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Longevity Library · Lab reference

Written by Daniel Tagge, MD
Updated October 23, 2026
Reviewed October 24, 2026
40 sources · Measured in µg/g of stool

System: Gut-Immune Health

Fecal calprotectinFaecal calprotectin · Stool calprotectin · S100A8/A9

Fecal calprotectin is a neutrophil protein that reaches the stool when white cells pour into an inflamed gut. In adults with bowel symptoms it separates inflammatory bowel disease from irritable bowel with a pooled sensitivity of 0.93 and specificity of 0.96, and a value at or under 40 µg/g leaves about a 1 percent chance of inflammatory bowel disease; in people who have the disease it tracks healing and warns of relapse. Anti-inflammatory painkillers, acid suppressants, gut infections, diverticular disease and age all raise it, children run far higher than adults, and no study has asked what a raised value means in a person who feels well.

Calprotectin is the calcium- and zinc-binding protein that makes up a large share of a neutrophil's cytosol; it is stable in stool for days, so a single sample reports how many neutrophils crossed into the bowel. Most assays print under 50 µg/g as normal. The literature is strong for one job, triaging bowel symptoms and monitoring known inflammatory bowel disease, honest about the confounders, and silent about what the number means on a wellness panel in someone without symptoms.

01 · The scale

Where the laboratory range and the evidence sit.

Validated for one question in symptomatic adults, where a low value makes inflammatory bowel disease unlikely and a high one earns a scope, and as a monitor in known disease; raised by painkillers, acid suppressants, infection and age; never studied in people who feel well.

050100150200250300

  1. Healthy adult values in reference studies

    0 to 50 µg/g of stool · Tøn 2000; Joshi 2010 (ages 10 to 59)

  2. Normal on most assays

    0 to 50 µg/g of stool · BSG 2019 (normal defined as under 50)

  3. About a 1 percent chance of inflammatory bowel disease in adults with irritable bowel symptoms

    0 to 40 µg/g of stool · Menees 2015

  4. Borderline: most people here do not have inflammatory bowel disease; repeat before referral

    50 to 150 µg/g of stool · Waugh 2013 (NICE evidence review)

  5. Locally set trigger for colonoscopy in symptomatic adults

    100 to 250 µg/g of stool · BSG 2019

  6. Above 150 in quiet ulcerative colitis: 14 times the relapse risk

    150 and above µg/g of stool · Costa 2005

  7. Above 250 in Crohn's disease: large ulcers more likely; in ulcerative colitis, active mucosa with 100 percent specificity

    250 and above µg/g of stool · D'Haens 2012

  • Laboratory range
  • Evidence supports
  • Guideline goal or unstudied
  • Higher risk in studies
Scale in µg/g of stool. Assays differ (laboratory ELISA, point-of-care devices and several manufacturers' kits), there is no reference standard, and the cutoffs are assay-specific. Papers from the 1990s used an older extraction method and reported mg/L; those figures are not interchangeable with today's µg/g. Bands show where studies found something, not a recommendation for any one person.

02 · What it is

What Fecal calprotectin measures.

Calprotectin is a calcium- and zinc-binding protein of the S100 family, a heterodimer of the subunits S100A8 and S100A9, found mainly in neutrophils, where it accounts for a large share of the protein in the cytosol (estimates run from about 45 to 60 percent), and at lower concentrations in monocytes and macrophages. When the gut wall is inflamed, neutrophils migrate from the blood into the mucosa and part of them cross into the lumen; the calprotectin they carry is excreted in stool, and the stool concentration correlates with the number of neutrophils in the lumen.1,2,3Grade C

Its validated job is to sort bowel symptoms. In a meta-analysis of 13 prospective studies in patients with suspected inflammatory bowel disease, six in adults (670 people, disease confirmed by endoscopy in 32 percent) and seven in children and teenagers (371), the pooled sensitivity and specificity were 0.93 and 0.96 in adults and 0.92 and 0.76 in children. Screening with the test would cut the number of adults needing endoscopy by 67 percent, at the cost of a delayed diagnosis in the 6 percent with a false negative. English guidance has recommended it since 2013 as an option for adults with recent-onset lower bowel symptoms in whom cancer is not suspected, and the 2021 American irritable bowel guideline suggests checking it in suspected irritable bowel with diarrhea to rule out inflammatory bowel disease.4,5,6Grade A

Its second job is to watch inflammatory bowel disease once it is diagnosed. Pooling 19 studies of 2,499 symptomatic patients against endoscopy, calprotectin detected active disease with a sensitivity of 0.88 and specificity of 0.73, against 0.49 and 0.92 for blood C-reactive protein, and it was more sensitive in ulcerative colitis than in Crohn's disease. In 13 studies of 744 people with ulcerative colitis and 727 with Crohn's disease, the area under the curve for active disease against remission was 0.89; at a 50 µg/g cutoff sensitivity was 0.92 and specificity 0.60, at 250 µg/g 0.80 and 0.82. The 2021 international treat-to-target consensus names normalization of fecal and serum markers a short-term treatment target, with endoscopic healing the long-term one.7,8,9Grade A

03 · Origins

Where it came from, and where it sits in the network.

Calprotectin belongs to the S100 family of calcium-binding leukocyte proteins, more than 24 members in vertebrates and evolutionarily conserved; in mammals it is built from two of them, S100A8 and S100A9. A radioimmunoassay for the granulocyte protein was published in 1980, the complex was then rediscovered independently in several inflammatory conditions before the findings were reconciled in 1988, and the name chosen, calprotectin, recorded two properties: it binds calcium and it kills the yeast Candida albicans. The 'protectin' is the older half of the story.3,2,10Grade C

What it protects against is bacteria, and the weapon is starvation. In staphylococcal abscesses in mice, neutrophil-derived calprotectin inhibited bacterial growth by chelating the nutrient metals manganese and zinc, which reprogrammed the bacterial transcriptome; the abscesses of mice lacking calprotectin were rich in metal, and the bacteria multiplied in them. The same metal sequestration limits invasive and commensal gut bacteria, which depend on those ions for their enzymes and signaling, and many microbes have evolved high-affinity metal transporters to escape it; mice lacking the two subunits carry an altered intestinal microbiota. A protein this abundant in the cell that arrives first at any infection is an innate immune molecule that predates antibodies, and its presence in stool is a count of how many of those cells reached the gut.11,3Grade C

It makes a usable stool test because it survives. In the 1992 method paper that founded the test, calprotectin was stable in feces for 7 days at room temperature and a small sample taken from a 24-hour collection gave a reliable estimate of the whole; a 2015 study found concentrations unchanged after 3 days at room temperature and down by a mean of 28 percent after 7. In the network it is both readout and amplifier: acute inflammation recruits neutrophils to the mucosa, calprotectin released from them drives further neutrophil chemotaxis and activates pattern-recognition receptors such as Toll-like receptor 4, and the count rises. Blood C-reactive protein, by contrast, is made in the liver in response to inflammation anywhere, correlates poorly with intestinal activity, and was far less sensitive than calprotectin for active inflammatory bowel disease (0.49 against 0.88) in the pooled studies, which is why this entry asks that the two be read together rather than either alone.12,13,3,7Grade C

04 · The laboratory range

What a laboratory calls normal.

Under 50 µg/g normal on most assays; many laboratories flag 50 to 100 or 50 to 150 as borderline and above that as raised, and the lines differ by assay.

The 50 µg/g line comes from the improved assay of 2000, in which healthy adults had a median of 26 µg/g while samples from pancolitis ran up to 30,000, five spot samples from each of 47 stools agreed, and no interference from foods, oral medicines or nutraceuticals was found. Reviews place healthy adult values at roughly 10 to 50 µg/g depending on the cohort and the assay. The 2019 British guideline defines normal as under 50 but notes that the positive predictive value of values just above it is low, and recommends a higher, locally set threshold to trigger colonoscopy, generally between 100 and 250 µg/g, because of the variety of assays in use.14,3,15Grade B

The lines are assay-specific. Manufacturer-quoted cutoffs are similar, but the sensitivity and specificity at a given cutoff, and so the best cutoff, differ between assays, and there is no reference standard for calprotectin. In a 2019 systematic review of 38 studies, sensitivity at 50 µg/g across four assay types ranged from 0.85 to 0.94 and specificity from 0.67 to 0.88; a result from one kit is not the same number as a result from another.1,16Grade B

Age moves the reference range. In 132 healthy volunteers the median was 34 µg/g at 2 to 9 years, 22 at 10 to 59 and 27 at 60 and over, with age-related upper reference limits of 166, 51 and 112; adults over 60 ran higher than younger adults. Infants run far higher still: in 75 healthy children under 4, the 97.5th percentiles were 538 µg/g under 6 months, 214 from 6 months to 3 years and 75 from 3 to 4 years, and in Chinese infants aged 1 to 18 months the median was 174, falling with age from 375 in the first 3 months. Adult cutoffs do not apply to small children.17,18,19Grade C

05 · The evidence

What the studies support.

The evidence review behind the 2013 English guidance pooled 28 studies: in adults with irritable bowel symptoms against inflammatory bowel disease, laboratory ELISA assays gave a pooled sensitivity of 93 percent and specificity of 94 percent at 50 µg/g, with sensitivities across studies of 83 to 100 percent and specificities of 60 to 100; in children, sensitivities ran 95 to 100 percent and specificities 44 to 93. The reviewers called the management of borderline results, 50 to 150 µg/g, an area of uncertainty, noted that most people in that band do not have inflammatory bowel disease, and suggested repeat testing before referral. The 2019 British consensus makes a strong recommendation, on moderate-quality evidence, for calprotectin as a screening tool with a high negative predictive value in 16- to 40-year-olds presenting to primary care with chronic diarrhea that could be either disease, with the proviso that a significantly raised value first has an infective cause excluded.20,5,15Grade A

In a meta-analysis of prospective adult cohorts, eight for calprotectin, none of the blood or stool markers distinguished irritable bowel syndrome from healthy controls, but at a C-reactive protein of 0.5 mg/dL or less or a calprotectin of 40 µg/g or less the probability of inflammatory bowel disease was 1 percent or less. The authors' conclusion was that the two together essentially exclude inflammatory bowel disease in a person with irritable bowel symptoms, which is the strongest single thing this test does.21Grade A

The numbers are less tidy in primary care than in specialist clinics. A 2019 systematic review of 38 studies, five from primary care, found heterogeneity too great to pool by setting, sensitivity apparently lower in primary care and lower again at a 100 µg/g threshold, and concluded that the evidence to introduce the test in primary care was insufficient. A structured pathway can recover the performance: the first 1,005 primary care patients through the York pathway, which repeats borderline values, had a sensitivity of 0.94, a specificity of 0.92 and a negative predictive value of 0.99 at 6 months. Among 590 outpatients whose colonoscopy was normal, 36 percent had a calprotectin above 50 µg/g, with age, proton pump inhibitors, anti-inflammatory painkillers and aspirin each independently associated with the elevation.16,22,23Grade B

Against the endoscope, in 126 people with inflammatory bowel disease and 32 with irritable bowel who gave a stool sample before colonoscopy, median calprotectin was 175 µg/g in Crohn's disease, 465 in ulcerative colitis and 54 in irritable bowel. In Crohn's disease a value at or under 250 predicted endoscopic remission with 94.1 percent sensitivity and a negative predictive value of 96.6 percent, and above 250 indicated large ulcers with 60.4 percent sensitivity and 79.5 percent specificity; in ulcerative colitis above 250 had 71 percent sensitivity and 100 percent specificity for active mucosa. In an earlier series of 45 patients in clinical remission, 38 of the 45 with normal histology had a calprotectin within the reference range, the finding that made normalization of the number a proxy for mucosal healing. The treat-to-target consensus of 2021 adopted that logic: symptomatic relief and normalization of fecal and serum markers are short-term targets, endoscopic healing the long-term one.24,25,2,9Grade A

It warns of relapse. In 80 patients in clinical remission, 58 percent with Crohn's disease and 51 percent with ulcerative colitis relapsed within 12 months; median calprotectin in the relapsers was 122 and 123 mg/L in the original assay's units against 41.5 and 29.0 in those who stayed well, and at 50 mg/L of that assay the sensitivity for relapse was 90 percent and the specificity 83 percent. In 79 patients followed a year with a single baseline sample, a value above 150 µg/g carried twice the relapse risk in Crohn's disease and 14 times the risk in ulcerative colitis, where median values were 220.6 in relapsers against 67 in non-relapsers. A meta-analysis of six prospective studies and 672 patients put the pooled sensitivity for relapse at 78 percent and specificity at 73 percent, with an area under the curve of 0.83, comparable in the two diseases and more accurate in colonic than in other Crohn's disease.26,27,28Grade B

It sees the colon better than the small bowel. In a meta-analysis of seven capsule endoscopy studies and 463 patients with suspected or known Crohn's disease, a 50 µg/g cutoff had a sensitivity of 0.83 and specificity of 0.53 for active small-bowel disease, and 200 µg/g a sensitivity of 0.42 and specificity of 0.94; in suspected disease alone a value under 50 carried a negative predictive value of 91.8 percent. The endoscopy meta-analysis likewise found the test more sensitive in ulcerative colitis than in Crohn's disease, and the relapse meta-analysis could not assess isolated small-bowel Crohn's disease for lack of data.29,7,28Grade B

It is a poor cancer test. Across 30 studies and 5,983 patients, calprotectin diagnosed inflammatory bowel disease with a sensitivity of 0.95 and an area under the curve of 0.95, but colorectal cancer with a sensitivity of 0.36, a specificity of 0.71 and an area under the curve of 0.66; the authors said it could not be recommended for cancer screening. In 1,043 primary care patients referred with bowel symptoms, 60 percent had a calprotectin of 50 µg/g or more, and adding it to a fecal hemoglobin test found two more cases of inflammatory bowel disease, one more higher-risk adenoma and no additional cancers. That is why the English guidance limits the test to people in whom cancer is not suspected.30,31,5Grade B

What a raised value means in someone who feels well is not known. The closest evidence is retrospective: among 585 people whose colonoscopy was normal, 34 percent had a calprotectin above 50 µg/g, and over the next 3 years they were no more likely to be diagnosed with a lower gut disease (6.4 against 5.2 percent) or with cardiovascular disease or death than those with a normal value; upper gut diagnoses, mostly benign, were more frequent (9.9 against 4.7 percent) but not after adjusting for age, sex, painkillers and acid suppression. In 320 average-risk adults aged 50 to 70 recruited from the community, calprotectin rose with age, obesity and physical inactivity and fell with fiber and vegetable intake, the obesity link weakening once blood C-reactive protein was taken into account; the authors proposed low-level bowel inflammation as a route from lifestyle to colorectal cancer risk, which remains a hypothesis. No cohort has followed symptom-free adults by their calprotectin to see what becomes of them.32,33Grade C

06 · What moves it

The levers with evidence behind them.

What is listed here has been tested. The size of each effect, and the size of the study, are in the sentence, so a small effect reads as a small effect.

  • Anti-inflammatory painkillers (NSAIDs)

    raise it, often into the disease range

    In 312 patients taking 18 different NSAIDs, 44 percent had small-bowel inflammation by calprotectin, independent of which drug or what dose, and a fifth of those had levels comparable to inflammatory bowel disease. Two weeks of indomethacin or naproxen raised calprotectin in healthy volunteers from 4.7 to 9.0 and 8.0 mg/L in the original assay's units, and in a 2023 trial 39 percent of 32 healthy volunteers on two weeks of diclofenac exceeded the normal limit (median 70.8 µg/g, up to 1,080), returning to normal within 2 weeks of stopping. The question to ask before reading a borderline value is what was taken for pain in the previous month.34,35,36Grade B

  • Acid suppression (proton pump inhibitors)

    raises it

    Among 590 outpatients with a normal colonoscopy, proton pump inhibitor use carried an adjusted odds ratio of 3.8 for a calprotectin above 50 µg/g, higher than the 2.4 for NSAIDs and 2.9 for aspirin. In the 2023 volunteer trial, 53 percent on two weeks of a proton pump inhibitor alone had values above normal (median 85.3 µg/g) and 69 percent on the inhibitor plus diclofenac (median 101.5); values normalized within 3 weeks of stopping, and the authors recommend repeating the test at least 3 weeks after cessation.23,36Grade C

  • Gut infection

    raises it, often strongly, for as long as the infection lasts

    In 2,383 consecutive adults with acute diarrhea, calprotectin identified culture-positive bacterial infection with a sensitivity of 83 percent and specificity of 87 percent, better than lactoferrin or occult blood. Medians reported during Salmonella, Campylobacter and Clostridioides difficile infection run in the hundreds of µg/g, and the British guideline is explicit that in acute infectious diarrhea the test will not separate inflammatory bowel disease from gastroenteritis, so a stool culture comes first. Viral infections can raise it too.37,3,15Grade C

  • Body fat, inactivity and low fiber

    track with higher values in one cross-sectional study

    In 320 average-risk adults aged 50 to 70, calprotectin was higher with obesity and physical inactivity and lower with fiber and vegetable intake, and the obesity association weakened after adjusting for blood C-reactive protein, which suggests part of it is systemic inflammation. No trial has changed diet, activity or weight in healthy adults and measured calprotectin, so what moves it in a well person is inferred, not shown.33Grade C

  • Treating inflammatory bowel disease

    lowers it toward normal as the mucosa heals

    Normalization is the marker of healing: in patients in remission with normal histology the value was within the reference range in 38 of 45, and a value at or under 250 µg/g predicted endoscopic remission in Crohn's disease with a negative predictive value of 96.6 percent. In the DEAR trial cited by the British guideline, people with quiet ulcerative colitis and a calprotectin above 50 who had their aminosalicylate dose increased were more likely to stay in remission and to have a value under 50 at 6 weeks than controls. In people who already have the disease, a falling calprotectin is the treatment working.25,2,24,15Grade B

  • Other inflammation in the bowel

    raises it, without being inflammatory bowel disease

    Calprotectin was raised in acute uncomplicated diverticulitis and in symptomatic diverticular disease, correlated with the inflammatory infiltrate on biopsy, was normal in asymptomatic diverticulosis and in irritable bowel, and fell to normal after treatment. In collagenous colitis the median was 80 µg/g in active disease against 6.25 in controls, yet 38 percent of active cases had a normal value, so a normal result does not exclude microscopic colitis. Gastrointestinal bleeding is associated with moderately raised values of about 50 to 200.38,39,3Grade C

07 · Reading it well

Caveats, and what belongs with a physician.

One sample is not a baseline. In 18 people with active ulcerative colitis who collected two samples at every bowel movement for 2 days, the coefficient of variation between movements on the same day was 52 percent, concentrations rose with the time since the previous movement, and the authors recommended the first stool of the morning. In 14 people with a normal colonoscopy giving eight samples each the within-person coefficient of variation was 58 percent. In 143 people with quiet Crohn's disease sampled on three consecutive days, agreement was good (intraclass correlation 0.84) and the reliability of calling a 'case' above 50 µg/g was moderate (kappa 0.65), so a single sample is reasonable in known remission; a borderline value in anyone else is a value to repeat.13,2,40Grade C

It is sensitive, not specific. The stool count rises with any cause of neutrophils in the gut: bacterial and viral gastroenteritis, diverticular disease, NSAID and aspirin enteropathy, proton pump inhibitors, bleeding, and age. A raised value says there is inflammation; it does not say why. The British guideline's first instruction after a significantly raised result is to exclude infection, and the 36 percent of normal colonoscopies that came with a value above 50 µg/g are the measure of how often a raised value has no colonic disease behind it.3,15,23Grade B

Children are a different reference population. Healthy infants run medians in the hundreds of µg/g in the first months of life, upper limits for children under 4 are several times the adult line, and specificity in children with suspected inflammatory bowel disease was 0.76 against 0.96 in adults, a difference the meta-analysis found significant. English guidance recommends the test in children only after referral for specialist assessment.19,18,4,5Grade B

A normal calprotectin does not exclude colorectal cancer, which the test detects with a sensitivity of 0.36; in symptomatic primary care patients, fecal hemoglobin, not calprotectin, was the test whose negative result ruled out cancer. Bowel symptoms with bleeding, weight loss or iron deficiency are investigated on their own merits whatever the calprotectin shows.30,31Grade B

The test was built and validated for a person with symptoms, and every guideline that endorses it frames it that way: adults with recent-onset lower bowel symptoms, people with suspected irritable bowel and diarrhea, people with known inflammatory bowel disease. On a wellness stool panel in a person who feels well it is being asked a question it was not designed to answer. The one study that followed people with a raised value and a normal colonoscopy found no excess of significant gut disease over 3 years. A raised number on such a panel is a prompt to ask about painkillers, acid suppression, a recent stomach bug and symptoms the person may have discounted, and to repeat the test, not a diagnosis.5,6,9,32Grade C

See a physician

  • Blood in the stool or black stools, whatever the calprotectin result; the British guideline sends bloody diarrhea to endoscopy regardless of the number.
  • Diarrhea or abdominal pain that wakes you at night, unexplained weight loss, fever, or symptoms that have lasted more than a few weeks.
  • Iron deficiency or anemia alongside bowel symptoms, or a low ferritin without an obvious reason.
  • A calprotectin that stays above your laboratory's cutoff on repeat with bowel symptoms, particularly in the 100 to 250 µg/g range that UK guidance uses to trigger colonoscopy, or any value far above it.
  • New bowel symptoms after 50, or a family history of inflammatory bowel disease or colorectal cancer, where a normal calprotectin does not rule out cancer.

This page is education, not individual medical advice, and reading it creates no physician-patient relationship.

08 · Open questions

What the literature does not settle.

  • No cohort has followed healthy, symptom-free adults by their fecal calprotectin to see whether a raised value predicts anything; its meaning on a wellness stool panel is unstudied.
  • There is no reference standard for calprotectin, cutoffs differ by assay, and whether 50 or 100 µg/g is the right line in primary care is unresolved; the 2019 systematic review found the evidence insufficient to support routine primary care testing.
  • Normalizing calprotectin is a short-term treatment target in inflammatory bowel disease; whether treating to the number improves long-term outcomes beyond what endoscopic healing already predicts is still being tested.
  • Whether diet, activity or weight loss lower calprotectin in healthy adults rests on one cross-sectional study; no trial has measured it.
  • Adults over 60 run higher values than younger adults, and whether age-specific adult cutoffs should be used has not been settled.

09 · In practice

How Dr. Tagge reads it in his own practice.

I order fecal calprotectin when bowel symptoms make me want to separate inflammation from an irritable bowel without putting a scope in first: diarrhea that has gone on for weeks, pain with a change in bowel habit, a story that does not settle. One marker is a clue, three are a story, so I read it beside hs-CRP, ferritin, albumin, B12 and the blood count, and above all beside the history. A low value in that setting is reassuring, and the literature backs it. A high value in someone with symptoms earns a gastroenterologist, not a supplement. A mildly raised value I repeat before I act on it, a few weeks later, after asking about ibuprofen, naproxen, aspirin and acid suppression and after any recent stomach bug has passed, because each of those pushes the number up on its own. I carry no number of my own for this test; the cutoffs on this page are the assays' and the studies', stated as theirs. On the wellness stool panels that now carry calprotectin I am candid: the test was built to answer a question those panels are not asking. It was validated in people with symptoms, and nobody has shown what a raised value means in a person who feels well. I will say plainly where I am ahead of the evidence: I read a quietly raised calprotectin in a well person as a reason to look harder at the story, the medicines and the other markers, and to repeat it, not as a diagnosis, and no study yet tells me whether that is right.

A practice judgment, labeled as one (Grade D): it is how one physician reads the number for the people he cares for, not a recommendation for you.

10

Questions

11 · Sources

40 sources, read in full.

Numbered in the order they appear. Each line says what this page relies on from the paper; the link opens the record at PubMed or the publisher.

  1. 1.

    Pathirana WGW, Chubb SP, Gillett MJ, Vasikaran SD. Faecal Calprotectin. Clinical Biochemist Reviews. 2018. PMID 30828114.

    Review · Calcium- and zinc-binding S100 protein, mainly in neutrophils; stool presence follows neutrophil migration into the gut; manufacturer cutoffs similar but sensitivity and specificity at a cutoff differ by assay; no reference standard.

  2. 2.

    Walsham NE, Sherwood RA. Fecal calprotectin in inflammatory bowel disease. Clinical and Experimental Gastroenterology. 2016. PMID 26869808. DOI 10.2147/CEG.S51902.

    Review · Read in full text: first discovered 1980, about 60 percent of neutrophil cytosolic protein; within-person CV 58 percent in 14 normal-colonoscopy volunteers; Røseth 2004's 38 of 45 remission patients with normal histology within the reference range.

  3. 3.

    Jukic A, Bakiri L, Wagner EF, Tilg H, Adolph TE. Calprotectin: from biomarker to biological function. Gut. 2021. PMID 34145045. DOI 10.1136/gutjnl-2021-324855.

    Review · Read in full text: S100 family conserved across vertebrates, about 45 percent of neutrophil cytosolic protein, metal chelation limits gut bacteria, healthy values about 10 to 50 µg/g by assay, raised in infection, NSAID and proton pump inhibitor use and bleeding (50 to 200), infants under 4 run higher.

  4. 4.

    van Rheenen PF, Van de Vijver E, Fidler V. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ. 2010. PMID 20634346. DOI 10.1136/bmj.c3369.

    Systematic review and meta-analysis · 13 prospective studies: pooled sensitivity and specificity 0.93 and 0.96 in 670 adults, 0.92 and 0.76 in 371 children; screening would cut adult endoscopies by 67 percent with delayed diagnosis in 6 percent.

  5. 5.

    National Institute for Health and Care Excellence. Faecal calprotectin diagnostic tests for inflammatory diseases of the bowel (diagnostics guidance DG11, republished as HealthTech guidance HTG320). NICE, London. 2013.

    Guideline · Recommended as an option for the differential diagnosis of IBD or IBS in adults with recent-onset lower gastrointestinal symptoms if cancer is not suspected, and in children with suspected IBD referred for specialist assessment; reviewed 2017 with no change.

  6. 6.

    Lacy BE, Pimentel M, Brenner DM, et al.. ACG Clinical Guideline: Management of Irritable Bowel Syndrome. American Journal of Gastroenterology. 2021. PMID 33315591. DOI 10.14309/ajg.0000000000001036.

    Guideline · Suggests that fecal calprotectin be checked in patients with suspected IBS and diarrhea symptoms to rule out inflammatory bowel disease.

  7. 7.

    Mosli MH, Zou G, Garg SK, et al.. C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis. American Journal of Gastroenterology. 2015. PMID 25964225. DOI 10.1038/ajg.2015.120.

    Systematic review and meta-analysis · 19 studies, 2,499 patients: calprotectin sensitivity 0.88 and specificity 0.73 for endoscopic activity against 0.49 and 0.92 for CRP; more sensitive in ulcerative colitis than Crohn's disease.

  8. 8.

    Lin JF, Chen JM, Zuo JH, et al.. Meta-analysis: fecal calprotectin for assessment of inflammatory bowel disease activity. Inflammatory Bowel Diseases. 2014. PMID 24983982. DOI 10.1097/MIB.0000000000000057.

    Systematic review and meta-analysis · 13 studies, 744 UC and 727 CD patients: AUC 0.89 for active disease; at 50 µg/g sensitivity 0.92, specificity 0.60; at 100, 0.84 and 0.66; at 250, 0.80 and 0.82.

  9. 9.

    Turner D, Ricciuto A, Lewis A, et al.; International Organization for the Study of IBD. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021. PMID 33359090. DOI 10.1053/j.gastro.2020.12.031.

    Consensus statement · Symptomatic relief and normalization of serum and fecal markers (CRP, ESR, calprotectin) are short-term treatment targets; clinical remission and endoscopic healing are long-term targets.

  10. 10.

    Fagerhol MK, Dale I, Andersson T. A radioimmunoassay for a granulocyte protein as a marker in studies on the turnover of such cells. Bulletin Européen de Physiopathologie Respiratoire. 1980. PMID 7225633. DOI 10.1016/b978-0-08-027379-2.50028-4.

    Laboratory method study · The 1980 description of the granulocyte protein later named calprotectin, cited by the reviews as its discovery; the paper itself was not read.

  11. 11.

    Corbin BD, Seeley EH, Raab A, et al.. Metal chelation and inhibition of bacterial growth in tissue abscesses. Science. 2008. PMID 18276893. DOI 10.1126/science.1152449.

    Laboratory method study · Neutrophil-derived calprotectin inhibited Staphylococcus aureus growth in abscesses by chelating manganese and zinc; abscesses in mice lacking calprotectin were metal-rich and bacteria proliferated.

  12. 12.

    Røseth AG, Fagerhol MK, Aadland E, Schjønsby H. Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study. Scandinavian Journal of Gastroenterology. 1992. PMID 1411288. DOI 10.3109/00365529209011186.

    Laboratory method study · The founding method paper: calprotectin was stable in feces for 7 days at room temperature, a small sample estimated a 24-hour collection reliably, and within- and between-assay precision were 1.9 and 14.8 percent.

  13. 13.

    Lasson A, Stotzer PO, Öhman L, Isaksson S, Sapnara M, Strid H. The intra-individual variability of faecal calprotectin: a prospective study in patients with active ulcerative colitis. Journal of Crohn's and Colitis. 2015. PMID 25008478. DOI 10.1016/j.crohns.2014.06.002.

    Prospective cohort · 18 patients, 287 samples: within-day coefficient of variation 52 percent, levels rising with time since the previous movement (first morning stool recommended); unchanged after 3 days at room temperature, down 28 percent after 7.

  14. 14.

    Tøn H, Brandsnes, Dale S, et al.. Improved assay for fecal calprotectin. Clinica Chimica Acta. 2000. PMID 10686275. DOI 10.1016/s0009-8981(99)00206-5.

    Laboratory method study · The assay behind today's µg/g scale: healthy median 26 µg/g, pancolitis up to 30,000; five spot samples from each of 47 stools agreed; no interference from foods, oral pharmaceuticals or nutraceuticals.

  15. 15.

    Lamb CA, Kennedy NA, Raine T, et al.; IBD guidelines eDelphi consensus group. British Society of Gastroenterology consensus guidelines on the management of inflammatory bowel disease in adults. Gut. 2019. PMID 31562236. DOI 10.1136/gutjnl-2019-318484.

    Guideline · Strong recommendation for calprotectin as a screening tool in 16- to 40-year-olds in primary care with chronic diarrhea; normal under 50 µg/g, colonoscopy trigger set locally at 100 to 250; exclude infection first; bloody diarrhea goes to endoscopy regardless.

  16. 16.

    Freeman K, Willis BH, Fraser H, Taylor-Phillips S, Clarke A. Faecal calprotectin to detect inflammatory bowel disease: a systematic review and exploratory meta-analysis of test accuracy. BMJ Open. 2019. PMID 30852550. DOI 10.1136/bmjopen-2018-027428.

    Systematic review and meta-analysis · 38 studies, five in primary care: at 50 µg/g sensitivity by assay type 0.85 to 0.94 and specificity 0.67 to 0.88; sensitivity appears lower in primary care and at 100 µg/g; evidence insufficient to support primary care introduction.

  17. 17.

    Joshi S, Lewis SJ, Creanor S, Ayling RM. Age-related faecal calprotectin, lactoferrin and tumour M2-PK concentrations in healthy volunteers. Annals of Clinical Biochemistry. 2010. PMID 19740914. DOI 10.1258/acb.2009.009061.

    Cross-sectional study · 132 healthy volunteers: median calprotectin 34 µg/g at 2 to 9 years, 22 at 10 to 59, 27 at 60 and over; age-related upper limits 166, 51 and 112 µg/g.

  18. 18.

    Oord T, Hornung N. Fecal calprotectin in healthy children. Scandinavian Journal of Clinical and Laboratory Investigation. 2014. PMID 24568692. DOI 10.3109/00365513.2013.879732.

    Cross-sectional study · 75 healthy children under 4: 97.5th percentile cutoffs 538 µg/g under 6 months, 214 from 6 months to 3 years and 75 from 3 to 4 years.

  19. 19.

    Li F, Ma J, Geng S, et al.. Fecal calprotectin concentrations in healthy children aged 1-18 months. PLoS One. 2015. PMID 25742018. DOI 10.1371/journal.pone.0119574.

    Cross-sectional study · Healthy infants aged 1 to 18 months: median calprotectin 174.3 µg/g, 375.2 in the first 3 months, falling with age and higher than in older children and adults.

  20. 20.

    Waugh N, Cummins E, Royle P, et al.. Faecal calprotectin testing for differentiating amongst inflammatory and non-inflammatory bowel diseases: systematic review and economic evaluation. Health Technology Assessment. 2013. PMID 24286461. DOI 10.3310/hta17550.

    Systematic review and meta-analysis · 28 studies: in adults, IBS versus IBD, pooled sensitivity 93 percent and specificity 94 percent at 50 µg/g; borderline 50 to 150 µg/g an area of uncertainty where most do not have IBD; repeat testing may be appropriate before referral.

  21. 21.

    Menees SB, Powell C, Kurlander J, Goel A, Chey WD. A meta-analysis of the utility of C-reactive protein, erythrocyte sedimentation rate, fecal calprotectin, and fecal lactoferrin to exclude inflammatory bowel disease in adults with IBS. American Journal of Gastroenterology. 2015. PMID 25732419. DOI 10.1038/ajg.2015.6.

    Systematic review and meta-analysis · At CRP 0.5 mg/dL or less or calprotectin 40 µg/g or less, the probability of IBD was 1 percent or less; no marker separated IBS from healthy controls.

  22. 22.

    Turvill J, Turnock D, Holmes H, et al.. Evaluation of the clinical and cost-effectiveness of the York Faecal Calprotectin Care Pathway. Frontline Gastroenterology. 2018. PMID 30245791. DOI 10.1136/flgastro-2018-100962.

    Prospective cohort · First 1,005 primary care patients through a structured pathway built on NICE DG11: sensitivity 0.94, specificity 0.92 and negative predictive value 0.99 at 6 months.

  23. 23.

    Lundgren D, Eklöf V, Palmqvist R, Hultdin J, Karling P. Proton pump inhibitor use is associated with elevated faecal calprotectin levels. A cross-sectional study on subjects referred for colonoscopy. Scandinavian Journal of Gastroenterology. 2019. PMID 30676120. DOI 10.1080/00365521.2019.1566493.

    Cross-sectional study · 590 outpatients with a normal colonoscopy: 36 percent had calprotectin above 50 µg/g; adjusted odds ratios 3.8 for proton pump inhibitors, 2.4 for NSAIDs, 2.9 for aspirin and 1.05 per year of age.

  24. 24.

    D'Haens G, Ferrante M, Vermeire S, et al.. Fecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflammatory Bowel Diseases. 2012. PMID 22344983. DOI 10.1002/ibd.22917.

    Prospective cohort · 126 IBD and 32 IBS patients before colonoscopy: medians 175 (CD), 465 (UC), 54 (IBS) µg/g; 250 or less predicted endoscopic remission in CD with 94.1 percent sensitivity and 96.6 percent NPV; above 250 in UC had 100 percent specificity for active mucosa.

  25. 25.

    Røseth AG, Aadland E, Grzyb K. Normalization of faecal calprotectin: a predictor of mucosal healing in patients with inflammatory bowel disease. Scandinavian Journal of Gastroenterology. 2004. PMID 15513345. DOI 10.1080/00365520410007971.

    Prospective cohort · In 45 patients in clinical remission undergoing colonoscopy, 38 of the 45 with normal histology had a calprotectin within the reference range (figure read from the Walsham 2016 review; PubMed carries no abstract).

  26. 26.

    Tibble JA, Sigthorsson G, Bridger S, Fagerhol MK, Bjarnason I. Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology. 2000. PMID 10889150. DOI 10.1053/gast.2000.8523.

    Prospective cohort · 80 patients in remission: at 50 mg/L (original assay units) calprotectin predicted relapse within 12 months with 90 percent sensitivity and 83 percent specificity; medians 122 and 123 mg/L in relapsers against 41.5 and 29.0.

  27. 27.

    Costa F, Mumolo MG, Ceccarelli L, et al.. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn's disease. Gut. 2005. PMID 15710984. DOI 10.1136/gut.2004.043406.

    Prospective cohort · 79 patients in remission followed 12 months: calprotectin above 150 µg/g carried a 2-fold relapse risk in Crohn's disease and 14-fold in ulcerative colitis (medians 220.6 versus 67 in UC relapsers and non-relapsers).

  28. 28.

    Mao R, Xiao YL, Gao X, et al.. Fecal calprotectin in predicting relapse of inflammatory bowel diseases: a meta-analysis of prospective studies. Inflammatory Bowel Diseases. 2012. PMID 22238138. DOI 10.1002/ibd.22861.

    Systematic review and meta-analysis · Six prospective studies, 672 patients: pooled sensitivity 78 percent and specificity 73 percent for relapse, AUC 0.83, diagnostic odds ratio 10.3; comparable in UC and CD, more accurate in colonic CD, small-bowel CD not assessable.

  29. 29.

    Kopylov U, Yung DE, Engel T, et al.. Fecal calprotectin for the prediction of small-bowel Crohn's disease by capsule endoscopy: a systematic review and meta-analysis. European Journal of Gastroenterology and Hepatology. 2016. PMID 27415156. DOI 10.1097/MEG.0000000000000692.

    Systematic review and meta-analysis · Seven studies, 463 patients: at 50 µg/g sensitivity 0.83 and specificity 0.53 for small-bowel Crohn's disease on capsule endoscopy; at 200, 0.42 and 0.94; under 50 in suspected disease, NPV 91.8 percent.

  30. 30.

    von Roon AC, Karamountzos L, Purkayastha S, et al.. Diagnostic precision of fecal calprotectin for inflammatory bowel disease and colorectal malignancy. American Journal of Gastroenterology. 2007. PMID 17324124. DOI 10.1111/j.1572-0241.2007.01126.x.

    Systematic review and meta-analysis · 30 studies, 5,983 patients: sensitivity 0.95 and AUC 0.95 for IBD; sensitivity 0.36, specificity 0.71 and AUC 0.66 for colorectal cancer, so not recommended for cancer screening.

  31. 31.

    Mowat C, Digby J, Strachan JA, et al.. Faecal haemoglobin and faecal calprotectin as indicators of bowel disease in patients presenting to primary care with bowel symptoms. Gut. 2016. PMID 26294695. DOI 10.1136/gutjnl-2015-309579.

    Prospective cohort · 1,043 symptomatic primary care patients: calprotectin 50 µg/g or above in 60 percent; undetectable fecal hemoglobin had a 100 percent NPV for cancer; adding calprotectin found two more IBD cases and no additional cancers.

  32. 32.

    Hovstadius H, Lundgren D, Karling P. Elevated Faecal Calprotectin in Patients with a Normal Colonoscopy: Does It Matter in Clinical Practice? A Retrospective Observational Study. Inflammatory Intestinal Diseases. 2021. PMID 34124181. DOI 10.1159/000513473.

    Prospective cohort · 585 patients with a normal colonoscopy, 34 percent with calprotectin above 50 µg/g: over 3 years no excess of new lower gut disease (6.4 versus 5.2 percent) or cardiovascular disease or death; upper gut diagnoses more frequent (9.9 versus 4.7 percent) but not after adjustment.

  33. 33.

    Poullis A, Foster R, Shetty A, Fagerhol MK, Mendall MA. Bowel inflammation as measured by fecal calprotectin: a link between lifestyle factors and colorectal cancer risk. Cancer Epidemiology, Biomarkers and Prevention. 2004. PMID 14973103. DOI 10.1158/1055-9965.epi-03-0160.

    Cross-sectional study · 320 average-risk adults aged 50 to 70: calprotectin rose with age, obesity and physical inactivity and fell with fiber and vegetable intake; the obesity link was attenuated by adjusting for serum CRP.

  34. 34.

    Tibble JA, Sigthorsson G, Foster R, et al.. High prevalence of NSAID enteropathy as shown by a simple faecal test. Gut. 1999. PMID 10446103. DOI 10.1136/gut.45.3.362.

    Cross-sectional study · 312 patients on 18 NSAIDs: 44 percent had enteropathy by calprotectin, independent of drug type or dose; 20 percent of those had inflammation comparable to IBD.

  35. 35.

    Meling TR, Aabakken L, Røseth A, Osnes M. Faecal calprotectin shedding after short-term treatment with non-steroidal anti-inflammatory drugs. Scandinavian Journal of Gastroenterology. 1996. PMID 8726300. DOI 10.3109/00365529609006407.

    Randomized trial · Randomized crossover studies in healthy volunteers: 14 days of indomethacin or naproxen raised calprotectin from 4.7 to 9.0 and 8.0 mg/L (original assay units); lornoxicam did not.

  36. 36.

    Rendek Z, Falk M, Grodzinsky E, Kechagias S, Hjortswang H. Oral omeprazole and diclofenac intake is associated with increased faecal calprotectin levels: a randomised open-label clinical trial. European Journal of Gastroenterology and Hepatology. 2023. PMID 36468569. DOI 10.1097/MEG.0000000000002473.

    Randomized trial · 32 healthy volunteers: above-normal calprotectin in 39 percent on diclofenac (median 70.8 µg/g), 53 percent on omeprazole (85.3) and 69 percent on both (101.5); normal within 2 weeks of stopping diclofenac and 3 weeks of stopping omeprazole.

  37. 37.

    Shastri YM, Bergis D, Povse N, et al.. Prospective multicenter study evaluating fecal calprotectin in adult acute bacterial diarrhea. American Journal of Medicine. 2008. PMID 19028207. DOI 10.1016/j.amjmed.2008.06.034.

    Prospective cohort · 2,383 consecutive adults with acute diarrhea: calprotectin sensitivity 83 percent and specificity 87 percent for culture-positive bacterial diarrhea, against 78 and 54 for lactoferrin and 38 and 85 for occult blood.

  38. 38.

    Tursi A, Brandimarte G, Elisei W, Giorgetti GM, Inchingolo CD, Aiello F. Faecal calprotectin in colonic diverticular disease: a case-control study. International Journal of Colorectal Disease. 2009. PMID 18941760. DOI 10.1007/s00384-008-0595-9.

    Cross-sectional study · Calprotectin raised in acute uncomplicated diverticulitis and symptomatic diverticular disease, correlated with inflammatory infiltrate, normal in asymptomatic diverticulosis and IBS, and normalized after treatment.

  39. 39.

    Wildt S, Nordgaard-Lassen I, Bendtsen F, Rumessen JJ. Metabolic and inflammatory faecal markers in collagenous colitis. European Journal of Gastroenterology and Hepatology. 2007. PMID 17556903. DOI 10.1097/MEG.0b013e328058ed76.

    Cross-sectional study · Median calprotectin 80 µg/g in active collagenous colitis, 26 in remission and 6.25 in controls, but 38 percent of active cases had a normal value; not a reliable marker of microscopic colitis.

  40. 40.

    Naismith GD, Smith LA, Barry SJ, et al.. A prospective single-centre evaluation of the intra-individual variability of faecal calprotectin in quiescent Crohn's disease. Alimentary Pharmacology and Therapeutics. 2013. PMID 23347334. DOI 10.1111/apt.12221.

    Prospective cohort · 143 patients with quiescent Crohn's disease sampled on three consecutive days: intraclass correlation 0.84 and kappa 0.65 for a 'case' above 50 µg/g; day-to-day variability low in remission.

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