Stable isotope approaches, applications, and issues related to polyunsaturated fatty acid metabolism studies

The use of stable isotope tracers for investigating fatty acid metabolism in human subjects has increased substantially over the last decade. Advances in analytical instrumentation, commercial availability of labeled substrates, and safety considerations are major reasons for this increased use of stable isotope tracers. Several experimental design options are available for using either deuterium or carbon‐13 as tracers for fatty acid and lipid studies. Options include feeding a pulse dose of labeled fat or a mixture containing two or more labeled fats. Multiple doses of the labeled fat can be fed at timed intervals to increase enrichments. Administration by injection or continuous intravenous infusion is an alternative. Another option is to use diets containing foods from plants that have slightly higher natural carbon‐13 enrichment. Each basic experimental design has its specific strengths, and the best choice of experimental design depends on the study objectives. Stable isotope studies have been used to address a variety of questions related to unsaturated fatty acid metabolism in humans. Examples are provided that illustrate the use of stable isotopes to investigate oxidation of docosahexaenoic acid, desaturation of linoleic and linolenic acids in infants and adults, incorporation of long‐chain n−6 and n−3 fatty acids, bioequivalency of linolenic acid in primates, 13C nuclear magnetic resonance spectra of arachidonic acid in living rat brain, and effect of triacylglycerol structure on absorption. Radioisotope and stable isotope tracer studies in animals and humans are responsible for much of our understanding of fatty acid and lipid metabolism. However, tracer studies have limitations, and there are some unresolved issues associated with isotope studies. Examples of unresolved issues are quantification of isotope data, validity of in vivo fatty acid metabolite results, kinetic modeling, subject variability, and use of blood lipid data as a reflection of tissue lipid metabolism. Resolving these issues, developing novel methodology, and applying stable isotope tracer methods to questions related to PUFA metabolism are broad areas of interesting and challenging research opportunities.