Ready-to-use therapeutic food with elevated n-3 polyunsaturated fatty acid content, with or without fish oil, to treat severe acute malnutrition: a randomized controlled trial

Abstract

Background: Ready-to-use therapeutic foods (RUTF) are lipid-based pastes widely used in the treatment of acute malnutrition. Current specifications for RUTF permit a high n-6 polyunsaturated fatty acid (PUFA) content and low n-3 PUFA, with no stipulated requirements for preformed long-chain n-3 PUFA. The objective of this study was to develop an RUTF with elevated short-chain n-3 PUFA and measure its impact, with and without fish oil supplementation, on children's PUFA status during treatment of severe acute malnutrition.

Methods: This randomized controlled trial in children with severe acute malnutrition in rural Kenya included 60 children aged 6 to 50 months who were randomized to receive i) RUTF with standard composition; ii) RUTF with elevated short chain n-3 PUFA; or iii) RUTF with elevated short chain n-3 PUFA plus fish oil capsules. Participants were followed-up for 3 months. The primary outcome was erythrocyte PUFA composition.

Results: Erythrocyte docosahexaenoic acid (DHA) content declined from baseline in the two arms not receiving fish oil. Erythrocyte long-chain n-3 PUFA content following treatment was significantly higher for participants in the arm receiving fish oil than for those in the arms receiving RUTF with elevated short chain n-3 PUFA or standard RUTF alone: 3 months after enrollment, DHA content was 6.3% (interquartile range 6.0-7.3), 4.5% (3.9-4.9), and 3.9% (2.4-5.7) of total erythrocyte fatty acids (P <0.001), respectively, while eicosapentaenoic acid (EPA) content was 2.0% (1.5-2.6), 0.7% (0.6-0.8), and 0.4% (0.3-0.5) (P <0.001). RUTF with elevated short chain n-3 PUFA and fish oil capsules were acceptable to participants and carers, and there were no significant differences in safety outcomes.

Conclusions: PUFA requirements of children with SAM are not met by current formulations of RUTF, or by an RUTF with elevated short-chain n-3 PUFA without additional preformed long-chain n-3 PUFA. Clinical and growth implications of revised formulations need to be addressed in large clinical trials.

Trial registration: Clinicaltrials.gov NCT01593969. Registered 4 May 2012.

Figure 1

Trial flow diagram.

Figure 2

Erythrocyte fatty acid composition. Median and interquartile ranges shown for the three arms at baseline, day 28, and day 84. Graphs show (clockwise from top left) DHA, EPA, AA, n-6:n-3 ratio in LC-PUFA, and total LC-PUFA (n-6 and n-3). For between-arm comparisons (ANOVA) at each time point: *P ≤0.05; **P ≤0.01; ***P ≤0.001. For within-arm comparison (sign test) to baseline values: † P ≤0.05. LC indicates species with carbon chain >18.

Figure 3

Effect modification of baseline PUFA status on EPA and DHA enrichment in erythrocytes. (A) Erythrocyte DHA and EPA between both arms without fish oil (S-RUTF and F-RUTF) compared to FFO-RUTF. Participants are stratified on the basis of their baseline DHA or EPA values. Low indicates equal to or below the median, and high indicates above the median. *P ≤0.05; **P ≤0.01; ***P ≤0.001 (by sign test). (B) Change in erythrocyte DHA or EPA from baseline to day 84 plotted against baseline DHA or EPA. Regression lines are colored the same as corresponding group symbols, black regression line is for S-RUTF and F-RUTF combined. P value is for effect modification across the three arms as described in the text.