Background: An inverse relationship between saturated fatty acid (SFA) intake and Lp(a) concentration has been observed; however, there has been no quantification of this effect.

Objectives: The objective was to determine whether SFA consumption alters Lp(a) concentrations among adults without atherosclerotic cardiovascular disease (ASCVD).

Methods: A systematic review and meta-analysis of randomized controlled trials contrasting a lower SFA diet(s) with a higher SFA diet(s) among adults without ASCVD was conducted. PubMed, Cochrane Central Register of Clinical Trials, clinicaltrials.gov, and Web of Science databases and registers were searched through October 2023. The standardized mean difference (SMD) in Lp(a) between diets lower and higher in SFA [percentage of energy (%E)] was determined using random-effects meta-analysis. Analyses were also conducted to examine the effect of replacing SFA with carbohydrates (CHO), monounsaturated (MUFAs), polyunsaturated (PUFAs), or trans fatty acids (TFAs).

Results: In total, 6255 publications were identified in the systematic search. Twenty-six publications reporting 27 randomized controlled trials, including 1325 participants and 49 diet comparisons, were included. The mean difference in SFA between lower and higher SFA diets was 7.6%E (3.7%-17.8%E). After lower SFA diets, Lp(a) concentration was higher (SMD: 0.14; 95% confidence interval [CI]: 0.03, 0.24) than that after higher SFA diets. Subgroup analyses showed higher Lp(a) following diets where SFA was replaced by CHO (trials = 8; n = 539; SMD 0.21: 95% CI: 0.02, 0.40) or TFAs (trials = 8; n = 300; SMD: 0.32; 95% CI: 0.17, 0.48). No differences in Lp(a) were observed when MUFA (trials = 16; n = 641; SMD: 0.04; 95% CI: -0.08, 0.16) or PUFA (trials = 8; n = 415; SMD: 0.09; 95% CI: -0.04, 0.22) replaced SFA.

Conclusions: Lower SFA diets modestly increase Lp(a) than higher SFA diets among individuals without ASCVD. This effect appeared to be driven by replacement of SFA with CHO or TFA. Research investigating the atherogenicity of diet-induced Lp(a) changes is needed to inform dietary management of lipid/lipoprotein disorders. This trial was registered with PROSPERO as CRD42020154169.