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

Background: There is concern that the PUFA composition of ready-to-use therapeutic food (RUTF) for treatment of severe acute malnutrition (SAM) is suboptimal for neurocognitive recovery. Objective: We tested the hypothesis that RUTF made with reduced amounts of linoleic acid, achieved using high oleic (HO) peanuts, with or without added DHA, improves cognition when compared to standard RUTF (S-RUTF). Methods: 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 S-RUTF. The primary outcomes, measured in a subset of subjects, were the Malawi Developmental Assessment Tool (MDAT) global and 4 domain (gross motor, fine motor, language and social) z-scores and a modified Willatts problem solving assessment (PSA) intention score for 3 standardized problems, measured 6 months and immediately after completing RUTF therapy, respectively. Plasma fatty acid content, anthropometry and eye tracking were secondary outcomes. Comparisons were made between the novel PUFA RUTFs and S-RUTF. Results: Among the 2565 SAM children enrolled, global MDAT z-score was -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 to 0.38). The gross motor and social domains had higher z-scores among children receiving either DHA-HO-RUTF than S-RUTF. The PSA problem 3 scores did not differ by dietary group (Odds ratio 0.92, 95% CI 0.67 to 1.26 for DHA-HO-RUTF). After 4 weeks of treatment, plasma phospholipid EPA and a- linolenic acid were greater in children consuming DHA-HO-RUTF or HO-RUTF when compared to 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). Conclusions: Treatment of uncomplicated SAM with DHA-HO-RUTF resulted in an improved MDAT score, conferring a cognitive benefit six months after completing diet therapy. This treatment should be explored in operational settings.