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Allometric Scaling: Determining human equivalent doses for n‐3 PUFA in rodent diets
Author(s) -
Whelan Jay,
Jones Laura
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a550-a
Subject(s) - rodent , polyunsaturated fatty acid , docosapentaenoic acid , eicosapentaenoic acid , biology , rodent model , physiology , fatty acid , endocrinology , biochemistry , ecology
Dietary n‐3 PUFA are important for health promotion and disease prevention, and animal models are used to generate important data for pre‐clinical screening purposes. However, the levels used in rodent diets are poorly defined. A search of the literature reveals no guidelines for determining appropriate levels although extrapolation to human conditions is common. We generated a mathematical model based on caloric density to allometrically scale the levels of n‐3 PUFA in rodent diets to that of humans and tested this model in C57BL/6J mice. Mice were fed diets designed to approximate the Western diet (equivalent distribution of macronutrients and fatty acid composition). These diets were supplemented with α‐linolenic acid or eicosapentaenoic acid at three human equivalent doses (HED) (0.3, 0.8 and 1.4%en; where 1%en=2.2 g HED). Changes in plasma and erythrocyte phospholipid compositions were compared with archival human data from over 100 clinical trials. At all three doses, dietary ALA and EPA increased mouse EPA PL levels to a greater extent (3–4 fold) than that observed in humans, but had minimal impact on changing DHA levels (similar to humans). Reductions in AA levels were similar between mice and humans, suggesting the appropriateness of using n‐3 PUFA in rodent diets based on % calories when trying to determine a human equivalent dose. This is the first study to directly evaluate pharmacodynamic data of n‐3 PUFA between humans and rodents and provides a guideline for allometric dosing of n‐3 PUFA in rodent diets. (Supported by the TAES and in conjunction with the USDA multistate research group NC1167)