Lactoferrin in stool: what the test means

What is lactoferrin in stool, and is some of it normal?

It is a protein your own white blood cells carry, and everybody has a little of it in their stool. Lactoferrin is stored inside neutrophils, a type of white blood cell your body sends to deal with irritation and infection. Some of those cells break open in the lining of your gut as part of ordinary turnover, and what they were carrying leaves with stool. What a test measures is how much.

That is why a normal result is a band rather than a zero. Labcorp's quantitative test puts baseline at 0.0 to 7.2 µg of lactoferrin per gram of stool, so a measurable amount sits inside the printed reference interval. TECHLAB, which makes the ELISA kit several labs run, measured 55 healthy volunteers at an average of 1.55 µg/g, and 31 people with irritable bowel syndrome at 1.27. Both groups came in well under the cutoff without coming in at nothing.

A breastfed baby is a different case entirely

Breast milk is rich in human lactoferrin, so a nursing baby's stool carries what arrived in the milk rather than what came off the gut wall. The amounts are nowhere near an adult's. One study measured 48 mother and baby pairs at birth and again at one month. In the 34 full-term babies, fecal lactoferrin averaged 994 µg/mL at birth and 3,052 µg/mL at a month. In the 14 preterm babies it reached 7,633 µg/mL at a month. The authors recorded this as higher than the published amounts for healthy children and adults, and all of these babies were healthy. Among the term babies, how much was in the stool at a month tracked how much was in the mother's mature milk.

Two limits on those figures. They are micrograms per milliliter where Labcorp's 7.2 cutoff is micrograms per gram, so the two cannot be read against each other. And every standard deviation was larger than its own average, so one baby differed enormously from the next. What the study establishes is the size and the direction of the gap, not a figure for any individual baby.

TECHLAB tells labs not to run its test on samples from breastfed infants at all, and Labcorp warns of the same false positive in anyone taking a human lactoferrin supplement. Those figures are what that caution looks like as numbers. The assay cannot tell lactoferrin that came out of your own cells from lactoferrin that came in through your mouth. If the baby is on formula instead, that is a separate question, and the page on lactoferrin in baby formula covers what the label does and does not say.

Why this test exists

A small baseline is useful because the amount climbs steeply when many more neutrophils arrive. Inflammation draws them into the lining of your intestine, more of them break open there, and more of what they were carrying reaches stool.

So the test is not looking for lactoferrin because lactoferrin is a problem. It is using lactoferrin as a tracer for white blood cell activity in your gut.

How the sample is collected, and how long the result takes

You collect a stool sample at home in a container the lab provides, and then you wait somewhere between two days and about a week. Which end of that range you get depends on whether your lab runs the yes-or-no version or the one that returns a number.

That gap surprises people. ARUP runs its qualitative test every day of the week and reports it in 1 to 2 days. Labcorp's quantitative test takes 4 to 8 days. Neither lab's test page lists any fasting or diet preparation beforehand.

One detail in Labcorp's instructions is worth reading if the reason you are being tested is diarrhea: loose and watery stools are acceptable. You do not need to wait for a firmer sample. TECHLAB, which makes the ELISA kit several labs run, checked this directly and found no difference in results between liquid, semi-solid and solid specimens.

A few things get a sample rejected, which means collecting a second one. Labcorp will not run a specimen that is not stool, that has urine in it, or that has been sitting in a preservative, naming formalin, sodium acetate formalin and polyvinyl alcohol. It also asks you to keep toilet tissue out of the container and not to overfill it. ARUP rejects anything sent in transport media.

The two billing codes are different because they are two different tests, and that is the number to quote if you are checking what your insurer covers.

What a positive result narrows down

Its most common use is telling inflammatory bowel conditions apart from irritable bowel syndrome. Both cause pain, urgency and disrupted bowel habits, and from the outside they can look similar. Inflammatory conditions involve actual inflammation of the bowel wall. IBS, for all the misery it causes, generally does not.

A positive result pushes toward the inflammatory side, which usually means more investigation. If that is the result you have, read what a positive fecal lactoferrin result means next. A negative result is often the more immediately useful of the two, because it can spare someone a colonoscopy.

What the guidelines say about it

The American College of Gastroenterology tells doctors to check either fecal calprotectin or fecal lactoferrin, alongside a C-reactive protein blood test, when someone has suspected IBS with diarrhea and no alarm features, specifically to rule out inflammatory bowel disease. So the test is doing a recognized job, and that is the job it is doing for you.

There is a detail in that guideline worth knowing, because most sites leave it out. The recommendation is rated strong either way, but the quality of evidence behind it differs by which marker is used: moderate for calprotectin and C-reactive protein, and very low for fecal lactoferrin. Calprotectin is simply the better-studied of the two.

That does not make your result meaningless. It does mean a lactoferrin result is a prompt to look further rather than a verdict, and it is one reason your doctor may want a different test as well.

Lactoferrin vs calprotectin: two tests for one question

Both tests look for inflammation in your intestines, and both do it by measuring a protein that white blood cells leave behind. Calprotectin is the one the guidelines attach numbers to, and a lactoferrin test is still doing a recognized job. The one thing you cannot do is compare the two results, because they are different proteins measured on different scales, and a lactoferrin number means nothing read against a calprotectin range.

The practical differences show up most clearly at a single lab, because ARUP runs both. The sample you collect is the same, down to the vial. What changes is the information that comes back.

The first row is the one that changes your experience of the result. ARUP's lactoferrin test answers yes or no. Its calprotectin test gives you a number, two cutoffs and a defined middle ground, and it tells the doctor to re-check a borderline result in 4 to 6 weeks. Lactoferrin has no borderline band anywhere in its reference interval, so there is no printed advice for a result that sits close to the line.

Check the room temperature row before you collect anything. A calprotectin sample is not accepted after sitting at room temperature, where a lactoferrin sample keeps for two weeks at any of the three. If you are mailing a calprotectin sample back, keeping it cold is part of the test.

Labcorp runs quantitative versions of both, and its turnaround times run the other way around from ARUP's: 4 to 8 days for lactoferrin, test 123016, against 4 to 5 days for calprotectin, test 123255. Labcorp describes its calprotectin test as an aid to diagnosing inflammatory bowel disease and to telling it apart from irritable bowel syndrome alongside other clinical and laboratory findings, which is the job the ACG guideline gives both markers.

Labcorp also prints the same three bands for calprotectin that ARUP does: normal from under 5 up to 50 µg/g, borderline above 50 and up to 120, abnormal above 120. A borderline result gets the same instruction, re-evaluate in 4 to 6 weeks. Two labs running different assays arrived at the same middle ground and the same waiting period, so the borderline band is something the marker has rather than one lab's house style. Lactoferrin's lack of one works the same way. Neither lab prints a borderline range for it at all.

Why your doctor may have picked one

Often it comes down to what the lab runs and what the ordering system offers, and the choice belongs to the clinician either way. Where the published evidence does separate the two, it favors calprotectin.

When researchers pooled the studies on telling IBS apart from inflammatory bowel disease, the gap showed up as a count. They screened 140 articles covering four markers. Eight calprotectin studies met their inclusion standards and two lactoferrin studies did. In that analysis a calprotectin result of 40 µg/g or less put the probability of inflammatory bowel disease at 1% or under, and lactoferrin on its own was judged to be of little clinical use for the same task.

The same analysis carries a finding that cuts against both markers. None of the four tests reliably told people who had IBS apart from healthy controls. These are inflammation detectors, and IBS generally does not involve inflammation of the bowel wall, so a normal result on either marker is ruling something out rather than naming what you do have.

The American Gastroenterological Association's ulcerative colitis guideline shows the same asymmetry in a sharper form, and the page on high lactoferrin in stool sets it out: the panel put a numeric threshold in its calprotectin recommendations and set none at all for lactoferrin.

If you are checking what your insurer covers, quote the billing code rather than the name. The two markers bill separately, CPT 83630 or 83631 for lactoferrin depending on which version your lab runs, and CPT 83993 for calprotectin.

What it does not tell you

It does not name a condition. Inflammation has many causes, including infections and some medications, and the test cannot tell them apart. For the full list of what causes positive lactoferrin in stool, including what a Clostridioides difficile infection does to the number, see the page on positive results.

It does not measure how bad things are in any way you can read off the number yourself. On what high lactoferrin in stool does and does not say about how serious a condition is, including why the American Gastroenterological Association sets no threshold for this marker, see the page on positive results. What your report looks like depends on which version of the test your lab ran, and the next section covers that.

It is not a cancer screen. If that was your first thought on seeing the result, it is an understandable one, and it is not what this test is for.

What counts as a normal range

That depends on which of the two tests you had, and they produce very different reports.

A quantitative test gives you a number: micrograms of lactoferrin per gram of stool, written µg/g. Labcorp's fecal lactoferrin test, number 123016, sets baseline at 0.0 to 7.2 µg/g and calls anything above 7.2 elevated. The cutoff comes from the assay itself. TECHLAB, which makes the ELISA kit, puts baseline at 0 to 7.24 µg/g and elevated at 7.25 and up.

A qualitative test gives you no number at all. ARUP runs its fecal lactoferrin ELISA as a yes or no, and the reference interval printed on the report is the single word "Negative".

Same protein, same idea, two different reports. Only the numbers can be compared with anyone else's, and only when both came from the same lab running the same assay.

How far above the cutoff results run

TECHLAB measured 235 people while validating its kit. These are the group averages it published.

The top two rows are the ordinary baseline this page opened with. Active disease is the part worth looking at here: it averaged in the hundreds and thousands, two and three orders of magnitude above the healthy groups, and inactive disease sat between the two.

Read those as group averages and nothing more. The standard errors are large because the spread inside each group was large, so this is not a scale you can slide your own number onto. Where yours sits is a question for the doctor who ordered the test.

Why the same sample can give two different numbers

TECHLAB ran nine positive stool samples repeatedly over three days. Between runs the results varied by 12.0% to 47.7%, averaging 33.5%. Within a single run, by 7.9% to 16.0%, averaging 12.0%.

Your number is an estimate with real room around it. A result sitting a little over the cutoff is best read as a little over the cutoff, not as a precise quantity.

Things that move the result for reasons unrelated to your gut

Labcorp lists several, and two of them matter if you take a supplement. Bovine lactoferrin, the kind in dairy products, is a different protein from the human version and the assay does not detect it. Human lactoferrin is another matter: Labcorp says someone taking a human lactoferrin supplement carries a risk of a false positive. Check which kind is on your lactoferrin supplement label, and tell whoever ordered the test that you take one.

Nursing babies are in the same position, and the figures are startling enough that they have their own section above: see what lactoferrin in stool is for how much of it a healthy breastfed baby produces.

Labcorp adds one more: a low neutrophil count can push a result down, since the test measures what those cells release.

How accurate is the test?

In the study TECHLAB ran to validate its kit, the test found about 4 in 5 people whose inflammatory bowel disease was active, and read baseline for about 24 in 25 of the comparison group. The thing those figures were checked against matters as much as the figures, and most pages that quote them leave it out: the comparison was a scored clinical assessment, not a camera.

Those four cells are where the published percentages come from, and each one answers a different question:

• Sensitivity, 81.5%. Of the people counted as having active disease, this share tested elevated. Seventeen of them did not.
• Specificity, 96.5%. Of the comparison group, this share tested baseline. Three did not.
• Positive predictive value, 96.2%. Of everyone whose test came back elevated, this share was from the active disease group.
• Negative predictive value, 83.0%. Of everyone whose test came back baseline, this share was from the comparison group.

The two that matter to you are the bottom pair, because they run in the direction you are reading: you have a result and you want to know what it says about you. An elevated result was right nearly every time. A baseline result was right about 5 times in 6, so a negative is the weaker of the two answers here. Both of those depend on how much active disease was in the group being tested, and here it was about half of them. Test a group with less active disease in it than that, and a positive result is right less often than 96.2%.

Now the part that limits all four. The study ran at three sites in 180 patients with IBS or inflammatory bowel disease, against 56 healthy people. Active disease was defined by the Harvey Bradshaw Activity Index, a scored clinical assessment, at 4 or more. The test was graded against how a patient was judged to be doing, not against what an endoscope saw. The insert's own counts do not quite reconcile either: the study is described as 180 patients and 56 healthy people, while the accuracy table covers 178.

One line in the same document argues against reading those three elevated results as plain errors. TECHLAB reports that a significant number of patients the index scored as inactive had elevated fecal lactoferrin, which it takes as inflammation the score did not catch. If that is right, part of what counts as a false positive here is the test seeing something the comparison standard missed. An accuracy figure is never better than the thing it was checked against.

What the test does not pick up by mistake

TECHLAB grew more than 40 kinds of gut organism to high density, at or above 100 million bacteria per milliliter of broth, and ran them through the assay. None of them reacted, and the list includes C. difficile, Salmonella, Shigella, Campylobacter jejuni and E. coli. So a positive result is not the lab picking up the bacteria themselves. It is picking up a protein your own white blood cells left behind, which is the same thing whatever started the inflammation.

TECHLAB states the limit on its own test plainly, and it is worth quoting because it comes from the company with the most to gain from overstating it. A lactoferrin concentration should not be treated as absolute evidence that a gastrointestinal illness is present, and whether disease is active or inactive should rest on a complete clinical evaluation, which may include more than one lactoferrin measurement. The firm that makes the kit is telling whoever reads your report not to read it on its own. That is the same answer this page gives you: your result belongs with your symptoms, your history and the doctor who ordered it.

What usually happens next

Typically a conversation, then possibly more tests. Depending on your symptoms and history, that can mean blood tests, stool cultures to rule out infection, or referral for a camera test to look at the bowel directly and take samples.

Bring the actual report to the appointment, including the number and the units, because the reference range depends on which test the lab ran.