Effects of L-Carnitine Supplementation on the Rate of Weight Gain and Biomarkers of Environmental Enteric Dysfunction in Children with Severe Acute Malnutrition: A Double-Blind Randomized Controlled Clinical Trial.

BACKGROUND: Severe acute malnutrition (SAM) is a major public health concern among low- and middle-income countries, where the majority of the children encountering this acute form of malnutrition suffer from environmental enteric dysfunction (EED). However, evidence regarding the effects of L-carnitine supplementation on the rate of weight gain and EED biomarkers in malnourished children is limited. OBJECTIVES: We aimed to investigate the role of L-carnitine supplementation on the rate of weight gain, duration of hospital stays, and EED biomarkers among children with SAM. METHODS: A prospective, double-blind, placebo-controlled, randomized clinical trial was conducted at the Nutritional Rehabilitation Unit (NRU) of Dhaka Hospital, International Centre for Diarrheal Disease Research, Bangladesh. Children with SAM aged 9-24 mo were randomly assigned to receive commercial L-carnitine syrup (100 mg/kg/d) or placebo for 15 d in addition to standard of care. A total of 98 children with Weight-for-Length-z-score (WLZ) < -3 Standard deviation were enrolled between October 2021 and March 2023. Analyses were conducted on an intention-to-treat basis. RESULTS: The primary outcome variable, "rate of weight gain," was comparable between L-carnitine and placebo groups (2.09 ± 2.23 compared with 2.07 ± 2.70; P = 0.973), which was consistent even after adjusting for potential covariates (age, sex, Weight-for-Age z-score, asset index, and WASH practices) through linear regression [ß: 0.37; 95% confidence interval (CI): -0.63,1.37; P = 0.465]. The average hospital stay was ∼4 d. The results of adjusted median regression showed that following intervention, there was no significant difference in the EED biomarkers among the treatment arms; Myeloperoxidase (ng/mL) [ß: -1342.29; 95% CI: -2817.35, 132.77; P = 0.074], Neopterin (nmol/L) [ß: -153.33; 95% CI: -556.58, 249.91; P = 0.452], alpha-1-antitrypsin (mg/mL) [ß: 0.05; 95% CI: -0.15, 0.25; P = 0.627]. Initial L-carnitine (µmol/L) levels (median, interquartile range) for L-carnitine compared with placebo were 54.84 (36.0, 112.9) and 59.74 (45.7, 96.0), whereas levels after intervention were 102.05 (60.9, 182.1) and 105.02 (73.1, 203.7). CONCLUSIONS: Although our study findings suggest that L-carnitine bears no additional effect on SAM, we recommend clinical trials with a longer duration of supplementation, possibly with other combinations of interventions, to investigate further into this topic of interest. This trial was registered at clinicaltrials.gov as NCT05083637.

Role of L-Carnitine supplementation on rate of weight gain and biomarkers of Environmental Enteric Dysfunction in children with severe acute malnutrition: A protocol for a double-blinded randomized controlled trial.

BACKGROUND: Severe acute malnutrition (SAM) and environmental enteric dysfunction (EED) are highly prevalent among children residing in resource-limited countries like Bangladesh. L-carnitine may play a role in improving the growth and ameliorating the EED among nutritionally vulnerable children. OBJECTIVE: To investigate the role of L-carnitine supplementation on the rate of weight gain, duration of hospital stays, and EED biomarkers among children with severe acute malnutrition. METHODS: This study is a double-blinded, placebo-controlled, randomized clinical trial aiming to enroll diarrheal children with SAM between 9-24 months of both sexes attending the nutritional rehabilitation unit (NRU) of Dhaka Hospital of icddr,b. It is an ongoing trial including two arms where one arm receives L-carnitine supplementation, and the other arms receive a placebo for 15 days in addition to the existing standard treatment of SAM. The primary outcome is the rate of weight gain, and the secondary outcomes include duration of hospital stay and EED biomarkers. Outcomes are assessed at baseline and 15 days of post-intervention. We hypothesize that the L- carnitine supplementation for 15 days in children with SAM will improve the rate of weight gain and biomarkers of EED. TRIAL REGISTRATION: ClinicalTrials.gov # NCT05083637. Date of registration: October 19, 2021.

Evidence of gut enteropathy and factors associated with undernutrition among slum-dwelling adults in Bangladesh.

BACKGROUND: Adult undernutrition (BMI <18.5 kg/m2) is responsible for immune deficits, increased risk of disease burden, and higher rates of mortality. The prevalence of adult undernutrition in Bangladesh is substantial, but there have been few studies on the etiology of this condition for the inhabitants of urban slums. OBJECTIVE: The aim of this study was to identify the factors associated with undernutrition among slum-dwelling adults in Bangladesh. METHODS: A case-control study was conducted in the Bauniabadh area of Dhaka, Bangladesh. 270 adult participants (135 cases with a BMI <18.5 and 135 controls with a BMI between 18.5 and 24.9) aged 18-45 y were enrolled between October 2018 and January 2019. Sociodemographic variables, dietary diversity, micronutrient deficiencies, psychological symptoms, infection, and biomarkers of gut health were assessed to identify the factors associated with undernutrition using multivariable logistic regression analysis. RESULTS: A higher number of siblings [adjusted odds ratio (aOR): 1.39; 95% CI: 1.11, 1.77], increased self-reporting questionnaire-20 score (an instrument to screen mental health disorders and detect psychological symptoms) (aOR: 1.12; 95% CI: 1.04, 1.23), elevated fecal concentration of α-1 antitrypsin (aOR: 4.82; 95% CI: 1.01, 25.29), and anemia (aOR: 3.63; 95% CI: 1.62, 8.58) were positively associated with undernutrition in adults. Age (aOR: 0.90; 95% CI: 0.84, 0.96), dietary diversity score (aOR: 0.75; 95% CI: 0.56, 0.99), C-reactive protein (aOR: 0.82; 95% CI: 0.73, 0.92), Helicobacter pylori infection (aOR: 0.11; 95% CI: 0.05, 0.23), and always washing hands before eating or preparing foods (aOR: 0.33; 95% CI: 0.12, 0.87) were associated with reduced odds of undernutrition among the study population. CONCLUSIONS: Our results indicate that undernutrition in slum-dwelling adults in Bangladesh is associated with numerous physiological and sociodemographic factors, including evidence of gastrointestinal inflammation and altered intestinal permeability.

Serum Adipokines, Growth Factors, and Cytokines Are Independently Associated with Stunting in Bangladeshi Children.

Growth in young children is controlled through the release of several hormonal signals, which are affected by diet, infection, and other exposures. Stunting is clearly a growth disorder, yet limited evidence exists documenting the association of different growth biomarkers with child stunting. This study explored the association between different growth biomarkers and stunting in Bangladeshi children. A quasi-experimental study was conducted among 50 stunted (length-for-age Z-score (LAZ) < -2 SD) and 50 control (LAZ ≥ -2 SD) children, aged 12-18 months, residing in a Bangladeshi slum. The enrolled stunted children received an intervention package, which included food supplementation for three months, psychosocial stimulation for six months, and routine clinical care on community nutrition center at the study field site. The controls received routine clinical care only. All children were clinically screened over the study period. Length, weight, fasting blood and fecal biomarkers were measured. All biomarkers levels were similar in both groups except for oxyntomodulin at enrolment. Leptin (adjusted odds ratio, AOR: 4.0, p < 0.01), leptin-adiponectin ratio (AOR 5.07 × 108, p < 0.01), insulin-like growth factor-1 (IGF-1) (AOR 1.02, p < 0.05), and gamma interferon (IFN-γ) (AOR 0.92, p < 0.05) levels were independently associated with stunting at enrolment. Serum leptin, leptin-adiponectin ratio, interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α), and fecal alpha-1-antitrypsin (AAT) levels increased significantly (p < 0.001), while IFN-γ levels significantly decreased among stunted children after six months of intervention. Leptin, leptin-adiponectin ratio, IGF-1, and IFN-γ are independently associated with stunting in Bangladeshi children. This trial was registered at clinicaltrials.gov as NCT02839148.