Dietary Recommendations for Familial Hypercholesterolaemia: Time to reject the ‘Diet-Heart Hypothesis’

Familial hypercholesterolaemia (FH), is a genetic condition in which increased low-density lipoprotein cholesterol (LDL-C) is associated with an increased risk for coronary heart disease (CHD). [Ref: Diamond DM, Alabdulgader AA, de Lorgeril M, et al. BMJ Evidence-Based Medicine Epub ahead of print: [please include Day Month Year]. doi:10.1136/ bmjebm-2020-111412]

Recommendations for FH individuals have emphasised a low saturated fat, low cholesterol diet to reduce their LDL-C levels. The basis of this recommendation is the ‘diet-heart hypothesis’, which postulates that consumption of food rich in saturated fat increases serum cholesterol levels, which increases risk of CHD.

We have challenged the rationale for FH dietary recommendations based on the absence of support for the diet-heart hypothesis, and the lack of evidence that a low saturated fat, low cholesterol diet reduces coronary events in FH individuals.

Research has shown that the subset of FH individuals that develop CHD exhibit risk factors associated with an insulin-resistant phenotype (elevated triglycerides, blood glucose, haemoglobin A1c (HbA1c), obesity, hyperinsulinaemia, high‐sensitivity C reactive protein, hypertension) or increased susceptibility to develop coagulopathy. The insulin-resistant phenotype, also referred to as the metabolic syndrome, manifests as carbohydrate intolerance, which is most effectively managed by a low carbohydrate diet (LCD).

Therefore FH individuals with signs of insulin resistance should be made aware of the benefits of an LCD. Our assessment of the literature provides the rationale for clinical trials to be conducted to determine if an LCD would prove to be effective in reducing the incidence of coronary events in FH individuals which exhibit an insulin-resistant phenotype or hyper-coagulation risk.

Key points

  • Current dietary guidelines for management of coronary heart disease (CHD) risk in familial hypercholesterolaemia (FH) are based on the diet-heart hypothesis, which is outdated and unsupported.
  • There is no evidence to support the recommendation that FH individuals should consume a low saturated fat, low cholesterol diet.
  • A low carbohydrate diet (LCD) significantly improves cardiovascular disease biomarkers, compared with a low fat diet.
  • There is sufficient rationale for conducting clinical trials to assess the effects of an LCD on FH individuals with an insulin-resistant phenotype.
  • Extensive research has documented that hypercoagulation is a more important risk factor for CHD than low-density lipoprotein cholesterol in FH. Therefore, LCD trials should include FH subjects with an elevated risk of hypercoagulation.

Are some diets “mass murder” ? Richard Smith, BMJ 

Bold policies have been based on fragile science, and the long term results may be terrible. Jean Mayer, one of the “greats” of nutrition science, said in 1965, in the colourful language that has characterised arguments over diet, that prescribing a diet restricted in carbohydrates to the public was “the equivalent of mass murder.”

John Ioannidis, the scourge of poor biomedical science, has shown the great unreliability of most studies linking nutrition to disease and mortality,7 and perhaps we fail to recognise the complexity of relations between diet and disease when we pick out single components, whether it’s total fat, saturated fat, trans fats, sugar, or salt.

I’m left with the impression that the same accusation of “mass murder” could be directed at many players in the great diet game. 


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