Many of my clients report “die off” reactions to antimicrobials or even probiotics. Die off or herxheimer reactions are nasty flu like symptoms that you can experience when large numbers of microbes are killed off. When microbes die, they can bust apart and leave your system overloaded with microbial toxins and byproducts that can make you feel worse when you start treating the overgrowth.

Many SIBO sufferers celebrate their die-off reactions because they believe it means that they are effectively killing the overgrowth. The SIBO world perpetuates a common belief that you are supposed to feel worse, before you feel better. But, should we really be celebrating die off reactions?

No, you should not be celebrating die-off reactions and I will explain why in this post. That is not to say that a minor headache or increase in symptoms is going to cause you harm.  But, if you believe bad die off reactions are to be expected in treatment, you are more likely to push through significant and life disrupting symptoms.

This assumption that bad die off is to be expected can get you into trouble. Instead of viewing die-off as a good thing, you should view bad detox reactions as a sign that your detox pathways are overwhelmed or congested.  If starting a new protocol has totally zapped your energy and disrupted your ability to function, you need to slow down and work on your detox pathways.

Let’s Breakdown Detoxification:

Let’s talk about the basics of detoxification. There are three phases of detoxification. Phase one involves preparing toxins, chemicals and drugs for phase two. Phase one can create very reactive and inflammatory metabolites.

Phase two involves conjugation, a process that makes the chemical, toxin or drug less reactive and more water soluble, so it can be easily excreted from our cells. Adequate glutathione, a molecule that conjugates toxins, is crucial for phase two detoxification.

Phase three involves the transportation of toxins out of the cell into the bile, which then allows for excretion via the feces or the urine. Phase three is often neglected in many detox protocols.

Here is a great overview of the phases of detox for you to reference from one of Chris Masterjohn’s helpful videos on glutathione:

Masterclass with Masterjohn

Why are you having die-off reactions?

If you have had longstanding gut issues or inflammation, your detox pathways can very easily become blocked up! A clog in your detox pathway will leave you feeling miserable when you add in any supplements that will increase toxin release such as pharmaceutical or herbal antibiotics.

Dr. Chris Shade is a researcher and expert in human detoxification. He wrote a detailed article about detoxification that I will highlight throughout this blog.

He writes “Many are familiar with the importance of the liver and kidneys as organs of detoxification, yet neglect awareness of the role of the intestines, the mucosal lining of which expresses high levels of the proteins important for all phases of detoxification. When any of these systems are impaired, a backup in processing of toxins will occur, with a greater burden being placed on other organs.”

To summarize the quote above: when the gut is inflamed and leaky, detoxification can be challenging. Endotoxins (LPS) from gut bacteria can seep into the blood stream when the gut is inflamed and leaky. Dr. Shade points out four big reason’s why endotoxins can disrupt detoxification:

First, high endotoxins downregulate detoxification enzymes and phase three transporters that bring toxins, chemicals and drugs out of our cells.

Second, if endotoxins can not be efficiently detoxed, inflammation and gluthatione depletion occurs in our cells.

Third, high endotoxin levels can also cause kidney inflammation and damage that can further limit our ability to excrete toxins. Leaving toxins to recirculate in our bodies, which will drive more inflammation.

Fourth, High endotoxin levels can also hinder bile flow. Endotoxins inhibit bile salt and phase 3 transport proteins, which causes bile salts and toxins to accumulate in liver cells. This accumulation of bile acid and toxins cause inflammation and damage to liver cells.

The cell will adapt to protect itself from harm by dumping toxins back into the blood, where it recirculates. Dr. Shade argues that poor bile flow is the main reason why someone would have bad detox reactions, because toxins will just recirculate in the blood and cause inflammation versus being properly excreted.

Bile also promotes motility and keeps bacterial levels low in the small intestines. Poor bile flow will not only clog detox pathways, but it can also create an optimal environment for SIBO.

High beta-glucuronidase levels prevent proper detox

Glucuronidation is a phase two detox process that is similar to glutathione conjugation. Glucuronidation is a process that involves conjugating toxins and hormones making them more soluble so that they can be excreted.  Certain gut bacteria can produce an enzyme called beta-glucuronidase that de-conjugates toxins/hormones preventing excretion and prompting reabsorption into the blood.

Gut imbalances can lead to high or low levels of beta-glucuronidase (both of these can be problematic). Estrogen metabolism can be completely thrown out of balance due to beta-glucuronidase levels. Bacteria that produce this enzyme are collectively called “the estrobolome”.

Estrogens are conjugated and deactivated in the liver and released into the bile to be excreted. Beta glucuronidase deconjugates and activates these estrogens preventing their excretion in the feces. Instead, the estrogens will be reabsorbed by the intestines and will re-enter the blood.



You want the right amount of beta-glucuronidase producing bacteria to have optimal estrogen levels. High levels of beta-glucuronidase can lead to estrogen dominance and bad PMS symptoms. Low beta-glucuronidase levels can lead to lower estrogen levels and conditions like PCOS.

How to prevent detox reactions!!

Raise glutathione levels

Increasing glutathione levels can increase your ability to detox your cells. You can raise your glutathione through supplementation or naturally.

Chris Masterjohn has great resources on how to raise glutathione naturally. This video is particularly helpful. His approach centers on making sure that you have the basic building blocks to make glutathione and on strategies to upregulate glutathione synthesis.

For the building blocks, you need 3 amino acids: glutamate, cysteine and glycine. Typically, we eat enough cysteine and glutamate if we are eating about 0.5g of protein per pound of body weight.  However, glycine is often lacking in our diets. Dr. Masterjohn recommends consuming about 10-20 grams of collagen or gelatin a day to supply your body with enough glycine to make glutathione.

Insulin upregulates an enzyme that makes glutathione as shown above. In addition, you can see that glycine is needed to convert gamma glutamylcysteine into glutathione.   Source:

To increase production of glutathione, Dr. Masterjohn also recommends getting enough carbohydrates. Insulin often gets a bad wrap, but insulin signaling can let our body know that we have enough fuel to produce glutathione. Most SIBO and gut healing diets slash carbohydrates, which could lower insulin signaling and glutathione production.

Eating more polyphenol rich foods like fruits, vegetables and spices will increase glutathione production in your cells as well. Dr. Masterjohn says to shoot for 5-9 servings of fruit and vegetables a day.

Here are a few other tips he mentions for boosting glutathione levels:

  • Eating an adequate level of Magnesium
  • Consuming whey protein (if tolerated)
  • Making sure to address any diseases that mess with cellular energy status like hypothyrodism or diabetes

You can also supplement with glutathione to help boost your status. I have found that adding glutathione supplementation can drastically improve detox reactions in my clients.

Optimizing bile production and flow

A crucial building block of bile is phosphatidylcholine. Inadequate intake of choline can result in impaired biliary excretion. Dr Shade points out that inadequate intake of choline is very common with one study showing that only 8% of American adults consume the recommended adequate intake of choline.

Without choline, you won’t be able to eliminate toxins effectively due to poor bile production and flow. Foods that are high in choline include egg yolks, liver and beef. Here is a resource with choline rich foods.

Dr. Shade also points out that bitter herbs can stimulate bile production and flow. The bile supporting herbs that he uses for his detox protocols are gentian, dandelion, myrrh and milk thistle.

Green tea has been shown in a couple of rodent studies to increase bilary secretion of carcinogenic compounds. If you tolerate caffeine, drinking green tea may help you detox toxins more efficiently.

As I have discussed in the past, physical activity can also increase bile flow to help you digest and detox better.

Toxin Binders

Endotoxins released from the gut can kick off inflammatory process throughout the body that will hinder detoxification. Adding in compounds that can bind to endotoxins is a necessary step to optimizing detoxification pathways.

My favorite binder is serum bovine immunoglobulin (SBI). It will bind to endotoxins and remove them before your immune system is activated by them. SBI will lower inflammation in the gut and enhance immune function in the gut.

Activated charcoal and certain clays can also bind to microbial toxins. You have to be a little careful with these, because they can disrupt your digestion and absorption of some minerals.

For high beta-glucuronidase, try calcium d-glucarate

Calcium d-glucarate can be a helpful addition when you have high beta-glucuronidase levels (which you can see on a comprehensive stool test). D-glucarate is a natural acid found in many fruits and vegetables with oranges, apples, grapefruit, and cruciferous vegetables having the highest concentrations.

D-glucarate can inhibit beta glucuronidase. As we discussed earlier, beta-glucuronidase can de-conjugate toxins and hormones preventing their excretion. By blocking beta-glucuronidase activity, d-glucarate promotes the proper excretion of toxins/hormones.

Treating gut imbalances is the most important step to reducing beta-glucuronidase levels. But, if your levels are high, you can increase your ability to detox by increasing your intake of d-glucarate rich foods or your can take calcium d-glucarate as a supplement.

Bottom Line:

Die-off should be seen as a red flag not something to celebrate. If you are having bad detox reactions, work on repairing your detox pathways!

Want to work with me?

Contact me to schedule a free 20 minute consult

  • Just found your site. Very interesting. Thanks!
    Where do you get your SBI? Doesn’t appear to be readily accessible by notable/reputable sources.

    • Hi Kelly! SBI can be purchased through licensed practitioners. There are pharmaceutical products that actually have SBI that have been used for years to treat IBD and IBS. The supplements like SBI Protect from orthomolecular products and MegaIgG2000 from Microbiome Labs are also SBI but are purer than the pharmaceutical versions. I hope this helps