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Fatty acid-free albumin has been the standard carrier for intravenous infusion of fatty acids to study in vivo lipid metabolism. However, subjects can have adverse reactions to infusion of albumin. We sought an alternative to albumin as a carrier for intravenous infusion of fatty acids, using the pig as a model. Cyclodextrins are naturally occurring water-soluble molecules that can serve as carriers for lipid-soluble compounds. 13C-palmitate was complexed to either 20% methyl-β-cyclodextrin, 20% 2-hydroxypropyl-β-cyclodextrin, or 5% porcine albumin (isotopic purity of infusates: 99.22±0.06%). 13C-palmitate-albumin was infused under fed conditions and 13C-palmitate-methyl-β-cyclodextrin was infused under fasted and fed conditions in 50-kg pigs. Palmitate remained in solution at 4°C in methyl-β-cyclodextrin, but precipitated at 25-30°C in 2-hydroxypropyl-β-cyclodextrin. Pigs infused with 13C-palmitate-methyl-β-cyclodextrin maintained normal body temperature and appetite; those infused with 13C-palmitate-albumin became anorexic and exhibited other negative side effects to albumin. Palmitate oxidation rates under fed conditions were similar using either 13C-palmitate-methyl-β-cyclodextrin or 13C-palmitate-albumin complexes. Fasting increased 13C-palmitate-methyl-β-cyclodextrin oxidation by approximately eight-fold. These data suggest that methyl-β-cyclodextrin may be a suitable substitute for albumin in fatty acid metabolism studies in swine.