Impact of Diet on Plasma Lipids in Individuals with Heterozygous Familial Hypercholesterolemia: A Systematic Review of Randomized Controlled Nutritional Studies

Background: Conclusive data on the effectiveness of dietary interventions in heterozygous familial hypercholesterolemia (HeFH) management are unavailable. Whether this is due to a true lack of effects or biases in intervention designs remains unsettled. We systematically assessed the impact on LDL-C of published dietary randomized controlled trials (RCTs) conducted among individuals with HeFH in relation to their design and risk of bias. Methods: We systematically searched PubMed, Web of Science, and Embase in November 2020 to identify RCTs that assessed the impact of: (1) food-based interventions; (2) dietary counseling interventions; or (3) dietary supplements on LDL-C in individuals with HeFH. We evaluated the risk of bias of each study using the Cochrane Risk of Bias 2 method. Results: A total of 19 RCTs comprising 837 individuals with HeFH were included. Of those, five were food-based interventions, three were dietary counseling interventions and 12 were dietary supplement-based interventions (omega-3, n = 3; phytosterols, n = 7; guar gum, n = 1; policosanol, n = 1). One study qualified both as a food-based intervention and as a dietary supplement intervention due to its factorial design. A significant reduction in LDL-C levels was reported in 10 RCTs, including eight dietary supplement interventions (phytosterols, n = 6, omega-3, n = 1; guar gum, n = 1), one food-based intervention and one dietary counseling intervention. A total of 13 studies were judged to have some methodological biases in a way that substantially lowers confidence in the results. Studies at low risk of biases were more likely to report significant reductions in LDL-C concentrations, compared with studies at risk of bias (chi-square statistic: 5.49; p = 0.02). Conclusion: This systemic review shows that the apparent lack of effectiveness of diet manipulation in modulating plasma levels of LDL-C among individuals with HeFH is likely due to biases in study designs, rather than a true lack of effects. The likelihood of reporting significant reductions in LDL-C was associated with the concurrent risk of bias.