Randomized Clinical Trial. Nutrients. 2024; 16(16):2608. https://doi.org/10.3390/nu16162608
Chicago/Turabian StyleWunderle, Carla, Luana Haller, Rahel Laager, Luca Bernasconi, Peter Neyer, Franziska Stumpf, Pascal Tribolet, Zeno Stanga, Beat Mueller, and Philipp Schuetz. 2024. "The Association of the Essential Amino Acids Lysine, Methionine, and Threonine with Clinical Outcomes in Patients at Nutritional Risk: Secondary Analysis of a Randomized Clinical Trial" Nutrients 16, no. 16: 2608. https://doi.org/10.3390/nu16162608