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

Abstract

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.

Association of dietary patterns and components with atherosclerosis risk biomarkers in familial hypercholesterolemia

“…Roy et al [34 ▪ ], conducted a systemic review on the impact of diet on the lipid profile of people with FH and concluded that the apparent lack of effectiveness of diet manipulation in modulating LDL-C levels and other plasma lipids is likely due to biases in study designs, rather than a true lack of effects. This finding highlights the need to conduct randomized clinical trials assessing the impact of dietary patterns on cardiovascular health in individuals with FH.…”

Nutritional Treatment in a Cohort of Pediatric Patients with Familial Hypercholesterolaemia: Effect on Lipid Profile

“…In the Cochrane review published in 2010 [ 22 ], the authors stated that there is not enough evidence on the efficacy of cholesterol lowering diet on lowering lipid values in a subject with FH. In a recent meta-analysis [ 23 ] looking at the impact of diet on lipid profile in patients with FH, a total lack of efficacy of nutritional intervention on LDL-cholesterol values was reported. In this meta-analysis, the authors hypothesised that this result is mainly determined by biases in study designs rather than by a true lack of effect.…”

“…They highlighted that a qualitative nutritional counseling, if compared to a quantitative one, not only improves general macro-nutrients consumption but also grants a lower allostatic load and a better compliance. As previously stated, currently published systematic reviews are not conclusive on the efficacy of nutritional intervention on improving lipid profiles in children with FH [ 22 , 23 ].…”

Nutritional Approach to Prevention and Treatment of Cardiovascular Disease in Childhood

“…This systematic review first highlighted that the lack of effectiveness of diet in modulating LDL-C levels is likely due to biases in study designs rather than a true lack of effects. In fact, most RCTs with a low risk of bias were more likely to report significant reduction in LDL-C [ 67 ]. Diet and healthy lifestyle efficacy in children with FH is variable and it is modulated by genetic factors, such as Apolipoprotein E genotype (ApoE genotype E3/E4 is related to higher lipid profile but with a better response to diet intervention) [ 59 ].…”