Clinical evidence showing linoleic acid reduces risk for metabolic diseases including type 2 diabetes

Abstract: Cross sectional and prospective studies have revealed that higher levels of linoleic acid (LA; 18:2n6) in either the diet or body are associated with lower risk for metabolic diseases including metabolic syndrome and type 2 diabetes. Although measuring a causal effect of LA to reduce disease prevalence may be difficult, rigorously designed, double blind, randomized controlled trials (RCTs) have revealed many of the risk factors for metabolic disease, including central obesity, chronic inflammation, insulin resistance, and disproportionate adipokines, are corrected after LA oil supplementation in adults. LA and oxylipin metabolites may reduce metabolic disease risk by working as signaling molecules to activate PPARs and other nuclear hormone receptors. Additionally, LA is the preferred acyl component of cardiolipin in the inner mitochondrial membrane. Because cardiolipin is the required phospholipid for scaffolding the electron transport chain complex, mitochondrial respiration and energy metabolism are dependent on adequate LA for carrying out energy metabolism. We recently found that mitochondria-rich tissues, e.g., liver, brown adipose tissue and skeletal muscle from mice fed LA-fortified diet have higher mitochondrial respiration that mice fed a control diet. Some, but not all (e.g., cardiolipin and mitochondrial function) of these mechanisms overlap with effects of long chain omega-3 fatty acids. Like alpha-linolenic acid, LA is an essential nutrient that is required in the diet. However, there had not been sufficient evidence for setting a dietary recommended intake (DRI). Perhaps it’s time to rethink the need and sufficiency of evidence for setting an DRI for LA. This work was supported by the Ohio Agriculture Research and Development Center (Wooster, OH).