Efeitos da suplementação de chocolate enriquecido com leucina e aconselhamento nutricional em variáveis nutricionais e funcionais de pacientes em acompanhamento pré-transplante hepático: ensaio clínico aleatorizado multicêntrico.

Abstract

Leucine (LEU) supplementation can be a promising alternative to stimulate protein synthesis in patients with cirrhosis. However, the bitter taste of this amino acid and the difficult dissolution in water can limit adherence to the supplementation. This is a multicenter, double-masked, randomized clinical trial aiming to evaluate the impact of supplementing a chocolate enriched with LEU on the muscle strength of patients undergoing assessment for a liver transplant (LTx). We included patients with cirrhosis of both sexes, regularly followed at three outpatient LTx clinics in Belo Horizonte – MG. Patients were excluded if they had a diagnosis of diabetes, dry-Body Mass Index (BMI) values > 30 kg/m², hepatocellular carcinoma or any type of cancer, any chronic disease that could impact the metabolism or nutritional status, utilization of amino acid or protein supplements, indication for multi-organ transplant or retransplant, cow’s milk protein allergy or lactose intolerance, and if they did not like chocolate. Patients were randomly allocated to consume 40g of blend chocolate (milk chocolate and semisweet chocolate) enriched with 7.5 g/day of LEU (intervention group) or chocolate without enrichment (active control group). The chocolate was offered in 20g bars twice a day (one after lunch and one with the late-evening snack) during 12 weeks. All patients received an individualized dietary plan and specific nutritional counseling. The patients were assessed on three different occasions during the study: initial assessment (T0), after six weeks (T6), and after 12 weeks (T12). Clinical, nutritional, and functional data were collected. To assess adherence, patients were asked to fill out a specific form regarding the days and times in which the chocolate was consumed. The same form was used to assess the occurrence of adverse effects. The clinical trial was approved by the Ethics Committee (protocol number 3.134.996) and registered in REBEC (code RBR-9snttn). The first randomized patients were assessed in a pilot study aiming to assess the adherence and adverse effects associated with the supplementation. The data was analyzed following the intention-to-treat principle. The effects of the time and treatment on the primary outcome and secondary outcomes were evaluated by Generalized Estimating Equations models adjusted by sex, age, MELD-sodium, percentage of adherence to supplementation, and food intake (kcal * protein). In the pilot study, twenty patients were randomly allocated to Group 1 (n=10) or Group 2 (n=10) between September 2021 and September 2022. Most patients (75%) presented an adherence higher than 80% of the chocolate in T6 and T12, without significant differences between the groups. We did not observe important adverse effects besides mild gastrointestinal symptoms in both groups in T6 and in one patient of Group 2 in T12. Due to adequate adherence and the absence of relevant adverse effects, we proceeded to finish the complete clinical trial, in which 49 patients were analyzed (25 in the intervention group and 24 in the active control group). Most patients were men (77,6%), the median age was 53.0 (47.0-60.0) years, the most common etiologic was alcoholic cirrhosis (46.9%) and 87.8% (n=43) of the patients were malnourished according to the Subjective Global Assessment. The median adherence to the supplementation was 66.0% (2.5-92.0), being 61.0% (0.2-99.0) in the active control group, and 66.0% (7.0-91.0) in the intervention group (p=0.857). There were no effects of the supplementation in any of the primary or secondary outcomes. However, the values for dry-BMI, arm circumference, triceps skinfold thickness, non-dominant adductor pollicis muscle thickness, and caloric intake increased over time, regardless of the allocation group. In conclusion, supplementing 7.5g/day of LEU using an enriched chocolate did not have significant effects on the muscle strength of patients undergoing assessment for a LTx. Nevertheless, both groups presented an increase in anthropometrical variables after 12 weeks of supplementation.