Obesity increases the risk for insulin resistance (IR) and type-2 diabetes. Lifestyle interventions (LI) and dietary supplementation can help mitigate IR. We investigated the effect of calanus oil (CO) supplementation, combined with LI, on glucose homeostasis in obese subjects. CO, a novel marine oil, contains omega-3 fatty acid wax esters as well as plant sterols and astaxanthin. In the double-blind, randomized, placebo-controlled 12-week intervention study, 266 subjects with distinct IR phenotypes were assigned to four groups: 2 g CO/day, 4 g CO/day, 2 g CO/day + LI, and placebo. The effect of CO on HOMA index reduction was influenced by the initial (t