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Review ArticlePMC Full Text2015

Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk

Koenig G, Seneff S • Dis Markers

Key Finding

Framingham: highest GGT quartile HR 1.67 for CVD, HR 2.54 for MetS; Austrian study: GGT >56 U/L men/>36 U/L women = 100% increased mortality risk

Key Findings

  • 1Highest GGT quartile: 67% increased CVD incidence (Framingham)
  • 2GGT >56 U/L (men) or >36 U/L (women): 100% increased mortality (Austrian)
  • 3MetS risk: HR 2.54 for highest vs lowest GGT quartile
  • 4GGT ≥64 U/L: CHD mortality HR 2.58 (Finnish study)

Original title: “Gamma-Glutamyltransferase: A Predictive Biomarker of Cellular Antioxidant Inadequacy and Disease Risk”

Plain English Summary

Review establishing GGT as predictor of CVD, diabetes, metabolic syndrome, and all-cause mortality beyond its role as liver disease marker.

In-Depth Analysis

Study Details

Authors: Gerald Koenig, Stephanie Seneff
Institutions: Health-e-Iron/Iron Disorders Institute, MIT
Journal: Disease Markers, 2015; 2015:818570
PMCID: PMC4620378

Key Statistics (from original paper)

GGT as Predictor

"Elevated GGT is linked to increased risk to a multitude of diseases and conditions, including cardiovascular disease, diabetes, metabolic syndrome (MetS), and all-cause mortality."

Framingham Offspring Study (20-year follow-up)

Metabolic Syndrome Risk (vs Q1):

  • •Q2: HR 1.46
  • •Q3: HR 1.83
  • •Q4: HR 2.54

CVD Incidence:

  • •Highest quartile: 67% increase (HR 1.67, 95% CI 1.25-2.22)

Heart Failure:

  • •Above gender-specific median: 1.71-fold risk
Austrian Study (n=283,483, up to 13 years)

Highest GGT category (>56 U/L men, >36 U/L women):

  • •All-cause mortality: 100% increased risk
  • •Cancer mortality: 130% increase
  • •Vascular/ischemic heart disease: 60% increase
  • •Stroke: 40% increase
Finnish Study (n=28,838)

CHD Mortality HRs (men):

  • •GGT 16-24 U/L: HR 1.37
  • •GGT ≥64 U/L: HR 2.58 (95% CI 1.86-3.58)

Source: PMC full text (PMC4620378)

Paradigm Relevance

How this study applies to different clinical perspectives:

Standard Medical

Relevant

Conventional clinical guidelines used by most doctors

Why it matters:

Supports including GGT in routine liver panels. Values significantly above reference ranges warrant investigation for liver/biliary disease.

Research Consensus

Relevant

Current scientific understanding, often ahead of guidelines

Why it matters:

Establishes evidence-based thresholds much lower than standard lab ranges. GGT in upper-normal range is a significant risk marker even without overt disease.

Metabolic Optimization

Relevant

Proactive targets for optimal health, not just disease absence

Why it matters:

Validates GGT as oxidative stress biomarker. Target <20 U/L for men, <15 U/L for women. Elevated GGT signals need for antioxidant support and glutathione optimization.

Study Details

Type
Review Article
Methodology
Review article synthesizing epidemiological evidence on GGT and disease outcomes from Framingham, Austrian, and Finnish cohorts.

Evidence Quality

Review from PMC4620378. Iron Disorders Institute authors.

Topic

Liver HealthCardiovascularInflammation

Related Biomarkers

GGTLIVER ENZYMESGLUTATHIONE

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GGT

Evaluator

Oxidative stress and liver health marker

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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