To understand how bacteria mess with our methylation cycle, we need to learn about phenol. Phenols are volatile chemical compounds that come from plants and bacteria. Everyone has phenols in their body; they are a normal part of our gut environment.
Phenols in the gut are also called volatile organic compounds, or VOCs. You’ve likely seen this phrase when shopping for paint or reading about toxins released from petroleum products such as vinyl flooring. It is fascinating to realize that the same chemicals that pollute our external environment are also found in our internal environment. It’s not a question of whether we are exposed to phenols; it is a question of how many toxic phenols we have to deal with. Everyone has a different tolerance to volatile organic compounds, aka organic acids, before symptoms develop. Some phenols, such as resveratrol and green tea catechins, have enormous health benefits. I use these compounds regularly with patients with excellent results. But just because some phenols give us benefits doesn’t mean that all phenols are helpful. In fact, phenols in high amounts can be a big problem for the brain, liver, and methylation cycle in general.
Because they have similar chemical shapes, the phenolic compounds such as those produced by our gut bacteria compete with estrogen, adrenaline, and dopamine for metabolism through the COMT phase II detoxification pathway. By slowing down the COMT pathway, phenols increase the half-life of estrogen and catecholamines, the stress neurotransmitters known as dopamine, norepinephrine, and epinephrine. Therefore, if the imbalanced gut is causing too many phenols to leak into our body, it will slow the clearance of estrogen and stress hormones. I recognize not everyone reading this studies genetics and biochemistry, so all these pathways and chemicals can get a little confusing. So to make these points a little clearer, I’ll explain further.
Estrogens, reproductive hormones, are removed from our body mainly by the gallbladder. Any problem that increases estrogens, such as a gut-phenol issue, will put a lot of stress on the gallbladder as it tries to manage the excess estrogen. We know that high estrogen is a trigger for gallbladder issues to start, which is why women experience the vast majority of gallbladder problems. That is a problem that will develop even without inherited polymorphisms in the COMT, MTHFR, and related pathways. In other words, you don’t have to have problem genes to experience gallbladder issues; all you really need is a gut problem loading up your liver with phenols. That will create the same situation as having a genetic imbalance. And if you happen to have a genetic imbalance as well as a gut phenol problem, your body will truly struggle to create optimum health. The phenols compete with estrogen for detoxification, which causes estrogen levels to build up. In this way, the hormonal system in the body is greatly influenced by the bacteria in the gut. (You will learn more about fascinating connections between hormones and methylation in chapter 12.) I wish phenol problems were limited to messing with hormones, but that would miss another important aspect to this story.
As you are beginning to realize, bacteria aren’t just silent neighbors living in our gut. They can impact not only our hormone levels, as I have just described, but they also change how we tolerate the stress of daily life. These bacterial waste products have the capacity to influence our methylation cycle greatly by inhibiting the breakdown of catecholamines. These bacteria-derived phenol compounds increase the half-life of adrenaline and catecholamines in our bodies. The longer the half-life of a chemical, the longer it will be active. Because gut-based phenols slow the detoxification of catecholamines, they significantly reduce how much stress we can handle. The problem here is that interfering with the detoxification of adrenaline will cause it to build up inside the body. And you don’t need to be a doctor to realize that excess adrenaline is a bad idea. Individuals with this gut-based issue often experience symptoms such as insomnia, anxiety, worry, and chronic pain. I am sure many of you reading this consider these symptoms to be very familiar. Despite changing their diet and taking supplements, many people with phenol issues cannot find relief from symptoms like these without treating the gut-based problem first.
The key point to understand is that phenols are a normal part of the gut environment. Even healthy bacteria produce these chemicals on a daily basis. Recent research has shown that many common species of gut bacteria such as Bifidobacterium, Clostridium difficile (C. diff), Escherichia coli (E. coli), and Lactobacillus produce phenols, leading our bodies to excrete from 50 to 100mg of volatile phenols each day.2 Understand that phenols are a normal part of our gut environment and they always leak into our body to some degree; this is a natural and healthy process and no cause for alarm. Yet when the bacteria get out of hand, the amount of phenols the body must detoxify increases dramatically. Since each phenol molecule from the gut will have to be processed through our methylation and sulfation detoxification pathways, excess gut phenols will have a serious impact on our body’s biochemistry. And the last thing we all need is slowed detoxification and methylation.
To illustrate this concept, we turn to research that is more than 40 years old. In the first study published in 1970, researchers injected benzoic acid (a type of phenol) into mice and measured how much it slowed down the activity of COMT. Incredibly, after injecting phenols into the mice, their liver COMT function slowed by 100 percent for more than 45 minutes.3 In the second study published in 1973, researchers confirmed these findings when they determined that a phenol called pyrogallol also effectively inhibited COMT function inside the body.4 What this scientific research proves is that phenols are capable of interfering with our methylation cycle and detoxification pathways. This is exactly how imbalances in the gut can change genetic responses inside of our body.
As anyone who understands drug metabolism will tell you, if you increase the half-life of a chemical you are going to increase the length of time it will be effective. In other words, if you block the breakdown of adrenaline, dopamine, and estrogen by slowing the COMT pathways, you will create a stronger stress reaction. This will make an individual less tolerant of stress, since each time the body releases adrenaline, it is staying active far longer than normal. All the intolerance to life’s various stressors can be traced back to how the gut bacteria is influencing our genetics.
Because most of you reading this book aren’t scientists or doctors, I think a metaphor can help clarify this idea. If the gut is producing a lot of phenols (during SIBO or other gut infections), the body cannot detox stress hormones and estrogens very well, because the phenols sit in the same parking space in the COMT enzyme as adrenaline, dopamine, and estrogen. High phenol levels from the gut can lead to pain, anxiety, insomnia, fatigue, low thyroid, fibroids, endometriosis, obesity, and more, just by interfering with the COMT pathway and putting excess pressure on other sulfur-based phase II detoxification systems. But that is not all that gut-derived phenols can do.
Phenols are also metabolized through the sulfation pathway, and processing phenols can lower sulfate levels.5 The SULT1A1 and SULT1A2 genes are responsible for taking a toxin, neurotransmitter, bile acid, or hormone, and gluing it to a molecule of sulfate.6 This sulfate transfer is important to phase II detox. All phenols, whether they come from the gut or the diet, must be processed through the SULT pathway in the liver. When phenols are metabolized this way, they will permanently remove sulfate from the body; the more phenols get into the body, the more sulfate is needed to remove them. And as you learned in chapter 5, sulfate is often lacking in people with imbalanced methylation, oxalate problems, and other chronic diseases.
Individuals with SULT SNPs have slower sulfation pathways already, and when phenols from the gut enter their bodies in high amounts, they slow down their phase II sulfur detoxification even more.7 In this way, excessive phenol production from the gut bacteria can greatly impair the body’s detox system, increasing sensitivity to smells, foods, chemicals, and more. The phenol connection to methylation is the idea behind the Feingold Diet for the treatment of autism and other neurological and developmental issues. The end result is that our bodies become progressively dysfunctional as phenols spill from the gut into the liver, aggravating our detoxification and methylation pathways. Even more, as adrenaline levels rise and flare our symptoms, it puts more pressure on the COMT and MAO systems, two pathways that are already genetically slowed in many people.