Cholesterol, Dietary Fat, the Ketogenic Diet, Saturated Fat, Apolipoprotein B, and Lipoprotein(a): An Evidence-Based Perspective

Cholesterol, Dietary Fat, the Ketogenic Diet, Saturated Fat, Apolipoprotein B, and Lipoprotein(a): An Evidence-Based Perspective (2025)

Cholesterol and Dietary Fat:

Cholesterol metabolism and cardiovascular risk are tightly linked to dietary fat intake, especially saturated fat (SFA). Most guidelines recommend limiting SFA to <10% of daily energy, as higher intake generally raises LDL cholesterol (LDL-C), a causal risk factor for atherosclerotic cardiovascular disease (ASCVD).[1][2] However, the effect of SFA is nuanced: different types (e.g., palmitic vs. stearic acid) have variable impacts on LDL-C, and individual responses depend on genetics, metabolic health, and other factors.[2][3]

Ketogenic Diets and Lipids:

Ketogenic diets (very low carbohydrate, high fat) can induce marked changes in lipid profiles. While they often improve triglycerides, HDL-C, and markers of insulin resistance, they may cause substantial increases in LDL-C and apolipoprotein B (apoB) in some individuals—especially lean, metabolically healthy "hyper-responders".[4][5][6] The National Lipid Association notes that most people experience modest LDL-C increases, but a subset may see dramatic rises (>190 mg/dL), raising concern for ASCVD risk.[2] If this occurs, guidelines recommend substituting unsaturated fats for SFA, reducing dietary cholesterol, and considering lipid-lowering therapy or discontinuing the diet.[2]

Saturated Fat: Controversies and Adaptation Models:

Recent models (e.g., the Homeoviscous Adaptation to Dietary Lipids, HADL) suggest that SFA-induced LDL-C increases may be a normal adaptive response in healthy individuals, not always pathological.[3] However, in those with insulin resistance or other risk factors, SFA may exacerbate atherogenic dyslipidemia and inflammation.[1][2] Replacing SFA with polyunsaturated fats consistently lowers ASCVD risk.[1]

Apolipoprotein B (apoB):

ApoB is the structural protein of all atherogenic lipoproteins (VLDL, LDL, Lp(a)), and its concentration reflects the total number of atherogenic particles. ApoB is now recognized as a superior marker for ASCVD risk compared to LDL-C alone, and is increasingly used in risk assessment and treatment targets.[7][8] Ketogenic diets may increase apoB in parallel with LDL-C, especially in hyper-responders.[4][9][5]

Lipoprotein(a) [Lp(a)]:

Lp(a) is a genetically determined, highly atherogenic lipoprotein and independent risk factor for ASCVD. Unlike LDL-C, Lp(a) is less responsive to diet, but recent evidence shows SFA reduction may paradoxically increase Lp(a) even as it lowers LDL-C.[10][11] The clinical significance of this is still being clarified, and precision nutrition approaches are needed. The impact of ketogenic diets on Lp(a) is under investigation, with early data suggesting variable effects.[10]

Summary:

Dietary fat quality, not just quantity, is critical for cardiovascular health. While ketogenic diets can improve many cardiometabolic markers, they may raise LDL-C and apoB in some, necessitating individualized monitoring. SFA should generally be limited, and unsaturated fats favored. Lp(a) and apoB are emerging as key risk markers, and their response to diet is complex and increasingly relevant for precision nutrition and ASCVD prevention.[10][11][7][1][2][8][5][6]

Key Takeaway:

Personalized lipid management—considering LDL-C, apoB, and Lp(a)—is essential, especially when adopting high-fat or ketogenic diets. Regular lipid testing and adjustment of dietary fat types are recommended to optimize cardiovascular risk.

References

1. Saturated Fats and Cardiovascular Health: Current Evidence and Controversies. Maki KC, Dicklin MR, Kirkpatrick CF. Journal of Clinical Lipidology. 2021 Nov-Dec;15(6):765-772. doi:10.1016/j.jacl.2021.09.049.

2. Obesity, Dyslipidemia, and Cardiovascular Disease: A Joint Expert Review From the Obesity Medicine Association and the National Lipid Association 2024. Bays HE, Kirkpatrick CF, Maki KC, et al. Journal of Clinical Lipidology. 2024 May-Jun;18(3):e320-e350. doi:10.1016/j.jacl.2024.04.001.

3. The Homeoviscous Adaptation to Dietary Lipids (HADL) Model Explains Controversies Over Saturated Fat, Cholesterol, and Cardiovascular Disease Risk. Zinöcker MK, Svendsen K, Dankel SN. The American Journal of Clinical Nutrition. 2021;113(2):277-289. doi:10.1093/ajcn/nqaa322.

4. Evidence That Supports the Prescription of Low-Carbohydrate High-Fat Diets: A Narrative Review. Noakes TD, Windt J. British Journal of Sports Medicine. 2017;51(2):133-139. doi:10.1136/bjsports-2016-096491.

5. The Impact of Carbohydrate Restriction-Induced Elevations in Low-Density Lipoprotein Cholesterol on Progression of Coronary Atherosclerosis: The Ketogenic Diet Trial Study Design. Javier DAR, Manubolu VS, Norwitz NG, et al. Coronary Artery Disease. 2024;35(7):577-583. doi:10.1097/MCA.0000000000001395.

6. Review of Current Evidence and Clinical Recommendations on the Effects of Low-Carbohydrate and Very-Low-Carbohydrate (Including Ketogenic) Diets for the Management of Body Weight and Other Cardiometabolic Risk Factors: A Scientific Statement From the National Lipid Association Nutrition and Lifestyle Task Force. Kirkpatrick CF, Bolick JP, Kris-Etherton PM, et al. Journal of Clinical Lipidology. 2019 Sep - Oct;13(5):689-711.e1. doi:10.1016/j.jacl.2019.08.003.

7. The Present and Future of Lipid Testing in Cardiovascular Risk Assessment. White-Al Habeeb NMA, Higgins V, Wolska A, et al. Clinical Chemistry. 2023;69(5):456-469. doi:10.1093/clinchem/hvad012.

8. A Modern Approach to Dyslipidemia. Berberich AJ, Hegele RA. Endocrine Reviews. 2022;43(4):611-653. doi:10.1210/endrev/bnab037.

9. Short-Term Hyper-Caloric High-Fat Feeding on a Ketogenic Diet Can Lower Low-Density Lipoprotein Cholesterol: The Cholesterol Drop Experiment. Feldman D, Huggins S, Norwitz NG. Current Opinion in Endocrinology, Diabetes, and Obesity. 2022;29(5):434-439. doi:10.1097/MED.0000000000000762.

10. Lipoprotein(a) and Effects of Diet: Time for Reassessment. Enkhmaa B, Berglund L. Nutrients. 2025;17(10):1714. doi:10.3390/nu17101714.

11. Lipoprotein(a) and Diet-a Challenge for a Role of Saturated Fat in Cardiovascular Disease Risk Reduction?. Law HG, Meyers FJ, Berglund L, Enkhmaa B. The American Journal of Clinical Nutrition. 2023;118(1):23-26. doi:10.1016/j.ajcnut.2023.05.017.