Ketogenic Diets and Low-Density Lipoprotein Cholesterol in Adults With Normal Weight: An Emerging Clinical Challenge

Abstract

Ketogenic diets (KDs) are increasingly being adopted by adults with normal body mass index for health and performance-related reasons. Accumulating evidence shows that this population is susceptible to large increases in low-density lipoprotein cholesterol (LDL-C) when consuming KDs, raising concerns about long-term atherosclerotic cardiovascular disease (ASCVD) risk. This review synthesizes current evidence on KD-induced LDL-C elevations among individuals with normal body mass index, explores potential mechanisms underlying this phenotype, and discusses implications for ASCVD risk assessment and clinical management. Short-term clinical trials in healthy individuals with normal body mass index consuming KDs report mean LDL-C increases ranging from 18 to 70 mg/dL. Although it has been proposed that these LDL-C elevations may be benign in otherwise metabolically healthy individuals, supporting evidence is lacking. Strong and consistent evidence supports LDL-C as a causal, cumulative risk factor for ASCVD. However, the long-term ASCVD consequences of KD-induced LDL-C elevation in lean individuals have not been directly studied. Limited coronary imaging data are available in this population, but they do not establish cardiovascular safety. Emerging case reports suggest that moderate carbohydrate reintroduction (50-100 g/d) can substantially reverse KD-induced LDL-C elevations, with further reductions achievable using pharmacologic therapy. Clinicians should be prepared to manage patients who choose to follow KDs, especially those with extreme LDL-C elevation. Regular lipid monitoring and patient-centered risk communication are essential for individuals choosing to follow a KD, particularly those of normal body mass index who may otherwise appear at low ASCVD risk.