The main objective of this randomized clinical trial is to evaluate the effects of the adapted Brazilian Cardioprotective Diet (DICA Br) supplemented or not with phytosterols and/or krill oil in patients with a probable or definitive diagnosis of familial hypercholesterolemia (FH) according to the the Dutch Lipid Clinic Network (Dutch MEDPED) criteria. In addition, the following will be considered secondary objectives: to perform participants´ whole genome sequencing (WGS); to evaluate the effects of the interventions on lipid profile biomarkers; to evaluate the frequency of mild, moderate and severe adverse events according to study groups; and to evaluate adherence rates according to study groups. In this study, 300 individuals will be randomly enrolled into four groups: 1) DICA Br adapted to the FH context (DICA-FH) + phytosterol placebo + krill oil placebo (control group); 2) DICA-FH + 2g/day of phytosterol + krill oil placebo; 3) DICA-FH + phytosterol placebo + 2g/day of krill oil; and 4) DICA-FH + 2g/day of phytosterol + 2g/day of krill oil. Primary outcomes will be LDL-cholesterol for groups phytosterol vs. placebo and lipoprotein(a) for groups krill oil vs. placebo after 120 days of follow up.

DICA-FH study is a superiority, factorial, and in parallel multicenter randomized placebo-controlled (double-dummy) clinical trial. The randomization will be in blocks stratified by research center, and the allocation ratio will be 1:1:1:1. Participants will come from at least 20 center sites in different Brazilian geographic regions.

Inclusion Criteria:

• Age ≥16 years;
• Definitive (certainty) or probable diagnosis of FH by the Dutch MEDPED criteria;
• Using one of the following treatment regimens for ≥6 weeks according to age:

>= 20 years -> simvastatin 40 mg; lovastatin 40 mg; pravastatin 80 mg; atorvastatin 20 mg; rosuvastatin 10 mg; pitavastatin 4 mg; fluvastatin 80 mg; atorvastatin 40- 80 mg; rosuvastatin 20 - 40 mg; atorvastatin 40 - 80 mg + ezetimibe 10mg; rosuvastatin 20 - 40 mg + ezetimibe 10mg; or simvastatin 40mg + ezetimibe 10mg.

16 to 19 years -> simvastatin 10 - 40 mg; lovastatin 10 - 40 mg; pravastatin 10 - 40 mg; atorvastatin 10 - 40 mg; rosuvastatin 5 - 40 mg; cholestyramine 4 to 16 mg; ezetimibe 10mg (in combination with statin).

Exclusion Criteria:

• Having a "possible" FH result according to the Dutch MEDPED criteria;
• TG ≥ 500mg/dL up to 6 months before screening for the study;
• Diagnosis of hypercholesterolemia due to a secondary cause recorded in the medical record;
• Food allergies (foods, dyes, preservatives);
• Contraindication to the use of phytosterols (for example: diagnosis of sitosterolemia);
• HIV positive on treatment with detectable viral load or AIDS;
• Chronic inflammatory or autoimmune diseases;
• Known liver disease, chronic kidney disease on dialysis or pancreatitis (acute and chronic);
• Cancer being treated or life expectancy < 6 months;
• Episode of acute coronary syndrome in the last 60 days;
• Chemical dependency/alcoholism;
• Chronic use of anti-inflammatories, anticonvulsants and immunosuppressive drugs;
• Use of PCSK9 inhibitors (alirocumab, evolocumab, inclisiran);
• Pregnancy or lactation;
• Individuals who are unable to perform an anthropometric assessment, at the discretion of the investigator;
• Grade III/severe obesity (body mass index [BMI] ≥40kg/m² for adults or percentile >99.9 or z-score >+3 according to WHO/2006 growth curves for BMI/Age indicator for adolescents);
• Use of dietary supplements that may interfere with the outcomes of interest (dietary fiber modules, n-3 PUFA, essential fatty acids);
• Participation in other randomized clinical trials;
• Refusal to participate in the study, due to failure to sign the Free and Informed Consent Form.

The data supporting the findings of the DICA-FH study will be available upon reasonable request. Broader public access to the study database will be provided in due course, as soon as possible, in accordance with the Hcor Research Institute (IP-Hcor) data-sharing policy.

The data will be available in due course, as soon as possible, from the time the manuscript reporting the main study results is published, for an indefinite period.

The study protocol, as well as the informed consent form and the statistical analysis plan will be made publicly available once the design paper is published. The clinical study report, analytic code, and clinical data will be available upon reasonable request, in accordance with the data-sharing policies of the IP-Hcor.