Have you ever taken a supplement because your genetics suggested you needed it, only to find that you actually felt worse?
This is something I’ve encountered repeatedly in clinical practice, and it raises an important question: What if the problem isn’t the supplement itself, but the environment in which that supplement is being used?
When we look at genetics, methylation, neurotransmitter metabolism, gut function, and environmental exposures separately, we can miss how interconnected these systems really are. A patient may have a genetic pattern that suggests they would benefit from supporting a particular pathway, but if there is another problem interfering with that pathway, pushing it harder may not produce the response we expect.
In one recent case, this distinction became particularly clear.
Genetics Are Only One Piece of the Puzzle
The patient had developed significant insomnia and had lost approximately 40 pounds without being able to regain the weight. His symptoms began after a bout of food poisoning, and further evaluation revealed severe SIBO (small intestinal bacterial overgrowth), a condition in which excessive amounts of bacteria are present in the small intestine. Testing also showed markedly elevated catecholamines, a group of hormones and neurotransmitters that includes dopamine, norepinephrine, and epinephrine and plays an important role in the body’s stress response.
What interested me was that his biochemical picture didn’t simply suggest that he needed more support. Instead, it suggested that something was interfering with how his body was processing what it was already producing. This is an important distinction. Genetic testing can tell us a great deal about how someone may be predisposed to process nutrients and biochemical compounds, but genes don’t exist in a vacuum. What a person’s body is doing today can be influenced by gut health, environmental exposures, nutrient status, and many other factors.
That’s why I don’t like to look at a genetic result and immediately conclude, “This person needs more of X.” I want to understand the entire pathway. One of the tools I use to get a better picture of what is happening in these interconnected pathways is the Organic Acid Test (OAT), which can provide information about gut function, nutrient metabolism, and other biochemical processes. I discuss this testing approach in more detail in my previous article here: Organic Acid Test – An Essential Tool for Gut-Methylation Problems.
The Problem With Simply Pushing a Pathway
One of the concepts I use to explain this is the difference between production and clearance. Think about a sink. You have water coming into the sink through the faucet, and you have a drain that is responsible for getting the water out. If the faucet is running normally and the drain is functioning properly, everything stays in balance. But what happens if you turn the faucet up while the drain isn’t capable of keeping up? The sink starts to fill.
I think about biochemical pathways in a similar way. We can sometimes focus so heavily on increasing production or supporting a particular pathway that we forget to ask whether the body has the capacity to appropriately process what is being produced. That’s particularly important when we’re dealing with neurotransmitters.
When Dopamine Becomes Part of the Problem
In this patient, dopamine was extremely elevated. At the same time, the downstream conversion of dopamine toward norepinephrine and epinephrine appeared to be impaired. In other words, the system seemed to be getting driven toward dopamine, but the pathway wasn’t efficiently moving beyond that point.
This helps explain why simply adding more methylation or dopamine support isn’t always the answer. If we continue turning up the faucet without addressing the drain, we’re not necessarily solving the problem. We may simply be increasing the amount of material that has to be processed downstream. In a patient who is already experiencing significant insomnia and elevated catecholamines, that’s an important consideration.
What Does the Gut Have to Do With It?
This is where the patient’s history became particularly relevant. His symptoms began after food poisoning, and he subsequently developed severe SIBO, or small intestinal bacterial overgrowth. SIBO occurs when excessive amounts of bacteria are present in the small intestine, where they can interfere with normal digestion and create a variety of downstream effects. In my experience, SIBO can be associated with much more than digestive symptoms. It can affect energy, sleep, mood, and the body’s ability to properly process nutrients and other compounds.
When I see a case like this, I don’t want to think about the gut and the brain as completely separate systems. The gut can generate a tremendous amount of metabolic activity, and bacterial byproducts can place additional demands on the body’s ability to process and clear compounds. This is one reason why I believe it is important to look beyond simply trying to eliminate the excess bacteria and instead consider why the gut environment allowed the overgrowth to develop in the first place.
I’ve written more extensively about this approach in my previous article, Solving SIBO: 5 Strategies to Prevent and Eliminate SIBO Naturally, which includes an informative video where I explain the underlying factors that contribute to SIBO and discuss strategies for supporting a healthier gut environment. In that video, I discuss why addressing the function of the stomach, gallbladder, pancreas, and intestines can be an important part of addressing SIBO rather than focusing solely on eliminating the excess bacteria.
The gut can generate a tremendous amount of metabolic activity. Bacterial byproducts, including compounds called phenols, can place additional demands on the body’s ability to process and clear compounds. Phenols are chemicals that can be produced during the breakdown of certain foods and other substances, including through bacterial activity in the gut. When I see elevated levels in the context of other clinical findings, I want to consider whether the gut may be contributing to the overall metabolic burden.
This is one reason I became interested in looking more closely at what the gut and its bacteria may be producing and how those compounds could be affecting the body’s ability to process other substances.
I’ve had patients who were taking supplements that, based on their genetics, should theoretically have been helpful—but they were getting worse instead. That forced me to ask a different question: What if we’re trying to support a pathway while something else is interfering with it?
When a Patient Gets Worse, Pay Attention
I think an unexpected response to treatment is clinically meaningful. If a patient takes an intervention and feels worse, the answer isn’t necessarily to conclude that the supplement is “bad.” But I also don’t think we should automatically increase the dose, add another supplement, or simply push forward because the intervention theoretically makes sense.
Instead, I want to step back and ask what the intervention was supposed to accomplish, what happens to the compound after it is produced, and whether the downstream pathways can keep up. I also want to consider what is happening in the gut and whether environmental factors could be contributing. Perhaps most importantly, I want to ask: What might be getting in the way?
In this particular case, the patient’s gut dysfunction, elevated phenols, neurotransmitter abnormalities, and insomnia all needed to be considered together rather than as isolated findings.
The Bigger Clinical Lesson
This case is a good reminder that biochemical pathways don’t operate independently. It’s tempting to look at a genetic result and say, “This pathway isn’t working well, so let’s support it.” But sometimes the more important question is why that pathway isn’t functioning properly in the first place.
A genetic variant may tell us something about a person’s potential vulnerability. It doesn’t necessarily tell us what is happening physiologically at this moment. That’s why I believe we need to look beyond the obvious intervention.
If someone is taking the “right” supplements but isn’t improving—or is actually getting worse—that response should make us curious. Sometimes the answer isn’t that we need to add more. Sometimes we need to find the reason the body can’t appropriately process what we’re already giving it.
In complex cases, the unexpected response may be one of the most valuable clues we have.
The goal isn’t simply to push a biochemical pathway harder. The goal is to understand the entire system well enough to determine what is getting in the way of normal function.
Looking for Personalized Support?
If you’re struggling with persistent digestive issues, sleep problems, fatigue, or other symptoms that haven’t improved despite doing all the “right” things, I can help you look deeper.
At Red Mountain Natural Medicine in Boise, Idaho, I work with patients to identify underlying factors involving gut health, genetics, methylation, nutrition, environmental exposures, and other areas that may be affecting their health.
I see patients both in person and via telemedicine. To learn more or schedule a consultation, visit Red Mountain Natural Medicine.
