A Randomized Controlled Trial on the Effects of Leucine-Supplement Combined with Nutritional Counseling on Body Composition in Mix Cancer Older Men.

BACKGROUND: Malnutrition and metabolic alterations of cancer cachexia are often associated with negative weight loss and muscle mass wasting. In this sense, protein supplementation can be a strategy to help counteract the loss and/or maintenance of mass in these patients. The aim of this study was to evaluate the effect of leucine supplementation on body composition in outpatients with gastrointestinal tract cancer. METHODS: It was a randomized, blinded, controlled, parallel trial, performed in male patients with a cancer diagnosis of the gastrointestinal tract and appendix organs undergoing chemotherapy. All the patients were allocated to one of the protocol groups: L-leucine supplement or the control group, during 8 weeks of intervention. We evaluated the body composition through bioelectrical impedance analysis, the cancer cachexia classification, and the diet intake before and after the intervention protocol. The intention-to-treat approach was performed to predict the missing values for all patients who provide any observation data. RESULTS: The patients were an average age of 65.11 ± 7.50 years old. In the body composition analysis with patients who finished all the supplementation, we observed a significant gain in body weight (61.79.9 ± 9.02 versus 64.06 ± 9.45, p = 0.01), ASMM (7.64 ± 1.24 versus 7.81 ± 1.20, p = 0.02) in the Leucine group, whereas patients in the control did not present significant variation in these parameters. There was no significant intergroup difference. While in the analysis included the patients with intention-to-treat, we found a significant increase in body weight (p = 0.01), BMI (p = 0.01), FFM (p = 0.03), and ASMM (p = 0.01) in the Leucine group. No significant intergroup differences. These results also similar among cachectic patients. CONCLUSION: A balanced diet enriched with free-Leucine supplementation was able to promotes gains in body weight and lean mass in older men diagnosticated with gastrointestinal and appendix organs of digestion cancer after 8 weeks. However, the fact that most men are non-cachectic or pre-cachectic is not clear if the increase in muscle mass was due to a high intake of leucine, since no difference between groups was detected. Moreover, we know that benefits on body composition are due to adequate calorie and macronutrients consumption and that balanced feeding according to nutrition Guidelines seems crucial and must be advised during the oncological treatment.

MSRA has low concordance with skeletal muscle mass index in mixed cancer patients: A preliminary and feasibility study.

BACKGROUND AND AIMS: Currently, there are no studies evaluating the agreement between the Mini Sarcopenia Risk Assessment (MSRA) questionnaire and skeletal muscle mass index (SMI) in cancer patients. Thus, this study aimed to evaluate the agreement of the MSRA questionnaire with SMI in cancer patients. METHODS: Cross-sectional study with 132 unselected cancer patients. The risk of sarcopenia was determined using the MSRA of 5 and 7 questions. Men and women were divided into subgroups with and without risk of sarcopenia, according to MSRA. SMI was assessed by the muscle mass divided by heigh using the Lee's formula. The ROC curve was used to estimate sensitivity, specificity, and area under the curve between MSRA 5 and 7 versus SMI. The Kappa index was used to assess the agreement between them. RESULTS: MSRA 5 and 7 showed better sensitivity values in women when compared to men. However, better specificity values were obtained in men when compared to women. Although, there was better agreement between MSRA 5/7 and SMI in women, kappa values indicated low agreement in both sexes (MSRA 5: women: 0.36 vs. men: 0.07 and MSRA 7: women: 0.22 vs. men: - 0.07). CONCLUSION: MSRA 5 and 7 questionnaires has low agreement with SMI to identify risk of sarcopenia in unselected cancer patients.

Charlson comorbidity index is not associated with neutrophil-lymphocytes ratio in unselected hospitalized cancer patients: A cross-sectional study.

This study sought to evaluate the association between Charlson Comorbidity Index (CCI) and neutrophil lymphocyte ratio (NLR). Cross-sectional study evaluated 134 patients of both sexes diagnosed with several types of cancer. NLR was calculated by dividing the absolute value of neutrophils by lymphocytes count, and the CCI questionnaire was used to assess the risk of comorbidities and mortality. The sample was dichotomized in CCI < 5 or ≥5. Student's t-test and Chi-square test were calculated to analyze the differences. The association between CCI and NLR was investigated by logistic regression analysis, performed with model 1 (crude) and model 2 (adjusted). The patients in the CCI ≥ 5 group were older, with higher neutrophil levels and prevalence of solid tumor type. There was no difference between groups regarding type of treatment, body weight, body mass index, performance status, lymphocyte count and NLR. There was no association between CCI and NLR, in both crude model (OR: 1.04 [95% CI: 0.99-1.09], p = 0.09), as well as adjusted for sex, age, physical activity, alcohol consumption, smoking habit, type of treatment, and performance status (OR: 1.04 [95% CI:0.97-1.12], p = 0.19). In hospitalized unselected cancer patients, despite of small sample size and design of study, we showed the presence of comorbidities is not related to the NLR.

Absence of risk of sarcopenia protects cancer patients from fatigue.

BACKGROUND: Cancer and its treatments often lead to sarcopenia and fatigue. However, whether these factors are associated remains unproven. OBJECTIVE: To evaluate whether the risk of sarcopenia predicts the presence of fatigue. METHODS: A cross-sectional study was completed and included 198 cancer patients of both sexes, undergoing in- and outpatient treatment. The Strength, Assistance for walking, Rise from a chair, Climb stairs, and Falls (SARC-F) and the Functional Assessment of Cancer Therapy Fatigue (FACT-F) were used to assess the risk of sarcopenia and the presence of fatigue, respectively. The cut-off values used to identify the risk of sarcopenia and the severity of fatigue scale were SARC-F ≥ 4 and Fatigue <34, respectively. Logistic regression analysis was performed to evaluate the association between SARC-F and the FACT-F. RESULTS: Out of 198 patients, 35% were at risk of sarcopenia and of these 87% had fatigue. Patients at risk of sarcopenia had lower scores in the FACT-F subscales, lower handgrip strength, lower performance status, were mostly hospitalized and were sedentary. Logistic regression analysis revealed that patients with SARC-F < 4 had a lower risk of fatigue in both models, crude (OR: 0.83; CI 95% [0.79-0.88], p < 0.0001) as well as adjusted for age, gender, BMI, physical activity, current use of alcoholic beverages, smoking, performance status, cancer type, clinical setting and use of supplements (OR: 0.87; CI 95% [0.81-0.92], p < 0.0001). CONCLUSION: In patients with cancer, 35% presented risk of sarcopenia and of these 87% had fatigue. In addition, the absence of sarcopenia was considered protective against fatigue.

High neutrophil to lymphocytes ratio is associated with nutritional risk in hospitalised, unselected cancer patients: a cross-sectional study.

Cancer patients possess metabolic and pathophysiological changes and an inflammatory environment that leads to malnutrition. This study aimed to (i) determine whether there is an association between neutrophil-to-lymphocyte ratio (NLR) and nutritional risk, and (ii) identify the cut-off value of NLR that best predicts malnutrition by screening for nutritional risk (NRS 2002). This cross-sectional study included 119 patients with unselected cancer undergoing chemotherapy and/or surgery. The NRS 2002 was applied within 24 h of hospitalisation to determine the nutritional risk. Systemic inflammation was assessed by blood collection, and data on C-reactive protein (CRP), neutrophils, and lymphocytes were collected for later calculation of NLR. A receiver operating characteristic (ROC) curve was used to identify the best cut-point for NLR value that predicted nutritional risk. Differences between the groups were tested using the Student's t-, Mann-Whitney U and Chi-Square tests. Logistic regression analyses were performed to assess the association between NLR and nutritional risk. The ROC curve showed the best cut-point for predicting nutritional risk was NLR > 5.0 (sensitivity, 60.9%; specificity, 76.4%). The NLR ≥ 5.0 group had a higher prevalence of nutritional risk than the NLR < 5.0 group (NLR ≥ 5.0: 73.6% vs. NLR < 5.0: 37.9%, p = 0.001). The NLR group ≥ 5.0 showed higher values of CRP and NLR than the NLR < 5.0 group. In addition, patients with NLR ≥ 5.0 also had higher NRS 2002 values when compared to the NLR < 5.0 group (NLR ≥ 5.0: 3.0 ± 1.1 vs. NLR < 5.0: 2.3 ± 1.2, p = 0.0004). Logistic regression revealed an association between NRS and NLR values. In hospitalised unselected cancer patients, systemic inflammation measured by NLR was associated with nutritional risk. Therefore, we highlight the importance of measuring the NLR in clinical practice, with the aim to detect nutritional risk.

Low phase angle is associated with the risk for sarcopenia in unselected patients with cancer: Effects of hydration.

OBJECTIVE: Individuals with cancer are affected by a loss of cell membrane integrity due to electrolyte imbalance between the intra- and extracellular fluids. Cell membrane integrity and hydration status can be assessed according to the phase angle (PhA) and the risk for sarcopenia, by using the Strength, Assistance for walking, Rise from a chair, Climb stairs, and Falls (SARC-F) questionnaire. To our knowledge, this approach has not been validated in patients with cancer. The aims of this study were to verify the prevalence of the risk for sarcopenia, and to analyze the association between PhA and the risk for sarcopenia with and without adjustment for extracellular water content. METHODS: This was a cross-sectional study conducted with 124 male and female cancer patients (77.4% men). PhA and hydration status were assessed using bioelectrical impedance analysis (BIA), and the risk for sarcopenia (cutoff ≥4) was assessed using the SARC-F questionnaire. RESULTS: Of the 124 patients, 28 (22.5%) were at risk for sarcopenia (SARC-F ≥4). There was no association between PhA and the risk for sarcopenia in the crude model, nor in the model adjusted for age, sex, smoking, alcohol consumption, and physical activity, nor after adjusting for use of supplements, body mass index, treatment type, performance status, and type and stage of cancer. However, we found an association between lower PhA values and a higher risk for sarcopenia after adjusting for hydration abnormalities (odds ratio, 1.74; 95% confidence interval, 1.03-2.93; P < 0.035). CONCLUSION: We found that 22.5% of patients with cancer presented with a risk for sarcopenia. Additionally, an association between lower PhA values and enhanced risk for sarcopenia highlighted the importance of adequate hydration and evaluation of fluid status via BIA as a new recommendation to prevent sarcopenia.

SARC-F has low correlation and reliability with skeletal muscle mass index in older gastrointestinal cancer patients.

BACKGROUND & AIMS: The evaluation of function and muscle mass in older cancer patients is essential to reduce comorbidities. We hypothesized that Simple Questionnaire to Rapidly Diagnose Sarcopenia (SARC-F) questionnaire is useful to assessment the muscle function, but not muscle mass. Thus, the purpose of this study was to evaluate the correlation and reliability between the SARC-F and skeletal muscle mass index (SMI) in older gastrointestinal cancer patients. METHODS: A cross-sectional observational study enrolled 108 (63.55 ± 8.9 y) gastrointestinal cancer patients. The patients were evaluated using the SARC-F questionnaire and the muscle mass index (SMI). SMI was calculated using Lee's equation: the appendicular muscle mass (ASM) was divided by height. Pearson's correlation was used to examine the correlation between SARC-F and SMI. The Bland-Altman plot and Cohen's kappa coefficient were used to determine the concordance and reliability between them. Statistical difference was set at p < 0.05. RESULTS: The Bland-Altman plot showed that the difference between methods were within agreement (±1.96; p = 0.001). However, SARC-F has low concordance (κ = 0.20; standard error = 0.14) and correlation (r = -0.303; p = 0.0014) with SMI. CONCLUSION: In older cancer outpatients, we found that SARC-F has low correlation and reliability with SMI.

Phase angle is not associated with fatigue in cancer patients: the hydration impact.

Cancer patients suffer from metabolic and pathophysiological changes that contribute to malnutrition. These metabolic changes lead to loss of cell integrity, which induces dehydration intracellular and increase extracellular fluid. Bioelectrical impedance analysis (BIA)-derived phase angle (PhA) is considered a good tool to evaluate hydration status, but in cancer patients it is not fully elucidated. Thus, in cancer patients the aims of this study were to (1) verify the association between PhA and fatigue, (2) verify the association between PhA and fatigue after adjustment for extracellular fluid accumulation, and (3) assess the prevalence of fatigue. This cross-sectional study was conducted with 124 patients of both genders on cancer treatment. Body weight, height, body mass index, handgrip strength, performance status, and cachexia were collected. In addition, body composition was evaluated by BIA to obtain hydration status and PA. The cut-off point used to classify patients with low PhA was set <4°. To identify fatigue, the Functional Assessment of Cancer Therapy Fatigue questionnaire was applied. Of the 124 patients evaluated (n = 98/79% men), 26% had fatigue. The prevalence of fatigue was higher in patients with lower PhA <4° (65.63%). In the logistic regression analyses, we found that patients with PhA >4° had lower risk for fatigue (OR: 0.92 95% CI [0.86-0.99], p = 0.03) in the crude model, however after adjustments by weight loss percentage in 6 months, age, sex, and hydration the association was not maintained (OR: 0.94 95% CI [0.85-1.04], p = 0.26). In conclusion, we found that ~26% of cancer patients have fatigue. In spite of adjustment for extracellular fluid, PhA is not associated with fatigue. The importance of measuring PhA to assess intra and extracellular hydration in cancer patients is highlighted.

A high-protein diet, not isolated BCAA, is associated with skeletal muscle mass index in patients with gastrointestinal cancer.

OBJECTIVES: Patients with cancer are susceptible to experiencing the loss of skeletal muscle mass. Thus, the purpose of this study was to evaluate whether a high-protein diet (HPD) or isolated branched-chain amino acid (BCAA) intake is associated with an increased skeletal muscle mass index (SMI) in patients with cancer of the gastrointestinal tract. METHODS: This cross-sectional, observational study included 106 patients with gastrointestinal tract tumors. Food consumption was estimated using 24-h food recall. Patients were divided into two groups: a low-protein diet (LPD) group (≤1.2 g · kg · d-1) and a high-protein diet (HPD) group (>1.2 g · kg · d-1). Appendicular muscle mass (ASM) was calculated using Lee's formula, and its values were divided by the square of the height of the patient to obtain SMI values. Differences were considered significant when the probability they occurred by chance was <5% (P < 0.05). RESULTS: Of 106 patients assessed, 69 (65%) consumed a diet consistent with specifications of the LPD group and 37 (35%) consumed a diet consistent with HPD intake. Logistic regression after adjusting for sex and caloric and carbohydrate consumption showed an association between SMI and HPD (odds ratio, 4.19; 95% confidence interval, 1.06-16.56; P < 0.001) but not with BCAA. Daily total protein intake, but not isolated BCAA or leucine, was able to predict an increase in SMI in 43% of patients considered (P = 0.006). Thus, HPD was associated with SMI, and total protein intake was a better predictor of SMI than BCAAs. CONCLUSION: HPD is a cost-effective way to enhance SMI, rather than focusing on the ingestion of isolated BCAAs.

Dietary Amino Acids and Immunonutrition Supplementation in Cancer-Induced Skeletal Muscle Mass Depletion: A Mini-Review.

Cancer patients display systemic inflammation, which leads to an increase in protein catabolism, thus promoting the release of free amino acids to further support metabolism and remodelling of muscle proteins. Inflammation associated with tumor growth leads to malnutrition, a factor that increases the risk of developing cachexia. With cancer-induced cachexia, nutritional interventions have gained traction as a preventative method to manage this condition. Currently, cancer consensus recommendations suggest a protein intake above 1.0 g/kg.day-1 up to 2.0 g/k.day-1 for cancer patients, although an ideal amount for some amino acids in isolation has yet to be determined. Due to controversy in the literature regarding the benefits of the biochemical mechanisms of various muscle mass supplements, such as L-leucine (including whey protein and BCAA), ß-hydroxy-beta-methyl butyrate (HMß), arginine, glutamine and creatine, several studies have carefully examined their effects. L-leucine and its derivatives appear to regulate protein synthesis by direct or indirect activation of the mTORC1 pool of kinases, further promoting muscle protein balance. Arginine and glutamine may act by reducing inflammation and infection progression, thus promoting improvements in food intake. Creatine exerts anabolic activity, acting as an immediate energy substrate to support muscle contraction further increasing lean mass, mainly due to greater water uptake by the muscle. In this narrative review, we highlighted the main findings regarding protein consumption and amino acids to mitigate cancer-induced skeletal muscle depletion.

Muscle function loss is associated with anxiety in patients with gastrointestinal cancer.

OBJECTIVE: To verify the prevalence of patients with muscle function loss (MFL) and whether it is associated with anxiety and depression scores in gastrointestinal (GI) cancer patients. METHODS: A cross-sectional study with seventy-one adult GI cancer patients was conducted. The MFL was evaluated by the SARC-F questionnaire, and participants were divided into MFL (cut-off ≥4 SARC-F) and normal muscle function (NMF) groups (cut-off <4 SARC-F). Anxiety and depression were analyzed using the Hospital Anxiety and Depression Scale (HADS). RESULTS: From 71 patients, 25.4% (n = 18) were classified as MFL and 74.6% (n = 53) as NMF. Body weight was lower in the MFL group when compared to the NMF group (MFL: 57.6 ± 11.3 vs. NMF: 64.8 ± 11.6 kg, p = 0.032). MFL showed higher anxiety (MFL: 7.5 (0-21) vs. NMF: 2 (0-17), p = 0.030) and depression scores (MFL: 6.5 (0-13) vs. NMF: 2 (0-17), p = 0.034) compared to NMF. A positive correlation between the SARC-F and the anxiety (r = 0.34, p = 0.004) and depression score (r = 0.32, p = 0.006) was found. When adjusted by sex and body weight, MFL saw an increase with the anxiety score (OR: 1.15 95%CI(1.01-1.31), p = 0.023), but not with the depression score. In addition, LMF was responsible for anxiety in 12% of the population. CONCLUSION: In our study, 25% of GI cancer patients presented LMF and an association with the anxiety score.