Low linoleic acid foods with added DHA given to Malawian children with severe acute malnutrition improve cognition: A randomized, triple-blinded, controlled clinical trial

Authors: STEPHENSON, KEVIN - Washington University; CALLAGHAN-GILLESPIE, MEGHAN - Washington University; MALETA, KENNETH - Kamuzu Central Hospital; NKHOMA, MINYANGA - Kamuzu Central Hospital; GEORGE, MATTHEWS - Kamuzu Central Hospital; PARK, HUI GYU - University Of Texas At Austin; LEE, REGINALD - Washington University; HUMPHRIES-CUF, IONA - Project Peanut Butter; LACOMBE, R J SCOTT - University Of Texas At Austin; WEGNER, DONNA R - Washington University; CANFIELD, RICHARD L - University Of Texas At Austin; BRENNA, J THOMAS - Cornell University; MANARY, MARK J - Children'S Nutrition Research Center (CNRC)

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/28/2021
Publication Date: 11/2/2021
Citation: Stephenson, K., Callaghan-Gillespie, M., Maleta, K., Nkhoma, M., George, M., Park, H., Lee, R., Humphries-Cuff, I., Lacombe, R., Wegner, D., Canfield, R., Brenna, J., Manary, M. 2021. Low linoleic acid foods with added DHA given to Malawian children with severe acute malnutrition improve cognition: A randomized, triple-blinded, controlled clinical trial. American Journal of Clinical Nutrition. https://doi.org/10.1093/ajcn/nqab363.
DOI: https://doi.org/10.1093/ajcn/nqab363

Interpretive Summary: Severe acute malnutrition (SAM) is a global insult to the young child's developing mind and body. Polyunsaturated fats (PUFA) constitute more than 10% of all brain tissue and severely malnourished children are deficient in these fats. A clinical trial was conducted to compare cognitive recovery in malnourished children with added PUFA versus standard care. Children receiving added PUFA demonstrated improvement in long-term cognition, these findings call for changes in international feeding specifications. The need to enhance cognitive recovery in SAM is substantial, even crucial, as this affects tens of millions of children annually.

Technical Abstract: There is concern that the PUFA composition of readyto-use therapeutic food (RUTF) for the treatment of severe acute malnutrition (SAM) is suboptimal for neurocognitive recovery. Objectives: We tested the hypothesis that RUTF made with reduced amounts of linoleic acid, achieved using high-oleic (HO) peanuts without added DHA (HO-RUTF) or with added DHA (DHA-HORUTF), improves cognition when compared with standard RUTF (SRUTF). A triple-blind, randomized, controlled clinical feeding trial was conducted among children with uncomplicated SAM in Malawi with 3 types of RUTF: DHA-HO-RUTF, HO-RUTF, and SRUTF. The primary outcomes, measured in a subset of subjects, were the Malawi Developmental Assessment Tool (MDAT) global z-score and a modified Willatts problem-solving assessment (PSA) intention score for 3 standardized problems, measured 6 mo and immediately after completing RUTF therapy, respectively. MDAT domain zscores, plasma fatty acid content, anthropometry, and eye tracking were secondary outcomes. Comparisons were made between the novel PUFA RUTFs and S-RUTF. Among the 2565 SAM children enrolled, mean global MDAT z-scores were –0.69 +/- 1.19 and –0.88 +/- 1.27 for children receiving DHA-HO-RUTF and S-RUTF, respectively (difference 0.19, 95% CI: 0.01, 0.38). Children receiving DHA-HO-RUTF had higher gross motor and social domain z-scores than those receiving S-RUTF. The PSA problem 3 scores did not differ by dietary group (OR: 0.92, 95% CI: 0.67, 1.26 for DHA-HO-RUTF). After 4 wk of treatment, plasma phospholipid EPA and a-linolenic acid were greater in children consuming DHA-HO-RUTF or HO-RUTF when compared with S-RUTF (for all 4 comparisons P values < 0.001), but only plasma DHA was greater in DHA-HO-RUTF than S-RUTF (P < 0.001). Treatment of uncomplicated SAM with DHA-HORUTF resulted in an improved MDAT score, conferring a cognitive benefit 6 mo after completing diet therapy. This treatment should be explored in operational settings.