Phase 1 and Phase 2 Liver Detox: Dr. Jarod's Poked Bear, Explained

"Liver detox" gets used for everything from juice cleanses to foot pads. Inside your body, it means something specific: a set of chemical steps your liver runs all day to turn unwanted compounds into something you can get rid of. Researchers split those steps into phases. Dr. Jarod Ward explains them with bears.

The whole goal is to make things water-soluble so you can get rid of them

Your body has a steady list of compounds to clear: medications, chemicals from plastics, and its own used hormones. A review of liver metabolism describes how: compounds "are converted to more polar products to facilitate their elimination from the body." Polar means water-friendly. The review divides the process into three phases.

Phase 1 changes the molecule, and for a moment it can be more reactive

Phase 1 is "functionalization." The liver chemically changes the molecule, often with enzymes from the cytochrome P450 family. Sometimes the in-between product is rougher than what came in. Dr. Jarod's picture:

"Phase one is like when it takes the really toxic guy and does a little bit of conversion. And it's actually kind of a little bit more dangerous at this point, because you kind of poked the bear, right? We found the bear, we poked it, but it's not neutralized yet."

Acetaminophen shows exactly this. About 10 percent of a normal dose goes through phase 1, where it becomes "a highly reactive toxic metabolite" called NAPQI. That's a poked bear.

Phase 2 attaches a tag that calms it down

Phase 2 is conjugation: the liver attaches a small molecule, like glutathione, glucuronic acid or sulfate, that makes the compound water-soluble and safe to move out. In Dr. Jarod's words, the poked bear "needs to go to phase two, where then it's like, turns into a nice little teddy bear."

Back to acetaminophen. At normal doses, NAPQI gets "rapid conjugation by hepatic GSH," meaning the liver's glutathione, "to form non-toxic" compounds "that are excreted in urine." Most of the dose, about 90 percent, goes straight to phase 2 tagging. In an overdose, the phase 2 routes get saturated, glutathione is used up, and NAPQI builds up in the liver.

The same tagging handles everyday exposures. BPA from plastics leaves the body tagged as a glucuronide, and in a human dosing study that tagged form cleared from the blood with a half-life of less than six hours. Estrogens and their breakdown products are cleared through phase 2 tags too: sulfate, glucuronide, methyl and glutathione conjugates.

Phase 3 moves the finished product out

Phase 3 is "transporter-mediated elimination," usually "via liver, gut, kidney, or lung." Tagged compounds get pumped out of liver cells into bile, which carries them to the gut, or into the blood, where the kidneys send them out in urine. Bile is one of the main exits, explained in What Is Bile?

The phases work best when they keep pace with each other

Dr. Jarod calls this one of the coolest things the liver does: "It will literally take a toxin, a dangerous one, and it'll unpack it, reformulate it, and now it's actually neutral and doesn't hurt you."

That works when phase 2 keeps up with phase 1. The acetaminophen overdose is the extreme example of what happens when it doesn't: the tags run short, and the reactive in-between product piles up. The authors of the acetaminophen review describe the body as needing "a delicate balance between production and detoxification/transport of harmful reactive species." Dr. Jarod puts the cost in plainer terms. The liver can take "a really terrible toxin," he says, "and it can work really hard and maybe even damage itself in the process, but turn it into something less damaging to your brain, heart and the rest of your body."

Dr. Jarod's caffeine rule comes from the phase 2 step

Caffeine is a job for the liver too. One phase 1 enzyme, CYP1A2, metabolizes 95 percent of the caffeine you take in. Dr. Jarod's concern is what caffeine does downstream:

"Well, caffeine totally shuts down phase two. And so now instead of bears, we have a bunch of poked bears, and they have nowhere to go."

That's why caffeine sits out for all three weeks of the Love Your Liver cleanse. How that feels in the first few days, and how long it lasts, is in Can You Drink Coffee on a Liver Cleanse?

The tags come from food

Phase 2 runs on raw materials. Glutathione is built from amino acids, including cysteine and glycine, which come from protein. Broccoli sprouts supply sulforaphane, an inducer of glutathione S-transferases, the enzymes that attach glutathione. In a 12-week trial, a broccoli sprout drink raised excretion of glutathione-tagged benzene by 61 percent compared with placebo. What else belongs on the plate is in Foods That Support Liver Health.

The full plan comes with the cleanse

Love Your Liver is Dr. Jarod's 21-day guided liver cleanse, and it's self-paced. The full meal plan, supplement schedule, shopping list and daily texts come with the cleanse. Your supplements ship to your door, and Day 1 starts the moment you tap start.

Prefer to start with a conversation? Dr. Jarod runs functional medicine and lab testing at Crown Chiropractic in Fort Myers. Call (239) 441-2275 to book a consultation.

Sources

• Dr. Jarod Ward, Crown Chiropractic. Liver episode on YouTube, 11:22 to 12:21.
• Almazroo OA, Miah MK, Venkataramanan R. Drug metabolism in the liver. Clinics in Liver Disease 2017;21(1):1-20.
• Yoon E, Babar A, Choudhary M, et al. Acetaminophen-induced hepatotoxicity: a comprehensive update. Journal of Clinical and Translational Hepatology 2016;4(2):131-142.
• Völkel W, Colnot T, Csanády GA, et al. Metabolism and kinetics of bisphenol A in humans at low doses following oral administration. Chemical Research in Toxicology 2002;15(10):1281-1287.
• Raftogianis R, Creveling C, Weinshilboum R, Weisz J. Estrogen metabolism by conjugation. Journal of the National Cancer Institute Monographs 2000;(27):113-124.
• Nehlig A. Interindividual differences in caffeine metabolism and factors driving caffeine consumption. Pharmacological Reviews 2018;70(2):384-411.
• Sekhar RV, Patel SG, Guthikonda AP, et al. Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. American Journal of Clinical Nutrition 2011;94(3):847-853.
• Egner PA, Chen JG, Zarth AT, et al. Rapid and sustainable detoxication of airborne pollutants by broccoli sprout beverage: results of a randomized clinical trial in China. Cancer Prevention Research 2014;7(8):813-823.