Effect of topical applications of sunflower seed oil on systemic fatty acid levels in under-two children under rehabilitation for severe acute malnutrition in Bangladesh: a randomized controlled trial

Abstract

Background: Children with severe acute malnutrition (SAM) have inadequate levels of fatty acids (FAs) and limited capacity for enteral nutritional rehabilitation. We hypothesized that topical high-linoleate sunflower seed oil (SSO) would be effective adjunctive treatment for children with SAM.

Methods: This study tested a prespecified secondary endpoint of a randomized, controlled, unblinded clinical trial with 212 children with SAM aged 2 to 24 months in two strata (2 to < 6 months, 6 to 24 months in a 1:2 ratio) at Dhaka Hospital of icddr,b, Bangladesh between January 2016 and December 2017. All children received standard-of-care management of SAM. Children randomized to the emollient group also received whole-body applications of 3 g/kg SSO three times daily for 10 days. We applied difference-in-difference analysis and unsupervised clustering analysis using t-distributed stochastic neighbor embedding (t-SNE) to visualize changes in FA levels in blood from day 0 to day 10 of children with SAM treated with emollient compared to no-emollient.

Results: Emollient therapy led to systematically higher increases in 26 of 29 FAs over time compared to the control. These effects were driven primarily by changes in younger subjects (27 of 29 FAs). Several FAs, especially those most abundant in SSO showed high-magnitude but non-significant incremental increases from day 0 to day 10 in the emollient group vs. the no-emollient group; for linoleic acid, a 237 μg/mL increase was attributable to enteral feeding and an incremental 98 μg/mL increase (41%) was due to emollient therapy. Behenic acid (22:0), gamma-linolenic acid (18:3n6), and eicosapentaenoic acid (20:5n3) were significantly increased in the younger age stratum; minimal changes were seen in the older children.

Conclusions: SSO therapy for SAM augmented the impact of enteral feeding in increasing levels of several FAs in young children. Further research is warranted into optimizing this novel approach for nutritional rehabilitation of children with SAM, especially those < 6 months.

Trial registration: ClinicalTrials.gov : NCT02616289 .

Keywords: Bangladesh; Children; Emollient; Fatty acids; Malnutrition; Sunflower seed oil; Topical application.

Conflict of interest statement

The following authors are current or former employees and shareholders of GlaxoSmithKline: Daniel Sevin, Lindsay Kendall, Xinyi Zhu, Krishan Singh, Sunita Singh, Jonathan Crowther, and Rachel Gibson.

Figures

Fig. 1

Trial profile

Fig. 2

t-distributed stochastic neighbor embedding (t-SNE) performed on the full dataset of absolute fatty acid concentrations (29 analytes, 415 samples), plotting data points (each representing a sample) as scatter plots colored according to metadata variable values shown. Triangles indicate samples from emollient-treated and circles from no-emollient patients. a) Analysis of all samples based on time of sample collection. b) Analysis of day-10 samples based on treatment group. c) Analysis of day-10 samples based on age strata

Fig. 3

t-distributed stochastic neighbor embedding (t-SNE) difference-in-difference analysis performed between day-10 and day-0 samples of each patient, plotting data points (each representing a patient) as scatter plots colored according to treatment group, and shown for patients ages a) 2 to 24 months, b) 2 to < 6 months, and c) 6 to 24 months. Triangles indicate samples from emollient-treated and circles from no-emollient patients

Fig. 4

Box-and-whisker plots showing fatty acid concentration differences for a) palmitic acid (16:0), b) oleic acid (18:1n9), and c) linoleic acid (18:2n6) by treatment group and age strata. Individual data points represent the difference from day 0 to day 10 for the indicated fatty acid for an individual subject. Box-and-whisker plots represent data as mean (heavy horizontal line), lower and upper quartile (box edges), most extreme data points below 1.5 inter-quartile ranges from box edges (whiskers), and datapoints beyond 1.5 inter-quartile ranges from box edges (points beyond whiskers)

Fig. 5

Mean log2 fold changes in fatty acids levels between day 10 and day 0 in emollient treated vs. not-emollient-treated patients in the following age groups: a) 2–24 months, b) 2- < 6 months, and c) 6–24 months. Fatty acids are identified by numbers referenced in Supplemental Table 10. Fatty acids with a raw p-value < 0.05 in the difference-in-difference analysis (Table 3) are highlighted in red