The estrogenic burden is an ever increasing concern in modern life.
We’re constantly exposed to estrogenic substances, whether it be natural (soy, flax, clover, polyunsaturated fats, soot, etc.) or synthetic (such as red colorants, plastics, cosmetics, deodorants, etc.). Our bodies need to get rid of those substances or it can build up and we become too estrogenic.
We can get rid of phyto- and xeno-estrogens and other toxins via the enzymatic action of UDP-glucuronosyltransferases in the liver.
The detox process
Glucuronic acid is a key metabolite of glucose involved in the detoxification of estrogen and xenobiotic compounds. These compounds that need to be detoxed, undergo liver glucuronidation, in which they are conjugated (combined) to glucuronic acid via the enzymatic action of UDP-glucuronosyltransferases. This process makes it more water-soluble, and increases solubility in bile, facilitates urinary excretion, and is a key step in the phase II metabolism of these compounds required for their effective clearance from the body.
Step 1 (or in this case, phase II) of detoxification is to add a glucuronic acid to the compound that needs to be detoxed via the enzyme UDP-glucuronosyltransferases. Then the body can easily excrete it.
However, there are enzymes, namely β-glucuronidases, (found in most tissues, such as the liver, kidney, spleen, intestinal epithelium, and endocrine and reproductive organs) that can remove the glucuronic acid and “re-activate” the compound that was about to be detoxed. β-glucuronidases counters the detoxification process.
As you can see, this creates a situation where you can’t properly detox.
This study found that glucuronic acid increases with age and predict future healthspan-related outcomes (R). Elevated serum levels of glucuronic acid have been reported in human studies of diabetes, hepatocellular carcinoma, hepatitis, cirrhosis, and obstructive jaundice. Impairment of glucuronidation by β-glucuronidase can cause organ toxicity, inflammatory disorders, and carcinogenesis.
Elevated glucuronic acid indicates the excess activity of β-glucuronidases, which is inversely correlated with longevity and healthspan (R).
How do we lower β-glucuronidases?
About a quarter of bacterial species in the human gut produce β-glucuronidase, which has been directly linked to increased xenobiotic-induced toxicity rescuable by inhibition of the enzyme (R).
Most of the Bifidobacterium, Bacteroides thetaiotaomicron and some Firmicutes (which is elevated in obesity and diabetes) within clostridial clusters XIVa and IV (namely Clostridium, Streptococcus, Lactobacillus, Ruminococcus) have β-glucuronidase activity (R).
β-glucuronidase found almost everywhere else in the body, is induced by inflammation, specifically NFκB.
So in order to lower β-glucuronidase, we have to focus on the gut and also to lower inflammation.
Strategies to lower β-glucuronidase
Cardamom extract/spice is able to reduce beta-glucuronidase, mucinase (prevent excess mucin degradation) and urease (reduce ammonia production) (R). Just 4g daily of the spice should be enough for a potent effect.
Silymarin (milk thistle extract) and Reishi intake are inversely correlated with β-glucuronidase activity (R). Perhaps because both are great against inflammation, and especially milk thistle is great for the liver.
High D-glucaric acid intake (R). Citrus fruit (grapefruit > oranges), apples, broccoli, cabbage and Brussel sprouts are foods with the highest amounts. D-glucaric acid is converted into D-glucaro-1,4-lactone which competitively inhibits β-glucuronidase and has been shown to reduce chemical carcinogen-mediated mammary, liver, and skin tumors in animals (R).
Caloric restriction (R). It’s not so much the calorie restriction, but rather avoiding the harmful foods that produce inflammation and gut dysbiosis.
β-glucuronidase is positively correlated with gamma-tocopherol (soy intake anyone?) (R). I don’t think it’s so much the gamma-tocopherol, but rather the foods or oils that are rich in gamma-tocopherol, such as soy, canola, corn, camelina, and walnut.
High calcium, iron, and magnesium intake are inversely correlated with β-glucuronidase (R). This makes milk a great food since it’s rich in calcium and contains a highly bioavailable source of magnesium.
Things that can inhibit NFκB include curcumin, aspirin, vitamin D, quercetin, vitamin E, milk thistle, Pau d’arco, camphor, emodin, gallic acid, ginger, ursolic acid and a host of other compounds found in fruits, vegetables, mushrooms, herbs, spice, etc (R, R). Endotoxins are one of the most potent inducers of NFκB, so lowering endotoxins by restoring gut balance is key.
My go to foods to lower β-glucuronidase and promote proper detoxification include grapefruit (not too much as grapefruit in turn can inhibit proper phase II detoxification) and oranges, milk and cardamoms.
If you’re interested in lower estrogen, check out these articles as well:
- How to inhibit the aromatase
- How to block the estrogen receptors
- How to promote estrogen detoxification through the liver
- Top foods that inhibit the aromatase
As always, thanks so much for reading my article. Let me know in the comments below if you have any questions. And if you found this article to be insightful and helpful please like and share so this information can help others as well.
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