I wrote here on the liver’s six main pathways for Phase 2 Detoxification. This is going to be a deep dive into one of the six: glucuronidation.
What Glucuronidation Does
Glucuronic acid is a derivative of glucose. As with all of the liver’s Phase 2 pathways, this renders a toxic substance less toxic and also water soluble, so that it can get eliminated. This primarily happens in the liver, but glucuronidation enzymes (UGTs) are also found in other areas of the body that particularly need to be protected from acute toxicity: the brain, gut, kidneys, pancreas, placenta, prostate, and breasts.
Substances generally removed include up to 70% of pharmaceuticals, plus sex and thyroid hormones (hence the presence of UGTs in the prostate and breasts), and anything bound to bile, which includes fat-soluble vitamins and fat-soluble toxins.
Your Gut and Glucuronidation
Most of the UGTs are in the liver, as mentioned above. The liver then dumps the now water soluble toxins into the small intestine. But the gut flora produces an enzyme called beta-glucuronidase, which can cleave the bond of the glucuronic acid from the toxin, causing the toxin to recirculate. Most gut flora should reside in the colon, not in the small intestine, but when bacteria overgrows in the small intestine (as in SIBO), this can decrease the effectiveness of the glucuronidation pathway and lead to increased toxicity.
Not too surprisingly, then, there’s an association between elevated beta-glucuronidase and cancers, including especially colon cancer, as a prerequisite for dysplasia in the gut is an unhealthy gut. There is also an association with breast and prostate cancers as well, as glucuronidation is necessary for elimination of sex hormones.
Conversely, good flora L. casei and B. breve have been shown to lower beta-glucouronidase activity, as do prebiotics, or food for the good gut flora.
So basically, a healthy gut means a less toxic body.
Meds and Toxins that Decrease Glucuronidation
Certain medications also decrease UGT activity, including common meds like NSAIDs, sedatives, and anxiety medications. This is another good reason to treat the reason why you need these medications in the first place, so that your ability to detoxify is not impaired.
Smoking decreases UGT activity as well. (Another great reason to quit!)
Foods that Support Glucuronidation
In addition to keeping your gut healthy in general, certain foods are especially supportive for the glucuronidation pathway—particularly cruciferous vegetables (which is all those veggies that “flower outward” such as cauliflower, broccoli, bok choy, brussels sprouts, etc). These are high in a compound called sulforaphane, which stimulates detoxification in general, including UGTs. Incidentally, cruciferous veggies are also high in sulfur, which makes them supportive to the sulfation and glutathione transferase pathways as well (assuming you don’t have H2S SIBO or another cause for sulfur intolerance. If you do, you’ll have to get that addressed before you’ll be able to tolerate cruciferous veggies.)
Another family of veggies called the apiaceous family, including carrots, parsnips, celery, and parsley, also upregulates UGT enzymes.
In general the more plants you eat, the lower beta-glucuronidase activity tends to be. This makes sense, for several reasons: because fiber tends to keep the gut healthier, because many fruits and veggies produce a natural beta-glucuronidase inhibitor, and because your gut flora is directly related to what you eat. (If you feed the good stuff, it will grow!)
Your beverage choices can help too. Green tea, rooibos and honeybush tea, and coffee also support glucuronidation. (Caveat here, though: caffeine generally tends to inhibit elimination of sex hormones, which is one of the things that the glucuronidation pathway eliminates. If you choose an organic decaf version of the coffee or green tea, you should be able to get the benefits without the drawbacks.)
Supplements that Support Glucuronidation
Extracts of some of the foods listed above can be taken in supplement form to increase concentration. But far and away, my favorite supplement to support this pathway is calcium D-glucarate, which inhibits activity of beta-glucuronidase. I often add this in to protocols intended to aid in metabolism of sex hormones especially.
Big picture: naturopathic medicine is about identifying and removing obstacles to cure, as well as giving the body the building blocks it needs to heal itself. Supporting the liver’s pathways for detoxification is an important part of removing obstacles to cure. But by supporting your glucuronidation pathway, you’ll be supporting most of the others too, as a healthy microbiome and a healthy diet are important for all of them!
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