Glucuronidation: Detox, Balance Hormones, & Genes

Metabolic inactivation of estrogens in breast tissue by UDP-glucuronosyltransferase enzymes: an overview

Glucuronidation: Detox, Balance Hormones, & Genes

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Detoxing from Detox

Glucuronidation: Detox, Balance Hormones, & Genes

Many of us are aware of the concept of a ‘meme,’ an idea that spreads from person to person within a culture as some sort of phenomenon. Memes are sticky, that song you can’t get your head no matter how hard you try.

‘Detoxification’ is one such meme; as a concept it has meaning to almost everyone, but the significance of that meaning may be quite different from person to person. On its most basic level, detoxification implies the removal of ‘toxins’ and again, this word can mean different things to different people.

For example, one might see toxins as things made via improper metabolism or internal microbial over-activity. These are usually considered ‘auto-toxins’ in the sense that they are generated the internal environment. Others might focus on the ever-increasing amounts of external toxins that are the result of chemical industrialization.

These are usually termed ‘environmental toxins’ or ‘xenobiotics,’ chemical compounds such as drugs, pesticides or carcinogens not normally found in living organisms. There is little doubt about their penetration into human physiology. For example, a toxic component of rocket fuel has been found in breast milk of women in 18 states.

The chemical, perchlorate, leaches into groundwater from various military facilities.

If you think this is all just a curse of modern living, you might be surprised to know that a lot of the genetic variation in our ability to effectively detoxify substances such as hydrocarbons is the result of our attempt to deal with the combustion byproducts of a very long history of crowding around smoky campfires.

Science or Commerce?

Detoxification has become big business. There is no shortage of products and nostrums that claim to ‘flush out toxins.

’ Most of the time these are simply harmless ways of wasting money, except when they delay proper analysis and treatment of a more serious medical condition.

More insidiously, they perpetuate the notion that the body is a helpless accumulator of all things malevolent, and desperately needs our help to do what it is incapable of doing itself.

Nothing could be farther from the truth. Detoxification is a well-understood biochemical process and there is no shortage of science behind it. Let’s take a look at how it works and what you can intelligently do to support it. I promise to keep things simple.

Most chemical detoxification occurs in the liver, the basic chemical powerhouse of the body. Toxins might come in via respiration, the digestive tract or some other means, but if they get into the blood, they’re going to the liver. There, they trigger a series of reactions that have been grouped into two ‘phases.’

In order to better understand the detoxification process, I will be discussing Phase I and Phase II separately, but actually, both of these occur simultaneously; an automated car wash, where one car might be getting air-dried while another has just gone under the soap; at any given point in time, various toxins will be in either phase of detoxification, although all will eventually go through both phases.

Phase I – Metabolism and Breakdown of Toxins

Phase I detoxification enzymes are intimately involved with drug metabolism and breakdown, which is why one has to be aware that foods, herbs and supplements can influence cytochrome activity and why, if you are using them and taking prescription medicines, you should be monitored by a physician who is skilled in their combination. If I feel a generalized boost to Phase I detoxification is in order, I’ll often recommend these natural products in various combinations:

Phase I detoxification is often not very gentle.

Conversion of these compounds involves sending a lot of free oxygen and hydrogen around and, in their high energy states, they can be very reactive and irritable.

The end products of Phase I detoxification can sometimes be even more problematic than the molecule they started with. The only ‘improvement’ is that, at the very least, they are now on the way out.

Phase II – Preparation of Metabolites for Excretion

After a toxin finishes Phase I, it passes on to the second stage of its processing, Phase II detoxification. Phase II involves picking up the toxin from where it was left off by Phase I and twiddling it so that it can be safely be excreted from the body. Because the products of Phase I can be very reactive, having our Phase II detoxification mechanism in sync is very important.

Think of it this: a toxin is similar to a baton used in a relay race. Phase I and Phase II are the runners running the race. Phase I takes its lap around the track, does its job on the toxin and then passes the baton to Phase II so that it can do its job on the toxin.

However, Phase II has to be able to very quickly determine whether Phase I has passed it a real baton or lit stick of dynamite.

If Phase II gets it wrong, the very effectiveness of Phase I instead becomes a problem; or as one of my patients, a choreographer, once explained modern dance to me: ‘40% of every dance is the ending.’

To be able to effectively handle the pass-off from Phase I, Phase II can call on a bevy of deactivation pathways that can pin all sorts of things on the baton to tone it down. The two most amenable to lifestyle modification are known as conjugation and glucuronidation.

I know I promised to keep it simple, so let me describe these as best as I can. marriage, conjugation involves wedding an antioxidant known as glutathione to the baton. Glutathione is made from the amino acid NAC (n-acetylcysteine) and is about as close to a ‘metabolic currency’ as you’ll find in biochemistry.

There are genetics involved, and some people make it better than others. However, having ample NAC is critical.

I might also add that an extra level of attention can be provided by supplementing NAC with the herb milk thistle (silymarin), as this herb has been shown to help increase the level of glutathione inside the cells, which is where you want it.

This doesn’t necessarily pertain to detoxification, but there is a strong and emerging evidence basis for using NAC for the treatment of psychiatric disorders.

NAC appears to reduce the negative symptoms of schizophrenia and also appears to be effective in reducing craving in substance use disorders, especially for the treatment of cocaine and cannabis use among young people, in addition to preventing relapse in already abstinent individuals.

NAC has also show some benefit in obsessive-compulsive and related disorders, as well as on mood disorders. (Biomed Res Int. 2018; 2018: 2469486.) All of this has been speculated to be the result of its ability to increase glutathione.

Glucuronidation is a very long word used to describe plunking a molecule known as glucaric acid (or its stable form, calcium glucarate) onto the Phase I baton.

During Phase II liver detoxification, certain hormones and various fat-soluble toxins will undergo glucuronidation and be excreted through the bile or urine. Calcium glucarate helps this elimination process occur without interruption.

Apples, grapefruits, bean sprouts, and cruciferous vegetables cabbage, broccoli and Brussels sprouts tend to be high in calcium glucarate.

So, which phase should you try to maximize? In most situations, you’ll want to assist both Phase I and Phase II at the same time. However, if you smoke, are drug sensitive or are caffeine sensitive, you might want to emphasize enhancing Phase I.

Phase II detoxification involves the synthesis and secretion of bile, a carrier in which many toxic substances eventually are passed into the intestines.

If you notice delayed reactions to foods, problems with digesting fats or a simple ‘sick feeling’ after eating certain heavy foods, you might want to work on optimizing Phase II.

These are supplements I’m fond of using to aid in the overall detoxification process:

Finally, a word of encouragement. We are not biochemical bubbles who need to be protected from the big bad world out there. We’re designed to handle environmental challenges and even metabolize them.

In fact, the process of learning how to master these challenges is part of the process of engineering health itself.

 Eating right, exercising, sweating a little, expressing yourself, spending time in Nature, and limiting your exposure to toxic media and toxic people gives the innate wisdom of your body time to do what it does best: sort things out over time.


Liver Detoxification – To detox or not to detox?

Glucuronidation: Detox, Balance Hormones, & Genes

To detox or not to detox?

Ah, the detox. We’ve all heard it. It seems everywhere we look, there is someone talking about detoxing, needing to detox, or going on a cleanse. But, what is a “detox” and when should you consider one??

What does it even mean?

Detoxification in our body is essentially a normal metabolic process by which toxins are excreted. In fact, detoxing is something that takes place all the time in the body, without us even thinking twice. One of the main ways our body rids itself of toxins is through the liver.

The liver serves both as a defense front by limiting entry of toxic substances into the bloodstream, and as a clearance organ, by extracting potentially toxic metabolic products, converting them to chemical forms that can then be eliminated via the aid of our bowels and kidneys.

1 Depending on the efficiency with which these molecules are extracted by hepatocytes (fancy word for liver cells), little or none of the absorbed substance may make it into the systemic circulation.1 But that’s not all our liver does.

In addition to ridding the body of toxins, it also processes hormones, stores essential vitamins and minerals, and even produces the bile we use to digest fat. You can only imagine, if our liver isn’t functioning optimally, we won’t be either.2

These toxins, by the way, are fat soluble for the most part.  This means we store them in the parts of our body that are rich in fat (for example the brain, breast, and thyroid).

One of the big roles of the liver is to convert these fat soluble toxins to a water soluble format. These water soluble formats can then be eliminated via bile to the bowel and via the kidney.

This basic liver detoxification process is accomplished by optimizing phase I (known as cytochrome P450 pathway) and II (known as conjugation) liver detoxification.

Phase I Liver Detox

Phase I detoxification works to provide protection from various toxins by using chemical reactions such as reduction, oxidation, hydrolysis, which create free radicals (reactive molecules that damage cells) that the body then neutralizes with antioxidants.3 The end goal of this pathway is for the end product to be water soluble and ready for urinary or bowel elimination.3

If the body is deficient in antioxidants then the attempt at phase I toxin removal can create greater toxicity.  This is why it is important to maintain adequate levels of the antioxidant vitamin E, vitamin C, SOD, and carotenoids – these antioxidants are considered longevity nutrients.3

Phase I (P450) detoxification also relies on vitamin and mineral cofactors to do its job; cofactors include vitamin B3, magnesium, riboflavin, iron, and some cruciferous vegetable indoles.3

The free radicals that are not neutralized in Phase I can damage cell DNA, RNA, and protein.  To protect against this the body relies on Phase II detoxification.

Some toxins (pesticides, alcohol, saturated fat, paint fumes, exhaust fumes), drugs, and metabolites can induce or cause over-activity of the P450 system resulting in high free radical concentrations that put great demand on our antioxidant supply.3,4

Phase II Liver Detox

Phase II detoxification will rely on something called conjugation to render toxic drugs, chemicals or hormones less harmful.

  Conjugation involves the addition of sulphur molecules, glycine, or cysteine to make toxins water soluble and ready for excretion.  To conjugate, the body uses glutathione, glycine, sulphate or glucuronide conjugation.

3,4 Therefore, supplemental or nutrient sources of glutamine, glycine, inositol or choline are essential to phase II detox!

Glutathione is made in the liver with the protein building blocks glutamine, glycine and cysteine.  Glutathione-S-transferase (GSH-T) is the glutathione enzyme used by Phase II detox.

  It is a powerful antioxidant that is depleted more readily when we have a large toxic burden (e.g. drugs) or when we have a toxic release during a state of fasting or starvation.

3,4 Glutathione building blocks can be maintained if we have adequate protein intake.

Glycine is useful for detoxifying benzoate food preservatives, salicylate drugs, environmental toxins/agents, carcinogens, drugs, insecticides, and naturally occurring foreign compounds.

3 Foods high in glycine include fish, meat, dairy, beans, spinach, cabbage, kale, cauliflower, cucumber, pumpkin, soybean, kiwi , and banana.

  Glycine can also be formed in the body by using amino acid protein building blocks readily available when you maintain a high quality protein diet.6

Sulphation is essential for the elimination of steroid hormones, neurotransmitters, drugs (e.g. acetaminophen), xenobiotic, and phenolic compounds.

  Sulphur foods or sulphur amino acids (taurine, cysteine) can stimulate Phase II detox.

3 Sulphur-containing foods considered to have a cleansing action that stimulates phase II conjugation include eggs, cruciferous vegetables (cabbage, broccoli, cauliflower and brussel sprouts), onions, garlic, shallots and leeks.5

Glucuronidation is essential in the detox of steroid hormones, some fungal toxins, some nitrosamines, and aromatic amines, among other things.3,4 Glucuronidation also helps to get rid of thyroid T4 hormone and estrogen after they have been utilized by the body.  Foods that can assist in glucuronidation include those that contain limonene, so for example citrus peel.5

To detox or not to detox?

Unfortunately, our environment can play a major role in contributing to our toxic load. From industrial pollution in the great outdoors, to the things we eat and drink, and to what we put on our bodies, most of us will be bombarded with loads of pollutants everyday. For that reason alone, if you’ve never done one, then it might be wise to consider a liver cleanse at some point.

What should you be looking for?

A liver that is not functioning optimally will allow for toxic buildup, resulting in a number of signs and symptoms seen in both physical and the mental sphere.2

  • Hormonal imbalance (menstrual irregularities, infertility, early menopause)
  • Headaches
  • Sluggishness, fatigue, brain fog
  • Dizziness
  • Weight gain and inability to lose weight
  • Issues with digestion (stomach pain, bloating and gas, acid reflux, nausea, poor appetite)
  • Constipation, dark urine
  • Skin and/or eyes that are yellowish (a symptom of jaundice)
  • Bruising easily
  • High blood pressure
  • Excessive sweating
  • Moodiness, anxiousness, or depression
  • Rosacea and other skin issues (ie acne)

How to go about it

Fortunately, you can improve your liver’s functioning with a liver cleanse, which can have you feeling better in a couple of weeks

A diet high in processed foods, refined sugars, and hydrogenated fat, can be toxic to your system. Replace these foods with healthy choices, which include whole foods, organic and GMO free when possible.

Fresh foods such as leafy greens packed with magnesium, chlorophyll, Vitamins A and C, along with fresh vegetables and fresh fruits are best. Of note, organic fruits and vegetables also contain higher amounts of Vitamin A, Vitamin C, and sulfur, which all boost liver detoxification and cleansing.

Broccoli, brussels sprouts, kale, collards, apples, onions, garlic, and squash are all great choices.

The liver as we mentioned is also responsible for producing bile that breaks down fats. Eating healthy fats almonds, coconut, walnuts, hemp, chia, and flax, along with pumpkin and sunflower seeds, olives, and avocado are all the best sources of fat for your diet. Avoid saturated fats and trans fats (aka hydrogenated) which can lead to inflammation in your body and hinder liver health.

Ditch the alcohol

You might be sad to hear it, but alcohol is a toxin in any form and your liver will have to use a deal of energy getting rid of it. During this process, metabolic energy used up, and quite a bit of it, so consequently this can actually lead to weight gain, fatigue, and even sleepiness.

The lemon water fix

Lemon and all citrus fruits contain vitamin C and other minerals that can boost your body’s ability to sweep away waste, as well as minerals that boost bodily functions and enhance the cleansing process. Aim to drink as many glasses a day as you possibly can.

Raw Vegetable Juicing

If you’re finding it difficult to get in your 4-5 servings of vegetables per day, you might want to consider juicing a variety of raw vegetables. Even vegetables that don’t peak your interest can be enjoyed in a fresh vegetable juice.

With impaired liver function, juicing vegetables has the added benefit of making the vegetables easier to digest, and more readily available for absorption. Vegetables ideal for a liver cleanse include cabbage, cauliflower, and brussels sprouts.

Remember, you can also add fresh herbs including mint, parsley, and others to make the juices tasty.

Milk Thistle

Milk Thistle is considered one of the best detoxifying herbs, and so it’s not wonder it’s ideal for a liver cleanse. Milk thistle helps to eliminate the buildup of heavy metals, prescription medications, environmental pollutants and alcohol in the liver. The active ingredient, silymarin, has been proven to help strengthen the liver cells, while also supporting healthy regeneration!7

Dandelion Root

A powerhouse of a flower and is packed with vitamins and minerals. In addition, dandelion root has a natural diuretic effect, allowing your liver to actually eliminate toxins more quickly. In addition, it is a great botanical to help strengthen the immune system, balance blood sugar and soothe digestive upset. 8


Also, another powerhouse, tumeric works on many fronts. In addition to supporting healthy liver tissue and metabolism, it is also a great overall anti-inflammatory.9

Coffee enemas are thought to help aid in liver detoxification. During the enema, organic coffee is retained in your bowel, allowing the fluid to enter the liver through the intestinal wall.

10 This has a stimulating effect which will increase bile flow, contributing to revving up your liver and gallbladder.

This sparks the production of the chemical glutathione, a strong cleansing compound that helps to release the build up of toxins in your system.10

Now that you know the ins-and-outs of liver detoxification remember, before thinking of beginning your detox, it is essential you come up with a strategy how best to proceed.

Although it has amazing benefits in the long run, the process of stimulating the body’s natural detox systems may cause feelings of fatigue, irritability, soreness, mood swings, and even the onset of cold or flu symptoms.

Work with a qualified professional who can assist you during your first detoxification so that you can begin to understand the processes you are undergoing.

In addition, if you can significantly reduce the level of pollution in your home, choose the best quality food you can, and be wise about the products you use on your body, half the battle is already won … but I suppose that is a conversation for another day….

To your liver,

Dr. Afrouz


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