Linoleic Acid‐Rich Oil Alters Circulating Cardiolipin Species and Fatty Acid Composition in Adults: A Randomized Controlled Trial

Abstract

Scope Higher circulating linoleic acid (LA) and muscle‐derived tetralinoleoyl‐cardiolipin (LA4CL) are each associated with decreased cardiometabolic disease risk. Mitochondrial dysfunction occurs with low LA4CL. Whether LA‐rich oil fortification can increase LA4CL in humans is unknown. The aims of this study are to determine whether dietary fortification with LA‐rich oil for 2 weeks increases: 1) LA in plasma, erythrocytes, and peripheral blood mononuclear cells (PBMC); and 2) LA4CL in PBMC in adults. Methods and results In this randomized controlled trial, adults are instructed to consume one cookie per day delivering 10 g grapeseed (LA‐cookie, N = 42) or high oleate (OA) safflower (OA‐cookie, N = 42) oil. In the LA‐cookie group, LA increases in plasma, erythrocyte, and PBMC by 6%, 7%, and 10% respectively. PBMC and erythrocyte OA increase by 7% and 4% in the OA‐cookie group but is unchanged in the plasma. PBMC LA4CL increases (5%) while LA3OA1 CL decreases (7%) in the LA‐cookie group but are unaltered in the OA‐cookie group. Conclusions LA‐rich oil fortification increases while OA‐oil has no effect on LA4CL in adults. Because LA‐rich oil fortification reduces cardiometabolic disease risk and increases LA4CL, determining whether mitochondrial dysfunction is repaired through dietary fortification is warranted.

Differences in Plasma Fatty Acid Composition Related to Chronic Pancreatitis

“…47 Linoleic acid supplementation of less than one serving of oil per day increases plasma linoleic acid and tetralinoleoyl cardiolipin (important in mitochondrial function) in peripheral blood mononuclear cells of healthy subjects. 48 Our unexpected finding of higher linoleic acid and lower oleic acid in CP with diabetes may be related to an increased use in diabetic drugs modulating FA uptake and metabolism or that the combined endocrine and exocrine dysfunction may modify these FAs within CP in a previously unreported fashion. Therefore, further assessment of FAs and their metabolism within CP and diabetes will be needed to understand the complex regulation of FAs.…”

“…In addition, high linoleic acid levels are also associated with improved glycemic control and a reduced incidence of diabetes 46 and reduces diabetes in preclinical models 10 and clinical trials 47 . Linoleic acid supplementation of less than one serving of oil per day increases plasma linoleic acid and tetralinoleoyl cardiolipin (important in mitochondrial function) in peripheral blood mononuclear cells of healthy subjects 48 . Our unexpected finding of higher linoleic acid and lower oleic acid in CP with diabetes may be related to an increased use in diabetic drugs modulating FA uptake and metabolism or that the combined endocrine and exocrine dysfunction may modify these FAs within CP in a previously unreported fashion.…”

Linoleate-Enrichment of Mitochondrial Cardiolipin Molecular Species Is Developmentally Regulated and a Determinant of Metabolic Phenotype

“…These observations suggesting that LA-enrichment promotes and regulates fatty acid utilization may provide a potential therapeutic opportunity by supporting ß-OX and oxidative metabolism in cardiac diseases via modulation of the CL profile with diet or pharmacologic agents that promote CL remodeling. Indeed, our prior work has shown that the proportion of L 4 CL could readily be increased through LA dietary supplementation in Spontaneously Hypertensive Heart Failure rats, and in human subjects ingesting LAenriched cookies, presenting a potential therapeutic strategy to an energy-starved failing heart [11,20,27].…”

Unraveling the mechanisms of cardiolipin function: The role of oxidative polymerization of unsaturated acyl chains

“…However, it has been observed that supplemental linoleic acid attenuated, to some extent, the impaired contractile phenotype in vitro in tafazzin knocked-down soleus [ 31 ]. Furthermore, the supplementation of linoleic acid in Barth syndrome fibroblasts restored cardiolipin levels [ 32 ], and the use of linoleic acid-rich oil altered circulating cardiolipin species and fatty acid composition in adults [ 33 ].…”