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Lean mass hyper-responder (LMHR)

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Lean mass hyper-responder (LMHR) is a term used to describe particular individuals who develop a specific dyslipidaemia when on a low carbohydrate ("ketogenic") diet:

  • LDL-C (cholesterol) ≥200 mg/dl (5.17 mmo/L),
  • HDL-C ≥80 mg/dl (2.1 mmol/l), and
  • TG (triglyceride) ≤70 mg/dl (0.8 mmol/l)

A favourable reduction in triglycerides and an increase in high-density lipoprotein-cholesterol levels is often observed in the ketogenic diet (1)

  • however, people vary significantly in their low-density lipoprotein-cholesterol (LDL-C) response to the dietary change
  • LMHR is a term used to describe a specific dyslipidaemic triad that occurs with individuals on a low carbohydrate diet
  • it has been shown that the LMHR dyslipidaemic profile can be reversed by consumption of carbohydates (2)
    • in a single subject cross-over experiment it was shown that the LMHR dyslipidaemia could be "treated" with either a statin (rosuvastatin 20mg per day) or increased carbohydrate intake (consuming 12 Oreo biscuits per day)
      • in this study the subject achieved a LMHR lipid profile on a low carbohydrate diet and then consumed the increased carbohydrate load resulting in reduction in LDL of 71%; there was then a "washout" period and renewed adherance to the low carbohydrate diet. After similar lipid levels were achieved as prior to the carbohydrate load intervention, the subject had rosuvastatin 20mg per day for four weeks and achieved an LDL reduction of 32.5%

The influence of increased levels of LDL-C resulting from a carbohydrate-restricted ketogenic diet on the progression of atherosclerosis in otherwise metabolically healthy individuals is currently poorly understood (3).

Reference:

  • Naveh N, Avidan Y, Zafrir B. Extreme Hypercholesterolemia Following a Ketogenic Diet: Exaggerated Response to an Increasingly Popular Diet. Cureus. 2023 Aug 18;15(8):e43683.
  • Norwitz NG, Cromwell WC. Oreo Cookie Treatment Lowers LDL Cholesterol More Than High-Intensity Statin Therapy in a Lean Mass Hyper-Responder on a Ketogenic Diet: A Curious Crossover Experiment. Metabolites. 2024 Jan 22;14(1):73.
  • Javier DAR, Manubolu VS, Norwitz NG, Kinninger A, Aldana-Bitar J, Ghanem A, Ahmad K, Vicuna WD, Hamidi H, Bagheri M, Elsayed T, Villanueva B, Ichikawa K, Flores F, Hamal S, Feldman D, Budoff MJ. The impact of carbohydrate restriction-induced elevations in low-density lipoprotein cholesterol on progression of coronary atherosclerosis: the ketogenic diet trial study design. Coron Artery Dis. 2024 Jun 13.

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