This is the second of two blog posts discussing how to optimize detoxification.  The reason why I put together these posts is because many people do things to detoxify their liver, but most don’t have a good understanding of phase one and phase two detoxification.  And while you don’t need to be an expert in this area to do a liver detoxification, having a basic understanding of the pathways involved can help you to have a better detox.  In the last post I focused on phase one detoxification, and in this post I’m going to focus more on phase two detoxification.

Before talking about phase two detoxification, I want to briefly summarize phase one detoxification.  If you recall, phase one detoxification is a process of biotransformation, as it’s when the liver transforms fat soluble compounds into reactive intermediates with the help of CYP enzymes.  In phase two these reactive intermediates are then turned into water soluble molecules so that they can easily be excreted in the bile and feces.

Phase two involves six different pathways.  And while I hope you found the first blog post on phase one detoxification to be interesting (and not too confusing), since phase two is more nutrient-dependent I’m hoping that you will find this post to be even more valuable.  After all, while the biotransformation process involved in phase one is of course very important, most people who do a liver cleanse are focusing more on phase two detoxification by eating certain foods, along with taking certain supplements and herbs.

The Six Different Pathways Of Phase Two Detoxification

Remember that phase one results in the production of a reactive intermediate.  Conjugation is the process where a substrate is coupled with the reactive intermediate, which in turn makes this less active and water soluble.  This allows the toxin to be easily excreted, and the actual excretion is considered to be phase three detoxification.  So with that being said, let’s go ahead and look at the different phase two detoxification pathways.  And probably the most important factor to pay attention to with each pathway is the nutrients involved.

1. Glucuronidation.  This process involves a few steps, and if you recall, earlier I mentioned that conjugation involves the substrate coupling with the reactive intermediate that is produced in phase one, and this makes the xenobiotic/chemical less active and more water soluble.  With glucuronidation, when the substrate is conjugated with the reactive intermediate it leads to something called a glucuronide.  This process also involves an enzyme called Uridine 5′-diphospho-glucuronosyltransferase, which is also known as UGT.  There are different types of UGTs, and these enzymes help to catalyze the conversion of the compounds into water soluble molecules.

Some of the compounds that are conjugated in this pathway include bilirubin, thyroid hormone, and the steroid hormones.  So glucuronidation helps with the detoxification of thyroid hormone, along with other hormones.  If someone has reduced glucuronidation the person won’t be able to detoxify these compounds, which can lead to numerous problems.

But why would someone have reduced glucuronidation, or a reduction in any of the other pathways?  Well, there can be a few reasons.  One reason is because they are not consuming the required nutrients to support that pathway, which I’ll discuss shortly.  Another reason is because someone can have a genetic defect that affects the enzymes involved in these pathways.  An example of this is seen with Gilbert’s syndrome, which involves a genetic defect in UGT1A.  This results in an impaired ability to conjugate bilirubin with glucuronic acid, and as a result can lead to jaundice.  One potential sign of Gilbert’s syndrome on a blood test is when someone has consistently elevated bilirubin levels.  If someone has this genetic defect then they not only can have problems conjugating bilirubin, but other compounds as well.

Ideally you want to try to do things to induce, or accelerate glucuronidation.  Some of the nutrients and phytonutrients that can help accomplish this include quercitin, curcumin, resveratrol, milk thistle, grape seed extract, and hawthorn.  You also want to make sure to consume omega 3 fatty acids, and magnesium.  Probiotics and calcium d-glucarate can help to inhibit beta glucuronidase, which I’ll briefly discuss below.  Foods which support glucuronidation include apples, kale, broccoli, and watercress.

What is Beta-glucuronidase?

Beta-glucuronidase is an enzyme produced by bacteria in the gut.  You ideally want to have low levels of this, and the reason for this is because if this enzyme is active then it results in uncoupling of the substrate and the phase one intermediate, and the toxin therefore gets reabsorbed into the enterohepatic circulation, which isn’t a good thing.  In fact, elevated beta-glucuronidase is associated with an increased risk of certain types of cancers.  One of the ways to test for beta-glucuronidase is through the Metametrix comprehensive stool panel.  Some of the nutrients and herbs which can inhibit this enzyme include broccoli, Brussels sprouts, apricots, watercress, calcium d-glucarate, milk thistle, and licorice.

The Role of Thyroid Hormone In Glucuronidation

Thyroid hormone is also involved in glucuronidation, as T3 influences some of the UGT enzymes (UTG1A1 and UTG1A6).  Vitamin A also plays an important role in this (1).  As a result, even if someone has sufficient T3 levels, but has a vitamin A deficiency, then this will have a negative effect on glucuronidation.

2. Sulfation.  Sulfation involves multiple steps, but the end result is conjugation with the substrate, which as you know by now will make the xenobiotic inactive and water soluble.  An enzyme called 3-phosphoadenosine-5-phosphosulfate is a coenzyme involved in sulfation.  An enzyme called sulfite oxidase catalyzes the conversion of sulfite to sulfate, which is necessary to break down sulfur-containing amino acids such as methionine and cysteine.  What’s important for you to understand are the nutrients required in this pathway, and vitamin B6 and molybdenum are required cofactors for this enzymatic reaction.  As a result, a deficiency of either one of these can cause problems with this pathway.  Having problems with sulfation can result in food sensitivities, chemical sensitivities, or an intolerance to acetaminophen.

3. Methylation. I’m not going to get into detail about methylation, but I did speak about this process in an article entitled “Methylation, MTHFR, and Thyroid Health“.  With regards to detoxification, methylation involves conjugating phase one intermediates with methyl groups.  Three of the more important nutrients required to help support methylation include folate, vitamin B12, and vitamin B6.  These are the main cofactors of S-Adenosyl-l-methionine (SAMe), which is the main methyl donor.  Once again, for more detailed information on methylation I would read the article I wrote on this topic.

4. Glutathione Conjugation. Many people reading this are familiar with glutathione, which is an antioxidant that helps to protect us from free radicals, but also plays an important role in phase two detoxification.  N-acetylcysteine is a precursor of glutathione that I commonly recommend to my patients to help support phase two detoxification.  Another option is to take an acetylated or liposomal form of glutathione.  There are also numerous cofactors of glutathione, including selenium, magnesium, niacinamide, vitamin C, and alpha lipoic acid.  Fruits and vegetables usually contribute over 50% of dietary glutathione.  In addition, having healthy butyrate levels can also lead to healthy glutathione S transferase levels.  Butyrate is a short chain fatty acid that is produced by the gut flora.

5. Amino Acid Conjugation.  Not surprisingly, amino acid conjugation requires amino acids such as glycine, taurine, and glutamine.  Of these, glycine is the amino acid most commonly used for amino acid conjugation, although taurine is also commonly used.  So in order to support amino acid conjugation you want to make sure you are eating enough protein.

6. Acetylation. Acetylation involves conjugating toxins with acetyl Co-A.  If someone has a condition such as multiple chemical sensitivity then they will usually be a “slow” acetylator.  Acetylation is involved in eliminating excess histamine, serotonin, and sulfa drugs.  Nutrients which enhance acetylation include Vitamin C, B1, B2, B5, magnesium, and lipoic acid.  N-acetyltransferases (NATs) are drug-metabolizing enzymes that play a role in this pathway.

How Do You Get All Of The Nutrients To Support Phase Two Detoxification?

As for how to get the necessary nutrients to support phase two detoxification, you want to get as many of these nutrients through diet.  Eating plenty of fruits and vegetables is of course important, but you also want to make sure you eat sufficient protein as well.  While you want to get as many nutrients as you can through your diet, taking nutritional supplements and herbs can also help to support phase two detoxification.  Throughout this post I listed nutrients associated with each of these pathways.  So for example, to support glucuronidation I mentioned food sources such as apples, kales, and broccoli, but you can also supplement with curcumin, resveratrol, or milk thistle. Similarly, diet plays an important role in methylation, although if someone has an MTHFR defect then they might need to supplement with methyl folate or other supplements.

So hopefully you have a better understanding of phase two detoxification.  In phase two detoxification, the reactive intermediates that were formed in phase one are made water soluble so that they can be excreted. There are six different pathways associated with phase two, including glucuronidation, sulfation, methylation, glutathione conjugation, amino acid conjugation, and acetylation.  You want to get most of the nutrients to support these pathways through diet, although taking certain nutritional supplements can be beneficial at times.

Most people reading this are aware that the liver is involved in detoxification.  However, many don’t realize how complex of a system this is, as there are many different factors that can affect the detoxification pathways.  And if any one of these factors are negatively impacted then you very well might have problems with detoxification.  Plus, remember that detoxification isn’t just about removing harmful chemicals, but hormones as well, including thyroid hormone, estrogen, etc.  There is so much to discuss that I’ve decided to split this up into two different blog posts, as in this post I will talk about how to optimize phase one detoxification, and in the next post I will focus on how to optimize phase two detoxification.

One thing I do want to point out is that while most detoxification takes place in the liver, keep in mind that the gut, lungs, kidney, and skin also play a role in detoxification.  As a result, if one or more of these other areas are compromised then this can affect detoxification.  For example, I’ll be talking about the CYP enzymes, which play a role in phase one detoxification.  And while these enzymes are primarily located in the liver, they are also located in the gut as well.  And this is one reason why having a healthy gut is important for optimal detoxification.

Understanding The Basics of Detoxification

Phase one detoxification is all about the transformation of fat soluble compounds into reactive intermediates.  I’ll explain what this means in a minute, but I first want to mention that this transformation requires the help of the CYP enzymes I briefly mentioned earlier, which I’ll expand on shortly.  While I’ll be focusing on phase two during the next blog post, I did want to mention here how this phase is involved in conjugation with the reactive intermediate to form a water soluble metabolite that will get excreted.

In order to better understand this let’s look at an example.  If someone uses a skincare product that includes a xenobiotic (a foreign chemical substance), as part of the phase one detoxification process the liver will use certain enzymes to transform this chemical, which in turn will become water soluble after the phase two reactions.  The same concept applies when someone is eating a vegetable with pesticides, as the body will transform the chemicals that are in the pesticide, and eventually these chemicals will become water soluble.

This is a simplified example, as in phase one what frequently happens is that the transformation process turns the environmental toxin into a more harmful reactive intermediate.  This in turn can form free radicals and cause damage to your DNA, RNA, and proteins.  And while a properly functioning phase two system is important for the detoxification of these chemicals, you need an abundance of antioxidants to help minimize the damage caused by these reactive intermediates produced in phase one.

So for example, if someone doesn’t eat a good amount of fresh vegetables and fruits, which are filled with antioxidants, then this will lead to increased damage during phase one detoxification.  Taking antioxidant supplements such as vitamin C, vitamin E, and glutathione can also help to some extent, but you need to eat a healthy diet in order to minimize any negative reactions from phase one detoxification.  In addition, certain factors can induce phase one activity.  In other words, certain factors can speed up the transformation that takes place in phase one.  This might sound like a good thing, but if someone doesn’t have sufficient antioxidants, or if there are problems with their phase two detoxification pathways, then this can cause a lot of oxidative stress, which of course isn’t a good thing.

The Role of The Phase One Detoxification Enzymes

Earlier I mentioned how certain enzymes are required for phase one detoxification, and these are called cytochrome P450 enzymes.  These enzymes are necessary for the biotransformation process.  However, certain nutrients, herbs, and drugs can either induce (i.e. speed up) or inhibit these enzymes.  Having certain genetic defects can also affect these phase one detoxification enzymes.  But what’s the significance of this?  Well, if something induces one of these CYP450 enzymes, then this increase in enzyme activity can in turn cause an increase in the reactive intermediates, which can cause further damage…unless if the phase two system is upregulated as well.  On the other hand, downregulating or slowing down these enzymes to some extent can be beneficial.  In other words, while you don’t want to completely inhibit these phase one enzymes, taking certain nutrients to slow down the activity of phase one detoxification can reduce the oxidative stress and damage.

It’s also important to understand that inhibiting or inducing these enzymes can cause problems when someone is taking one or more medications that are metabolized by the same enzyme.  Let’s look at an example of this.  CYP3A4 is a phase one enzyme that is involved in the metabolism of many drugs.  And grapefruit juice has compounds that can inhibit the CYP3A4 enzyme.  As a result, if someone is taking a certain drug that is metabolized by the CYP3A4 enzyme and the same day they take the drug they decide to drink some grapefruit juice, then this will decrease the metabolism of this drug, causing it to build up in the system.  On the other hand, the herb St. John’s Wort can lead to an increase in the metabolism of the CYP3A4, which can decrease the effectiveness of certain drugs.  This is one reason why St. John’s Wort is contraindicated when taking certain medications.

Does this mean you should never drink grapefruit juice or take St. John’s Wort?  Of course not, but if you are taking medication you might want to do some research to see if it is metabolized by the CYP3A4 enzyme, and if this is the case you probably would want to refrain from drinking grapefruit juice or taking St. Johns Wort.  Click here for a list of drugs that are metabolized by CYP3A4 and 3A5.  For those who take bioidentical hormones, you’ll notice that CYP3A4 and 3A5 metabolizes estradiol, progesterone, and testosterone.  The point I’m trying to make is that nutrients or herbs that inhibit or slow down these phase one enzymes can cause certain drugs to build up in the bloodstream, while speeding up the enzymes will increase the metabolism of certain drugs, which can reduce their effectiveness.

Understanding Some of The Phase One Detoxification Enzymes

What I’d like to do below is discuss a few of the more common CYP450 enzymes so you can better understand how they help to biotransform certain chemicals in the body.  However, it’s important to understand that these enzymes can have multiple roles.  For example, I’ll discuss how the CYP1A2 enzyme plays a role in metabolizing caffeine, but this enzyme is also important for estrogen metabolism.

Let’s go ahead and take a look at some of these enzymes:

CYP3A4 and 5.  As I mentioned earlier, the CYP3A4 enzyme is primarily involved in drug metabolism, and it is involved in the metabolism of certain hormones.  The CYP3A5 enzyme also is involved in drug metabolism.  In fact, 40 to 45% of all drugs are metabolized through these enzymes.  This includes acetaminophen, codeine, cyclosporin A, diazepam and erythromycin (1).

Earlier I mentioned how grapefruit juice can inhibit the CYP3A4 enzyme, which can cause certain medications to build up in the bloodstream.  Other agents that can inhibit this enzyme include antifungal medications, along with resveratrol.  I also mentioned how St. John’s Wort can cause induction of this enzyme, which in turn will speed up the clearance of certain medications from the body.  Red wine and licorice root can also induce this enzyme.

Can Grapefruit Juice Affect Thyroid Hormone Metabolism?

Getting back to grapefruit juice, one small study looked at the effect of grapefruit juice on levothyroxine metabolism (2).  The study showed that grapefruit juice might slightly delay the absorption of levothyroxine, but it only has a minor effect on its bioavailability.  I couldn’t find any studies which showed if grapefruit juice can affect the absorption or bioavailability of antithyroid medication, but one study  I came across showed that methimazole can cause a dramatic decrease of CYP3A4 activity, while partially decreasing the activities of some other CYP enzymes (3).  What this means is that if someone is taking one or more medications along with Methimazole, and if those medications are metabolized by the phase one detoxification enzymes that are affected by Methimazole, then the blood levels of some or all of these can be greatly increased.

CYP2D6.  This enzyme is involved in 25-30% of drug metabolism, as it helps to transform many antidepressants, antipsychotics, analgesics and antitussives, some beta blockers, antiarrythmics and antiemetics (4).  CYP2D6 genetic polymorphisms are very common (4).  Smoking cigarettes and eating charlbroiled meat can induce this enzyme (5) (6).  So if someone is taking a medication that is metabolized by the CYP2D6 enzyme and is a smoker, or eats a very well-done grilled hamburger, then this can actually increase the metabolism of the drug.

Earlier I mentioned how CYP2D6 genetic defects are very common. Tamoxifen is one of the drugs metabolized by CYP2D6, and this drug is commonly recommended as a treatment for some cases of breast cancer.  And just to show the impact these phase one enzymes can have, one research study shows that after taking tamoxifen for five years, women who had reduced CYP2D6 metabolism had an increased incidence of relapsing or dying at a rate that was 2.5 times higher than women with normal CYP2D6 (7).  In other words, if someone has a genetic polymorphism of the CYP2D6 gene, then they probably shouldn’t be given tamoxifen.  Fortunately this can be tested for, which I’ll talk more about shortly.

CYP1A2.  Although this enzyme is involved in the biotransformation of some drugs, it also plays a big role in the metabolism of caffeine.  I’ve spoken about this in a past blog post, as if someone has an upregulated CYP1A2 gene then they are considered to be a fast metabolizer of caffeine, and thus they are able to clear caffeine rapidly from the body.  On the other hand, if someone has a downregulated CYP1A2 gene then they will be a slow metabolizer of caffeine, and these are usually the people who have problems sleeping when drinking coffee, especially later in the day.  The CYP1A2 enzyme is also important in the biotransformation of 2-OH estradiol, which is considered to be one of the “good” estrogen metabolites.

CYP1B1.  This enzyme helps to transform certain pro-carcinogenic (cancer causing) chemicals into reactive intermediates.  For example, it helps to transform estrogen into the 4-OH metabolites, which is considered to be a “bad” estrogen metabolite.  Other chemicals can induce the CYP1B1 enzyme, such as PCBs, the chemicals in cigarette smoke, UV light, and even xenoestrogens.  In other words, exposure to these chemicals will cause the body to convert more of these chemicals into reactive intermediates.

Is this a good thing or a bad thing?  Well, it can be a good thing if you have a properly functioning phase two system (which I’ll talk about in the next blog post), as this will help to convert these reactive intermediates into water soluble molecules that will be excreted.  On the other hand, if someone has problems with their phase two detoxification pathways then these reactive intermediates can build up, which can increase the risk of cancer and other chronic health conditions.

But even if they have a properly functioning phase two system, if they are exposed to a high amount of environmental toxins then this still can be a problem, and in this case you might want to do things which can inhibit or downregulate this enzyme.  CYP1B1 is downregulated by DHEA, polyphenols, resveratrol, and pomegranate.  So if someone is exposed to large amounts of cancer-causing chemicals which are transformed into reactive intermediates, it probably would be a good idea to increase your consumption of polyphenol by consuming more vegetables, fruits, and spices, or perhaps you can take some resveratrol or eat some pomegranate.

CYP2E1.  This enzyme is involved in the metabolism of many different chemicals, including acetaldehyde, acetaminophen, acrylamide, aniline, benzene, butanol, carbon tetrachloride, diethylether, dimethyl sulfoxide, ethyl carbamate, ethylene chloride, halothane, glycerol, ethylene glycol, N-nitrosodimethylamine, 4-nitrophenol, pyrazole, pyridine, and vinyl chloride (8).  It is induced by ethanol, benzene, and styrene, and inhibited by grape seed extract, resveratrol, garlic, licorice root, and watercress.

It’s important to keep in mind that when I list certain nutrients, or herbs, and medications that can induce or inhibit a specific enzyme, these are just a few examples.  You’ll notice that with some enzymes I’ll list more inducers and inhibitors than others, and one reason is because with some enzymes we have a greater knowledge of the inducers and inhibitors.  And unfortunately there is the possibility that there are nutrients, herbs, and drugs which can induce or inhibit a specific enzyme but this hasn’t yet been discovered.

The Role Of Diet In Phase 1 Detoxification

Although phase two is more dependent on nutrients, eating well in phase one is of course important.  Earlier I spoke about the importance of antioxidants in helping to minimize the damaging effects of the reactive intermediates formed in phase one detoxification.  And while you can take antioxidant supplements, you really do want to make sure you eat a good amount of antioxidant rich foods such as vegetables, fruit, and even certain beverages such as green tea.  It’s also important to know that the CYP450 enzymes are heme-dependent, which means that they require iron to function properly.

This is one of the reasons why I have just about all of my patients get a full iron panel.  It’s also important to know that fasting can induce certain CYP450 enzymes.  This includes CYP2B1, CYP2B2, and CYP2E1 (9).  So in other words, fasting can help to increase the metabolism of these enzymes, which can increase the clearance of certain chemicals.  While this might sound like a good thing, if someone is exposed to a lot of environmental toxins and/or has inefficient phase two detoxification pathways, then this can lead to the buildup of reactive intermediates and make the person feel sick.  I’m not suggesting that fasting is never a good idea, but you do want to be cautious.

This might explain why many people (although not everyone) feels better when doing a juice fast, while some people might feel lousy when doing a water fast for a few days.  A juice fast involves plenty of antioxidants, which helps to quench the free radicals produced in phase one, but the nutrients in the fruits and vegetables also help to support phase two detoxification.  The problem is that phase two detoxification also requires sufficient protein, and so while there have been some great success stories involving people who did a juice fast for a prolonged period of time, it can also be problematic if you do it for too long.

How Genetic Mutations Can Affect Phase One Detoxification

I’m not going to get into great detail about genetic polymorphisms (SNPs), which are common genetic mutations.  But one can’t overlook these, as if someone has a genetic defect of one or more of the phase one detoxification enzymes then this can cause a lot of problems.  For example, in this blog post I mentioned how CYP3A4 and CYP2D6 are both involved in the metabolism of many different medications.  And if someone has a genetic defect in one or both of these phase one detoxification enzymes then this can affect the absorption of medications that are metabolized by these enzymes.  And of course people can have genetic polymorphisms of other phase one detoxification enzymes as well.

So the next question you probably have is…”how can I determine if I have a genetic polymorphism of the CYP3A4 or CYP2D6 enzyme, or other phase one detoxification enzymes?”  Fortunately genetic testing is available, as many labs offer it, and many people use a company such as 23andme, although this also requires using a third party service such as Genetic Genie or Nutrahacker to list the specific genetic polymorphisms.  If a medical doctor prescribes a drug that is metabolized by one of these enzymes, it would be a good idea to have the person do some genetic testing, although I realize that there are times when time is a factor and the person might need to take a certain medication sooner than later.  This is one reason why I think that genetic testing will become more routine in the future, as there will be a time and place when medical doctors will take into account the person’s genetics when prescribing certain medications.

What’s The Best Way To Support Phase One Detoxification?

I realize that this blog post was advanced for some people, and so I’ll summarize everything here so that you will better understand how to support and optimize phase one detoxification.

1. Consume plenty of antioxidants. You learned that phase one involves the transformation of fat soluble molecules into reactive intermediates. And so one thing you want to do is to make sure you consume plenty of antioxidants. While taking supplements to increase glutathione production is something some people need to consider, you also want to eat plenty of antioxidant-rich foods, such as vegetables, fruits, and green tea.

2. Downregulate phase one detoxification enzymes. You also learned about inhibiting and inducing phase one enzymes. While there can be benefits of both induction and inhibition, the main concern with inducing one or more of the phase one enzymes is that it can lead to an excess of reactive intermediates. And so typically you will want to do things to inhibit or downregulate these phase one enzymes. And while different nutrients are required to inhibit certain enzymes, some of the more common nutrients that can help to slow down the phase one enzymes include resveratrol, polyphenols, pomegranate, and garlic.

3. Consider doing genetic testing. You also might want to consider doing some testing to determine which genetic polymorphisms of the phase one detoxification enzymes you have. Notice I didn’t say “if” you have genetic polymorphisms, as pretty much everyone has certain genetic polymorphisms, although some are more significant than others. Although I personally obtained a 23andme test a few years ago, I currently don’t recommend genetic testing to all of my patients, and I’m admittedly not an expert when it comes to interpreting the results of such tests. But I am continuously trying to expand my knowledge in this area, and as I mentioned earlier, I do think that such testing will become more routine in the future.

So hopefully you have a better understanding of phase one detoxification.  It admittedly can be complex, and one of the big keys to optimizing phase one detoxification is to make sure you consume sufficient antioxidants to help offset the damage caused by the reactive intermediates.  You also learned about how certain nutrients and herbs can induce and inhibit the phase one detoxification enzymes.  And while the topic of genetic polymorphisms is complex, hopefully you realize that certain genetic defects of the phase one detoxification enzymes can affect the metabolism of different medications.

Soy is definitely one of the more controversial foods with regards to thyroid health.  While there are some health benefits of eating organic, fermented soy, there are also some negative health effects that soy can have.  In this blog post I’m going to discuss four reasons why people with thyroid and autoimmune thyroid conditions should consider avoiding soy while restoring their health.

1. Many people have soy allergies and sensitivities.  The Food and Agriculture Organization of the United Nations includes soy in its list of the 8 most significant food allergens, and at least 16 potential soy protein allergens have been identified (1).  There is evidence that approximately 50% of children with a soy allergy outgrew their allergy by age 7 years (2).  But of course this means that 50% don’t outgrow the allergy.  Plus, many people don’t have IgE-mediated soy allergies, but instead have an IgG-mediated soy sensitivity.

But what’s the difference between a soy allergy and a sensitivity to soy?  I’m not going to get into detail about this here, as if you’d like more information you can read an article I wrote entitled “Food Allergies, Sensitivities, and Thyroid Health“.  But essentially a soy allergy involves an immediate reaction, whereas a soy sensitivity involves a delayed reaction.  In other words, if someone has a soy allergy they typically will have a negative reaction within a few minutes of consuming soy.  On the other hand, if someone has a soy sensitivity they might not have a negative reaction for a few hours, or perhaps even a few days after consuming soy.

What’s wrong with continuing to eat soy if you have an allergy or sensitivity?  The problem with eating any food that you have an allergy or sensitivity to is that this will result in inflammation.  This in turn can interfere with the healing process.  And while you can run a food allergy or food sensitivity panel to determine if you react to soy, these tests aren’t completely accurate.

2. Most soy is genetically modified.  Unfortunately most of the soy is genetically modified.  Some actually think this is a good thing, and there are a few studies which suggest that genetically modified soy might be less allergenic than non-GMO soy (3) (4).  But the problems with GMOs doesn’t just relate to allergies.  One of the main concerns is that genetically modified soybeans contain high residues of glyphosate.

I spoke about glyphosate in greater detail in an article entitled “Does Glyphosate Have a Negative Effect on Thyroid Health?“.  Glyphosate is the active ingredient in the herbicide Roundup, and while it can have an adverse effect on our health in numerous ways, one of the main problems is that it can have a negative effect on our gut microbiota.  This gut dysbiosis can make someone more susceptible to developing an autoimmune condition such as Graves’ Disease and Hashimoto’s Thyroiditis.

3. Soy has goitrogenic properties.  Goitrogens are substances which inhibit thyroid function.  And a few studies have shown that soy has goitrogenic effects (5) (6) (7).  One of these studies demonstrated that the effect on the thyroid hormones was minimal, although the study involved short-term soy consumption, lasting only seven consecutive days.  On the other hand, another study involving soy supplementation for eight weeks in those with subclinical hypothyroidism showed that there is a 3-fold increased risk of developing overt hypothyroidism, although soy also helped to decrease insulin resistance, inflammation, and blood pressure (8).

Should other goitrogenic foods be avoided as well, such as cruciferous vegetables?  I usually don’t recommend for my patients with hypothyroidism and Hashimoto’s Thyroiditis to avoid cruciferous vegetables.  After all, foods such as broccoli, kale, cabbage, and cauliflower have numerous health benefits, and I think that most people should be eating these foods on a daily basis.  I’m not suggesting for people to eat four or five cups of raw cruciferous vegetables per day, but having one or two servings of these foods usually won’t cause any problems from a goitrogenic standpoint.

4. Soy has phytates.  Phytic acid is an anti-nutrient that is found in grains, nuts, seeds, and legumes, including soybeans.  And studies show that the phytates in soy can lead to a decrease in iron and calcium absorption (9) (10).  The good news is that soaking and fermenting soy can significantly decrease the levels of phytic acid.

Should You Be Concerned About the Estrogenic Properties of Soy?

Isoflavones are a type of phytoestrogen found mostly in soy products, and there is some controversy over whether phytoestrogens can be harmful to our health.  I wrote an article on this entitled “The Truth About Soy, Flaxseed, And Other Phytoestrogens“.  While some consider soy as being an endocrine disruptor, the research I have found doesn’t show this, and there are actually numerous benefits to phytoestrogens.  However, I will admit that I try to avoid soy as much as I can, and most of the phytoestrogens I get are from other sources, such as flaxseed.

In summary, soy should be avoided in those with thyroid and autoimmune thyroid conditions.  While there are some health benefits of eating organic, fermented soy, many people have soy allergies and sensitivities.  In addition, soy has goitrogenic properties, and it also has phytates, which can interfere with the absorption of nutrients.  As a result, I usually recommend for my patients to avoid eating soy.

Many people with autoimmune conditions such as Graves’ Disease and Hashimoto’s Thyroiditis follow an autoimmune paleo (AIP) diet.  I’ve spoken about this diet numerous times in other blog posts and articles.  An AIP diet is similar to a “standard” paleo diet, but also excludes eggs, nightshades, and nuts/seeds.  I commonly recommend this diet to my patients, and while some people do great when following it, others don’t do as well.

In the past I wrote a blog post entitled “Should Everyone With Graves’ Disease and Hashimoto’s Thyroiditis Follow an Autoimmune Paleo Diet?“.  Although I commonly recommend an autoimmune paleo diet to my patients, in this blog post I spoke about some of the common “flaws” of this diet.  The truth is that there is no diet that perfectly fits everyone, and this applies to the autoimmune paleo diet.

Anyway, for those who have already followed an autoimmune paleo diet, or are currently following an autoimmune paleo diet, I’d like for you to share your experience in the comments below.  If you followed an autoimmune paleo diet and noticed an improvement in your symptoms and test results please let me know!  Or if you followed an AIP diet and felt worse please let me know!  Please feel free to be as specific as possible, as I’d love to hear how you felt from a symptomatic standpoint when following an AIP diet, if there were any positive or negative changes in your test results, etc.  Thank you in advance for participating!

Recently I listened to Dr. Josh Axe’s book “Eat Dirt” on Audible.  As a side note, if you’re not familiar with Audible it’s something to check out, as I frequently listen to audiobooks while driving, working out, preparing my meals, etc.  Anyway, getting back to Dr. Axe’s book, I thought it was very good and is worth reading (or listening to).  He talks a lot about leaky gut syndrome, but he also talks about the hygiene hypothesis, and there is some evidence in the research that discusses how this might play a role in the development of autoimmune conditions such as Graves’ Disease and Hashimoto’s Thyroiditis.

Well before Dr. Axe wrote his book, there was an article released by the New England Journal of Medicine entitled “Eat Dirt-The Hygiene Hypothesis and Allergic Diseases” (1).  This article starts out by discussing how there has been an epidemic of both autoimmune and allergic diseases, which is more common in Western, industrialized countries.  And the basis behind the hygiene hypothesis is that we’re not being exposed to as many microorganisms (both good and bad), and this essentially weakens or suppresses our immune system.  This in turn can make us more susceptible to developing infections, allergies, and autoimmune conditions.

This might seem to be counterintuitive to some people, as many believe that is a good idea to avoid all “bad” microorganisms.  After all, this is one of the reasons why there are so many vaccines given during childhood these days, and why many people receive the flu shot on an annual basis.  I’m not suggesting that it’s beneficial to get the flu, or serious illnesses such as polio or tetanus.  However, we are going to extremes to avoid exposure to all of these microorganisms, and the hygiene hypothesis suggests that there can be negative consequences of taking this approach.

But why are we not being exposed to as many microorganisms?  Well, there are a few reasons for this:

1. We spend too much time indoors and not enough time in our environment.  This is true with both children and adults.  As a child I didn’t have access to all of the electronics that are available these days, and so I frequently went outside to play with my friends.  These days many children spend too much time on electronic devices (i.e. computers, video game systems, IPads, etc.), and not enough time exploring the environment.  On average, adults are spending more and more time indoors as well.  After all, who needs to go out and socialize when you can simply login to Facebook or chat with someone through Skype?

2. We are becoming too sanitary.  Widespread access to clean water, soap, and chemicals to aid in cleaning dates back to the end of the 19th century (2), and so this is unlikely to be a big factor in the development of autoimmunity.  But one thing that has changed greatly is the use of hand sanitizers.  For example, when I was a child there wasn’t the widespread use of hand sanitizers as there is today.  And while soap was available, chemicals such as Triclosan weren’t in all of the soaps like they are these days.  Not too long ago I wrote a blog post entitled “Hand Sanitizer, Triclosan, and Thyroid Health“.  Triclosan is commonly used in soaps and hand sanitizers, and while the post focused on some of the health risks associated with this chemical, perhaps the main concern is that overuse of this will lead to a decreased exposure to microorganisms, which in turn can have a negative effect on our immune system health.

3. The birth process.  Most births take place in a hospital setting, and frequently the baby is bathed too soon. Babies are born covered in a white substance called vernix, and this is a protective material that helps to prevent common infections.  So while this blog post has focused on how we should be exposed to a greater number of microorganisms, in this situation you want to delay bathing a newborn due to the antimicrobial properties of the vernix (3).  This is why some hospitals enforce “delayed bathing.

The increase in Cesarean deliveries can also play a role in the development of autoimmunity related to the hygiene hypothesis (4).  The reason for this is because being born via a C-section can potentially lead to a change in long term colonization of the developing intestinal tract, which in turn can alter the development of the immune system (4).  Approximately one third of births in the United States are through cesarean delivery.  And while some of these are necessary, many others are due to maternal request.

4. Vaccines.  I’m not going to go into much detail about the controversy behind vaccines, but many more vaccines are given these days than in the past, which further reduces the chances of children and teenagers getting infections.  I realize that some of these infections can be life-threatening, and everything of course comes down to risks vs. benefits.  While it’s understandable for parents to be concerned about their children developing certain infections, they also should be concerned about the risks associated with vaccines as well, not only as they relate to the hygiene hypothesis, but also the additives included in them.  According to the Center for Disease Control (who is in favor of vaccines), some of the common substances found in vaccines include aluminum, antibiotics, formaldehyde, monosodium glutamine (MSG), and thimerosal (5).

So What Can You Do?

If the hygiene hypothesis is one of the factors responsible for the increase in autoimmunity over the last few decades, then what can be done to help prevent the development of autoimmune conditions?  Here are a few suggestions:

Eat some dirt.  Okay, so you probably won’t eat dirt, but I definitely would try to spend more time outdoors.  This admittedly is something I need to do more of, as without question I spend too much time indoors.

Use more natural soaps and avoid soaps and hand sanitizers with Triclosan.  If you frequently use antimicrobial soaps and hand sanitizers then I would encourage you to switch to more natural products.  There are plenty of natural options with regards to soaps and hand sanitizers, including essential oils.

Sleep with your pet.  If you have a dog or a cat that spends times outside then consider inviting him or her into your bed at night.  This is especially true if you don’t spend much time outdoors.

Be cautious about taking antibiotics, and educate yourself about vaccinations.  Once again, I’m not going to get into the vaccine controversy, but I will recommend to educate yourself about vaccines, especially if you have young children, or are planning on having children.  Even if you are in favor of vaccinations, consider spacing them out.

Read Dr. Axe’s book.  I’m not getting anything for promoting Dr. Axe’s book, but I do think it’s worth reading, or listening to on Audible like I did.

In summary, the hygiene hypothesis suggests that autoimmune conditions such as Graves’ Disease and Hashimoto’s Thyroiditis might be more common due to a decreased exposure to microorganisms.  Some of the reasons behind this decreased exposure includes not spending as much time outdoors, using too many chemically-laden soaps and hand sanitizers, the birth process, and too many vaccines.  So while there are many factors that can lead to the development of an autoimmune condition, with regards to the hygiene hypothesis, some of the things we can do to help prevent the development of autoimmunity include spending more times outdoors, using less soaps and hand sanitizers with Triclosan, sleeping with your pet, and being cautious about taking antibiotics and vaccines.