Keto-induced high cholesterol needs treatment

Clinical takeaway: Start a statin for LDL-C of 190 mg/dL or higher even if the patient stays on keto, consider early ezetimibe, then recheck lipids four to 12 weeks after any change. The authors call this approach guideline-concordant but untested in this specific patient group. 

Keto has moved well beyond its origins in drug-resistant childhood epilepsy and is now promoted for athletic performance and general health. For many patients the diet does not raise lipids significantly. A recent randomized trial found no differences in low-density lipoprotein cholesterol (LDL-C) between keto and two other diets, with keto ahead on liver fat and glucose control. Patients with obesity or type 2 diabetes, similar to those in the study, tend to see LDL-C rise modestly if at all. 

Lean, insulin-sensitive patients are often an exception to this rule, and their LDL-C can climb substantially. These adopters may argue that large, less atherogenic LDL particles and a healthy metabolism blunt the risk. But a recent cardiology viewpoint takes up what clinicians should do when LDL-C does rise, including in those who won’t give up the diet. 

The authors argue that LDL-C elevation on keto should be managed like any other. The approach is guideline-concordant but untested specifically in these types of patients. Therapy is indicated at LDL-C of 190 mg/dL or higher regardless of calculated risk. Statins remain first-line, although response may be blunted, and adding ezetimibe is reasonable, with a stronger response reported among keto adopters. The goal is LDL-C under 100 mg/dL, with lipids rechecked four to 12 weeks after any change. 

Apolipoprotein B, a direct count of atherogenic particles, rises alongside LDL-C in these patients, and long-term data supporting the large-particle claim have never been reported. The only coronary imaging comes from a small cohort of metabolically healthy keto adopters whose calcium and plaque burden matched controls despite LDL-C about 149 mg/dL higher. The viewpoint authors warn against reading the imaging as reassurance. In addition, the one-year follow-up report from this study was subsequently retracted for methodologic concerns. 

For patients who want to stay on the diet, imaging that shows subclinical atherosclerosis can make the risk tangible and engage them in lowering it. A coronary calcium score of zero should not mean deferred therapy. The authors call for stopping keto when severe elevation resists diet changes and drug therapy, or the patient declines both. 

The viewpoint authors urge trials on two fronts: why LDL-C rises so steeply in some patients, and why those patients respond atypically to lipid-lowering drugs. Serial imaging in well-matched cohorts could track plaque progression and composition, since event-driven outcome trials are impractical. But imaging only stands in for outcomes and cannot establish cardiovascular safety. 

“Pending such trials, KD-induced hypercholesterolemia should not be presumed benign on the basis of mechanistic theory or a favorable metabolic milieu, and uncertainty about the magnitude of risk does not justify departing from established principles,” the authors conclude. 

Source: Avivi I, et al. (2026 Oct 21) J Am Coll Cardiol. Managing Ketogenic Diet-Induced Hypercholesterolemia