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Updated: Sep 2, 2025

Assessing Whole-Body Lipid-Handling Capacity in Mice
Published on: November 24, 2020
Short-term hyper-caloric high-fat feeding on a ketogenic diet can lower low-density lipoprotein cholesterol: the
David Feldman1, Siobhan Huggins1, Nicholas G Norwitz2
1Citizen Science Foundation, Las Vegas, Nevada.
Purpose Of Review:
Conventional knowledge holds that saturated fat is the primary dietary driver of increases in low-density lipoprotein-cholesterol (LDL-C), and that high LDL-C seen among some persons consuming low-carbohydrate, high-fat diets is driven by increased saturated fat intake. This simple paradigm cannot account for the lipid patterns, nor for the magnitude of effect, observed in 'lean mass hyper-responders' on low-carbohydrate diets. The Lipid Energy Model (LEM) provides an alternative explanation for LDL-C increases seen in persons without obesity who adopt ketogenic diets and makes testable predictions, including that acute overfeeding, including increased saturated fat consumption, would decrease LDL-C levels.
Recent Findings:
This study reports data from an n = 1 experiment, performed in duplicate, in which the subject consumed three ketogenic diets for 5 days that varied in caloric content: weight-maintenance (2278 kcal/day), hypo-caloric (1135 kcal/day), and hyper-caloric (4116 kcal/day). Consistent with the LEM, LDL-C and apolipoprotein B increased following caloric restriction and decreased following overfeeding, despite increased saturated fat consumption. Data from a case series of 24 individuals who underwent similar protocols similarly found that overfeeding on a ketogenic diet decreased LDL-C.
Summary:
This n = 1 study and associated case series provide data that short-term overfeeding can lower LDL-C in the context of carbohydrate restriction.
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