A low-carbohydrate diet can lead to profound metabolic benefits, particularly for weight management and glucose regulation. However, some individuals following this dietary pattern experience a phenomenon known as being a Lean Mass Hyper-Responder (LMHR). This group exhibits significant increases in LDL cholesterol (LDL-C) without accompanying negative changes in other cardiometabolic markers such as triglycerides or HDL cholesterol.
Below, we explore what this means, why it happens, and whether overweight or obese individuals need to worry about this phenomenon.

What is a Lean Mass Hyper-Responder?
The LMHR profile is characterized by:
Very high LDL cholesterol (often exceeding 5.2 mmol/l or 200 mg/dL),
High HDL cholesterol (above 2.07 mmol/l or 80 mg/dL),
Low triglycerides (below 0.79 mmol/l or 70 mg/dL),
Leanness or low body fat percentage.
This pattern emerges in a subset of individuals, typically those who are lean and metabolically healthy, when following a low-carb or ketogenic diet. The response is believed to result from adaptations in energy metabolism, where the body increases reliance on fat and circulating lipoproteins for energy as carbohydrate intake is minimized.
This adaptation aligns with a proposed "Lipid Energy Model", which theorizes that elevated LDL-C in LMHRs may be linked to increased energy trafficking rather than pathologic cholesterol accumulation.
What Does the Research Say?
Recent studies and case reports provide insights into the LMHR phenomenon:
LDL Increases and Metabolic Health: Research has shown that LDL-C levels can rise dramatically in LMHRs (in some cases, exceeding 12.9 mmol/l or 500 mg/dL) without evidence of metabolic dysfunction or systemic inflammation. Other markers, like HDL-C and triglycerides, remain favourable, suggesting that overall cardiovascular risk might differ for this subgroup compared to those with typical dyslipidaemia (1).
Reversibility of LDL Elevation: In one case study, an individual who increased their carbohydrate intake by eating Oreo biscuits as a N=1 experiment, experienced significant reductions in LDL-C without losing other metabolic benefits of a low-carb diet. This suggests that the LDL response is highly dependent on carbohydrate restriction levels. (2)
Risk Implications: While elevated LDL-C traditionally correlates with increased cardiovascular risk, some researchers propose that the unique lipid profile in LMHRs might not carry the same risk due to favourable HDL and triglyceride levels. However, this remains speculative, and long-term outcomes have yet to be studied in-depth (3)
Genetic Factors: Current evidence suggests that the LMHR phenotype is not primarily genetic but metabolic, linked to energy demands and body composition (4)
Budoff, M, Manubolu, V, Kinninger, A. et al. Carbohydrate Restriction-Induced Elevations in LDL-Cholesterol and Atherosclerosis: The KETO Trial. JACC Adv. 2024 Aug, 3 (8) .
https://doi.org/10.1016/j.jacadv.2024.101109
Should Overweight or Obese Individuals Be Concerned?
The LMHR phenomenon is primarily observed in lean, athletic individuals, not those with significant overweight or obesity. Overweight individuals on a low-carb diet typically show reductions in LDL-C alongside improvements in HDL-C and triglycerides. Thus, the risk of developing an LMHR profile is likely minimal for this group.
For obese or overweight individuals who do experience rising LDL-C levels:
Look at the Full Lipid Profile: LDL-C should not be evaluated in isolation. Favourable trends in HDL (increased) and triglycerides (decreased) often mitigate cardiovascular risk.
Lifestyle Adjustments: Introducing moderate carbohydrates while maintaining a low-carb framework may help manage LDL-C without compromising metabolic benefits.
Seek Medical Advice: It is essential to work with healthcare providers to assess individual risk and consider other factors such as genetics, inflammation markers, and family history of cardiovascular disease.
Current and Ongoing Research
Several studies are underway to clarify the risks and mechanisms associated with the LMHR phenotype:
Coronary Artery Plaque Studies: Ongoing trials aim to track plaque progression in LMHRs, exploring whether high LDL-C translates into increased cardiovascular events. (5)
Lipid Energy Model: Researchers are investigating how fat-based metabolism in low-carb diets affects lipoprotein function and long-term health outcome (6)
Final Thoughts
The LMHR phenomenon highlights the complexity of cholesterol and its role in health. For the average overweight or obese individual, a low-carb diet is generally beneficial, improving metabolic markers and aiding weight loss. However, anyone experiencing unexpected increases in LDL-C should discuss these changes with their healthcare provider to tailor the diet for optimal outcomes. Continued research will provide clarity on how best to manage lipid responses in low-carb diets for all individuals.
Comments