Increase estrogen detoxification through the liver

Estrogen is the opposite of the manly hormones, namely DHEA, testosterone and DHT. Men are thought to have way less estrogen than women, but in reality, some men have equal amounts and even higher than some women. This increase in estrogen can be seen as a result of reduced mitochondrial function, liver problems, sluggish thyroid, nutrient deficiencies, high cortisol, etc.

In this article, I’ll be discussing how to boost the detoxification of estrogen through the liver, but in my other articles, you can read about how to inhibit the aromatase and block the estrogen receptor for other strategies on how to reduce estrogen and its symptoms.

The medical reference range for estrogen in men is between 10-40pg/dl, but just because the medical range says 40pg/dl is normal, doesn’t mean it is optimal. Below 20pg/dl would be best and around 10pg/dl would be optimal.

If you are already focusing on blocking the aromatase but are still experiencing high estrogen symptoms, focusing on improving liver function and detoxification might be your best option.

The body inactivates and detoxes estrogen mainly by the liver. It does so via phase I & II detoxification and also via COMT in the methylation cycle.

COMT

COMT, or Catechol-O-methyltransferase, is an enzyme that metabolizes estrogen, catecholamines, etc., and uses magnesium and SAMe as cofactors. For this reason, be sure to eat enough protein daily (∼100g daily if sedentary and higher if active and training) to supply methionine (methionine is converted to SAMe) and magnesium-rich foods, such as cocoa powder, spinach, kale, milk, oats, blackstrap molasses, etc., to aid in lowering estrogen via this mechanism.

Phase I liver detoxification

The first phase (phase I uses the enzymes CYP1A1/1A2 and CYP1B1) detoxification is done via the CYP450 enzyme. Low CYP1A2 activity, for example, has been linked to a higher risk of testicular cancer. However, excessive activity of the CYP1A1/1A2 and CYP1B1 enzymes (which catalyze the 2-hydroxylation and 4-hydroxylation of estrogens, respectively) without adequate phase II support may enhance estrogen-related carcinogenesis, via the production of free radicals and related cellular damage. So just boosting phase I activity to get rid of estrogen might be dangerous.

Nevertheless, a few foods and compounds that boost phase I detoxification include cruciferous vegetables, tea (black and green), garlic, seafood, etc., and a few inhibitors include, black raspberry, blueberry, ellagic acid, black tea, quercetin, grapefruit, kale, garlic, chamomile, peppermint, dandelion, 7,8-benzoflavone, etc. (1). However, some of these compounds have both a promoting and inhibitory effect, and that depends on the dose. Small doses, as obtained from some foods, have a promoting effect, whereas large doses, as obtained through supplementation, can have an inhibitory effect.

Phase II

After the estrogen has gone through the process of being converted to a more hydrophilic compound (more water soluble for easier detoxification) by phase I, phase II conjugates an endogenous hydrophilic substance to its reactive site so that it’s even more water soluble and ready for detoxification. Conjugation involves the transfer of a number of hydrophilic compounds (via their corresponding enzymes), and in the case of estrogen, it’s mainly processed via glucuronidation. Glucuronidation is the transfer of the glucuronic acid component of uridine diphosphate glucuronic acid to a substrate (in this case estrogen) by any of several types of UDP-glucuronosyltransferase (UGT) enzymes.

A few foods and substances that enhance this pathway (UGT enzymes) include cruciferous vegetables, citrus foods, dandelion, rooibos tea, honeybush tea, rosemary, ellagic acid, ferulic acid, curcumin, astaxanthin, ferulic acid, etc.

Foods that supply the D-glucaric acid for the UGT enzymes include: mung bean seeds, adzuki bean sprouts, oranges, spinach, apples, carrots, alfalfa sprouts, cabbage, Brussel sprouts, cauliflower, broccoli, grapefruit, grapes, peaches, plums, lemons, apricots, sweet cherries, corn, cucumber, lettuce, celery, green pepper, tomato, potato, etc.

After glucuronidation has added a glucaric acid to the estrogen, it’s ready for detoxification, but there is also an enzyme, beta-glucuronidase, that reverses the UGT conjugation reactions, converting estrogen back into its more potent form again and preventing detoxification. Inflamed tissue contains high amounts of this enzyme so lowering inflammation would be key to keeping this enzyme low. Other things that lower the activity of this enzyme are saturated fat (polyunsaturated fat promote this enzyme) and proanthocyanidins rich foods, such as strawberries, blackcurrant, cocoa, calcium, magnesium, vitamin C, Gotu Kola, etc.

Nuclear factor (erythroid-derived 2)-like 2, also known as Nrf2, is a transcription factor that increases the promotes the activity of phase II detoxification and antioxidant enzyme genes in the body. In vivo (meaning studies done in living beings, such as humans and animals) evidence shows curcumin, broccoli constituents, garlic, epicatechins, ginger, purple sweet potato, isoflavones, coffee, rosemary, pomegranate, naringenin, ellagic acid, astaxanthin, γ-tocopherol, chlorophyll, blueberries and EGCG promote Nrf2 activity, and thus promote phase II detoxification (2).

Conversely to its role in cancer prevention, overexpression of Nrf2 is found in many cancer cells and has been shown to promote tumor growth and resistance to anticancer therapy. Overexpression of Nrf2 and CYP2E1 has also been associated with impaired GLUT4 activity and insulin resistance. Vitamins A, C, and E, N-acetyl cysteine (NAC),  luteolin and quercetin and have also been implicated as Nrf2 inhibitors at high doses (2). And keep in mind, that small doses can promote the activity of detoxification, whereas high doses can inhibit it.

Beware of DIM

DIM is an acid-catalyzed dimer of indole-3-carbinol (I3C), a phytochemical found in cruciferous vegetables such as broccoli, kale, collard greens, wasabi etc. which helps to metabolize estrogen by increasing P450 activity in the liver. Only low doses are found to lower estrogen, whereas higher doses actually promote cellular damage, activate the estrogen receptor, inhibit mTOR, reduce testosterone, etc (3, 4). So it’s basically a dangerous compound to supplement with as its anti-androgenic. If you do want to ingest DIM, only do so via food, and keep the amount low.

Calcium-d-glucarate

Calcium-D-glucarate is the calcium salt of D-glucaric acid, a substance produced naturally in small amounts by mammals, including humans, and is involved in phase II liver detoxification which regulates estrogen metabolism. It’s mainly found in berries, but not in amounts present in supplements. Many people report a decrease in estrogen symptoms from using this supplement. But the bad thing about it is that it doesn’t only aid in the detoxification of estrogen, but also the other beneficial steroid as well, such as testosterone, DHEA, DHT, etc. So just keep that in mind before using this supplement.

Other things that will aid in estrogen detoxification:

• Exercise – increases cytochrome P450 activity (5). Check out my training courses to help you get you to your goal.
• Desiccated liver tablets – Liver contains the cytochrome P450 enzymes. Cooking the liver will degrade these enzymes, so getting a desiccated freeze-dried product that hasn’t been heat treated should have all these enzymes preserved.
• Caffeine (6)
• Vitamin B1 (7)
• Vitamin B2 (7)
• Vitamin B3 + methylene blue – increase NAD:NADH ratio, lower inflammation and increase tissue oxygenation (8).
• Vitamin C (9)
• Taurine – stimulates bile excretion (estrogen is excreted through the bile)

Conclusion

So apart from a good diet, there are a few really beneficial supplements. Keeping the liver in a healthy condition will also ensure proper function and estrogen detoxification. If you don’t know how to fix your liver and are experiencing estrogenic symptoms, contact me and I’d be sure to help you recover.