Lost in Translation: Allometric scaling of bioactive dietary n-3 and n-6 fatty acids

Abstract

Background: Experimental animal models are the primary tool to test nutritional intervention strategies for health promotion and prevention and/or treatment of human diseases. These kinds of experiments test hypotheses that otherwise could not be done in humans. These models generate data important for pre-clinical screening purposes; however, their ability to predict human responses has been disappointing, particularly when it comes to dietary n-3 and n-6 polyunsaturated fatty acids (PUFA). Many times, it is difficult to recapitulate the data as a result of diet between pre-clinical experiments and clinical trials, in part, because we lack fundamental understanding as to how to effectively translate diet between species. The diets in experiments using rodent models are preferentially designed to generate positive results (i.e., perform a dose response and pick the dose that works) with little thought on applicability to humans. As such, the levels of n-3 and n-6 PUFA used in rodent diets are typically on the extreme and rarely justified. A search of the literature reveals no guidelines establishing appropriate levels for the use of PUFA in rodent diets, although extrapolation to human conditions is quite common despite being inappropriate. The goal of this paper is to examine allometric scaling models between species for dietary PUFA using similar endpoints with the hypothesis that equivalent physiological changes in rodents and humans support the mathematical model. Keywords:, alpha-linolenic acid, allometric scaling, arachidonic acid, docosahexaenoic acid, eicosapentaenoic acid, linoleic acid, n-6, n-3, plasma fatty acids, polyunsaturated fatty acids

Conversion of dietary polyunsaturated fats between humans and rodents: A review of allometric scaling models

“…These data were overlaid upon the human data (diamonds). Note: Reproduced with modifications from reference [24] under the terms of the Creative Commons Attribution Licenses (http://creativecommons.org/licenses/by/2.0) and with permission of the author. model.…”

“…Note: Reproduced with modifications from reference [24] under the terms of the Creative Commons Attribution Licenses (http://creativecommons.org/licenses/by/ 2.0) and with permission of the author. phospholipid fatty acid composition in plasma and erythrocytes in mice and humans [2,33].…”

“…For example, when a random set of scientific papers were reviewed for the levels of PUFAs supplemented to a control diet (typically corn oil-based) and compared to either the median intakes of ALA in the US population, or what is recommended by the American Heart Association (i.e., long chain n-3 PUFA), the levels far exceeded typical intakes or authoritative recommendations (Fig. 1) [24]. 1.3.4.…”

“…1. Levels of alpha-linolenic acid (ALA) or long chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) supplemented to corn oil-based rodent background diets (randomly selected studies) [24]. The line at the bottom left represents the typical intake of ALA in the US diet (~0.6%en).…”