The Role of α-Linolenic Acid and Its Oxylipins in Human Cardiovascular Diseases

Abstract

α-linolenic acid (ALA) is an essential C-18 n-3 polyunsaturated fatty acid (PUFA), which can be elongated to longer n-3 PUFAs, such as eicosapentaenoic acid (EPA). These long-chain n-3 PUFAs have anti-inflammatory and pro-resolution effects either directly or through their oxylipin metabolites. However, there is evidence that the conversion of ALA to the long-chain PUFAs is limited. On the other hand, there is evidence in humans that supplementation of ALA in the diet is associated with an improved lipid profile, a reduction in the inflammatory biomarker C-reactive protein (CRP) and a reduction in cardiovascular diseases (CVDs) and all-cause mortality. Studies investigating the cellular mechanism for these beneficial effects showed that ALA is metabolized to oxylipins through the Lipoxygenase (LOX), the Cyclooxygenase (COX) and the Cytochrome P450 (CYP450) pathways, leading to hydroperoxy-, epoxy-, mono- and dihydroxylated oxylipins. In several mouse and cell models, it has been shown that ALA and some of its oxylipins, including 9- and 13-hydroxy-octadecatrienoic acids (9-HOTrE and 13-HOTrE), have immunomodulating effects. Taken together, the current literature suggests a beneficial role for diets rich in ALA in human CVDs, however, it is not always clear whether the described effects are attributable to ALA, its oxylipins or other substances present in the supplemented diets.

Elevated phospholipid hydroperoxide glutathione peroxidase (GPX4) expression modulates oxylipin formation and inhibits age-related skeletal muscle atrophy and weakness

“…8 ). Oxylipin levels (pg/mg tissue) were reduced more than 50% for 7 out of 12 detected species generated enzymatically by the activity of lipoxygenase from arachidonic acid (AA): 5- and 15-HETE [ 40 , 41 ], linoleic acid (LA): 13-HODE [ 40 ], alpha linoleic acid (ALA): 9- and 13-HOTrE [ 42 , 43 ], dihomo gamma linoleic acid (DGLA): 15-HETrE [ 44 ], eicosapentaenoic acid (EPA): 15-HEPE [ 45 ], and docosahexaenoic acid (DHA): 14-HDoHE [ 46 ]. Likewise, 11 detected oxylipins generated by COX or CYP activity or non-enzymatically, including 11-HETE, PGD2, PGE2, PGF2α (AA metabolites) [ 41 ], 9,10-DiHOME (LA metabolite) [ 47 ], 17,18-DiHETE (EPA metabolite) [ 40 ], 10-, 13-, 14-16-, 20-HDoHE (DHA metabolites) [ 46 ], and 9-HODE (LA metabolite) [ 48 ], were also reduced by GPX4 overexpression in aging muscle.…”

Nutritional Status, Selected Nutrients Intake, and Metabolic Disorders in Bariatric Surgery Patients

“…Another study showed that the preoperative level of LA in the blood was a predictive factor of BMI reduction, which might be suggestive of its favorable influence on weight loss [72]. ALA is a substrate for the production of EPA and DHA, which present a multidirectional positive potential in the body [69][70][71]. They demonstrate the following properties: neuroprotective, anti-depressive, anti-inflammatory [34,[69][70][71][72][73], hypotensive, anti-thrombotic, and hypolipidemic (mainly diminishing plasma TGs, suppressing their synthesis in the intestinal wall and liver, and increasing their disintegration in the process of β-oxidation in the mitochondria) [69][70][71].…”

“…However, the consumption of other ω-3 group acids, i.e., EPA and DHA, was insufficient (57% and 20% of the reference values, respectively) compared to the requirements (250 mg/d), which might increase the risk of circulatory system diseases in the study group. PUFAs (ω-3 and ω-6) need to be provided with food, as they are not synthesized by the body [24,[69][70][71]. It is known that, depending on the dose, the regular consumption of ALA is a substrate for the production of EPA and DHA, which present a multidirectional positive potential in the body [69][70][71].…”

“…PUFAs (ω-3 and ω-6) need to be provided with food, as they are not synthesized by the body [24,[69][70][71]. It is known that, depending on the dose, the regular consumption of ALA is a substrate for the production of EPA and DHA, which present a multidirectional positive potential in the body [69][70][71]. Moreover, it was demonstrated that the total consumption of PUFA, LA, and ALA was negatively correlated with abdominal obesity and hypertension [65].…”

Alternative sources of bioactive omega-3 fatty acids: what are the options?

“…Chia seeds are also rich in ALA (60% of fatty acids). ALA has some biological properties in its own right; for example, it lowers total and low-density lipoprotein cholesterol [69 ▪ ] and is a precursor to oxylipins [70 ▪ ] some of which are bioactive [71 ▪▪ ]. There is a pathway by which ALA is converted to EPA and on to DHA (Fig.…”