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.

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 SAM.

METHODS: A prospective, double-blind, placebo-controlled randomized clinical trial was conducted at the nutritional rehabilitation unit (NRU) of Dhaka Hospital, icddr,b. Children with SAM aged 9-24 months were randomly assigned to receive commercial L-carnitine syrup (100mg/kg/day) or placebo for 15 days in addition to standard of care. Total 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 vs. 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%CI:(-0.63,1.37), p:0.465]. The average hospital stay was ∼four days. 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 for L-carnitine vs. 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).

CONCLUSION: 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.

TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov#NCT05083637(https://classic.

CLINICALTRIALS: gov/ct2/show/NCT05083637) on October 19,2021.