Detoxification Breakdown: Phase 1 vs Phase 2 and Why We Need to Support Both Phases

The term detox has gotten very trendy in recent years. We’re constantly being exposed to ads that say things like “a five day juice cleanse to detox your body” or “try this product to remove toxins”.


But are these programs and products actually effective? Isn’t that what our liver is for? Why would we need help with detoxification?


The short answer is yes, your liver is in charge of detoxification. It plays a role in the break down and removal of toxins that accumulate in our bodies from exposure to things like pesticides, pollution, processed foods, BPA, and heavy metals. Along with toxins, your liver also helps in the break down and removal of medications and excess hormones including sex hormones like estrogen, progesterone, and testosterone.


So if your liver already does all of this, why would you need to do a detox?

Sometimes your liver gets bogged down with everything it is expected to do and gets backed up on its to do list. There are many different things that slow down our detoxification process. These include things like medications, poor diet, chronic illnesses, smoking, alcohol intake, air pollution, pesticides, and anything else that causes inflammation in your body. You are most likely exposed to one or more of these things on a daily basis and that means your body is working hard to overcome the burden you are putting on it. Also, if your liver doesn’t have the necessary cofactors to aid in the breakdown of toxins like B vitamins, Glutathione and Flavonoids, then that can prevent it from doing its job as effectively as we would like.


This is when detox support comes in. Keep in mind, detox support can mean many different things. It can mean supplementing with some of those cofactors mentioned above. It can mean utilizing things like the sauna, exercise and fasting. It can also mean removing whatever toxins you are being exposed to in the first place.


It’s important to understand the two different phases of detoxification and the roles that they play in detoxing. Once you understand the phases, you can better understand how to support your own body in its detoxification. It will also make more sense as to why the detox products you see advertised really only address one phase of detoxification, usually the first phase. If the second phase isn’t also supported then your detox won’t be effective and could even end up causing damage.


So let’s get into it.


What is detoxification?

Detoxification is a multi step process. When people think of detoxing, it’s usually phase 1 of detoxification that they are considering.


Phase 1 occurs in the liver and is the process of breaking down toxins, medications, and hormones and transforming them into their intermediate forms. These intermediate forms can then be easily removed from the body. The enzymatic process of breaking down the chemicals, metals, nutrients, hormones, etc. in this first phase also creates what are known as free radicals. Free radicals cause inflammation and DNA damage when they are left in the body for too long. Think of this phase as filling up a bathtub. The toxins that are being broken down can be considered the water that's filling up the tub.


Phase 2 detoxification is the process of removing the intermediates while also neutralizing the free radicals that were made in Phase 1 before they can be reabsorbed back into the body. Think of this phase as draining the tub that you filled up with toxins. If the tub isn't draining as quickly as it is filling up, then the water (aka the intermediates and free radicals) will start overflowing out of the tub and back into your body.


Phase 2 is the one that a lot of the detox programs and products you see advertised are missing, and this is why incorrectly detoxing can be ineffective and can also cause damage. Free radicals cause inflammation and DNA damage when they are left in the body for too long. This is why it’s crucial that Phase 2 of detoxification is also running smoothly and efficiently, so the free radicals can be removed quickly before damage is caused.





I thought detoxing was for toxins. Why would we need to detox hormones?

Once your hormones have done their job in your body, they are no longer needed. This is when your liver comes into play. Your liver breaks down or metabolize the hormones so that they can be removed and don’t accumulate in your body. When hormones aren’t being adequately removed and begin to accumulate you will have symptoms of estrogen dominance or excess testosterone for example. The symptoms may be things like irritability, acne, heavy periods, bloating, weight gain, difficulty sleeping and anxiety. This is why we need to make sure we are effectively detoxing or removing hormones.


So let’s dive deeper into the two phases of detoxification and see if we can get a better understanding of what is going on and how to support each phase..


PHASE 1 DETOXIFICATION: TOXIN BREAKDOWN

Phase 1 is the process of oxidation. Cytochrome P450 enzymes that are found in the liver come in and breakdown toxins to transform them into less harmful water-soluble molecules that can be eliminated from the body. During the process of converting toxins into water-soluble molecules free radicals are also created.


Free radicals are also known as reactive oxygens species. When you hear the term antioxidant, you should then think of free radicals. Antioxidants come in and fight against the oxidative damage that is caused by free radicals. Free radicals can lead to inflammation and tissue damage if they are left to circulate in your body for too long. This is why we have to remove them from the body as quickly as possible. The longer free radicals are left circulating in your body the more damage they are causing.


Other things that cause free radical formation in our bodies include air pollution, pesticides, tobacco smoke, poor diet, alcohol consumption, stress and UV damage.


Some of the more well-known antioxidants include Vitamins C, E, and A, Zinc, CoQ10, Pycnogenol, Glutathione, and EGCG (found in green tea). When you hear foods being described as “super foods” or “antioxidant rich” it means they are good sources of some of the antioxidant nutrients we just mentioned.


There are certain cofactors that are needed to support Phase 1 detoxification. These include B2, B3, B6, B9, B12, Glutathione, choline, branched chain amino acids, flavonoids, and phospholipids. A common pharmaceutical that can deplete your body of a lot of these cofactors is oral contraceptive pills. Talk to your doctor to find out how you can replenish these cofactors if you are deficient.


PHASE 2 DETOXIFICATION: ELIMINATION SUPPORT

Phase 2 detoxification is also known as the conjugation pathway. This phase occurs in the liver and is the process of attaching another molecule to the intermediate that was made in phase 1 to make the intermediate molecule less harmful and easier to eliminate.


Remember, if this stage is not also being supported, the free radicals that were a byproduct of phase 1 detoxification are left to circulate in the body and cause damage to your cells and DNA.


There are 6 different types of conjugation pathways and they each do different things and need different support in order to function optimally.


The six conjugation pathways:

1. Glutathione Conjugation

2. Methylation

3. Sulfation

4. Glucoronidation

5. Acetylation

6. Glycination


How can you best support the different conjugation pathways?

GLUTATHIONE CONJUGATION

Glutathione is one of the most important antioxidants in our body and can bind to and get rid of so many different toxins including pesticides, heavy metals, alcohol and medications (Tylenol is the most common one you hear about). There are many chronic illnesses that are associated with glutathione deficiency, which makes it difficult for those people to combat the effects of the oxidative stressors previously mentioned.


Some different ways you can support glutathione conjugation include:

  • Liposomal Glutathione or N-Acetyl Cysteine (NAC)

  • Vitamin C and Vitamin E

  • Omega-3s

  • Alpha lipoic acid

  • Selenium

  • Cruciferous veggies like broccoli, brussel sprouts, cauliflower, and bok choy

  • Protein rich diet


METHYLATION

Methylation is the detoxification pathway that the majority of us are most familiar with. Methylation is involved in a lot of different biochemical processes in our bodies including the breakdown of histamine, estrogen, catecholamines (norepinephrine, epinephrine), heavy metals, phenols which are found in plastics, and PAHs aka polyaromatic hydrocarbons found in cigarette smoke, perfumes, adhesives, pesticides.


Methylation can be inhibited by genetics, oral contraceptive pills, PPIs, antibiotics, artificial sugar, and nutrient deficiencies.


S-adenosylmethionine (SAM) is the main contributor of the methyl groups used in our bodies during this conjugation process. Methionine, choline, B12, and folate are all required for the synthesis of SAMe.


Some different ways you can support methylation include:

  • SAMe

  • Methionine

  • Methylated B vitamins

  • Magnesium

  • Zinc

  • Choline

  • Animal protein

  • Green leafy veggies

SULFATION

Sulfation is the main pathway for the detoxification of steroid hormones and thyroid hormones. Steroid hormones include estrogen, progesterone, DHEA, and Melatonin. Sulfation also plays a role in the breakdown of catecholamines, food additives, and some drugs.


When sulfation is impaired it can cause neurodegenerative diseases, migraines, chronic fatigue syndrome, asthma, chemical sensitivities, and intestinal disorders.


Things that support sulfation include:

  • Sulphur rich foods like cruciferous veggies (broccoli, broccoli sprouts, brussel sprouts, cauliflower, cabbage and kale) and onions

  • Cysteine, methionine and taurine are all amino acids that contain sulphur and can be found in protein rich foods like eggs, fish and meats.

  • NAC and Glutathione

  • Sunshine


GLUCORONIDATION

Glucoronidation is a hugely important detoxification pathway that breaks down estrogens, bilirubin and drugs including NSAIDS, Benzodiazapines, Tylenol and Morphine. If you are on any of these medications it’s especially important to make sure that you are supporting this pathway. When this pathway is impaired, the risk of hormone related cancers increases.


How to support glucuronidation

  • Resveratrol, curcumin, quercitin

  • Calcium d-glucarate

  • Probiotics

  • A low meat diet

  • Foods include cruciferous veggies, dandelion, rosemary, and cruciferous veggies


ACETYLATION

The acetylation pathway detoxifies caffeine, Benzodiazepines, Histamine and aromatic amines found in cigarette smoke, dyes, perfumes, adhesives, pharmaceuticals, among many other things.


Acetylation is supported by Vitamins B1, B5, and Vitamin C


GLYCINATION

This pathway is essential for breaking down amino acids and plays a role in detoxifying Aspirin, Alka seltzer, NSAIDS, food dyes and Toluene- found in paint thinners, cleaners, nail polish, glue,


Foods that support glycination include proteins such as turkey, pork, fish, beef, and chicken, seaweed, eggs, pumpkin seeds, almonds, sunflower seeds, lentils.


RESOURCES

“Detoxes” and “cleanses”: What you need to know. (2019). https://www.nccih.nih.gov/health/detoxes-and-cleanses-what-you-need-to-know

Kurutas EB. (2016). The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: Current state. nutritionj.biomedcentral.com/articles/10.1186/s12937-016-0186-5

Ketterer, B., Coles, B., Meyer, D. The role of glutathione in detoxification. (1983). Environmental Health Perspectives.

Grant, D.M. (1991). Detoxification Pathways in the Liver. In: Harkness, R.A., Pollitt, R.J., Addison, G.M. (eds) Journal of Inherited Metabolic Disease. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-9749-6_2

Armstrong, L. (2015). Nutritional Aspects of Detoxification in Clinical Practice. Alternative Therapies. https://d1wqtxts1xzle7.cloudfront.net/55017389/Cline__nutritional_aspects_detox-with-cover-page-v2.pdf?