The Lactulose Mannitol Test: Pros and Cons of Leaky Gut Testing

Interested in being tested for a leaky gut? A lactulose mannitol test is likely your best option. Here, Hannah, one of our resident nutrition experts, breaks down exactly what this test is, how it works, and when you should consider taking it!

Lactulose mannitol tests have gained popularity in the last decade as we have become more accepting of testing for gut disorders.

Let’s break down what the lactulose mannitol test is, how to carry it out, where to find it, and what, exactly, it tells you about your gut.

What is Leaky Gut?

“Leaky gut” refers to excessive intestinal permeability.  

Simply put, in a healthy gut, intestinal permeability is the ability of your gut wall to regulate which molecules leave your intestines.

It is like border security.  It decides if a molecule has the correct credentials to leave the gut.  Each cell along your gut wall has a junction, like a barrier arm at a toll booth, opening and closing for the right molecules to pass through.

However, if your gut is not properly looked after (if the toll booths are not maintained) you start getting gaps.  Through these gaps substances such as bacteria and toxins can slip past “border security” and into your body. 

This alerts your immune system (the equivalent of the border police in my analogy, here).  Your activated immune system starts causing inflammation in the area, leading to a whole host of symptoms.  (I’ll discuss these in detail in a bit!)

Leaky Gut: Symptom or Disease?

It is important to note here that “leaky gut” is not a recognized medical condition.

In fact, it has been the victim of an ugly debate in the medical and scientific community for a while now.  

As recently as five years ago, a large percentage of the medical community argued that “leaky gut” was a completely made-up condition.

Today, the discussion has moved on ever so slightly.  Many (if not most) doctors and researchers agree “leaky gut” exists.  Now, there is a debate as to whether it is a symptom or a cause of disease. 

What does this mean?

Well, it means the whole thing is a bit of a scientific “chicken-or-egg” situation. 

Many scientific studies show that people with undiagnosed digestive conditions and those who are in relapse for chronic diseases are more likely to test positive for the leaky gut than those whose conditions are under control.  This has led some researchers to suspect that leaky gut is a symptom of these conditions not being managed.  They think the gut conditions are causing damage to the gut lining, leading to increased intestinal permeability, and then to a leaky gut.

Others argue that “leaky gut” is a condition in-and-of-itself.  Researchers in this camp suspect that the toxins allowed to move through a leaky gut cause digestive disorders to develop in the first place.

Let’s look at an example: celiac disease.

Those in the “it is a symptom” camp would say that eating gluten produces a chain of reactions which degrade the gut lining.  This leads to your gut becoming leaky which, in turn, leads to inflammation and the symptoms of gluten intolerance.

Those in the “it is a cause” camp would argue that leaky gut is a stand-alone condition that develops first.  It lets gluten, a normally harmless substance, into your body where it doesn’t belong. This causes your body to react to gluten as if it were harmful, leading to an inflammatory response and the symptoms of gluten intolerance. 

In both cases, the result is the same — you do not feel at all well after eating gluten because of inflammation caused by a leaky gut.  It’s just a question of whether the leaky gut came first or second.

We explored the debate around how leaky gut in great detail in our article “Is Leaky Gut Real?”.  If you want a deep dive, take a look.

Read Next: Top 5 Best Butyrate Supplements for Leaky Gut Cure

What Symptoms Suggest You Should Test for Leaky Gut?

If you are reading this, there is a good chance you already have some uncomfortable symptoms whose cause(s) you’d really like to get to the bottom of.  

Here are some reasons to suspect leaky gut could be part of your problem:

• bloating 
• gas
• constipation
• diarrhea 
• acne
• fatigue
• weight gain
• mood swings
• difficulty concentrating

If you’ve had a leaky gut for a long time, you may also have developed more serious conditions, such as:

• metabolic syndrome
• Alzheimer’s disease or dementia
• anxiety
• depression
• Parkinson’s disease

Finally, a leaky gut could potentially be an underlying factor in the development of autoimmune disorders, such as:

• Crohn’s disease 
• celiac disease
• type 1 diabetes
• autoimmune thyroid conditions

What is the Best Test for a Leaky Gut?

While I’m focusing on the lactulose mannitol test here, it’s important to mention that it is not the only leaky gut test available.  There are a few other tests that you may wish to try in addition to or instead of the lactulose mannitol test. 

Let’s take a look at other ways to potentially test for leaky gut.

Zonulin Testing

Zonulin is a protein which regulates the flow of molecules and nutrients out of the gut.  When zonulin levels rise in your blood (i.e. zonulin is in your blood, rather than in your intestinal wall where they should be), more substances are allowed through the walls of your small intestine.

So, scientists have hypothesized that testing zonulin levels might tell you how tight or leaky the junctions between the cells in your small intestine.

There are two potential ways to do this:

• a zonulin blood test
• a zonulin antibody test

Zonulin Blood Test

Here, your doctor draws blood and directly test the levels of zonulin.  High levels in the blood may suggest a leaky gut.

Unfortunately, direct zonulin blood tests might not always be completely accurate. 

This is because when you have zonulin in your bloodstream your body is very good at recognizing it and sending out an immune response to clean it up.  This means that sometimes zonulin levels in the blood can look “normal”, even though there are issues with intestinal permeability. 

Zonulin Antibody Test

One way to get around the instability of zonulin is to test for antibodies your body made to remove it from your blood.

A high number of zonulin antibodies in your body means your immune system’s been busy bringing zonulin levels down.  That is, of course, a good sign your zonulin levels have been too high!  

And as an added bonus, antibodies are a lot more stable than zonulin.  So, they stick around in your blood longer and are easier to pick up with a blood test, in general! 

Though this test sounds great in theory, there have been worrying studies which found major faults with some of the testing kits.  The studies showed that the kits weren’t able to tell the difference between zonulin and other proteins properly. 

Caution has been urged when using this method.

Related: The Best Microbiome Testing Companies: Gut Testing Made Easy

SIBO Testing

An SIBO test is a very indirect way of testing for a leaky gut. 

Rather than testing for a leaky gut itself, an SIBO test looks for small intestine bacterial overgrowth (SIBO) — an excess growth of bacteria in your small intestine.

Since SIBO and leaky gut are thought to go hand-in-hand, some health practitioners find testing for SIBO means testing for leaky gut at the same time.

And testing for SIBO has at least one serious advantage over testing for leaky gut directly: doctors know how to treat SIBO.  Eating a special type of diet (the FODMAP diet) has been proven to relieve symptoms and help clear up the bacterial overgrowth. 

So, it can be argued that an SIBO diagnosis is more useful than a leaky gut diagnosis because leaky gut has no specific “cure” (yet, at least).

The two avenues for this test are via:

• a stool test
• a breath test

SIBO Stool Test

A sample of your stool can be used to see if your gut microbiome (the teeny tiny bacteria living in your intestines and colon) are multiplying unhealthily.  By looking at the bacteria in your stool, doctors can analyze both the types of bacteria in your gut and whether they are at healthy levels. Abnormal test results can identify SIBO and, likely, a leaky gut. 

SIBO Breath Test

Rather than looking at the bacteria in your intestines directly, an SIBO breath test analyzes the gases produced by these bacteria living in your gut.  These gases make it to your lungs and exit your body when you exhale. If the gases in your exhaled breath are imbalanced, it is a good indication that you have SIBO and a leaky gut.  

Unfortunately, it takes quite a bit of skill to interpret the results of an SIBO breath test, so there is a high degree of false readings. 

Lactulose Mannitol Test

The lactulose mannitol test is the current gold standard of testing for leaky gut (which is why I’m covering it here!).  It is non-invasive, it’s results are accurate and easy to interpret, and it’s relatively inexpensive to carry out.

Let’s look at why it works and how to interpret the results.

How Does the Lactulose Mannitol Test Work? 

The theory behind the lactulose mannitol test is that, if you have a leaky gut, large lactulose molecules (a type of sugar) are able to pass through the gaps and get into your body.

To get the lactulose back out of your body, your blood dumps it into your urine.  You can then simply test your urine to see how much lactulose made it out of your intestine and into your body. 

By comparing the amount of lactulose to what “normally” makes it through, doctors can tell if your gut is letting through more than usual — i.e. “is leaky”.

The other half of this test is mannitol, another sugar molecule, which acts as a “control”.

Mannitol is a much, much smaller than lactulose.  It gets VIP access through your gut wall, straight into your body. 

Because you absorb mannitol so well, it tells your doctor about the health of your digestive tract, in general.  By seeing how much mannitol you absorb and how quickly, your doctor can see if food is moving through your gut normally and how well it’s absorbing nutrients, in general.

How Do You Take the Lactulose Mannitol Test?

The test itself is pretty easy and non-invasive. Here is how it works:

1. You will be asked to fast overnight and through the duration of your test.  This means no food or drink after a certain time starting somewhere between 7 pm and midnight the night before your test and then for the 6 hours you are testing.  Your medical provider or test supplier will let you know exactly what time you need to start fasting.

(Note: make sure to pick a day on which you will be able to fast for 6 straight hours — no scheduled parties or work lunches!)

2. When you wake up the morning of your test, you’ll collect the urine from your first trip to the bathroom.  

3. Next, you’ll drink the sugar solution for your test.  Make sure you finish all of it.

4. While you wait for the sugar to make its way through your intestines, blood, and kidneys, you’ll be asked to drink some plain water (starting 1 hour after you drink the sugar solution).  Typically, it is recommended that you drink at least 1L to make sure you have enough urine for the test to be accurate

5. Over the next 5-6 hours (depending on the test), you’ll either collect all the urine that you pass or you’ll collect a single sample at the 6-hour mark.  This is a great time to binge that Netflix series you’ve been dying to watch because you’re not going anywhere.

6. The test is finally over and you can eat again!  Phew!

Once your urine samples have been processed, you’ll get the results.  Typically, results take about a week to be ready.

What, exactly, do those results look like and how do you interpret them?

What Do the Results of a Lactulose Mannitol Test Mean?

In the results of your lactulose mannitol test, you will usually see three numbers.

1. the lactulose percent or level in your urine
2. the mannitol percent or level in your urine
3. a ratio of the percent of lactulose excreted in the urine to the percent of mannitol in the urine

Your test results will be shown on a graph.  The graph will highlight the “normal” reference range to 1 standard deviation (SD).  This is where 68% of the population would have their levels. 

Then it will show a 2 SD.  This expanded range is where 95% of the population would have their levels. 

If your results fall within 1 SD, it is very likely that you have normal intestinal permeability and digestive function.  

If they are within 2 standard deviations, it is still very likely you have normal permeability and digestive function.  But, if you are in the 2 SD range and are having digestive symptoms a follow-up test would be a solid idea.

If your results fall outside 2 SD, you almost certainly have increased intestinal permeability or other digestive abnormalities.

Note: The exact cutoffs for “normal” levels for each of these numbers will change depending on which laboratory is doing the test.  (There is a push to standardize the results of the lactulose mannitol test but it hasn’t happened yet.)

Result Combinations and Their Meanings

Your results will, of course, be unique to you!  And you must have a doctor or medical professional officially interpret your results for you because your medical history can seriously affect what your numbers actually mean (regardless of where the test company puts them in the SD ranges).

Nevertheless, there are some general combinations of numbers that usually point towards specific digestive diagnoses:

• high lactulose levels suggest you have a leaky gut.
• low or undetectable level of lactulose suggests your gut lining is healthy.
• high mannitol levels indicate your intestines are absorbing nutrients normally. 
• low mannitol levels suggest you may have problems with nutrient absorption or food moving far too slowly through your intestines.
• a high lactulose:mannitol ratio is characteristic of a leaky gut.
• a low lactulose:mannitol ratio suggests both healthy gut permeability and nutrient absorption.

Does the Lactulose Mannitol Test Have Side Effects?

Luckily, the lactulose mannitol test is pretty side effect free.  Diarrhea is the only reported side effect. And it only shows up in a small percent of tests.

How Can You Get a Lactulose Mannitol Test?

Each country has different ways to access a lactulose mannitol test. 

In the United States, there are a couple of major brands which produce test kits, including:  

• BioHealth
• Genova
• Doctors Data

The tests are then available to buy through:

• laboratories 
• online shops
• nutritionists 
• naturopaths
• functional or holistic doctors 

How Much Does a Lactulose Mannitol Test Cost?

The following are links to shops and labs where you can buy lactulose mannitol test kits and their costs.  The costs do not include the fees for interpretation by a health professional or costs of any treatments recommended based on your results. 

• True Health Labs $179
• Holistic Heal $135
• Walk in Lab $195
• Lab Tests Plus $210
• Direct Labs $129-$219 (read kit descriptions carefully as some do not come with the drink solution)

Pros and Cons of Doing a Lactulose Mannitol Test

The pros of a lactulose mannitol test are:

• it is quick and easy to carry out 
• it is relatively inexpensive 
• you can do it in the comfort of your own home
• it is currently the most reliable test and is widely used in clinical applications 
• you get results quickly, typically within about a week
• it provides an excellent way to see if your gut health is improving or worsening over time or with changes in diet or lifestyle

The cons of the lactulose mannitol test are:

• it is not standardized and your results are being compared to what is considered “normal” by the laboratory that created your kit
• your intestinal permeability changes day to day depending on many factors (medications you’ve taken, how your immune system is functioning, what you have eaten, etc), so results from one day may not accurately represent the health of your intestines 
• lactulose, although bigger than mannitol, is still a relatively small molecule making it difficult to know if increased gut permeability shown by the test necessarily means that larger food molecules can also get through into your body
• tests that ask for a single urine sample at the 6-hour mark may not be accurate, as a recent New Zealand study concluded that the best results are actually collected 2 ½ to 4 hours post sugar solution 
• the lactulose mannitol test can’t tell you what is causing your leaky gut, so it isn’t particularly helpful for figuring out a treatment plan moving forward

Take Home Message

The lactulose mannitol test is currently one of the best tools to determine if you have a leaky gut.  It uses the absorption and elimination of two sugars — lactulose and mannitol — in your urine to work out if your gut is absorbing nutrients normally.

While the test can’t give you concrete answers about what is causing your leaky gut (and its miserable symptoms), it does provide valuable information about what type of molecules your intestines are letting into your body, potentially causing inflammation and serious harm.

You should work with your health care provider both to interpret the results of a lactulose mannitol test and to make a plan for treatment moving forward.

Read Next: Top 5 Best Digestive Enzyme Supplements to Fix Leaky Gut