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Longevity Library · Lab reference

Written by Daniel Tagge, MD
Updated October 10, 2026
Reviewed October 12, 2026
30 sources · Measured in U/L

System: Exposomics

GGTGamma-glutamyl transferase · Gamma-GT

Laboratories print a GGT upper limit anywhere from about 40 to 70 U/L, but in a US cohort of 4,844 young adults the 15-year risk of diabetes rose from a GGT of about 12 U/L upward, 4 times higher at 25 to 36 and 5.5 times above 36, all inside the printed range. GGT tracks alcohol, body fat, insulin resistance and oxidative stress, and genetic studies find no causal effect of the enzyme itself, so the number is best read as a report on those drivers, most of which move it within weeks.

GGT is an enzyme on the surface of liver and other cells that recycles glutathione, the body's main antioxidant. It rises with alcohol, excess body fat, insulin resistance, smoking in drinkers and enzyme-inducing medicines, and it confirms that a raised alkaline phosphatase comes from the liver rather than bone. The printed range is wide because the people used to define it included drinkers and people with excess weight; healthy abstainers run lower, and risk in cohorts climbs from the bottom of the range.

01 · The scale

Where the laboratory range and the evidence sit.

In a US cohort of young adults, 15-year diabetes risk rose from the lowest quarter of GGT (under 12 U/L) upward, 4 times higher at 25 to 36 and 5.5 times above 36, with the laboratory calling 40 to 50 abnormal. Across 29 cohorts cardiovascular risk rose log-linearly with GGT, across 19 cohorts the top third carried 1.6 times the all-cause mortality of the bottom third, and in 163,944 Austrians the gradient was steepest under age 60. Genetic studies found no causal effect of GGT on diabetes or coronary disease, while the same methods did implicate ALT.

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  1. Common laboratory reference range

    5 to 65 U/L · Typical US laboratories; upper limit printed from about 40 to 70, higher for men

  2. Lowest quarter in US young adults: reference for diabetes and hypertension risk

    0 to 12 U/L · Lee 2003 (CARDIA)

  3. Diabetes hazard 1.6 to 1.7 times the lowest quarter; still inside every printed range

    12 to 25 U/L · Lee 2003 (CARDIA)

  4. Healthy-population upper limits: 35 to 45 in abstainers, 40 women and 68 men in the IFCC study

    35 to 68 U/L · Hietala 2005; Ceriotti 2010

  5. Diabetes hazard 4.0 times the lowest quarter; hypertension 2.3 times

    25 to 36 U/L · Lee 2003 (CARDIA)

  6. Top tenth: diabetes hazard 5.5; above the US survey limits, 1.5 times the all-cause mortality

    36 and above U/L · Lee 2003 (CARDIA); Ruhl 2009

  • Laboratory range
  • Evidence supports
  • Guideline goal or unstudied
  • Higher risk in studies
Scale in U/L. U/L is the same as IU/L. Bands show where studies found something, not a recommendation for any one person.

02 · What it is

What GGT measures.

GGT sits on the outer surface of cells and breaks down extracellular glutathione, the body's main antioxidant, so that its amino acids can be taken up and used to make more glutathione inside the cell. In the presence of iron the products of that reaction can themselves generate reactive oxygen species. Conditions that raise serum GGT, among them obstructive liver disease, high alcohol intake and enzyme-inducing drugs, all increase free radical production and threaten glutathione stores, which is why GGT within its normal range has been proposed as an early marker of oxidative stress.1,2Grade C

The oxidative-stress reading rests on epidemiology, not on a direct measurement. In a series of cohort analyses, serum and dietary antioxidant vitamins ran inversely with GGT across its normal range, dietary heme iron ran with it, and GGT within the normal range predicted F2-isoprostanes (a product of lipid oxidation), fibrinogen and C-reactive protein measured 5 or 15 years later, in dose-response fashion. The authors themselves called the field at a beginning stage.2Grade C

GGT is abundant in the liver and also present in the kidney, intestine, prostate and pancreas, but not in bone. The British gastroenterology guideline includes it in the initial liver panel with bilirubin, albumin, ALT and alkaline phosphatase, notes that it is most commonly raised by obesity, excess alcohol or drug induction, and that although it has low specificity for liver disease it is one of the best predictors of liver mortality. In 3,451 Framingham participants it ran with body mass index, blood pressure, LDL cholesterol, triglycerides and blood glucose.3,4Grade A

03 · Origins

Where it came from, and where it sits in the network.

Gamma-glutamyl transpeptidases are ubiquitous: bacteria, plants and animals all carry enzymes that cut the gamma-glutamyl bond of glutathione and glutamine and hand the glutamyl group to another amino acid or peptide. The job is old and conserved because glutathione is the cell's main small-molecule antioxidant and the enzyme is how its parts are recovered and reused, which places GGT at the junction of antioxidant defense, detoxification and inflammation.5Grade C

In humans the enzyme the blood test measures is GGT1, one of thirteen related genes of which at least six appear to be active. It is anchored to the outer cell membrane, normally on the apical surface of ducts and glands, where it salvages cysteine, glutamate and glycine from the glutathione in ductal fluids; cysteine is the rate-limiting ingredient for making new glutathione under oxidative stress. GGT1 also converts the leukotriene LTC4 to LTD4. Inherited GGT deficiency is rare; the few people described spill glutathione into their urine and cannot process LTC4.6,7Grade C

That membrane position explains the lab test. Serum GGT is enzyme shed from cell surfaces, mostly hepatobiliary, and the signal rises when more enzyme is made (induction by alcohol, drugs or oxidative stress) or when bile-duct cells are injured; because the enzyme is absent from bone, it separates a liver source of alkaline phosphatase from a bone source. The same salvage function is why tumors that overexpress GGT resist oxidant chemotherapy: they draw extra cysteine from blood glutathione.7,3,1Grade C

04 · The laboratory range

What a laboratory calls normal.

Up to about 40 to 70 U/L depending on the laboratory, with men's upper limits printed higher than women's.

When the international federation of clinical chemistry set out to define common reference intervals with standardized methods in 765 carefully screened adults, it arrived at 6 to 40 U/L for women and 12 to 68 for men, had to exclude the Nordic samples because their upper limits ran higher, and concluded that a single worldwide GGT interval is unlikely because populations differ. ALT and AST, measured in the same study, did not have that problem.8Grade B

The populations differ mostly in how much they drink and weigh. Among 2,485 healthy Finnish volunteers used to set reference intervals, moderate drinkers (1 to 40 grams of alcohol a day) had higher GGT than abstainers, and the upper limits derived from abstainers alone were 45 U/L in men and 35 in women, against 66 and 40 from moderate drinkers. Restricting further to normal-weight abstainers, a second analysis found 53 and 45 against 68 and 50 for moderate drinkers, with GGT running 54 percent higher in overweight and 125 percent higher in obese male moderate drinkers (25 and 75 percent in women). A laboratory that draws its range from the local population inherits the local drinking and the local waistline.9,10Grade B

The range is also wide because people differ from one another far more than any one person varies over time. In 91 healthy European adults sampled weekly for 10 weeks, within-person variation of GGT was 8.9 percent while between-person variation was 41.7 percent, the widest spread of the nine enzymes measured. Adding GGT to a liver panel raises the share of adults with at least one abnormal result from around 15 percent to 30 percent, which is one reason the guideline notes its low specificity.11,3Grade B

05 · The evidence

What the studies support.

In the CARDIA study, 4,844 Black and white US adults aged 18 to 30 were followed for 15 years. With GGT cut at the 25th, 50th, 75th and 90th percentiles (12, 17, 25 and 36 U/L, against laboratory limits of 40 in women and 50 in men), the hazard of new diabetes across the five categories was 1.0, 1.6, 1.7, 4.0 and 5.5, and of new hypertension 1.0, 1.2, 1.7, 2.3 and 2.3. Adjusting for alcohol, body mass index, smoking and physical activity weakened but did not remove the gradient. The whole curve sits inside what the laboratory called normal.12Grade B

GGT inside the normal range also predicts the liver's own injury signal. Among 6,523 Korean men with a normal ALT at baseline, the 4-year risk of a chronic ALT elevation, compared with a GGT under 10 U/L, was 2.5 times at 10 to 19, 4.7 at 20 to 29, 7.4 at 30 to 39 and 12.0 at 40 or more; among non-drinkers alone the gradient was 1.8, 3.8, 5.6 and 6.2. Baseline ALT did not predict a later abnormal GGT, so the enzyme moves first.13Grade B

Pooled across 21 prospective studies, each unit of log GGT carried a fully adjusted hazard of 1.92 for new diabetes, and the top fourth of the GGT distribution carried 2.94 times the risk of the bottom fourth, against 2.02 for ALT in the same studies, which made GGT the slightly stronger predictor (P = 0.05). The authors read both as signals of liver fat, which on ultrasound more than doubled diabetes risk.14Grade B

In 3,451 Framingham participants (mean age 44) followed for a mean of 19 years, each standard deviation of log GGT carried 1.26 times the risk of new metabolic syndrome, a 13 percent higher risk of cardiovascular disease and a 26 percent higher risk of death after adjustment for risk factors updated every four years and for C-reactive protein; the top quarter of GGT had 1.67 times the cardiovascular incidence of the rest.4Grade B

In 163,944 Austrian adults monitored for up to 17 years, cardiovascular mortality rose with GGT in a clear dose-response, 1.66 times per log unit in men and 1.64 in women, and the relationship was stronger under age 60 (2.03 in men, 2.60 in women). The signal came from chronic coronary disease, heart failure and stroke; acute myocardial infarction was not associated. In 28,838 Finnish adults followed 11.9 years, coronary hazards against the lowest quarter of GGT were 1.15, 1.25, 1.27 and 1.57 in men and 1.03, 1.22, 1.32 and 1.44 in women, again stronger under 60 and among drinkers.15,16Grade B

The meta-analyses agree and show the shape. Across 29 cohorts with over 1.23 million participants and 20,406 cardiovascular events, each standard deviation of log GGT carried 1.23 times the fully adjusted risk, with tests suggesting a linear relationship; ALT carried none. Across 19 cohorts with over 9.24 million participants and 242,953 deaths, the top third of GGT carried 1.60 times the all-cause mortality of the bottom third, 1.07 per 5 U/L. In 14,950 US adults without viral hepatitis followed 12 years, a GGT above 51 U/L in men or 33 in women carried 1.5 times the all-cause mortality, 13 times the liver-disease mortality, 1.5 times the cancer mortality and 3.3 times the diabetes mortality, with no significant cardiovascular excess (1.3, confidence interval 0.80 to 2.0).17,18,19Grade A

Genetics do not support the enzyme as the cause. In the Rotterdam Study, a 26-variant score that raised GGT gave a causal relative risk for type 2 diabetes of 0.96 (confidence interval 0.89 to 1.04) and for prediabetes of 0.97, against an observed hazard of 1.19 per standard deviation in the same 8,611 people. A bidirectional analysis with up to 64,094 diabetes cases and 607,012 controls found genetically higher ALT and AST raised diabetes risk and genetically higher GGT did not. Against coronary disease, genetically predicted GGT gave an odds ratio of 1.08 (0.97 to 1.19), and against diabetes 0.88 (0.75 to 1.04), while ALT in the same analysis carried 2.99 times the diabetes odds per doubling. The cohort associations are therefore read as confounding by the things that raise GGT, or as reverse causation, rather than as harm done by GGT.20,21,22Grade B

06 · What moves it

The levers with evidence behind them.

What is listed here has been tested. The size of each effect, and the size of the study, are in the sentence, so a small effect reads as a small effect.

  • Alcohol reduction

    lowers it by about a quarter within a month in regular drinkers

    In 94 healthy adults drinking a mean of 258 grams of alcohol a week who abstained for one month, GGT fell by a median of 28.6 percent (interquartile range 43.5 to 14.4 percent) and ALT by 14.5 percent, with no change in 47 who kept drinking; insulin resistance, blood pressure and weight fell too. In heavy drinkers, raised GGT usually returns to normal within 2 to 3 weeks of abstinence; in 32 patients with alcohol-related liver disease who stayed abstinent for 8 weeks, the half-life of the decline was 26 days, so a very high starting value can take months to settle. Even moderate drinkers (1 to 40 grams a day) ran higher than abstainers in the Finnish reference population.23,24,25,9Grade B

  • Weight loss

    lowers it modestly; ALT falls more

    Across 22 randomized trials in 2,588 adults with fatty liver, weight-loss interventions that produced 3.61 kg more weight loss than the comparison lowered GGT by 4.35 U/L (confidence interval 7.67 to 1.04) and ALT by 9.81 U/L, with high heterogeneity between trials, alongside less liver fat and less steatohepatitis. The GGT change is smaller than the ALT change because GGT answers to more than liver fat.26Grade A

  • Exercise without weight loss

    lowers liver fat; GGT change not demonstrated

    Pooling 21 randomized trials with 1,530 overweight adults or adults with fatty liver, exercise programs expending more than 10,000 kcal in total reduced liver fat by 3.46 percentage points and lowered free fatty acids and insulin, but ALT, AST and GGT were not significantly changed; in the four exercise-only trials that reported it, GGT moved by 3.52 U/L (confidence interval 8.37 lower to 1.34 higher). As with ALT, the enzyme can lag the fat it reflects.27Grade A

  • Coffee

    lower GGT in drinkers of 3 or more cups a day

    Among 27,793 US adults in the national survey, those drinking 3 or more cups of coffee a day had 31 percent lower odds of an abnormal GGT than non-drinkers (odds ratio 0.69, confidence interval 0.57 to 0.83), and 2 or more cups of decaffeinated coffee carried an odds ratio of 0.70 (0.49 to 1.00), so the effect is not the caffeine. A cross-sectional association; the alcohol-biomarker literature notes the same inverse relationship within heavy drinkers.28,24Grade C

  • Body fat and insulin resistance

    raise it; obesity more than doubled GGT in male drinkers

    In the Finnish reference population, GGT ran 54 percent higher in overweight and 125 percent higher in obese male moderate drinkers than in normal-weight ones (25 and 75 percent in women). In Framingham, GGT tracked body mass index, blood pressure, triglycerides and glucose at baseline and predicted new metabolic syndrome (1.26 times per standard deviation of log GGT), and the British guideline lists obesity first among the common causes of a raised GGT. Fasting insulin, triglycerides and waist size are the companions to read it with.10,4,3Grade B

  • Smoking, in people who drink

    multiplies the alcohol effect

    Among 8,465 Germans aged 50 to 74, drinking 100 grams or more of alcohol a week carried 1.7 times the odds of a GGT above 50 U/L compared with non-smoking abstainers, and smoking on its own was unrelated to GGT; but moderate-to-heavy drinking combined with heavy smoking carried 3.8 times the odds in men (confidence interval 2.2 to 6.6) and 2.9 in women, a statistically significant interaction in men.29Grade C

07 · Reading it well

Caveats, and what belongs with a physician.

The drinking of the previous two to four weeks is in the number. GGT returns to normal within 2 to 3 weeks of abstinence in most heavy drinkers, a month off alcohol lowered it by about a quarter in regular drinkers, and the decay half-life measured in abstinent patients with liver disease was 26 days. A draw after a holiday, a wedding week or a stretch of nightly drinks reads differently from one after a quiet month, and a persistently raised GGT after abstinence points to liver disease rather than to recent alcohol.24,23,25Grade B

Enzyme-inducing medicines raise GGT without liver injury. The review and the British guideline both list drug induction among the common causes, alongside obesity and alcohol. Whether a particular prescription is the explanation is a question for the prescriber, and a GGT that rose when a medicine started is read with that in mind rather than as a liver problem.1,3Grade C

GGT is how a raised alkaline phosphatase is sorted. Because GGT is not in bone, an elevated alkaline phosphatase with a normal GGT points away from the liver, most often to vitamin D deficiency or, in children, to growth, while a raised alkaline phosphatase and GGT together indicate cholestasis, whose common causes include primary biliary cholangitis, primary sclerosing cholangitis, bile-duct stones or strictures, hepatic congestion and drug-induced injury. Children with certain inherited disorders of bile acid transport are the exception: cholestasis with a low or normal GGT.3Grade A

It is a poor screen for drinking in the general population. The sensitivity of GGT for correctly classifying heavy drinkers varied from 29 to 67 percent and the false-positive rate from 0 to 27 percent depending on body mass index, and the alcohol-biomarker review calls it unsuitable for screening where obesity or non-alcoholic liver disease is common, because of low specificity. A normal GGT does not exclude heavy drinking, and a raised one does not establish it.10,24Grade B

Week-to-week noise is modest, so a real change is visible. Within-person variation was 8.9 percent in the European biological variation study and 13.4 percent in the older pooled database, against between-person variation above 40 percent in both. A shift of a few units is noise; a fall by a quarter after a month without alcohol is not. Compare results from the same laboratory and read the trend.11,30Grade C

Women run lower than men at every level of drinking and weight, and the reference limits say so: 40 versus 68 U/L in the standardized international study, 35 versus 45 among Finnish abstainers, with a measurable sex difference in biological variation. The US cohorts set their cutoffs accordingly (abnormal above 33 in women and 51 in men in the national survey). A single cutoff for both sexes under-reads women.8,9,11,19Grade B

See a physician

  • A GGT above about twice the laboratory's upper limit, or above about 100 U/L, the level at which the British guideline moves a drinker to an assessment for liver fibrosis.
  • Any GGT result alongside yellowing of the eyes or skin, dark urine, pale stools, itching, or pain under the right ribs.
  • A raised GGT together with a raised alkaline phosphatase, which points to the bile ducts or cholestasis and calls for imaging and specific blood tests rather than a repeat enzyme.
  • A raised GGT in someone whose drinking is above about one drink a day (women) or two (men), especially when they would like help changing it; the number is a useful aid to change and falls within weeks of cutting back.
  • A GGT that stays raised after a month without alcohol and without a new medicine, or a raised GGT with diabetes, a large waist, high triglycerides or a high fasting insulin, where a fibrosis estimate belongs in the workup.

This page is education, not individual medical advice, and reading it creates no physician-patient relationship.

08 · Open questions

What the literature does not settle.

  • No trial has treated healthy adults to a GGT target and measured outcomes. The gradients from the lowest category come from cohorts; whether lowering GGT, as opposed to removing what raised it, changes anything is untested, and the genetic studies suggest it would not.
  • Why GGT predicts cardiovascular death and all-cause mortality so consistently in cohorts when Mendelian randomization finds no causal effect is unresolved; candidates are alcohol, body fat, insulin resistance and oxidative stress, each of which raises GGT and each of which harms on its own.
  • The oxidative-stress interpretation rests on associations with antioxidant vitamins and later isoprostanes, fibrinogen and C-reactive protein; GGT has not been validated against a direct measure of redox state in a trial, and the physiology that links cell-surface GGT to the enzyme in serum is not fully worked out.
  • No healthy-population study has defined sex-specific upper limits for GGT in US abstainers of normal weight the way Prati did for ALT; the Finnish abstainer limits (45 men, 35 women) and the standardized international limits (68 and 40) disagree, and the international study concluded that one worldwide interval is unlikely.
  • The CARDIA gradient is in adults aged 18 to 30 at baseline; how much of the within-range risk carries to a well, middle-aged American, and whether the slope flattens with age as the Austrian and Finnish cohorts suggest, is unsettled.

10

Questions

11 · Sources

30 sources, read in full.

Numbered in the order they appear. Each line says what this page relies on from the paper; the link opens the record at PubMed or the publisher.

  1. 1.

    Whitfield JB. Gamma glutamyl transferase. Critical Reviews in Clinical Laboratory Sciences. 2001. PMID 11563810. DOI 10.1080/20014091084227.

    Review · GGT breaks down extracellular glutathione to supply cells; obstructive liver disease, high alcohol intake and enzyme-inducing drugs raise it; its reaction products can generate free radicals with iron; high GGT carries higher mortality partly independently of other risk factors.

  2. 2.

    Lee DH, Blomhoff R, Jacobs DR Jr. Is serum gamma glutamyltransferase a marker of oxidative stress?. Free Radical Research. 2004. PMID 15346644. DOI 10.1080/10715760410001694026.

    Review · Within its normal range, serum GGT ran inversely with antioxidant vitamins, positively with dietary heme iron, and predicted F2-isoprostanes, fibrinogen and C-reactive protein 5 or 15 years later in dose-response fashion.

  3. 3.

    Newsome PN, Cramb R, Davison SM, et al.. Guidelines on the management of abnormal liver blood tests. Gut. 2018. PMID 29122851. DOI 10.1136/gutjnl-2017-314924.

    Guideline · GGT belongs on the initial liver panel; it is present in liver, kidney, intestine, prostate and pancreas but not bone, so it confirms a hepatic origin for a raised alkaline phosphatase; most often raised by obesity, alcohol or drug induction; low specificity but one of the best predictors of liver mortality; GGT above 100 U/L in a drinker prompts a fibrosis assessment.

  4. 4.

    Lee DS, Evans JC, Robins SJ, et al.. Gamma glutamyl transferase and metabolic syndrome, cardiovascular disease, and mortality risk: the Framingham Heart Study. Arteriosclerosis, Thrombosis, and Vascular Biology. 2007. PMID 17095717. DOI 10.1161/01.ATV.0000251993.20372.40.

    Prospective cohort · In 3,451 participants followed 19 years, each SD of log GGT carried 1.26 times the risk of metabolic syndrome, 13 percent more cardiovascular disease and 26 percent more death; top quartile 1.67 times the cardiovascular incidence.

  5. 5.

    Castellano I, Merlino A. γ-Glutamyltranspeptidases: sequence, structure, biochemical properties, and biotechnological applications. Cellular and Molecular Life Sciences. 2012. PMID 22527720. DOI 10.1007/s00018-012-0988-3.

    Review · Gamma-glutamyltranspeptidases are ubiquitous enzymes that hydrolyze the gamma-glutamyl bond of glutathione and glutamine and transfer the group to amino acids or peptides, with roles in antioxidant defense, detoxification and inflammation.

  6. 6.

    Heisterkamp N, Groffen J, Warburton D, Sneddon TP. The human gamma-glutamyltransferase gene family. Human Genetics. 2008. PMID 18357469. DOI 10.1007/s00439-008-0487-7.

    Review · The clinical assay measures GGT1, a plasma-membrane-anchored extracellular enzyme; the human genome carries thirteen related genes, at least six apparently active; GGT1 converts LTC4 to LTD4; inherited deficiency is rare, with glutathione in the urine and failure to metabolize LTC4.

  7. 7.

    Hanigan MH. Gamma-glutamyl transpeptidase: redox regulation and drug resistance. Advances in Cancer Research. 2014. PMID 24974180. DOI 10.1016/B978-0-12-420117-0.00003-7.

    Review · GGT is a cell-surface enzyme normally on the apical surface of ducts and glands, salvaging glutamate, cysteine and glycine from glutathione in ductal fluids; cysteine is rate-limiting for glutathione synthesis under oxidative stress; tumors that express GGT over the whole membrane resist prooxidant chemotherapy.

  8. 8.

    Ceriotti F, Henny J, Queraltó J, et al.; IFCC Committee on Reference Intervals and Decision Limits. Common reference intervals for aspartate aminotransferase (AST), alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) in serum: results from an IFCC multicenter study. Clinical Chemistry and Laboratory Medicine. 2010. PMID 21034260. DOI 10.1515/CCLM.2010.315.

    Laboratory method study · In 765 screened adults with standardized methods, GGT reference intervals were 6 to 40 U/L (women) and 12 to 68 U/L (men); Nordic samples ran higher and were excluded; a common worldwide GGT interval judged unlikely.

  9. 9.

    Hietala J, Puukka K, Koivisto H, Anttila P, Niemelä O. Serum gamma-glutamyl transferase in alcoholics, moderate drinkers and abstainers: effect on gt reference intervals at population level. Alcohol and Alcoholism. 2005. PMID 16131497. DOI 10.1093/alcalc/agh201.

    Cross-sectional study · Among 2,485 healthy volunteers, moderate drinkers (1 to 40 g/day) had higher GGT than abstainers; upper limits from abstainers were 45 U/L (men) and 35 (women) against 66 and 40 from moderate drinkers.

  10. 10.

    Puukka K, Hietala J, Koivisto H, Anttila P, Bloigu R, Niemelä O. Obesity and the clinical use of serum GGT activity as a marker of heavy drinking. Scandinavian Journal of Clinical and Laboratory Investigation. 2007. PMID 17763184. DOI 10.1080/00365510601146035.

    Cross-sectional study · Upper limits from normal-weight abstainers were 53 U/L (men) and 45 (women) against 68 and 50 from moderate drinkers; GGT 54 percent higher in overweight and 125 percent higher in obese male moderate drinkers (25 and 75 percent in women); sensitivity for heavy drinking 29 to 67 percent and false positives 0 to 27 percent by BMI.

  11. 11.

    Carobene A, Røraas T, Sølvik UØ, et al.; European Biological Variation Study of the EFLM Working Group on Biological Variation. Biological Variation Estimates Obtained from 91 Healthy Study Participants for 9 Enzymes in Serum. Clinical Chemistry. 2017. PMID 28428356. DOI 10.1373/clinchem.2016.269811.

    Laboratory method study · In 91 healthy adults sampled weekly for 10 weeks, within-subject variation of GGT was 8.9 percent and between-subject 41.7 percent, with sex-related differences.

  12. 12.

    Lee DH, Jacobs DR Jr, Gross M, et al.. Gamma-glutamyltransferase is a predictor of incident diabetes and hypertension: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Clinical Chemistry. 2003. PMID 12881453. DOI 10.1373/49.8.1358.

    Prospective cohort · In 4,844 adults aged 18 to 30 followed 15 years, with GGT cutpoints of 12, 17, 25 and 36 U/L (laboratory limits 40 women, 50 men), hazards for diabetes were 1.0, 1.6, 1.7, 4.0 and 5.5 and for hypertension 1.0, 1.2, 1.7, 2.3 and 2.3.

  13. 13.

    Lee DH, Lim JS, Yang JH, Ha MH, Jacobs DR Jr. Serum gamma-glutamyltransferase within its normal range predicts a chronic elevation of alanine aminotransferase: a four year follow-up study. Free Radical Research. 2005. PMID 16036336. DOI 10.1080/10715760400016154.

    Prospective cohort · In 6,523 men with normal ALT, 4-year risk of chronic ALT elevation versus GGT under 10 U/L was 2.5, 4.7, 7.4 and 12.0 at 10 to 19, 20 to 29, 30 to 39 and 40 or more (1.8, 3.8, 5.6 and 6.2 in non-drinkers); baseline ALT did not predict later GGT.

  14. 14.

    Fraser A, Harris R, Sattar N, Ebrahim S, Davey Smith G, Lawlor DA. Alanine aminotransferase, gamma-glutamyltransferase, and incident diabetes: the British Women's Heart and Health Study and meta-analysis. Diabetes Care. 2009. PMID 19131466. DOI 10.2337/dc08-1870.

    Systematic review and meta-analysis · Across 21 prospective studies, the fully adjusted hazard for diabetes was 1.92 per unit of log GGT and 2.94 for the top versus bottom fourth, against 2.02 for ALT (P = 0.05); ultrasound fatty liver more than doubled risk.

  15. 15.

    Ruttmann E, Brant LJ, Concin H, Diem G, Rapp K, Ulmer H; Vorarlberg Health Monitoring and Promotion Program Study Group. Gamma-glutamyltransferase as a risk factor for cardiovascular disease mortality: an epidemiological investigation in a cohort of 163,944 Austrian adults. Circulation. 2005. PMID 16186419. DOI 10.1161/CIRCULATIONAHA.105.552547.

    Prospective cohort · In 163,944 adults followed up to 17 years, cardiovascular mortality rose with GGT in a dose-response, hazard 1.66 per log unit in men and 1.64 in women; 2.03 and 2.60 under age 60; chronic coronary disease, heart failure and stroke associated, acute myocardial infarction not.

  16. 16.

    Lee DH, Silventoinen K, Hu G, et al.. Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28,838 middle-aged men and women. European Heart Journal. 2006. PMID 16772340. DOI 10.1093/eurheartj/ehl086.

    Prospective cohort · In 28,838 Finns followed 11.9 years (1,467 coronary events), hazards against the lowest GGT quarter were 1.15, 1.25, 1.27 and 1.57 in men and 1.03, 1.22, 1.32 and 1.44 in women, stronger under age 60 and among drinkers.

  17. 17.

    Kunutsor SK, Apekey TA, Khan H. Liver enzymes and risk of cardiovascular disease in the general population: a meta-analysis of prospective cohort studies. Atherosclerosis. 2014. PMID 24998934. DOI 10.1016/j.atherosclerosis.2014.06.006.

    Systematic review and meta-analysis · Across 29 cohorts (over 1.23 million participants, 20,406 events), the fully adjusted relative risk of cardiovascular disease was 1.23 per SD of log GGT, log-linear; ALT and AST showed no association.

  18. 18.

    Kunutsor SK, Apekey TA, Seddoh D, Walley J. Liver enzymes and risk of all-cause mortality in general populations: a systematic review and meta-analysis. International Journal of Epidemiology. 2014. PMID 24585856. DOI 10.1093/ije/dyt192.

    Systematic review and meta-analysis · Across 19 cohorts (over 9.24 million participants, 242,953 deaths), the top third of GGT carried a relative risk of all-cause mortality of 1.60 versus the bottom third, 1.07 per 5 U/L, consistent with a linear dose-response.

  19. 19.

    Ruhl CE, Everhart JE. Elevated serum alanine aminotransferase and gamma-glutamyltransferase and mortality in the United States population. Gastroenterology. 2009. PMID 19100265. DOI 10.1053/j.gastro.2008.10.052.

    Prospective cohort · In 14,950 NHANES III adults without viral hepatitis followed 12 years, GGT above 51 U/L (men) or 33 (women) carried hazards of 1.5 for all-cause, 13.0 for liver-disease, 1.5 for cancer and 3.3 for diabetes mortality, and 1.3 (0.80 to 2.0) for cardiovascular mortality.

  20. 20.

    Nano J, Muka T, Ligthart S, et al.. Gamma-glutamyltransferase levels, prediabetes and type 2 diabetes: a Mendelian randomization study. International Journal of Epidemiology. 2017. PMID 28338987. DOI 10.1093/ije/dyx006.

    Mendelian randomization · In 8,611 Rotterdam Study participants, observed hazards per SD of GGT were 1.10 for prediabetes and 1.19 for diabetes, but a 26-variant genetic score gave causal relative risks of 0.97 and 0.96 (0.89 to 1.04); no causal role for GGT.

  21. 21.

    De Silva NMG, Borges MC, Hingorani AD, et al.; UCLEB consortium. Liver Function and Risk of Type 2 Diabetes: Bidirectional Mendelian Randomization Study. Diabetes. 2019. PMID 31088856. DOI 10.2337/db18-1048.

    Mendelian randomization · With up to 64,094 diabetes cases and 607,012 controls, genetically higher ALT and AST raised diabetes risk, ALP was modestly inverse, and GGT showed no association; genetically higher fasting insulin raised ALT.

  22. 22.

    Liu J, Au Yeung SL, Lin SL, Leung GM, Schooling CM. Liver Enzymes and Risk of Ischemic Heart Disease and Type 2 Diabetes Mellitus: A Mendelian Randomization Study. Scientific Reports. 2016. PMID 27996050. DOI 10.1038/srep38813.

    Mendelian randomization · Genetically predicted GGT was not associated with diabetes (odds ratio 0.88, 0.75 to 1.04) or coronary disease (1.08, 0.97 to 1.19), while genetically higher ALT carried 2.99 times the diabetes odds per 100 percent change.

  23. 23.

    Mehta G, Macdonald S, Cronberg A, et al.. Short-term abstinence from alcohol and changes in cardiovascular risk factors, liver function tests and cancer-related growth factors: a prospective observational study. BMJ Open. 2018. PMID 29730627. DOI 10.1136/bmjopen-2017-020673.

    Prospective cohort · In 94 healthy drinkers (mean 258 g/week) who abstained one month, GGT fell 28.6 percent (IQR 43.5 to 14.4) and ALT 14.5 percent, with insulin resistance, blood pressure and weight also down; no change in 47 controls who kept drinking.

  24. 24.

    Niemelä O. Biomarker-Based Approaches for Assessing Alcohol Use Disorders. International Journal of Environmental Research and Public Health. 2016. PMID 26828506. DOI 10.3390/ijerph13020166.

    Review · GGT is sensitive to changes in alcohol consumption but lacks specificity for screening where obesity or non-alcoholic liver disease is common; in alcoholics, raised values usually return to normal within 2 to 3 weeks of abstinence; coffee drinkers among heavy drinkers run lower.

  25. 25.

    Orrego H, Blake JE, Israel Y. Relationship between gamma-glutamyl transpeptidase and mean urinary alcohol levels in alcoholics while drinking and after alcohol withdrawal. Alcoholism: Clinical and Experimental Research. 1985. PMID 2859812. DOI 10.1111/j.1530-0277.1985.tb05038.x.

    Prospective cohort · In 32 patients with alcohol-related liver disease who stayed abstinent 8 weeks, the half-life of serum GGT decline was 26 days; GGT correlated with mean urinary alcohol (r = 0.69) in 42 patients.

  26. 26.

    Koutoukidis DA, Astbury NM, Tudor KE, et al.. Association of Weight Loss Interventions With Changes in Biomarkers of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis. JAMA Internal Medicine. 2019. PMID 31260026. DOI 10.1001/jamainternmed.2019.2248.

    Systematic review and meta-analysis · Across 22 randomized trials (2,588 participants), weight-loss interventions (3.61 kg more loss) lowered GGT by 4.35 U/L (7.67 to 1.04) and ALT by 9.81 U/L, with less steatosis and steatohepatitis.

  27. 27.

    Smart NA, King N, McFarlane JR, Graham PL, Dieberg G. Effect of exercise training on liver function in adults who are overweight or exhibit fatty liver disease: a systematic review and meta-analysis. British Journal of Sports Medicine. 2018. PMID 27317790. DOI 10.1136/bjsports-2016-096197.

    Systematic review and meta-analysis · Across 21 randomized trials (1,530 participants), exercise programs over 10,000 kcal reduced liver fat by 3.46 percentage points, but ALT, AST and GGT were not significantly changed; GGT in exercise-only trials -3.52 U/L (-8.37 to 1.34).

  28. 28.

    Xiao Q, Sinha R, Graubard BI, Freedman ND. Inverse associations of total and decaffeinated coffee with liver enzyme levels in National Health and Nutrition Examination Survey 1999-2010. Hepatology. 2014. PMID 25124935. DOI 10.1002/hep.27367.

    Cross-sectional study · Among 27,793 US adults, 3 or more cups of coffee a day carried an odds ratio of 0.69 (0.57 to 0.83) for abnormal GGT; 2 or more cups of decaffeinated coffee 0.70 (0.49 to 1.00).

  29. 29.

    Breitling LP, Raum E, Müller H, Rothenbacher D, Brenner H. Synergism between smoking and alcohol consumption with respect to serum gamma-glutamyltransferase. Hepatology. 2009. PMID 19152425. DOI 10.1002/hep.22727.

    Cross-sectional study · In 8,465 adults aged 50 to 74, alcohol 100 g/week or more carried 1.7 times the odds of GGT above 50 U/L; smoking alone was unrelated; alcohol plus heavy smoking carried 3.8 (men) and 2.9 (women).

  30. 30.

    Ricós C, Alvarez V, Cava F, et al.. Desirable Biological Variation Database specifications (2014 update of the Ricós database). Westgard QC. 2014.

    Laboratory method study · Serum GGT: within-subject biological variation 13.4 percent, between-subject 42.15 percent (10 papers).

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