Tests for gamma-glutamyl transferase (GGT) are important in the diagnosis of liver/biliary tract disease and useful in identifying alcohol abuse. More and more diseases are being linked to high GGT levels, and the test is even part of routine screening for life and health insurance applicants. Read on to learn more about the function of GGT, its health effects, and ways to lower GGT levels.
- What is GGT?
- Functions of GGT
- Normal and Optimal Levels of GGT
- Diseases Linked to High GGT Levels
- 1) Liver Disease
- 2) Biliary Tract Disease
- 3) Alcohol Consumption and Cigarette Smoking
- 3) Coronary Heart Disease (CHD)
- 4) Stroke
- 5) Arteriosclerosis
- 6) Heart Failure
- 7) High Blood Pressure
- 8) Cardiac Arrhythmias
- 9) Diabetes
- 10) Metabolic Syndrome
- 11) Cancer
- 12) Kidney Disease
- 13) Alzheimer’s Disease and Dementia
- 14) Thyroid Disease
- 15) Decreased Bone Mineral Density
- GGT: Mechanisms in Disease
- 11 Ways to Lower GGT Levels
- Conditions Associated with Low GGT Levels
- Factors That Increase GGT Levels
- Genetics of GGT
- Limitations and Caveats
What is GGT?
Gamma-glutamyl transferase (GGT) is a cell surface enzyme. It is located throughout the human body with the highest levels being in the kidneys, intestines, liver, prostate gland, and gallbladder. Smaller amounts are found in the pancreas, lungs, testis, and thyroid gland. The liver produces most of the GGT in the blood [R, R, R].
GGT is elevated in liver/biliary tract disease or as a result of moderate to excessive alcohol consumption.
Higher GGT levels also increase the risk of several diseases and may point to health problems. This article will cover the functions of GGT, its role in diagnosing or predicting disease, and ways to lower GGT levels in the body.
Functions of GGT
It increases the number of available amino acids (especially cysteine), that are used to make glutathione inside the cell [R].
GGT is also involved in:
- Breaking down drugs and toxins
- Forming amino acids important for the brain and heart (gamma-glutamyl-taurine to taurine)
- Transforming inflammatory molecules (leukotriene C4 to leukotriene D4) [R, R]
Normal and Optimal Levels of GGT
The reference ranges for GGT levels vary between sources and laboratories. Normal levels are dependent on age and sex. Generally, they are higher in adult males than in adult females. The reference ranges based on 1,160 alcohol abstainers are organized below (one retrospective meta-analysis and one clinical study) [R, R]:
The risk for heart disease increases around the middle of what is considered a “normal” range for both males and females (prospective clinical studies). Therefore, optimal levels of GGT are below the reference range midpoint (based on age and gender).
For example, a GGT level of approximately 9 to 25 U/L would be considered optimal in a 25-year-old male. When levels of GGT rise above optimal limits, the risk of developing certain chronic diseases increases [R, R, R, R, R].
Diseases Linked to High GGT Levels
GGT is useful in 3 ways:
- Diagnose disease: Used to screen for liver/biliary tract disease, and to identify alcohol abuse [R, R, R, R, R, R].
- Assess disease risk: Elevated levels of GGT are linked to increased risk of disease and disease-related death (morbidity and mortality) [R, R, R, R, R, R, R, R, R, R, R, R, R, R].
- All-cause mortality: Clinical studies show a relationship between higher levels of GGT and increased the chance of death from any cause [R, R, R, R, R, R].
1) Liver Disease
GGT is increased in patients with liver diseases, such as cirrhosis, hepatitis, and fatty liver. These conditions are caused by a number of factors, including drug and alcohol abuse, toxins, or viruses [R, R, R, R, R, R].
GGT levels are used with other liver enzyme tests to diagnose liver disease. For example, GGT levels are measured when alkaline phosphatase (ALP) is high. Elevated levels of both enzymes point to a liver or biliary tract disease. Normal levels of GGT in the presence of increased alkaline phosphatase (ALP) point to bone disease [R].
2) Biliary Tract Disease
High levels of GGT are also found in patients with biliary tract disease (cholestasis). This is usually caused by bile duct obstructions from one or more conditions including gallstones, inflammation, injury, infection, cysts, and/or carcinomas (cancer) [R, R, R, R].
Like with liver disease, GGT is used in combination with additional tests, such as alkaline phosphatase (ALP), for diagnosing biliary tract disease [R].
3) Alcohol Consumption and Cigarette Smoking
In a study of 165 heavy drinkers and 86 non- or moderate drinkers, increased levels of GGT in combination with another marker (carbohydrate-deficient transferrin (CDT) were better at predicting alcohol abuse than either test alone [R].
Cigarette smoking has also been linked to elevated GGT levels. One clinical study (prospective) conducted in 46,775 men found that regular alcohol consumption and daily cigarette smoking increased levels of GGT greater than each activity alone. Those subjects that drank and/or smoked more had higher levels of GGT [R, R].
3) Coronary Heart Disease (CHD)
CHD is a condition caused by the narrowing of the coronary arteries, potentially leading to a heart attack. Elevated GGT levels are associated with an increased risk for coronary heart disease (prospective clinical studies)[R, R].
The largest meta-analyses to date (10 prospective studies) found that higher levels of GGT increased the risk of stroke (independent of excessive alcohol consumption), but only in men [R].
Arteriosclerosis is a narrowing and clogging of the arteries, usually due to plaques. GGT is present in human plaques, and levels are higher in patients with plaques, especially in those with more severely clogged arteries. Therefore, GGT may be used to diagnose this condition [R, R].
6) Heart Failure
Heart failure is a condition where the heart is unable to supply enough blood to meet bodily demand. Clinical studies (prospective and retrospective) found an association between elevated GGT levels and an increased risk of heart failure, even when values fell within “normal” range [R, R, R].
7) High Blood Pressure
In-depth studies (meta-analyses of prospective clinical trials) found people with elevated levels of GGT also have an increased risk of high blood pressure (hypertension). As levels of GGT went up, so did the risk of developing hypertension [R, R].
8) Cardiac Arrhythmias
Atrial fibrillation causes rapid irregular heart beating. Higher levels of GGT were linked to an increased risk for atrial fibrillation in several studies (prospective).
Elevated levels of GGT may increase the risk of type 2 diabetes. However, a recent study (meta-analysis of prospective clinical studies) found no link between the two. Further studies looking at this relationship would be beneficial [R, R, R, R].
10) Metabolic Syndrome
Metabolic syndrome is 2 or more conditions including insulin resistance, high blood pressure, blood fat abnormalities (dyslipidemia), and obesity. Independent of other risk factors, a number of clinical studies (prospective) have found that elevated levels of GGT increased the risk of metabolic syndrome [R, R, R].
- Breast cancer: Those with higher GGT have a greater risk of developing several subtypes of breast cancer according to a study in 231,283 cancer-free women [R].
- Esophageal cancer: A study of 8,388,256 Koreans found an increased risk for esophageal cancer in those with levels of GGT > 18 U/L, a value considered “normal”. As the level of GGT rose, so did the risk of esophageal cancer [R].
- Liver cancer: Higher GGT levels were associated with a worse prognosis in hepatocellular carcinoma [R, R].
- Endometrial cancer: Elevated levels of GGT were associated with decreased survival rates for women with cancer in the uterus lining (endometrial carcinoma) and cervical cancer [R, R].
12) Kidney Disease
One study (prospective) in 10,337 Korean men found that the risk of chronic kidney disease was greater in patients with elevated GGT levels. Another study (retrospective), of 9,516 Americans found no such link [R, R].
Elevated levels of GGT may be associated with increased risk of chronic kidney disease in specific populations.
13) Alzheimer’s Disease and Dementia
GGT can be elevated in patients with Alzheimer’s disease. However, a genetic study looking at 26 GGT-related gene variations (single nucleotide polymorphisms (SNPs)) and the risk of Alzheimer’s disease found no correlation between the two [R, R].
One clinical (prospective) study in 2,415 men found elevated GGT levels to be associated with increased risk of dementia [R].
14) Thyroid Disease
GGT was slightly increased in patients with hypothyroidism in one study and decreased in another study. Additional research is needed to clarify the relationship between GGT and thyroid disease [R, R].
15) Decreased Bone Mineral Density
Bone mineral density (BMD) represents overall bone health and strength. One clinical study in 462 people found people with high GGT levels have low BMD (independent of alcohol consumption) [R].
GGT: Mechanisms in Disease
GGT alone does not directly cause a particular disease or disorder. High levels of GGT may contribute to disease by acting a pro-oxidant.
GGT may increase oxidative stress, starting with the breakdown of glutathione (and production of cysteinylglycine). Other toxic molecules are then formed, leading to tissue, cellular, and DNA damage [R, R, R].
GGT is present in plaques because it attaches itself to circulating fats (LDL). Once in the plaque, GGT can become pro-oxidant, injuring blood vessels (via oxidative stress), and contribute to heart disease [R, R, R].
11 Ways to Lower GGT Levels
1) Decrease Alcohol Consumption
Alcohol abuse increases GGT levels. GGT is only slightly elevated in moderate drinkers, but the increase is relevant. The best way to lower GGT is to simply abstain from alcohol use. Levels should return to “normal” after 2 to 6 weeks [R, R].
2) Avoid Pollutants
Certain environmental pollutants (such as lead, cadmium, dioxin, and organochlorine- containing pesticides) increase GGT levels [R].
3) Eat More Fruits and Vegetables
Many fruits and vegetables contain moderate to high amounts of natural antioxidants. A study of 3,146 persons in a diverse population (black and white men and women 17 to 35 years of age) found that eating fruits and/or vegetables 10 to 11 times per week, or drinking fruit juice 6 to 7 times a week for 10 years lowered GGT levels (independent of other factors) [R].
4) Eat Foods High in Protein
Consuming foods high in cysteine such as eggs, nuts/seeds, soy products, certain grains (oats and bran), and whey protein may lower the levels of GGT in the body. Cysteine is an important component of glutathione. Higher glutathione levels are thought to lower GGT, and vice versa.
A pilot clinical study of 38 people found that cysteine (20 grams of whey protein isolate for 12 weeks) increased glutathione levels [R].
5) Drink More Coffee
Drinking coffee decreased GGT levels in 1,353 Japanese men (independent of other risk factors) [R].
6) Eat Less Red Meat
Red meat contains large amounts of heme iron, the most readily absorbed form of iron. The same study that showed fruits and vegetables reduced GGT found that eating red meat over 10 years increased GGT levels [R, R].
Note: Vegetarian sources do contain varying levels of iron, but in the form that’s harder to absorb (non-heme iron). Vegetarian iron contributes to overall iron levels in the body much less than meat sources. This is one reason that vegetarians sometimes suffer from iron deficiency or anemia [R, R].
7) Moderate Exercise
One study of 10,159 participants found that moderate exercise (walking) was associated with decreased GGT levels in men, but not women [R].
8) Fish Oil
High doses of fish oil (4 grams/day) for 3 months significantly lowered GGT levels in 36 participants (DB-RCT) who had characteristics of non-alcoholic fatty liver disease [R].
10) Milk Thistle
Many clinical studies have investigated milk thistle’s ability to lower GGT levels in liver disease, with mixed results. This herb may decrease levels of GGT in specific liver conditions [R].
Six weeks of magnesium supplementation decreased levels of GGT in a group of chronic alcoholics [R].
12) Glutathione Supplementation
Supplementation with glutathione, and other substances that increase glutathione levels, such as n-acetylcysteine, selenium, alpha lipoic acid (ALA), and methionine, may reduce GGT levels. Usually, GGT levels fall as glutathione increases. Unfortunately, there is little evidence to support this theory.
Conditions Associated with Low GGT Levels
Rarely are low levels of GGT dangerous. However, a few conditions are associated with abnormally low levels of GGT. Whether this is cause for concern depends on other factors.
1) Inherited Disorders
Familial Intrahepatic Cholestasis (FIC) includes inherited (genetic) disorders, usually observed in infants and children. It is characterized by the decreased flow of bile from the liver. It can be:
- Benign (benign recurrent intrahepatic cholestasis), which rarely causes health concerns, or
- Progressive (progressive familial intrahepatic cholestasis), which is considered severe and may lead to serious health issues [R]
Mutations in the ATP8B1 gene are related to both the mild and severe forms of the disease. This gene controls the bile salt export pump, which drives bile flow [R].
2) Mid to Late Pregnancy
Women in their second and third trimesters may have lower levels of GGT in comparison to non-pregnant women. There is no indication that this is cause for concern [R].
Factors That Increase GGT Levels
High levels of GGT usually indicate present disease or a higher risk of disease. Here we give a summary of the factors that increase levels of GGT.
1) Medications/Prescription Drugs and Supplements
Several medications increase GGT levels and must be taken into consideration when interpreting test results. These include older anti-seizure medications (such as phenytoin, phenobarbital, and carbamazepine) [R, R, R, R].
3) Red Meat
Red meat intake over 10 years increased GGT levels [R].
One study of 62 healthy adults (pilot) found that GGT levels were increased by about 40% in those who drank kava [R].
5) Thyroid Hormone
Genetics of GGT
The GGT gene family consists of 13 members, with 6 considered to be “active,” The gene responsible for most of the GGT throughout the body is GGT1 [R].
Limitations and Caveats
The full range of functions for GGT is not known. It is a topic of continued scientific and clinical study.
There are diseases states such as diabetes, chronic kidney disease, and hypothyroidism where clinical studies show conflicting conclusions regarding risk and elevated GGT levels. Further studies need to be done to determine if high GGT levels increase the risk of these diseases.
Prospective and retrospective clinical studies show elevated GGT levels to be associated with the development of diseases even within what would be considered “normal” ranges. This is mostly the case with GGT and the risk of cardiovascular diseases. Future clinical studies need to address the risk of other disease states within “normal” GGT ranges.
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