Glucose vs. Lactulose: A Complete Guide for SIBO Breath Testing
Gut health has quickly become one of the most important and fastest-growing topics in modern medicine. Once overlooked, the gut is now recognized as a central player in everything from digestion and immunity to mood and metabolism. As the spotlight on the importance of gut health continues to grow, new research has emerged and our understanding of gut-related issues continues to evolve. While this progress towards a better understanding of our gut and how it functions (or malfunctions) is great for patients, it can often be difficult to find the answers you need.
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​The purpose of this article is to provide an overview of a specific type of gut malfunction called microbial overgrowth, with a special focus on how you can test for these types of overgrowths from the comfort of your home, and which type of test substrate might be best for you.
What is Breath Testing for Microbial Overgrowth?
Microbial Overgrowth is a general term for conditions where excessive amounts of microbes (tiny microorganisms such as bacteria and archaea) form in your intestines, producing gases that often lead to irritating and debilitating symptoms like bloating, pain, constipation, diarrhea, and bowel habit changes. Studies now indicate that millions of Americans are affected by microbial overgrowths each year, including up to 60-70% of patients suffering from IBS.
Fortunately, breath testing with the Trio-Smart 3-Gas Breath Test provides a straightforward, non-invasive way to detect the most common gases, helping you find possible causes for the gut discomfort you are experiencing. How does this work? After following a special preparation procedure, you drink a provided sugar solution called a “substrate”, which then travels through your gastrointestinal tract. Inside your gut, microbes ferment (break down) the sugars in the solution and release gases like hydrogen, methane, and hydrogen sulfide as by-products. These gases are absorbed into your blood and then exhaled in your breath. By collecting breath samples and measuring the levels of each gas, you can determine whether a microbial overgrowth is present.
Even better, by measuring the specific kind of gas and comparing it against known normal thresholds, your test results can help you and your healthcare providers determine the type of overgrowth you are experiencing:
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SIBO (Small Intestinal Bacterial Overgrowth) refers to an overgrowth of bacteria in the small intestine that produces hydrogen (H2) gas. SIBO is characterized by a variety of potential symptoms including bloating, abdominal pain, gas, indigestion, constipation, and diarrhea, with bloating being the most common symptom. A breath test showing an early rise in hydrogen suggests SIBO.
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IMO (Intestinal Methanogenic Overgrowth) is an overgrowth of archaea (a microbe that is similar to bacteria, but is recognized as a distinct form of life) that produces methane (CH4) gas. The most common symptom of IMO is constipation, and amounts of methane in your breath that are over the known threshold are strongly correlated with the presence of IMO.
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ISO (Intestinal Sulfide Overproduction) is an overproduction of hydrogen sulfide (H2S) gas caused by an overgrowth of bacteria that produce hydrogen sulfide. The most distinctive symptom of ISO is diarrhea, and it is often present in patients diagnosed with diarrhea-predominant IBS.
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For a more detailed description of each type of microbial overgrowth, testing thresholds, and common treatment options, please see our other resources under the SIBO Resources tab at the top of this page.
What Exactly Is this “Substrate” Used in Breath Testing?
One of the keys to successful breath testing is providing those microbes in your gut a solution that they can feed on and ferment. This solution is called a “substrate” which can be generally defined as a material that something else acts on to start a reaction. In this case the substrate provides an abundance of food in the form of a drinkable liquid made of sugars that the microbes are interested in breaking down. As a consequence of this process of breaking down sugars, those three important gases are produced.
There are two common substrates used in breath testing: glucose and lactulose. The goal of both substrates is to produce a successful and accurate breath test, but the sugars in each solution behave somewhat differently in your digestive tract, so their unique properties should be taken into account when choosing which substrate is right for you. Let’s define each substrate and then talk about their pros and cons.
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Glucose is a simple sugar (the same sugar that circulates in your blood as “blood sugar”). Your body absorbs glucose very fast, mostly in the first 2-3 feet of the small intestine. Under normal circumstances little to no glucose reaches the far end of your small intestine or makes its way into your colon.
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Lactulose is a synthetic sugar (made of two smaller sugar molecules) that humans cannot digest. It passes through your entire small intestine and reaches your colon without being absorbed. Because of its properties of not being absorbed in the intestines and its ability to be fermented by bacteria while drawing water into the bowels, it has sometimes been used as a laxative in high doses. But, the dose of lactulose used in breath testing is much smaller and just enough to detect microbial overgrowth without causing the laxative effect.
Glucose and lactulose travel through the gut differently because of the major differences in their rates of absorption, or lack of absorption. Perhaps you are familiar with the fable of the Tortoise and the Hare? The glucose is like the Hare–It jumps out of the gate and starts the race through your digestive tract at full speed. But, since it gets absorbed more quickly in the upper small intestine, it is fermented by microbes and absorbed by your body, so it never reaches the end of your intestines and doesn’t finish the race. Lactulose, on the other hand, is like the Tortoise. It steadily moves through your entire gut and reaches the end without running out of steam. Microbes feed on it all the way through, but because your intestines do not absorb it, much of the substrate is free to complete the journey.
Glucose Pros & Cons
Due to the behavior of glucose as a substrate, there are some advantages and disadvantages to its use, which might influence whether it is the right choice for you. Let’s take a look at each of these.
Advantages of Glucose
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High specificity (low false positives): Since glucose is mostly absorbed before it reaches the colon, it generally does not feed the bacteria that live in your colon. So, it is unlikely to result in a false positive result from normal colonic fermentation. For this reason, a positive glucose test is generally a reliable indicator of SIBO in the upper small intestine.
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Simpler interpretation: A breath test with glucose often produces an obvious early peak of hydrogen if positive. A second later peak due to colonic fermentation is not expected, which can make for clearer results. No rise in hydrogen usually means a reliable negative result, unless you are searching for SIBO in the distal portion of the small intestine. (See disadvantages below)
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Widely available: Glucose breath testing has been performed for quite some time and glucose solutions are usually readily available.
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Taste and consistency are sometimes preferred: Many people find the sweeter taste and thinner consistency of the glucose solution to be easier to drink than lactulose.
Disadvantages of Glucose
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Can miss distal SIBO (false negatives): Because glucose is absorbed so early, if your bacterial overgrowth is located in the distal (farther) end of the small intestine, the glucose may never reach those bacteria. The bacteria at the lower end of your small intestine are not presented with the substrate, so no gas is produced even though you may still have SIBO. As renowned gut expert Dr. Mark Pimentel explains, “Glucose gets absorbed very readily…so if you had overgrowth perhaps more distally in the small bowel, you won’t see it because the glucose will all be absorbed.”
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May not reach the small intestine: It’s somewhat rare, but if someone has extremely slow stomach emptying (gastroparesis) or is on certain medications that cause the substrate to sit in the stomach for too long (like GLP-1) the glucose may be entirely absorbed before reaching the intestines, which could result in a false negative or an inconclusive result.
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Unsuitable for diabetics or those with glucose intolerance: Since glucose can cause a spike in blood sugar, the American College of Gastroenterology guidelines favor using lactulose in patients with diabetes to avoid hyperglycemia. If you have diabetes or are known to have an adverse reaction to glucose, be sure to discuss the choice of substrate with your doctor.
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Dose variability: Due to normal variations in the size and shape of patients and their intestinal tracts, the effective amount of glucose that reaches your small intestine can vary from person to person. For example, a smaller, shorter person may have more glucose delivered to their bacteria than someone who is much larger. Since lactulose is not absorbed in any significant way, this is not an issue.
Lactulose Pros & Cons
Since lactulose is not absorbed in the human body, it has a different set of advantages and disadvantages.
Advantages of Lactulose
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Covers the entire small intestine (higher sensitivity): Lactulose will travel the entire length of your small bowel, potentially uncovering microbial overgrowth even in the far distal end. It casts a wide net, which means fewer false-negatives, even if your overgrowth is highly localized.
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Can more easily detect hydrogen sulfide-producing overgrowth (ISO): Especially if you have diarrhea-predominant IBS (IBS-D) or diarrhea is your most compelling symptom, you will likely want to test for hydrogen sulfide to see if you may have ISO. This can only be done with the Trio-Smart 3-Gas Breath Test, as it is the only breath test on the market that measures H2S levels in your samples. And lactulose is generally the preferred substrate to feed hydrogen sulfide-producing bacteria throughout your gut.
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More diabetic friendly: Since lactulose is not absorbed in your gut, it does not raise your blood glucose levels. This makes it safer for people with diabetes or who need to avoid glucose for health reasons. Research confirms that even a 20-30mg dose of lactulose does not significantly affect blood sugar in type 2 diabetics. So, lactulose is a better choice if glucose could pose health risks for you.
Disadvantages of Lactulose
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Risk of false positives (if not interpreted carefully): Because lactulose will eventually reach the colon and be fermented by normal bacteria, there’s a possibility of a false-positive, since the results might show a rise in gas that isn’t due to an overgrowth, but rather the colon bacteria eating the lactulose earlier than expected. This is especially true if someone has a rapid transit time, meaning food moves very quickly through their system. For patients known to have a very fast transit time, doctors may lean towards a glucose substrate to avoid confusion. Regardless of substrate, it’s important for your healthcare providers to carefully review your results and make sense of them in the context of your specific case.
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Possible discomfort during test: Since lactulose is essentially a fermentable laxative sugar, it can potentially cause more bloating, gas, or cramping during or after the test. The dose is small and only causes mild effects in most people, but it is something to be aware of in highly sensitive individuals. These effects are typically short-lived, however, and are potentially a sign that the substrate is working, as they indicate that fermentation is taking place.
FAQ
Is lactulose safe if I’m lactose intolerant?
In most cases, yes. Lactulose is a different sugar that does not require the lactase enzyme to digest. In fact, no human enzyme breaks it down at all. So, it is generally considered safe for lactose-intolerant patients. If you have a milk allergy (which is distinct from a lactose intolerance) or if you are still concerned, you should always check with your healthcare provider to determine which substrate is better suited to you.
