Lowering saturated fats in the diet for Familial Hypercholesterolemia is not supported by randomized controlled trials.
Familial Hypercholesterolemia (FH) is a genetic disorder characterized by increased low-density lipoprotein cholesterol (LDL-C) in the blood. High LDL-C is linked with a higher risk of coronary heart disease (CHD). For eight decades the dietary recommendations for FH have been a low cholesterol diet, which was thought to help reduce LDL-C and decrease CHD risk.
The first documentation of dietary guidance for FH was by Muller in 1939, who recommended a diet deficient in cholesterol: containing no butter, cream, fat milk, egg yolk, or any fat coming from an animal. In 2018 the American Heart Association (AHA) cholesterol guidelines recommended a “heart-healthy” diet to individuals with FH, including eating low-fat dairy and poultry products (no skin), non-tropical oils, and limiting saturated fat intake. Thus far, all the FH dietary recommendations are not fact-based and have no related randomized controlled trials (RCTs). Steven Nissen, Cleveland Clinic’s Chair of the Department of Cardiovascular Medicine, has said, “current and past U.S. dietary guidelines represent a nearly evidence-free zone.”
A new study published in BMJ Evidence-Based Medicine reviews several studies collecting evidence of several markers for CHD, including atherogenic dyslipidemia risk triad (ADRT), Lipoprotein (LP(a)), the hemostatic balance between coagulation and fibrinolysis and non-lipid CHD risk factors. Each biomarker was tested against LDL-C to determine if LDL-C played a role in the development of CHD. All the evidence pointed to LDL-C not being the leading cause of CHD development in patients with FH A subset of individuals with FH exhibit metabolic syndrome or insulin-resistant phenotype — high triglycerides (T.G.), hypertension blood glucose, hemoglobin A1c (HbA1c), hyperinsulinemia, high sensitivity C reactive protein — which is an intolerance to carbohydrates. So, what are the effects of LCD in individuals with FH who exhibit metabolic syndrome?
Some of the evidence is: the ADRT includes triglycerides (T.G.), high-density lipoprotein (HDL), and small, dense LDL associated with increased CHD risk. A study showed that individuals with FH and high T.G.>200 mg/dL developed a Myocardial Infarction (MI) three times as often as individuals with FH and low T.G. <200 mg/dL; the association of high levels of TGs in FH with a high rate of MI occurrence was independent of their LDL-C levels. According to Seed et al., lipoprotein or LP(a) is a more significant CHD indicator than LDL-C. Ravnskov et al.’s findings showed that hypercoagulation was a more reliable indicator of CHD than LDL-C. The platelets of patients with FH were quicker to aggregate in epinephrine than those of individuals who did not have FH.
Non-lipid CHD risk factors that affect the general population also affect those with FH. Galema-Boers et al. showed that patients with hypertension had CHD more than twice as often than individuals with FH, even with equivalent LDL-C levels. Miname et al. found that individuals with FH and a high coronary artery calcium (CAC) score had higher blood glucose levels at fasting than those with a low CAC, even though LDL-C levels remained the same. Gaudet et al. showed that individuals with FH, hyperinsulinemia, and abdominal obesity had a higher CAD incidence than those without FH. Individuals with FH type IIb (high LDL-C and TGs levels) have higher frequencies of MI than individuals with high LDL-C and low TG levels.
Currently, there is little agreement on how different foods contribute to CHD development. Some RCTs have shown a low carbohydrate diet (LCD) is equivalent if not superior in improving CHD biomarkers compared to a low-fat diet (LFD). LCD is the only dietary method that has been shown to to reduce Lp(a) levels significantly. Wood et al. demonstrated that the LCD group had better CHD risk factor improvement than the LFT group, which consumed one-third of the LCD group’s saturated fats. Clinical trials should be performed to determine the effects of LCD on individuals with FH with an insulin-resistant phenotype.
- Low saturated fat and cholesterol diets should not be recommended to individuals with FH due to the lack of evidence of their benefit.
- A low carbohydrate diet (LCD) improves CHD biomarkers better than a low-fat diet (LFD).
- Hypercoagulation is a better indicator of CHD than LDL-C and should be taken into consideration with future studies.
Diamond, David M et al. “Dietary Recommendations For Familial Hypercholesterolemia: An Evidence-Free Zone.” BMJ Evidence-Based Medicine, 2020, pp. bmjebm-2020-111412. BMJ, doi:10.1136/bmjebm-2020-111412.
Zahra Hashemy, PharmD. Candidate, USF Taneja College of Pharmacy