title: Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans.
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.
authors.affiliation: Section on Nutritional Neurosciences, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. chris.ramsden@nih.gov
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Ramsden
authors.forename: Amit
authors.initials: A
authors.lastname: Ringel
authors.forename: Ariel E
authors.initials: AE
authors.lastname: Feldstein
authors.forename: Ameer Y
authors.initials: AY
authors.lastname: Taha
authors.forename: Beth A
authors.initials: BA
authors.lastname: MacIntosh
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Hibbeln
authors.forename: Sharon F
authors.initials: SF
authors.lastname: Majchrzak-Hong
authors.forename: Keturah R
authors.initials: KR
authors.lastname: Faurot
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
authors.forename: Yewon
authors.initials: Y
authors.lastname: Cheon
authors.forename: Yoon-Mi
authors.initials: YM
authors.lastname: Chung
authors.forename: Michael
authors.initials: M
authors.lastname: Berk
authors.forename: J Douglas
authors.initials: JD
authors.lastname: Mann
mesh_terms: D000328:Adult; D004041:Dietary Fats / Q000097:blood / Q000378:metabolism; D005260:Female; D006261:Headache / Q000097:blood / Q000178:diet therapy / Q000378:metabolism; D006801:Humans; D019787:Linoleic Acid / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism*; D008041:Linoleic Acids / Q000097:blood / Q000378:metabolism; D044243:Linoleic Acids, Conjugated / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D055815:Young Adult
chemical_list: D004041:Dietary Fats; D008041:Linoleic Acids; D044243:Linoleic Acids, Conjugated; C024347:9-hydroxy-10,12-octadecadienoic acid; C024348:13-hydroxy-9,11-octadecadienoic acid; D019787:Linoleic Acid