Glucuronidation is an important detoxification reaction that inactivates and detoxifies estrogens, hormones, neurotransmitters, drugs, mold toxins, and cancer-causing toxins. In this post, we’ll explain glucuronidation and factors that increase or decrease it. In addition, we’ll also cover beta-glucuronidase, an enzyme produced by gut bacteria that undoes glucuronidation. Finally, we’ll review the genes that affect glucuronidation.
Glucuronidation involves the addition of glucuronic acid to a toxic molecule to make it :
- More water soluble
- Less toxic or reactive
- Easily transported throughout the body
- Possible to eliminate via urine
If toxins don’t get properly inactivated and removed, they cause cell and tissue damage and may initiate cancer.
Glucuronidation is one of the most important detox reactions taking place in our bodies .
It is responsible for the clearance of many drugs, cancer-causing chemicals, environmental toxins, and substances found in food .
Glucuronidation enzymes (UGTs) are found throughout the body: in the gut, kidney, brain, pancreas, and placenta. However, the majority are found in the liver .
In the brain, UGTs actively protect against the intrusion of harmful chemicals .
Enzymes responsible for glucuronidation are called UDP-glucuronosyltransferases or UGTs .
In humans, around 40 – 70% of all clinical drugs are cleared by UGTs .
There are 19 functional human UGTs. They belong to one of the three subfamilies: UGT1A, UGT2A, and UGT2B .
- Cancer-causing substances called polycyclic aromatic hydrocarbons, including benzo[a]pyrene, are found in cigarette smoke, wood smoke, and burnt foods [6, 7]
- BPA (Bisphenol-A), is a toxin used in plastics and linked to various human diseases including breast cancer 
- Some cancer-causing nitrosamines are found in tobacco smoke and in the gut of people who eat red meat 
- Heterocyclic amines (HACs) are found in red processed meat; PhIP is the most abundant one, found in well-done cooked meat, and it is inactivated by UGT1A enzymes 
- Some fungal toxins are found in moldy crops 
- Estrogen 
- Androgens (including testosterone) 
- T3 and T4 
- Bilirubin 
- Bile acids 
- Fat-soluble vitamins 
- Dopamine and serotonin (minor role) 
PhIP is a cancer-causing agent present in cooked food. A study with 20 non-smoking men found that brussels sprouts and broccoli increased PhIP glucuronidation .
A study in 12 smokers found that watercress increases UGT enzyme activity .
Citruses may especially benefit people with certain gene variants.
In a study with healthy nonsmokers (293 subjects), citruses increased UGT1A1 activity by about 30%, but only in women with two copies of the UGT1A1*28 variant . This is the variant associated with lower UGT1A1 activity and Gilbert’s syndrome.
These herbs and supplements increased glucuronidase activity in animal studies:
- Soy 
- Green tea [23, 24]
- Dandelion 
- Rooibos tea 
- Honeybush tea 
- Coffee 
- Rosemary (particularly UGT1A6) 
- Ellagic acid (found in walnuts, pecans, berries, grapes, and pomegranate) 
- Ferulic acid (found in coffee and whole grains) 
- Quercetin (found in many fruits and veggies, capers, onions, berries, and tea) 
- Tannic acid 
- Coumarin (found naturally in many plants like tonka bean, cassia cinnamon, and vanilla grass) 
- Fumaric acid 
- Curcumin (turmeric, found in curry powder) 
- Flavone 
- Astaxanthin and canthaxanthin (carotenoids) 
It’s important to stress that what’s found in animal studies, doesn’t always match what’s later found in humans. The findings from animal studies are given solely for information purposes and will be updated as soon as new findings from human studies become available.
There are a lot more foods and supplements that increase UGTs in isolated liver or gut cells. However, these results are often inconclusive and don’t translate well into animal or human studies.
However, in the studies above, piperine decreased the clearance of curcumin, resveratrol, and green tea. This is considered beneficial because it increases their bioavailability.
Adding black pepper may be a good way to increase curcumin, resveratrol, and green tea exposure and their health benefits.
A wide variety of foods and supplements decrease UGTs in isolated cells. These include curcumin, ginger extract, quercetin, silybin, ginseng, vitamin A, green tea, and its component epigallocatechin gallate (EGCG) [34, 35, 36, 37, 38]. However, these do not necessarily work in the same manner in living organisms.
Beta-glucuronidase is an enzyme produced by gut bacteria (such as E. coli) and gut cells .
This enzyme reverses the glucuronidation reaction and reactivates the inactivated toxins to their previous active form .
The same human study found a link between being overweight (BMI ≥ 25) and having higher beta-glucuronidase activity .
Researchers found that as we get older, beta-glucuronidase activity increases .
A study in 100 people suggests that smoking may increase this enzyme .
Researchers have found an increased activity of this enzyme in many diseases: liver inflammation, liver cirrhosis, jaundice, tuberculosis, and cancer .
Beta-glucuronidase activity was 1.7 times higher in colon cancer patients compared to healthy people .
In fact, this enzyme may be a sensitive indicator pointing to cell and tissue damage .
Drugs like phenobarbital and spironolactone were shown to increase this enzyme in rats .
However, more studies are needed to confirm the same effect in humans.i
A study in 279 people found that those who consumed more plants had generally lower beta-glucuronidase .
Another study also showed that this enzyme was lower with a higher intake of plant protein, fruit, and dietary fiber (203 subjects) .
Beneficial plants were those belonging to the gourd family (such as squash, pumpkin, zucchini, cucumber, and watermelon), the rose family (apples, pears, plums, cherries, peaches, raspberries, and strawberries), and legumes (peas and beans) .
However, another study with 63 volunteers found an increase in this enzyme on a diet enriched with crucifers, citrus, and soy .
In an initial study with 18 people, vitamin C decreased beta-glucuronidase activity by 25% .
The above study in 279 people found that those with higher dietary intakes of calcium, iron, and magnesium had lower beta-glucuronidase activity .
Prebiotics are basically fibers that stimulate the growth of beneficial bacteria in our bodies.
These decreased beta-glucuronidase activity in animal studies:
- Caloric restriction in rats and monkeys [58, 59]
- Blackcurrant in rabbits on high-fat diet 
- Strawberry pulp extract in rats 
- Black pepper in rats exposed to colon-cancer-causing chemicals 
- Cumin in rats exposed to colon-cancer-causing chemicals 
- Calcium-D-glucarate (D-glucaric acid) in rats . D-glucaric acid is found in many fruits and vegetables, with the highest levels in grapefruit, apples, oranges, and cruciferous vegetables. It is transformed in the stomach into D-glucaro-l,4-lactone, a natural inhibitor of beta-glucuronidase activity [44, 64].
- Lower colon pH [65, 66]
These decrease beta-glucuronidase in isolated cells:
- Licorice (G. uralensis) 
- Milk thistle (silymarin) 
- Reishi mushroom (G. lucidum) 
- Green tea (epigallocatechin gallate) 
- B. infantis 
- Kombucha 
Again, what’s found in cell and animal studies, doesn’t always match what’s later found in humans. The findings from animal and cell studies are given solely for information purposes and will be updated as soon as new findings from human studies become available.
Over 10% of the population have hereditary deficiencies in UGTs .
The UGT2 family enzymes are all produced by separate genes .
Before we dive into the research associated with glucuronidation, keep in mind that most of the studies below are largely based on association, suggesting that certain genetic variants are more or less common in people with these conditions. More research is needed to know what role, if any, these variants play in actually contributing to conditions such as heart disease, osteoporosis, and cancer.
In addition, all these conditions are dependent on a multitude of factors, and UGT variants may have only a minor effect. Therefore, just because you may have a certain UGT variant, that doesn’t necessarily mean you are at an increased or decreased risk of developing these conditions!
This is a variant in the shared part of the UGT1 gene (it is present in all UGT1A enzymes).
Studies suggest that people with this variant may clear Tylenol (paracetamol) from their system better .
UGT1A1 is the only enzyme that glucuronidates bilirubin.
It also inactivates some cancer-causing compounds and estrogen.
Patients with a rare inherited disorder called Crigler-Najjar syndrome have a complete or partial absence of this enzyme .
Complete UGT1A1 absence results in high levels of bilirubin, severe jaundice, and brain damage in infants. Those with a partial deficiency have milder jaundice and generally survive into adulthood without neurological or intellectual impairment .
Gilbert’s syndrome is a mild disorder caused by a mutation in the UGT1A1 gene. People with this syndrome have mildly elevated bilirubin levels .
Gilbert’s syndrome is found in about 10% of the population .
People with Gilbert’s syndrome also have reduced clearance of drugs like Tylenol .
This variant is also known as the UGT1A1*28 variant (also rs8175347, rs3064744 or rs35600288).
It is the most common cause of Gilbert’s syndrome. UGT1A1*28 occurs with a frequency of 26-31% in Whites, 42 – 56% of African Americans, and only 9 – 16% of Asians .
This variant results in 30 – 40% lower UGT1A1 levels .
Studies suggest that when people with this variant eat food containing cancer-causing chemicals, such as well-done red meat, less of the cancer-causing chemicals from the meat get deactivated .
A study in 765 people found that having two copies of UGT1A1*28 was associated with higher odds of having lung cancer .
On the other hand, UGT1A1*28 was associated with lower odds of having Crohn’s disease (751 patients and 930 controls) .
Additionally, a Framingham Heart study showed that people with two UGT1A1*28 copies had a 2/3 lower risk of developing heart disease over the 24 year follow-up period (1780 subjects) .
This relationship with heart disease, however, has not been confirmed in two other studies .
Studies suggest that UGTs1A6 is responsible for the detox of cancer-causing agents such as benezo[a]pyrene from cigarette smoke .
RS6759892 is also known as the UGT1A6*2 variant.
A study in 474 colon cancer patients and 563 healthy people found that NSAID use was associated with lowering the risk of colon cancer, but only in those carrying this variant .
Another study in 1062 women found the same for aspirin .
On the other hand, a study of 7418 cancer patients and 8,720 controls found that having two copies of this variant (GG) was associated with a higher risk of breast cancer .
Another study in 95 lung cancer patients and 100 controls found that this variant was associated with a higher risk of lung cancer .
UGT1A62 is often inherited together with UGT1A128, which may affect the association with cancer.
This enzyme is found in the gut and the lungs .
UGT1A7 is involved in inactivating cancer-causing agents present in tobacco smoke .
A meta-analysis of 22 studies with over 9000 people found that UGT1A7*3 was associated with increased risk of liver, lung, and bladder cancer risk in Asians .
This variant has also been linked with chronic pancreas inflammation and pancreatic cancer in a study of 433 people .
This variant is known as the UGT2B15*2 variant.
People with this variant seem to have a decreased clearance of Tylenol (paracetamol) (66 subjects) .
UGT2B17 is one of the most commonly missing genes in humans .
Some people have two copies, while others have a single copy or don’t have this enzyme at all .
UGT2B17 deletion is more common in Asians (67%) than Whites (9%) .
This enzyme inactivates steroid hormones, including testosterone and estradiol. It also inactivates a large number of drugs and toxins .
Men with higher testosterone levels are less likely to be obese. Accordingly, a study of 940 people found that men without UGT2B17 had lower BMI .
On the other hand, not having UGT2B17 has been associated with an increased risk of prostate cancer based on two meta-analyses (meta-analysis of 6 studies, 3,839 cases, and 3,190 controls) (meta-analysis of >25 studies, >17,000 subjects) [101, 102].
However, there is a study that found no association of UGT2B17 deletion and cancer risks (meta-analysis, 14 studies, 5,732 cases, and 5,112 controls) .
A study of over 2.3k women found that those without UGT2B17 tended to have higher bone mineral density .
Accordingly, a genome-wide copy variation study of over 3k people has found a link between UGT2B17 and osteoporosis .
However, there are also studies that found no link between UGT2B17 and osteoporosis (1,347 elderly women) .