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Endothelial function and insulin sensitivity during acute non-esterified fatty acid elevation: effects of fat composition and gender

As we know, dietary fat quality may be a contributing factor for insulin resistance, which in turn can impact the risk for cardiovascular diseases. Saturated fatty acids (SFAs) may be more detrimental in this regard, whereas omega-3 fish oils (FOs) are anti-inflammatory and protective. In order to investigate how SFAs and FOs differentially impact insulin sensitivity of the blood vessels, researchers from the UK recruited 30 young, lean, and healthy men and women to perform a single-blind crossover study in which they ingested one of two fat loads on two separate occasions and had insulin sensitivity measured.

After an overnight fast, the subjects consumed a bolus fat load (66g) of either palm stearin or palm stearin with fish oil, followed by smaller 22g doses every 30 minutes thereafter for the entire 390 minute test period. A hyperinsulinemic-euglycemic clamp was started at 240 minutes and continued for the remaining time. The composition of the fat drinks is summarized in the table below.



 (% fatty acids)


(% fatty acids)

Palmitic acid (16:0) 59 51
Stearic acid (18:0) 5 4
Oleic acid (18:1) 28 24
Linoleic acid (18:2) 6 5
EPA (20:5 ω3)   1.2
DHA(22:6 ω3)   10.4
Other PUFA   1.4

The results reveal some very interesting sex differences in how the fat is handled. Males had 10% greater insulin sensitivity during the FO condition compared to the SFA condition, but no difference between the two was noted in females. Similarly, the beneficial impact of FO on flow-mediated vasodilation (FMD) and endothelial function was only present in females, whereas the impairment of FMD with SFA was only seen in males. The oral fat load ultimately resulted in a two-fold elevation of blood fatty acids that was 70% greater in males than females and also higher during SFA compared to FO. Finally, there was a significant increase in the percentage weight of SFA in the blood after the fat loads in both group, but the FO group also showed a 3-fold increase in EPA and 5-fold increase in DHA.

Bottom line

The big takeaway here is that males were more responsive to both the negative effects of SFA on FMD response, and the positive effects of FO on insulin sensitivity, while females were more responsive to the beneficial effects of FO on FMD. Practically speaking, this suggests that fish oils are beneficial for both sexes, albeit for different reasons, while SFAs are most detrimental in males and may place them at a greater cardiovascular risk than in females.

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