Using metabolic profiling and gene expression analyses to explore molecular effects of replacing saturated fat with polyunsaturated fat—a randomized controlled dietary intervention study

A recent study has found positive metabolic changes following improvements in the fat quality of the diet.

Replacing saturated fatty acids (SFAs) with polyunsaturated fatty acids (PUFAs) has been linked to a reduced risk of CVD. In addition, controlled metabolic studies have shown the importance of fat quality on LDL cholesterol and randomised controlled trials have shown that replacing SFA with PUFA significantly reduces LDL cholesterol. What is less well known is the metabolic alterations that occur when replacing SFA with PUFA in the diet.

In an 8-week, double-blind randomised controlled trial involving 99 healthy subjects with moderate hypercholesterolaemia, dietary SFA was replaced with PUFA. The control group consumed a diet where 18% of calories came from SFA and 5.6% calories from PUFA. Whereas the intervention group consumed a diet with 11.5% of calories from SFA and 12% from PUFA. In addition, the protein intake was 1.5% of calories higher in the intervention group and fibre intake was 11.5g/ day higher. Comprehensive metabolic profiling was performed at baseline and after 8 weeks of follow-up.

After 8 weeks, among individuals with moderate hypercholesterolaemia, lipoprotein concentrations of the atherogenic particles (including LDL, IDL and all the VLDL particles) were reduced after replacing SFA with PUFAs. In addition, PCSK9, bile acids and 11 low-molecular-weight metabolites, many of which are associated with CVD risk, were favourably altered in the intervention group compared with the control group. In peripheral blood mononuclear cells (PBMC), the mRNA level of several genes involved in lipogenesis, cholesterol metabolism, β-oxidation and inflammation were changed during the intervention.

The favourable metabolic alterations observed in this study support recommendations to improve the fat quality of the diet.

Stine M Ulven, Jacob J Christensen, et al, The American Journal of Clinical Nutrition, Volume 109, Issue 5, May 2019, Pages 1239–1250,


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