Effect of Diet on Lipid Levels in Children/Adolescents with Familial Hypercholesterolemia

Abstract

There is enough evidence, that children and adolescents with Familial Hypercholesterolemia (FH) should be treated in order to reduce elevated Total chol and LDL-c levels and therefore avoid the risk of early cardiovascular diseases. There are many papers published in the last years dealing with drug treatment, several publications describe guidelines for the therapy, however most without any data on the effect of recommended measures. The effect of diet on lipid levels in children with FH is not well documented. The goal of this paper was to search for data describing the effect of various dietary regimes in children and adolescents with FH. Surprisingly, there are only few papers studying the effect of various dietary regimes: in general, low fat-, fat substitutedor soy bean protein substituted diets are able to lower total chol and LDL-chol on average of 10–15 %. These effects should be documented and then used before starting drug treatment. Therefore, an effect of diet could reduce drug treatment or possibly postpone for some years. Anyhow, a carefully planned and performed diet for approx. 3 months should be the basis for the treatment of all children and adolescents with FH.

Keywords: Children/Adolescents; Familial Hypercholesterolemia; Diet; Drugs

Introduction

There is a body of evidence and general acceptance that children and adolescents affected with FH should be treated as soon as possible in order to lower elevated LDL-Chol levels. To achieve this goal, first dietary measures and secondary drug treatment is necessary [27,33]. Although there are several papers describing the effects of drug treatment, mainly for short periods, there is a paucity of studies describing the effect of dietary treatment in young subjects with FH. Principles of the diet are the reduction of saturated fats, substituted by mono- and polyunsaturated fatty acids, an increased intake of vegetables, fruits and legumes, and a low intake of simple carbohydrates. Surprisingly, there are many publications describing recommendations for the treatment of children and adolescents without any data.

Methods

In order to find out studies which describe dietary regimen and their effects in young subjects affected with FH we made a search on the scientific data banks and found only few publications in that field. Database searches were made on PubMed and Medline between December 2021 and May 2022. Searches were conducted with keywords as “Familial Hypercholesterolemia” and “Diet”.

Findings

The first paper judging the effect of diet on lipids in children with FH we found was published by Jakulj in 1974: They found a reduction of chol by 7, 5 and LDL-C by 9, 2% after a 4-week diet with daily 500ml low-fat yoghurt enriched with 2g stanols [1].

Laurin et al described a diet trial in 1991 in children with FH with a soy protein (35% of protein energy) compared with a low-milk protein drink. After some weeks the soy beverage reduced significantly triglycerides and low density lipoprotein (p < 0,05) whereas HDL-C increased significantly [2].

In 1993 our group in Vienna reported a dietary treatment in 23 children with FH or polygenic hypercholesterolemia using a soy protein substituted diet compared with a conventional diet for 8 weeks. In the soy group the lowering effect on LDL-C was significantly greater (p < 0, 05) than in the low fat, low cholesterol group [3].

Gylling and co-workers studied in 1995 the effect of sitostanol (3g/day) ester dissolved in rapeseed oil margarine in one homozygous and 14 heterozygous children with FH for 6 weeks within a doubleblind design. Sitostanol margarine diet reduced total cholesterol, HDL-C and LDL-C by 11, 26 and 15% and increased HDL/LDL ratio by 27%. They did not use a group with a usual low-fat diet [4].

The next study in this field has been published in 2002 by Amundsen at al from Oslo [5]. They conducted a study using plant sterol esters enriched spread in a randomized double blind crossover study for 8 weeks: They were able to show a decrease of LDL-C by 10,2% (p < 0,003) after this diet compared with the control group.

Again, our group in Vienna reported in 2002 a study on 10 children with FH the effect of a 5 months diet containing rapeseed oil compound with a classical low-fat/low-cholesterol diet. It could be shown, that the rapeseed diet lowered TG by 29% [6].

Another study carried out in Amsterdam on 41 children with FH has been published by de Jonghi at al in 2003: They also used a plant sterol spread (mainly sitosterol and campesterol) for 6 weeks and reported a decrease of total cholesterol by 11%, LDL-C by 14% as compared to placebo, but no effect on the endothelial function has been found. A reduction of total cholesterol by 10%, LDL-C by 7% compared to the classical low-fat diet an additional pronounced lowering effect of TG and HDL-C could be shown [7].

In 2008 our group in Vienna published a study of the effect of a standard diet compared to a soy substituted diet (0, 25-0,5g/kg body weight) in 23 children with FH during 3 months. After the standard diet chol and LDL-C decreased by 11, 8% and 11,8%, whereas during soy substituted diet an additional decrease of 7,7% and 7,6% could be shown [8].

In a trial comparing the effect of rapeseed oil with sunflower oil substituted low-fat diet our group was able to show that the cholesterol and LDL-C could be lowered by 10-12%, both significantly. The rapeseed diet showed more favorable effects in regard to the total cardiovascular risk profile [9].

Discussion

It is surprising that in contrast to adult studies only 10 diet studies on children with FH have been published during the last 30 years. From these studies it is evident that a strict dietary regime is able to lower total cholesterol and LDL-cholesterol in children with FH. This is important because lifestyle modification which includes not only diet but also physical activity and other factors that influence the behavior are essential factors in regard to prevent atherosclerotic processes in young age. From a psychological point of view, it seems fundamental for the whole family is motivated to adhere to a healthy lifestyle. Also unaffected family members could have a benefit from a healthy lifestyle and behavior.

In this regard it is very interesting, that between 2000 and 2020 at least 31 papers have been published describing recommendations and guidelines for the treatment of children and adolescents with FH without any data of the effect of diet [11-41) (Table 2).

  


    
Study

    
Results

  

  


    
[1]

    
Children at the age    of 7-12 years


      Intake of 500ml    low-fat yoghurt daily enriched with 2g stanols over 4 weeks


      TC decreased by    7.5% and LDL by 9.2% (compared to control group)

  

  


    
[2] 

    
10 children


      Low-fat/low-cholesterol/high-protein    diet, 20% protein, 28% fat, less than 200 mg cholesterol per day, 35% of the    protein from soy products


      No effect on TC,    LDL Apo-Lipoprotein but significant reduction in TG and VLDL 

  

  


    
[3]

    
23 children average    age of 9 years,


      Group 1 (G1): Soy    protein diet over 8 weeks


      Group 2 (G2):    low-fat, low-cholesterol diet


      After an    interruption of 8 weeks each group was placed on the alternate regimen


      During the soy    protein diet decrease in TC by 16% in G1 and 18% in G2; LDL decreased in G1    by 22% and in G2 by 25%.


      During the low-fat,    low-cholesterol diet TC and LDL were reduced by 8% and 7% in G1 and by 12%    and 13% in G2.

  

  


    
[4] 

    
14 children


      Low-cholesterol    diet for 6 weeks with an intake of 3g sitostanol per day via rapeseed oil or    margarine;


      Reduction of TC,    IDL and LDL by 11, 26 and 15%, respectively; 27% increase in HDL/LDL ratio 

  

  


    
[5]

    
38 children


      Consumption of    approx. 18g/d spread enriched with plant sterols (1.6g/d) over 8 weeks


      LDL decreased by    10.2%, TC and ApoB decreased by 7.4% 

  

  


    
[6] 

    
17 children and    adolescents at the age of 4 – 19 years


      5 months diet    enriched with rapeseed oil (average 15 – 22 g/d)


      Decrease in TG by    29%, VLDL-chol by 27%, TC by 10%, LDL-chol by 7%

  

  


    
[7] 

    
41 children


      Daily consumption    of 15g spread enriched with 2.3g plant sterols for 4 weeks


      Decrease of TC by    11% and LDL by 14% compared to the control group

  

  


    
[8] 

    
16 children with    FH, average age 8.8 years, replacement of animal protein with soy products    over 3 months;


      Reduction of TC,    LDL and ApoB by 12.3, 11.8 and 10.6%

  

  


    
[9]

    
21 children at the    age of 6 -18 years,


      fat-modified diet    enriched with rapeseed or sunflower oil for 13 weeks; Reduction of TC by 9.4%    in both, LDL by 12.7% (in rapeseed oil) and 11.3% (in sunflower oil) 

  

  


    
[10] 

    
34 children


      Group 1 diet    supplemented with soy products; Group 2 Control group on a fat-modified diet    for 13 weeks


      LDL decreased more    significantly in the soy group compared to the control group (154.7 vs.    176.3)

  

Table 1: Overview of Studies on FH, with data on the effect of recommended measures.

  


    
Study

    
Guideline

  

  


    
[13] 

    
Guideline on Diagnosis, Guidance    on lifestyle modification and keeping appropriate body weight, initiate    lipid-lowering therapy at the same time; offering maximum tolerated dose of    statin and/or ezetimibe in combination; if insufficient effect add PCSK9    inhibitor and/or resin and/or probucol; if insufficient effect LDL-apheresis;


      No data on the effect of the recommended measures

  

  


    
[12] 

    
Review of diagnosis, screening    and treatment; Summary of recommendations:


      Management on FH: 1. Reduce LDL    level by = 50% from baseline, 2. Use high-dose statin as first-line therapy,    3. In patients who fail to achieve the reduction of = 50% in LDL levels with    statin therapy other LDL-lowering agents should be added as ezetimibe,    bile-acid sequestrants, fibrates or niacin


      No data on the effect of the recommended measures.

  

  


    
[25]

    
Overview of currently approved    therapeutics for lipid lowering with expected effects on lipid profiles from    data on pooled analysis;


      e.g. HMG-CoA reductase inhibitors    (statins) – LDL lowering up to 50%, HDL increase up to 10%, TG lowering up to    20%


      Bile acid sequestrants – LDL    lowering about 18%, HDL no significant change, TG variable


      Nicotinic acids – LDL lowering    12%, HDL increase 16%, TG lowering 20%


      Fibrates – LDL lowering 8%, HDL    increase 9 – 10%, TG lowering 30-36%


      No data on the diet.

  

  


    
[18]

    
Position Paper on Guidelines on    diagnosis and management of FH;


      Summary of Recommendations:


      Management should focus on a    combination of lifestyle, statin therapy and lipoprotein apheresis; the    lipid-lowering therapy should start as soon as possible; LDL apheresis can be    considered in all patients with HoFH, and can be started at the age of 5 and    not later than 8 years; Lomitapide and mipomersen should be considered as    additional treatments to further lower plasma LDL-c levels


      No data on the effect of the recommended measures

  

  


    
[22] 

    
Guideline for the Management of    FH,


      Diagnostic criteria: LDL-c = 180    mg/dl, tendon/skin xanthoma and a family history of FH or premature CAD


      Treatment: intensive lipid    control with statins and if necessary, with other drugs


      Control other risks of CAD such    as smoking, DM and hypertension


      No data on the effect of the recommended measures

  

  


    
[20] 

    
Review of Guidelines on Genetic    Testing and Management of FH


      Ten Guidelines were considered    appropriate and of good quality


      Most important thing: a early    detection of affected patients for effective prevention of CVD


      No data on the effect of the recommended measures

  

  


    
[19] 

    
Guideline for new horizons for    Diagnosis and Effective Management;


      Summary of management options for    FH with expected effect on lipid metabolism;


      Low cholesterol diet – to reduce    the cholesterol intake – reduction of LDL up to 10%


      Plant Sterols Statins – should    affect cholesterol absorption – no defined results


      Statins – inhibition of HMG-CoA    reductase - LDL reduction up to 80% in HeFH and 20% in HoFH,


      Ezetimibe – blocks the intestinal    absorption of cholesterol – reduction of LD up to 15 -20%


      No data on the effect of the recommended measures.


      Bile acid sequestrants – Increase    of feacal excretion of bile acids and LDL-R up regulation – Reduction of LDL    up to 18-25%


      Fish Oils – improve the lipid    profile (fewer/larger LDL, more/larger HDL particles) – Reduction of TG up to    20% and decrease in ApoB


      Lipoprotein apheresis – selective    mechanical lipid removal – LDL Reduction up to 25%, Lp(a) reduction up to 50-70%

  

Table 2: Overview of some Studies with Guidelines on FH, without any data on the effect of recommended.

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Citation: Widhalm K and Fallmann K. Effect of Diet on Lipid Levels in Children/Adolescents with Familial Hypercholesterolemia. Austin J Nutri Food Sci. 2022; 10(2): 1168.

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