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Reduction of Arachidonate Is Associated With Increase in B-Cell Activation Marker in Infants: A Randomized Trial

Miklavcic, John J.*; Larsen, Bodil M.K.; Mazurak, Vera C.*; Scalabrin, Deolinda M.F.; MacDonald, Ian M.§; Shoemaker, Glen K.*; Casey, Linda||; Van Aerde, John E.; Clandinin, Michael T.*

Journal of Pediatric Gastroenterology and Nutrition: March 2017 - Volume 64 - Issue 3 - p 446–453
doi: 10.1097/MPG.0000000000001283
Original Articles: Nutrition

Background: Infants who are not breast-fed benefit from formula with both docosahexaenoic acid (C22:6n3) and arachidonic acid (ARA; C20:4n6). The amount of ARA needed to support immune function is unknown. Infants who carry specific fatty acid desaturase (FADS) polymorphisms may require more dietary ARA to maintain adequate ARA status.

Objective: The aim of the study was to determine whether ARA intake or FADS polymorphisms alter ARA levels of lymphocytes, plasma, and red blood cells in term infants fed infant formula.

Methods: Infants (N = 89) were enrolled in this prospective, double-blind controlled study. Infants were randomized to consume formula containing 17 mg docosahexaenoic acid and 0, 25, or 34 mg ARA/100 kcal for 10 weeks. Fatty acid composition of plasma phosphatidylcholine and phosphatidylethanolamine, total fatty acids of lymphocytes and red blood cells, activation markers of lymphocytes, and polymorphisms in FADS1 and FADS2 were determined.

Results: Lymphocyte ARA was higher in the 25-ARA formula group than in the 0- or 34-ARA groups. In plasma, 16:0/20:4 and 18:0/20:4 species of phosphatidylcholine and phosphatidylethanolamine were highest and 16:0/18:2 and 18:0/18:2 were lowest in the 34-ARA formula group. In minor allele carriers of FADS1 and FADS2, plasma ARA content was elevated only at the highest level of ARA consumed. B-cell activation marker CD54 was elevated in infants who consumed formula containing no ARA.

Conclusions: ARA level in plasma is reduced by low ARA consumption and by minor alleles in FADS. Dietary ARA may exert an immunoregulatory role on B-cell activation by decreasing 16:0/18:2 and 18:0/18:2 species of phospholipids. ARA intake from 25 to 34 mg/100 kcal is sufficient to maintain cell ARA level in infants across genotypes.

Supplemental Digital Content is available in the text

*Alberta Institute for Human Nutrition, University of Alberta

Alberta Health Services, Edmonton AB, Canada

Clinical Research, Mead Johnson Nutrition, Evansville, IN, the Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT

§Ophthalmology and Visual Sciences, University of Alberta

||Department of Pediatrics, Alberta Health Services, Edmonton AB

Department of Pediatrics, University of British Columbia, Vancouver BC, Canada.

Address correspondence and reprint requests to Michael T. Clandinin, Department of AFNS, Faculty of ALES, Alberta Institute for Human Nutrition, University of Alberta, Edmonton AB, TG6 2R1 Canada (e-mail:

Received 23 July, 2015

Accepted 26 May, 2016

Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site ( registration number: NCT01058187.

J.J.M. was supported by the Queen Elizabeth II Doctoral Scholarship. M.T.C. is supported by grants from the Canadian Institute of Health Research and the National Sciences and Engineering Research Council of Canada. Support and formula products were provided by Mead Johnson Nutrition.

D.M.F.S. is employed by Mead Johnson Nutrition. A patent in this area of research issued to The University of Toronto for Clandinin's research expired approximately 7 years ago. The remaining authors report no conflicts of interest.

© 2017 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,