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Emerging Evidence
Review ArticlePMC Full Text2022

The Lipid Energy Model: Reimagining Lipoprotein Function in the Context of Carbohydrate-Restricted Diets

Norwitz et al. • Metabolites

Key Finding

LEM proposes carbohydrate restriction in lean individuals increases hepatic VLDL secretion with enhanced lipoprotein lipase turnover, generating elevated LDL without FH genetic markers

Key Findings

  • 1LMHR: LDL ~320 mg/dL, HDL ~99 mg/dL, TG ~47 mg/dL post-CRD
  • 2LEM: increased VLDL secretion + enhanced LPL turnover in lean individuals
  • 3Pattern lacks familial hypercholesterolemia genetic markers
  • 4Proposes adaptive energy trafficking rather than pathological hyperlipidemia

Original title: “The Lipid Energy Model: Reimagining Lipoprotein Function in the Context of Carbohydrate-Restricted Diets”

Plain English Summary

Proposes Lipid Energy Model to explain LMHR phenotype: lean individuals on CRD show elevated LDL-C (~320 mg/dL), high HDL-C (~99 mg/dL), low TG (~47 mg/dL) - inverse of typical pattern.

In-Depth Analysis

Study Details

Authors: Nicholas G Norwitz, Adrian Soto-Mota, Bob Kaplan, David S Ludwig, Matthew Budoff, Anatol Kontush, David Feldman
Institutions: Harvard Medical School, Lundquist Institute at UCLA, INSERM/Sorbonne
Journal: Metabolites, 2022 May; 12(5):460
PMCID: PMC9147253

Key Points (from original paper)

LMHR Phenotype Values
  • •Pre-diet LDL-C: ~145-148 mg/dL
  • •Post-diet LDL-C: ~320 mg/dL (some exceed 500 mg/dL)
  • •Post-diet HDL-C: ~99 mg/dL
  • •Post-diet triglycerides: ~47 mg/dL
The Lipid Energy Model (LEM)

Core Mechanism: Carbohydrate restriction in lean individuals leads to:

  1. •Increased hepatic VLDL secretion
  2. •Enhanced lipoprotein lipase-mediated turnover
  3. •Resulting lipid triad (high LDL, high HDL, low TG)

Key Distinction:

  • •Pattern occurs without genetic familial hypercholesterolemia markers
  • •Inverse of typical atherogenic dyslipidemia
Clinical Implications

Model proposes this represents adaptive energy trafficking in lean, carbohydrate-restricted individuals rather than pathological hyperlipidemia.

Source: PMC full text (PMC9147253)

Paradigm Relevance

How this study applies to different clinical perspectives:

Standard Medical

Conventional clinical guidelines used by most doctors

Not directly relevant to this paradigm

Research Consensus

Relevant

Current scientific understanding, often ahead of guidelines

Why it matters:

Proposes that elevated LDL in metabolically healthy, lean low-carb dieters may represent normal energy trafficking rather than pathology. Identifies inverse BMI-LDL relationship unique to carbohydrate restriction.

Metabolic Optimization

Relevant

Proactive targets for optimal health, not just disease absence

Why it matters:

The LMHR phenotype (LDL >200, HDL >80, TG <70 mg/dL) may indicate efficient fat-as-fuel metabolism. Consider this context when interpreting elevated LDL in lean, metabolically healthy low-carb individuals.

Study Details

Type
Review Article
Methodology
Theoretical model paper proposing mechanism for LMHR phenotype based on metabolic observations.

Evidence Quality

Hypothesis/model paper from PMC9147253. Multi-institutional author team including Harvard, UCLA.

Topic

Lipid MetabolismCardiovascular

Related Biomarkers

LDLHDLTRIGLYCERIDES

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LMHR Phenotype

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Lean Mass Hyper-Responder pattern assessment

Original Source

View on PubMedView DOIFull Text (Open Access)

DOI (Digital Object Identifier) is a permanent link to this publication. Unlike website URLs that can change, a DOI always resolves to the correct source.

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