Leucine supplementation provides muscle support in haemodialysis patients: study

All expect one participant enrolled in a recent Korean study showed improvements in at least one parameter for muscle mass, grip strength, and physical performance following daily administration of leucine (6g) with macro and micro-nutrients for 12 weeks.

In addition, daily exercise (stretching and full body exercises) led to improved gait speed and sit-to-stand time for 59.1% and 63.6% of participants, respectively.

“In HD patients, multiple factors promote a negative protein balance resulting in sarcopenia. Uraemia-induced poor oral intake is one reason for the imbalance of protein homeostasis,” ​the authors explain.

“Chronic low-grade inflammation originated from accumulated uremic toxins, gut dysbiosis, and dialysis membrane biocompatibility could promote protein degradation. Our data suggest that leucine-enriched amino acid supplementation and resistance exercise reduce inflammatory responses.”​

Sarcopenia prevalence​

A systematic review found higher sarcopenia prevalence among dialysis patients (28.5%), compared to the general population, primarily due to reduced exercise capacity and poor physical performance, the authors write in Frontiers in Nutrition​.

“Moreover, factors related to chronic kidney disease (CKD) or HD, such as uremic neuropathy, abnormal vitamin D metabolism, acidosis, hyperparathyroidism, and malnutrition, may contribute to muscle loss and weakness.”​

Furthermore, malnutrition caused by protein and calorie deficiency is common in HD patients, “resulting in poor nutritional status and increased morbidity and mortality,” ​they say.

CKD is also linked to chronic inflammation, which destroys structural and functional proteins, induces muscle proteolysis, and impedes exercise.

“Therefore, evaluation of muscle function in patients receiving HD is a critical component of clinical performance measurement.”​

Study protocol​

The single arm pilot study, carried out at Chungnam National University Hospital (Daejeon, Republic of Korea), comprised 22 patients undergoing maintenance haemodialysis (MHD).

Patients had received three four-hour HD sessions per week for more than six months at baseline and were aged 27 to 72 years (average age 55.3 years).

Six grams of leucine was administered daily for 12 weeks (three grams in capsule form and three as a drink containing macro- and micronutrients, including 8g protein, 10ug vitamin D and 290mg calcium), followed by a 12-week cool-off period without supplementation.

The exercise intervention comprised a daily one-hour workout, including stretching, arm exercises with dumbbells or a water bottle, leg exercises using a chair, and walking.

Muscle mass, grip strength, and physical performance were measured using the bioimpedance analyser (BIA), handgrip strength (HGS), and short physical performance battery (SPPB) protocols at baseline, 12 weeks, and 24 weeks.

Serum biochemistry, immunophenotype of peripheral blood mononuclear cells, and nutritional status was also analysed at the three time points, along with dietary intake.

Subjects exhibiting an increase of 5% in study parameters were defined as ‘responders’ ​(RES), indicating a positive outcome.

Significant improvements​

At baseline, only four patients (18.2%) met the recommended energy intake requirements, and only three (13.6%) consumed sufficient protein. However, after 12-week supplementation and exercise, energy and protein levels significantly increased, the authors report.

“Although the number of patients who met the energy and protein intake recommendations did not increase, the proportion of patients consuming less than half of the recommendations significantly decreased.”​

Researchers observed improvements in skeletal muscle index (SMI) and five times sit-to-stand test (5TSTS) in 14 patients (63.6%), HGS in seven (31.8%), and gait speed in 13 (59.1%). Older women with good exercise compliance were the main beneficiaries in terms of HGS improvement, they note.

There was no change in parameters for one patient, while gait speed was the only reported improvement during the non-intervention period.

“Collectively, results from this study suggest that leucine-enriched amino acid supplementation and resistance exercise protect against multiple factors that promote a negative protein balance,” ​the authors’ comment.

“Furthermore, baseline characteristics of lower total protein in HGS responders, lower haemoglobin and haematocrit in 5TSTS responders, and a lower naïve/memory T cell in ASM responders, compared to each non-responder group, suggest that responders have more baseline potential for improvement by the intervention.”​

Source: Frontiers in Nutrition​

Published online, April 28, 2023: https://doi.org/10.3389/fnut.2023.1069651​

‘Leucine-enriched amino acid supplementation and exercise to prevent sarcopenia in patients on haemodialysis: a single-arm pilot study’​

Authors: Sang-Hyeon Ju, Eu Jin Lee, Byeong Chang Sim, Ha Thi Nga, Ho Yeop Lee, Jingwen Tian, Kyu Jeong Cho, Hyoungsu Park, Dae Eun Choi, Young Rok Ham and Hyon-Seung Yi