title: 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.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT01593969. Registered 4 May 2012.
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, 230-80108, Kenya. kelsey.jones@imperial.ac.uk.|Centre for Global Health Research and Section of Paediatrics, Imperial College, Norfolk Place, London, W2 1PG, UK. kelsey.jones@imperial.ac.uk.
authors.forename: Kelsey D J
authors.initials: KD
authors.lastname: Jones
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, 230-80108, Kenya. rali@kemri-wellcome.org.
authors.forename: Rehema
authors.initials: R
authors.lastname: Ali
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, 230-80108, Kenya. mkhasira@kemri-wellcome.org.
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Khasira
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, 230-80108, Kenya. dodera@kemri-wellcome.org.
authors.forename: Dennis
authors.initials: D
authors.lastname: Odera
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton General Hosptial, Tremona Road, Southampton, SO16 6YD, UK. a.west@soton.ac.uk.
authors.forename: Annette L
authors.initials: AL
authors.lastname: West
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton General Hosptial, Tremona Road, Southampton, SO16 6YD, UK. g.koster@soton.ac.uk.
authors.forename: Grielof
authors.initials: G
authors.lastname: Koster
authors.affiliation: Valid Nutrition, Cuibín Farm, Derry Duff, Bantry, Co., Cork, Republic of Ireland. peterakomo@validnutrition.org.
authors.forename: Peter
authors.initials: P
authors.lastname: Akomo
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, 230-80108, Kenya. atalbert@kemri-wellcome.org.
authors.forename: Alison W A
authors.initials: AW
authors.lastname: Talbert
authors.affiliation: Southampton National Institute of Health Research Respiratory Biomedical Research Unit, Southampton General Hosptial, Tremona Road, Southampton, SO16 6YD, UK. v.ledger@soton.ac.uk.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Goss
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, 230-80108, Kenya. mngari@kemri-wellcome.org.
authors.forename: Moses
authors.initials: M
authors.lastname: Ngari
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, 230-80108, Kenya. jthitiri@kemri-wellcome.org.
authors.forename: Johnstone
authors.initials: J
authors.lastname: Thitiri
authors.affiliation: Kilifi County Hospital, Ministry of Health, Kilifi, 230-80108, Kenya. saidndoro@yahoo.com.
authors.forename: Said
authors.initials: S
authors.lastname: Ndoro
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, 230-80108, Kenya. miguel.garciaknight@ndm.ox.ac.uk.|Nuffield Department of Clinical Medicine, Centre for Tropical Medicine & Global Health, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford, OX3 7FZ, UK. miguel.garciaknight@ndm.ox.ac.uk.
authors.forename: Miguel A Garcia
authors.initials: MA
authors.lastname: Knight
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, 230-80108, Kenya. oduorkenneth@gmail.com.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Omollo
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, 230-80108, Kenya. shiroann2001@gmail.com.
authors.forename: Anne
authors.initials: A
authors.lastname: Ndungu
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, 230-80108, Kenya. mmulongo@kemri-wellcome.org.
authors.forename: Musa M
authors.initials: MM
authors.lastname: Mulongo
authors.affiliation: Valid International, 35 Leopold Street, Oxford, OX4 1TW, UK. paluku@validinternational.org.
authors.forename: Paluku
authors.initials: P
authors.lastname: Bahwere
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, 230-80108, Kenya. gfegan@kemri-wellcome.org.|Nuffield Department of Clinical Medicine, Centre for Tropical Medicine & Global Health, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford, OX3 7FZ, UK. gfegan@kemri-wellcome.org.
authors.forename: Greg
authors.initials: G
authors.lastname: Fegan
authors.affiliation: Centre for Global Health Research and Section of Paediatrics, Imperial College, Norfolk Place, London, W2 1PG, UK. j.o.warner@imperial.ac.uk.
authors.forename: John O
authors.initials: JO
authors.lastname: Warner
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton General Hosptial, Tremona Road, Southampton, SO16 6YD, UK. a.d.postle@soton.ac.uk.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Postle
authors.affiliation: Valid Nutrition, Cuibín Farm, Derry Duff, Bantry, Co., Cork, Republic of Ireland. steve@validinternational.org.uk.|Valid International, 35 Leopold Street, Oxford, OX4 1TW, UK. steve@validinternational.org.uk.
authors.forename: Steve
authors.initials: S
authors.lastname: Collins
authors.affiliation: Faculty of Medicine, University of Southampton, Southampton General Hosptial, Tremona Road, Southampton, SO16 6YD, UK. p.c.calder@soton.ac.uk.|National Institute of Health Southampton Biomedical Research Centre, Southampton General Hosptial, Tremona Road, Southampton, SO16 6YD, UK. p.c.calder@soton.ac.uk.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Calder
authors.affiliation: KEMRI-Wellcome Trust Research Programme, Kilifi, 230-80108, Kenya. jberkley@kemri-wellcome.org.|Nuffield Department of Clinical Medicine, Centre for Tropical Medicine & Global Health, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford, OX3 7FZ, UK. jberkley@kemri-wellcome.org.
authors.forename: James A
authors.initials: JA
authors.lastname: Berkley
mesh_terms: D000208:Acute Disease; D002675:Child, Preschool; D019587:Dietary Supplements; D004281:Docosahexaenoic Acids; D004311:Double-Blind Method; D015118:Eicosapentaenoic Acid; D057140:Fast Foods; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D005231:Fatty Acids, Unsaturated / Q000097:blood; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage*; D006801:Humans; D007223:Infant; D007630:Kenya; D008055:Lipids / Q000097:blood; D008297:Male; D044342:Malnutrition / Q000178:diet therapy*
chemical_list: D015525:Fatty Acids, Omega-3; D005231:Fatty Acids, Unsaturated; D005395:Fish Oils; D008055:Lipids; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid