Severe Hypercholesterolemia in Very-Low-Carbohydrate Diet

There is growing popularity and interest in very-low-carbohydrate (VLC) diets for a variety of established and perceived health benefits. While some impacts have been seen in cardiometabolic diseases such as diabetes, hypertension and short-term weight loss (particularly when paired with caloric restriction), other effects such as in energy levels, mood and sense of well-being are variable. In the extreme, these diets suggest restriction of dietary carbohydrates (CHO) to less than 20 grams daily and often encourage a compensatory increase in dietary fat to promote ketogenesis. There has been concern about the long-term effects of these changes, as well as unintended consequences of increased saturated fat intake. A minority of patients, such as in the case below, may experience exaggerated lipid changes, thought to be influenced by underlying metabolic and genetic factors. Meta-analyses have shown conflicting results of the effects of VLC diets on low density lipoprotein cholesterol (LDL-C) levels. A 63-year-old woman presented for outpatient consultation for markedly elevated LDL-C 524 mg/dL. The rest of her lipid panel was as follows: total cholesterol 637 mg/dL, triglycerides 152 mg/dL, HDL-C 83 mg/dL. She was asymptomatic. Record review of annual laboratory testing from her primary care physician revealed baseline LDL-C 114–134 mg/dL between 2012 and 2017. Her lipid panel in 2017 was as follows: total cholesterol 216 mg/dL, triglycerides 82 mg/dL, HDL-C 68 mg/dL, LDL-C 132 mg/dL. She described that in late 2017 she began a VLC diet for perceived metabolic benefits, and in the past year intensified CHO restriction to less than 15 grams daily. In 2018–2019, her LDL-C level increased to 303–316 mg/dL, and in 2020 to 524 mg/dL. She had no history of diabetes, liver or kidney disease, nephrotic syndrome, hypothyroidism or alcohol use. She took no prescribed medications. She reported over-the-counter use of magnesium and potassium. She denied use of any other supplements or herbal remedies. Her past medical history included osteoarthritis. Her family history included hyperlipidemia in her mother, and coronary artery disease in both parents with age of onset in their 70s. She was a lifelong non-smoker and did not drink alcohol. Her BMI was 21.5. On examination, she was normotensive, euthyroid-appearing, and had no stigmata of familial hypercholesterolemia. Other labs were grossly normal, including blood counts, comprehensive metabolic panel, thyroid function tests, hemoglobin A1c and urinalysis. She was counseled extensively regarding her laboratory results and concerns about her cardiovascular safety. This case demonstrates an exaggerated lipid response to a VLC diet, and supports the National Lipid Association scientific statement Class IIa recommendation to obtain baseline and follow-up lipid profiles in patients who follow such diets due to variation in lipid response.