Glucuronidation is an important detoxification reaction that inactivates and detoxifies bad estrogens, hormones, neurotransmitters, drugs, mold toxins, and cancer-causing toxins.

Increasing glucuronidation helps you better balance your hormones, like overcoming estrogen dominance and preventing cancers.

In this post, we outline foods and supplements that help you increase this beneficial detoxification reaction. In addition, you can modify your gut bacteria to inhibit beta-glucuronidase (an enzyme that undoes glucuronidation).

In this post, you also learn about genes that affect glucuronidation and whether your genetic susceptibility might mean that you should increase glucuronidation to prevent diseases.

What Is Glucuronidation?

Glucuronidation involves the addition of glucuronic acid to a toxic molecule to make it [R]:

  • More water soluble
  • Less toxic or reactive
  • Easily transported throughout the body
  • Possible to eliminate via urine

Why Is Glucuronidation Important?

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 [R].

It is responsible for the clearance of many drugs, cancer-causing chemicals, environmental toxins, and substances found in food [R].

Increasing glucuronidation enzyme activity improves the detox of xenoestrogens and cancer-causing agents, and thus contributes to the prevention of cancer [R].

Inefficient glucuronidation may also be linked with other diseases.

A study showed that the degree of glucuronidation was lower in children with autism [R].

This potentially leaves them more exposed to environmental chemicals. In fact, the exposure to environmental chemicals may trigger autism in genetically susceptible children [R].

If you are interested in balancing your hormones, overcoming estrogen dominance, or preventing cancer, you should look into ensuring that your glucuronidation works well.

Where Glucuronidation Takes Place

Glucuronidation enzymes (UGTs) are found throughout the body: in the gut, kidney, brain, pancreas, and placenta. However, the majority are found in the liver [R].

This is because the liver is the key organ for processing drugs and internal compounds such as hormones and bile acids [R].

On the other hand, some UGTs (UGT2B15 and UGT2B17) are found in the prostate where they control local testosterone levels [R].

Others (UGT1A10 and UGT2B7) are found in the breasts where they inactivate estrogen [R].

In the brain, UGTs actively protect against the intrusion of harmful chemicals [R].

Dopamine and serotonin are also processed by UGTs. However, the impact of UGTs to the overall dopamine and serotonin levels is minor [R].

What Gets Glucuronidated

Glucuronidation Helps Detoxify Cancer-Causing Toxins in Foods and Environments

  • Cancer-causing substances called polycyclic aromatic hydrocarbons, including benzo[a]pyrene, are found in cigarette smoke, wood smoke, and burnt foods [RR]
  • BPA (Bisphenol-A), is a toxin used in plastics and linked to various human diseases including breast cancer [R]
  • Some cancer-causing nitrosamines are found in tobacco smoke and in the gut of people who eat red meats [R]
  • 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 [R]
  • Some fungal toxins are found in moldy crops [R]

Glucuronidation Helps Detoxify Used Hormones, Bile Acids, Neurotransmitters, and Vitamins

  • Estrogen [R]
  • Androgens (including testosterone) [R]
  • T3 and T4 [R]
  • Bilirubin [R]
  • Bile acids [R]
  • Fat-soluble vitamins [R]
  • Dopamine and serotonin (minor role) [R]

Foods That Increase Glucuronidation (UGTs)

These factors (except for soy) are known to help with estrogen dominance and preventing cancers.

1) Broccoli Sprouts/Cruciferous Veggies/Sulforaphane

Sulforaphane, found in cruciferous vegetables (with the highest levels in broccoli sprouts), increases glucuronidation [R, R].

It is the most potent inducer of phase 2 detox enzymes (including UGTs) identified to date. It acts by activating Nrf2 (R, R). Nrf2 then activates UGTs.

PhIP is a cancer-causing agent present in cooked food. A study showed that in 20 non-smoking men, brussels sprouts and broccoli increased PhIP glucuronidation [R].

A diet enriched in cruciferous or cruciferous plus apiaceous vegetables also increased glucuronidation (UGT1A1) in 70 subjects [R]

2) Watercress

Watercress increases UGT enzyme activity in humans (12 subjects, smokers) [R].

3) Citruses

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 [R].

These Foods and Supplements May Increase Glucuronidation (UGTs)

These herbs and supplements increase glucuronidase activity in animal studies:

  • Soy [R]
  • Green tea [R, R]
  • Dandelion [R]
  • Rooibos tea [R]
  • Honeybush tea [R]
  • Coffee [R]
  • Rosemary (particularly UGT1A6) [R]
  • Ellagic acid (found in walnuts, pecans, berries, grapes, pomegranate) [R]
  • Ferulic acid (found in coffee and whole grains) [R]
  • Quercetin (found in many fruits and veggies, capers, onions, berries, tea) [R]
  • Tannic acid [R]
  • Coumarin (found naturally in many plants like tonka bean, cassia cinnamon, vanilla grass) [R]
  • Fumaric acid [R]
  • Curcumin (turmeric, found in curry powder) [R]
  • Flavone [R]
  • Astaxanthin and canthaxanthin (carotenoids) [R]

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.

These Decrease Glucuronidation (UGTs)

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) [RRRR, R].

However, these do not necessarily work in the same manner in living organisms.

For example, milk thistle is a strong glucuronidation inhibitor in isolated cells [R, R].

However, in humans, it didn’t have a significant effect [R].

1) Piperine

Piperine (from black pepper) inhibits UGTs (glucuronidation enzymes) in rats and mice [RR, R].

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.

2) Drugs

Analgetics, nonsteroidal anti-inflammatory drugs (NSAIDs), antiviral drugs, anticonvulsants and anti-anxiety meds/sedatives can decrease UGT activity [R].

Beta-glucuronidase

Beta-glucuronidase is an enzyme produced by gut bacteria (such as E. coli) and gut cells [R].

This enzyme reverses the glucuronidation reaction and reactivates the inactivated toxins to their previous active form [R].

Elevated beta-glucuronidase activity is associated with an increased risk of various cancers, such as colon cancer, and hormone-dependent breast and prostate cancers [R, R].

Factors That Increase Beta-glucuronidase

These factors may worsen estrogen dominance, increase toxic load, and increase cancer risks.

1) High-Fat Diet

People with higher total and saturated fat intake have higher beta-glucuronidase activity (279 subjects) [R].

A high-fat diet increased this enzyme in rabbits [R].

2) Being Overweight

People who are overweight (BMI ≥ 25) have higher beta-glucuronidase activity (279 subjects) [R].

3) Being Male

It seems men have more of this enzyme (279 subjects) [R, R].

4) Aging

As we get older, beta-glucuronidase activity increases [R].

5) Smoking

Smoking may increase this enzyme (101 subjects) [R].

6) Disease – Liver Inflammation and Colon Cancer

The activity of this enzyme increases in many diseases: liver inflammation, liver cirrhosis, jaundice, tuberculosis, and cancer [R].

Beta-glucuronidase activity was 1.7 times higher in colon cancer patients compared to healthy people [R].

In fact, this enzyme may be a sensitive indicator pointing to cell and tissue damage [R].

7) Drugs

Drugs like phenobarbital and spironolactone were shown to increase this enzyme in rats [R].

These Decrease Beta-glucuronidase

1) A Plant-Rich Diet

People who consume more plants have generally lower beta-glucuronidase (279 subjects) [R].

Another study also showed that this enzyme was lower with a higher intake of plant protein, fruit, and dietary fiber (203 subjects) [R].

Beneficial plants were those belonging to the gourd family (such as squash, pumpkin, zucchini, cucumber, watermelon), the rose family (apples, pears, plums, cherries, peaches, raspberries, strawberries), and legumes (peas and beans) (203 subjects) [R].

Both studies indicate that alpha- and beta-carotene and beta-cryptoxanthin decrease beta-glucuronidase [R, R].

However, another study with 63 volunteers found an increase in this enzyme on a diet enriched with crucifers, citrus, and soy [R].

2) Vitamin C

Vitamin C decreased beta-glucuronidase activity by 25% (18 subjects) [R]

3) Calcium, Iron, and Magnesium

People with higher intakes of these minerals had lower beta-glucuronidase activity (279 subjects) [R].

4) Gotu kola

A three-month treatment with a Gotu kola extract decreased the levels of this enzyme in patients with varicose veins [R].

5) Probiotics

The probiotic L. helveticus decreased beta-glucuronidase activity in elderly volunteers [R].

L. casei and B. breve also showed a tendency to decrease this enzyme (53 healthy volunteers) [R].

In mice, lactic acid bacteria (L. brevis, L. acidophilus or B. longum) lowered this enzyme [R].

Finally, L. rhamnosus decreased this enzyme in mice treated with cancer-causing PhIP [R].

6) Prebiotics

Prebiotics are basically fibers that stimulate the growth of beneficial bacteria in our bodies.

A study with 53 healthy volunteers showed that consuming prebiotics (lactulose or oligofructose-enriched inulin) decreased beta-glucuronidase activity [R].

These May Decrease Beta-glucuronidase

7) Berries

Extracts of certain berries may help reduce beta-glucuronidase.

The addition of blackcurrant extract to high-fat diet fed rabbits, decreased this enzyme [R].

Similarly, strawberry pulp extract decreased the enzyme in rats [R].

8) Black Pepper

Black pepper decreased the activity of beta-glucuronidase in rats exposed to colon-cancer-causing chemicals [R].

9) Cumin

Cumin also decreased the activity of this enzyme in rats exposed to colon-cancer-causing chemicals [R].

10) D-glucaric Acid or Calcium-D-Glucarate

D-glucaric acid is found in many fruits and vegetables, with the highest levels in grapefruits, apples, oranges, and cruciferous vegetables [R].

It is transformed in the stomach into D-glucaro-l,4-lactone, a natural inhibitor of beta-glucuronidase activity [R, R].

Calcium-D-Glucarate decreased the activity of this enzyme in rats [R].

11) Caloric Restriction

Caloric restriction decreased beta-glucuronidase in rats and monkeys [RR].

12) Lower Colon pH

Beta-glucuronidase is increased by higher pH. When human colon bacteria are transferred from pH5 to pH8, enzyme activity increases by almost 12 fold [R, R].

Similarly, the activity of the enzyme was 5 to 10 times higher at pH7 compared to pH6 [R].

These decrease beta-glucuronidase in isolated cells:

  • Licorice (G. uralensis) [R]
  • Milk thistle (silymarin) [R]
  • Reishi mushroom (G. lucidum) [R]
  • Green tea (epigallocatechin gallate) [R]
  • B. infantis [R]
  • Kombucha [R]

Technical: Key Glucuronidation Enzymes (UGTs)

Enzymes responsible for glucuronidation are called UDP-glucuronosyltransferases or UGTs [R].

In humans, around 40–70% of all clinical drugs are cleared by UGTs [R].

Apart from removing foreign substances, UGTs also participate in the clearance of bilirubin, steroid hormones, thyroid hormones, bile acids, and fat-soluble vitamins [R].

There are 19 functional human UGTs. They belong to one of the three subfamilies: UGT1A, UGT2A, and UGT2B [R].

Are You Genetically Susceptible to Worse Glucuronidation?

Having certain UGT variants may change one’s susceptibility to cancer or neurodegeneration [R].

Over 10% of the population have hereditary deficiencies in UGTs [R].

There is a single UGT1 gene that produces all UGT1A1 family members. Depending on how the enzyme is later processed, it becomes one of the 9 UGT1A enzymes [R, R].

The UGT2 family enzymes are all produced by separate genes [R].

UGT1A

  • RS8330

This is a variant in the shared part of the UGT1 gene (it is present in all UGT1A enzymes).

People with this variant have can clear Tylenol (paracetamol) from their system better [R].

People with this variant are therefore less likely to suffer liver damage or acute liver failure from unintentional Tylenol overdose [R].

UGT1A1

http://journal.frontiersin.org/article/10.3389/fncel.2014.00349/full

UGT1A1 is the only enzyme that glucuronidates bilirubin.

It also inactivates some cancer-causing compounds and estrogen.

Patients with a very rare inherited disorder called Crigler-Najjar syndrome have a complete or partial absence of this enzyme [R].

Complete UGT1A1 absence results in high levels of bilirubin, severe jaundice, and brain damage in infants. Patients with a partial deficiency have milder jaundice and generally survive into adulthood without neurological or intellectual impairment [R].

Gilbert’s syndrome is a mild disorder caused by a mutation in the UGT1A1 gene. People with this syndrome have mildly elevated bilirubin levels [R].

Gilbert’s syndrome is found in about 10% of the population [R].

People with Gilbert’s syndrome also have a reduced clearance of drugs like Tylenol [R].

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 [R].

This variant results in 30–40% lower UGT1A1 levels [R].

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 [R].

That is why this variant may increase the risk of cancer.

Having two copies of UGT1A1*28 may increase the risk of lung cancer (765 patients) [R].

UGT1A1*28 has also been associated with breast cancer (240 and 2130 subjects), and colon cancer (168 subjects) [R, RR].

On the other hand, UGT1A1*28 may lower the susceptibility to Crohn’s disease (751 patients and 930 controls) [R].

Additionally, a study showed that people with two UGT1A1*28 copies had a 2/3 lower risk of heart disease (1780 subjects) [R].

This relationship with heart disease, however, was not confirmed in two other studies [R].

This variant is also known as UGT1A1*6.

It is common in Asians. UGT1A1*6 is found in 13-23% of Japanese, Korean, and Chinese people [R].

UGT1A1*6 may increase the risk of breast cancer (74 subjects) and colon cancer (709) [RR].

On the other hand, having UGT1A1*6 improves survival in lymphoma patients on irinotecan therapy (27 subjects) [R].

However, it also increases the chance of severe toxicity due to irinotecan (meta-analysis, 11 studies) [R]

UGT1A6

UGTs1A6 is responsible for the detox of cancer-causing agents such as benezo[a]pyrene from cigarette smoke [R].

UGT1A6 also inactivates Tylenol, aspirin, estradiol, and serotonin (in small amounts) [R, R].

This variant is also known as the UGT1A6*2 variant.

It was long thought to cause decreased UGT1A6 enzyme activity [R].

However, more recent studies show people with this variant actually process aspirin faster (10 and 28 subjects) [R].

In people with this variant, NSAID use lowered the risk of colon cancer (474 adenoma cases and 563 controls) [R].

So did aspirin (1062 women) [R].

On the other hand, women who have two copies of this variant (GG) have increased breast cancer risk (7418 cases and 8720 controls) [R].

This variant may also increase lung cancer risk (95 patients and 100 controls) [R].

UGT1A62 is often inherited together with UGT1A128, which may affect the association with cancer.

UGT1A7

This enzyme is found in the gut and the lungs [R].

UGT1A7 is involved in inactivating cancer-causing agents present in tobacco smoke [R].

  • RS17868323

This variant is also known as UGT1A7*3. It has lower detox activity [R].

UGT1A7*3 increases liver, lung, and bladder cancer risk in Asians (meta-analysis, 22 studies, 3852 cases and 5604) [R].

This variant is also linked with chronic pancreas inflammation and pancreatic cancer (433 subjects) [R].

UGT2B15

This variant is known as the UGT2B15*2 variant.

People with this variant have a decreased clearance of Tylenol (paracetamol) (66 subjects) [R].

UGT2B17

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2556428/

UGT2B17 is one of the most commonly missing genes in humans [R].

Some people have two copies, while others have a single copy or don’t have this enzyme at all [R].

UGT2B17 deletion is more common in Asians (67%) than Whites (9%) [R].

This enzyme inactivates steroid hormones, including testosterone and estradiol. It also inactivates a large number of drugs and toxins [R].

People without UGT2B17 have higher levels of testosterone (by 15%) and estradiol [R, R].

Men with higher testosterone levels are 2.4 times less likely to be obese. Accordingly, a study found that men without UGT2B17 had lower BMI (940 subjects) [R].

On the other hand, not having UGT2B17 may increase the risk of prostate cancer (meta-analysis, 6 studies, 3,839 cases and 3,190 controls) (meta-analysis, >25 studies, >17,000 subjects [RR]).

However, another study indicates that not having UGT2B17 decreases the risk of colon cancer in men (665 patients and 621 controls) [R].

Finally, there is a study showing that UGT2B17 deletion is not associated with cancer risks (meta-analysis, 14 studies, 5,732 cases and 5,112 controls) [R].

The relationship of this gene and cancer is therefore still questionable.

People without UGT2B17 tend to have higher bone mineral density (2,379 women) [R].

Accordingly, having UGT2B17 may contribute to osteoporosis (700 elderly subjects, 799 subjects, 1689 subjects) [R].

Those having one or two UGT2B17 copies, and therefore, lower estrogen levels, benefit from hormone replacement therapy (2,379 women) [R].

However, there are also studies that found no link between UGT2B17 and osteoporosis (1,347 elderly women) [R].

Other Genes That May Increase the Need for Glucuronidation

Low COMT Activity (An Allele of RS4680, Stress, or Diets)

COMT inactivates toxic estrogens and other catechol substances. If COMT isn’t functioning well because of genetics, stress, or diet, it is important to compensate for it by overall increasing detoxification and increasing glucuronidation.

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The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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2 COMMENTS

  • ibh

    A lot of great info. Just wanted to add a comment regarding Gilbert’s Syndrome, as it made me a bit nervous to see it in bold in your article as a risk factor for cancer (I might have misunderstood). I do have Gilbert’s Syndrome and I thought I have read over the years that it is protective from CVD and cancer, due to slightly elevated billirubin’s significant antioxidant protection. A lot of reading is easily found on this subject and PubMed has a study ”Iatrogenic Gilbert syndrome — a strategy for reducing vascular and cancer risk by increasing plasma unconjugated bilirubin”. Anyway, just thought this might be useful info for those with Gilbert’s Syndrome 🙂

  • Jules

    Thank you for a very concise summary

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