Summary
Linoleic acid (LA), the most abundant polyunsaturated fat in modern diets and a key structural component of human tissues, is also the precursor to oxidized lipid metabolites known as OXLAMs—such as 9- and 13-HODE and 9- and 13-oxoODE—which have been linked to cardiovascular disease, chronic pain, Alzheimer’s disease, and fatty liver disease, and are even proposed as biomarkers for these conditions. Because humans cannot synthesize LA, dietary intake strongly determines the body’s OXLAM levels. This study tested the impact of lowering LA intake by measuring blood LA and OXLAMs in chronic headache patients before and after a 12-week LA-reduction diet, finding that reduced LA intake significantly decreased circulating OXLAMs—including inflammatory markers like 9-HODE and 13-HODE—and lowered LA content in multiple blood lipid fractions that act as storage pools, thereby reducing the body’s substrate for producing these oxidized products. In short, lowering dietary LA led to fewer harmful oxidized LA metabolites, supporting the idea that dietary LA directly shapes oxidative lipid burden and suggesting a potential therapeutic role for LA reduction in conditions involving inflammation, oxidative stress, and metabolic dysfunction, pending further clinical outcomes research.
PMID: 22959954
PMCID: PMC3467319
DOI: 10.1016/j.plefa.2012.08.004
Abstract
Linoleic acid (LA) is the most abundant polyunsaturated fatty acid in human diets, a major component of human tissues, and the direct precursor to the bioactive oxidized LA metabolites (OXLAMs), 9- and 13 hydroxy-octadecadienoic acid (9- and 13-HODE) and 9- and 13-oxo-octadecadienoic acid (9- and 13-oxoODE). These four OXLAMs have been mechanistically linked to pathological conditions ranging from cardiovascular disease to chronic pain. Plasma OXLAMs, which are elevated in Alzheimer's dementia and non-alcoholic steatohepatitis, have been proposed as biomarkers useful for indicating the presence and severity of both conditions. Because mammals lack the enzymatic machinery needed for de novo LA synthesis, the abundance of LA and OXLAMs in mammalian tissues may be modifiable via diet. To examine this issue in humans, we measured circulating LA and OXLAMs before and after a 12-week LA lowering dietary intervention in chronic headache patients. Lowering dietary LA significantly reduced the abundance of plasma OXLAMs, and reduced the LA content of multiple circulating lipid fractions that may serve as precursor pools for endogenous OXLAM synthesis. These results show that lowering dietary LA can reduce the synthesis and/or accumulation of oxidized LA derivatives that have been implicated in a variety of pathological conditions. Future studies evaluating the clinical implications of diet-induced OXLAM reductions are warranted.
Ramsden CE, Ringel A, Feldstein AE, Taha AY, MacIntosh BA, Hibbeln JR, Majchrzak-Hong SF, Faurot KR, Rapoport SI, Cheon Y, Chung YM, Berk M, Mann JD. Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans. Prostaglandins Leukot Essent Fatty Acids. 2012 Oct-Nov;87(4-5):135-41. doi: 10.1016/j.plefa.2012.08.004. Epub 2012 Sep 5. PMID: 22959954; PMCID: PMC3467319.