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 polyunsaturated fatty acid (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 without added DHA (HO-RUTF) or with added DHA (DHA-HO-RUTF), 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 z-score and a modified Willatts problem solving assessment (PSA) intention score for 3 standardized problems, measured 6 months and immediately after completing RUTF therapy, respectively. MDAT domain z-scores, 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, 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 (Odds Ratios 0.92, 95% CI 0.67, 1.26 for DHA-HO-RUTF). After 4 weeks of treatment, plasma phospholipid EPA and α-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.Trial registry: NCT03094247, clinicaltrials.gov.