In this article, we look at the stool test marker known as calprotectin. We explore what calprotectin is, what it means if your calprotectin levels are elevated and how to interpret your test results. We also look at natural ways you can lower calprotectin nutrition nutrition and lifestyle interventions.
Calprotectin is a biomarker that is commonly used to assess inflammation in the gastrointestinal (GI) tract. It is a protein complex primarily released by neutrophils, a type of white blood cell, during inflammation. When there is inflammation in the intestines, calprotectin is released into the intestinal lumen and subsequently excreted in the faeces (1,2).
Calprotectin was discovered in the early 1980’s and has been researched extensively since that time. The understanding of calprotectin's role in inflammatory processes and its potential as a biomarker has since emerged, with researchers finding that calprotectin is released by activated neutrophils during inflammation, primarily in response to infection or tissue damage. Its release occurs at various sites of inflammation, including in the gastrointestinal tract (1).
In the late 1990s and early 2000s, studies began to explore the utility of calprotectin as a marker for inflammatory bowel diseases (IBD), such as Crohn's disease (CD) and ulcerative colitis (UC) (1,2).
Nice (National Institute for health and care excellence) guidelines dictate the following regarding faecal calprotectin levels –
- Under <100mcg/g indicates possible IBS if the patients / client’s symptoms are persistent (3).
- Between 100-250mcg/g would require the patients calprotectin to be re-tested in 2 weeks to assess if the result is consistent (3).
- A high result of >250mcg/g would trigger the need for a colonoscopy to screen for IBD (3).
These guidelines are followed by all practitioners, be they GP’s, gastroenterologists or Nutritional therapists. With the latter, in the event of a very high calprotectin result, a referral would be made via the client to their GP or directly to their gastroenterologist should they have one.
Calprotectin is routinely used by GP’s and gastroenterologists to screen for IBD or IBS (irritable bowel syndrome). In Nutritional Therapy it’s used as a marker to identify inflammation in general, but also in relation to other functional markers, such as zonulin, Secretory IgA, anti-inflammatory short chain fatty acids (SCFA’s) and occult blood. Nutritional therapists will also investigate what may be causing an elevation of calprotectin in the absence of IBD. Functional stool tests include multiple health markers such as calprotectin to screen for inflammation, immune function, digestive function, and gut barrier health. They will also screen the digestive microbiome for beneficial and opportunistic bacteria levels which may be influencing what is being seen in the health marker results.
This approach gives greater context and a deeper level of investigation to relate back to elevated calprotectin levels and the reasons why it could be elevated (4,5).
Someone suffering from digestive symptoms may present similarly with both IBS or IBD. Common symptoms in both cases can be abdominal discomfort, bloating, diarrhoea and/or constipation, therefore testing for calprotectin amongst other markers can rule IBD in or out (1,2,6).
Calprotectin has a high diagnostic accuracy for IBD conditions such as UC and CD at approximately 93% sensitivity and 96% specificity when its elevated above 250mcg/g, however, if IBS is indicated with a lower level (<100mcg/g) of calprotectin, other markers need to be assessed in order to ascertain what could be causing the digestive symptoms (6).
Research has shown that people with elevated levels of calprotectin have a lower abundance in certain beneficial bacteria such as Faecalibacterium prausnitzii, Bifidobacterium species and Clostridium species, which produce anti-inflammatory substances such as SCFA’s (7). Generally, lower SCFA’s production equates to higher calprotectin levels in both IBD and IBS, as they are anti-inflammatory and also provide energy to the cells in the colon (8). For this reason, the microbiome needs to be carefully considered when assessing calprotectin levels in both IBS and IBD.
The scope of calprotectin assessment also stretches beyond the gut due to the impact gut health can have on each and every system in the body. Calprotectin was found to be increased, and SCFA decreased, in patients suffering with Parkinson’s disease (9). Early studies indicate this could also be the case in Alzheimer’s suffers, further raising the importance of gut health as we age (10).
Recently, in response to the broad range of side effects of the COVID-19 virus, research has found that faecal calprotectin levels were elevated in people suffering with COVID-19. This supports the hypothesis that COVID-19 caused intestinal damage and subsequent digestive symptoms, such as diahorrea (11).
Calprotectin can also be used as an early marker to help in the diagnosis of coeliac disease in children. Elevated calprotectin levels returned to normal once a gluten free diet had been implemented.
- Omega 3 fatty acid intake - EPA (Eicosapentaenoic Acid) found in fish oil, has been shown to reduce calprotectin levels in patients in remission with UC (13,14). Adding 2-3 portions of oily fish per week into your diet can provide adequate omega 3 fatty acid levels.
- Introduce prebiotic and probiotic foods – Inulin containing foods such as chicory, Jerusalem artichoke, garlic, leeks, asparagus, bananas may reduce calprotectin levels, as shown with oligofructose supplementation (14,15)
- Taking probiotic supplements – bacteria species such as lactobacillus and Bifidobacterium may be beneficial in modulating the immune system and reducing inflammation (14).
- Curcumin intake via supplementation and diet – Curcumin has been shown to reduce calprotectin levels in active UC sufferers (16). Curcumin can be found in the root turmeric which can be added to meals such as curries, in burger mixes or on fish. (Remember to always add black pepper as that contains a co-factor to help with curcumin absorption).
- Flaxseed intake – Flaxseed and flaxseed oil (which contains omega 3 fatty acids) have been found to reduce calprotectin levels significantly in suffers of UC (17). Flaxseed can be added to porridge or yoghurt in the morning for breakfast as well as gluten free bread mixes.
There is one major limitation to the calprotectin biomarker and that is, it alone, cannot indicate what is causing an increased inflammatory response in the gut. It can also be elevated in people who have had a normal colonoscopy which further adds to the need for deeper analysis into what is causing the calprotectin elevation (18).
- Khaki-Khatibi F, Qujeq D, Kashifard M, Moein S, Maniati M, Vaghari-Tabari M. Calprotectin in inflammatory bowel disease. Clinica Chimica Acta. 2020 Aug 18;510:556–65. doi:10.1016/j.cca.2020.08.025
- Jukic A, Bakiri L, Wagner EF, Tilg H, Adolph TE. Calprotectin: From Biomarker to biological function. Gut. 2021 Jun 18;70(10):1978–88. doi:10.1136/gutjnl-2021-324855
- Evaluation of guidelines for the use of faecal calprotectin testing in primary care [Internet]. 2015 [cited 2023 Jun 28]. Available from: https://www.nice.org.uk/sharedlearning/evaluation-of-guidelines-for-the-use-of-faecal-calprotectin-testing-in-primary-care
- GI Ecologix: Gut Health & Microbiome Stool test: Invivo [Internet]. Invivo; 2023 [cited 2023 Jun 28]. Available from: https://invivohealthcare.com/products/testing/gi-ecologix/
- Gi effects®: Genova Diagnostics: Europe [Internet]. Genova Diagnostics; 2022 [cited 2023 Jun 28]. Available from: https://www.gdx.net/uk/products/gi-effects
- Sherwood R, Walsham N. Fecal calprotectin in inflammatory bowel disease. Clinical and Experimental Gastroenterology. 2016 Jan 28;21. doi:10.2147/ceg.s51902
- Klingberg E, Magnusson MK, Strid H, Deminger A, Ståhl A, Sundin J, et al. A distinct gut microbiota composition in patients with ankylosing spondylitis is associated with increased levels of fecal calprotectin. Arthritis Research &amp; Therapy. 2019 Nov 27;21(1). doi:10.1186/s13075-019-2018-4
- Parada Venegas D, De la Fuente MK, Landskron G, González MJ, Quera R, Dijkstra G, et al. Short chain fatty acids (scfas)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Frontiers in Immunology. 2019 Mar 11;10. doi:10.3389/fimmu.2019.00277
- Aho VT, Houser MC, Pereira PA, Chang J, Rudi K, Paulin L, et al. Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in parkinson’s disease. Molecular Neurodegeneration. 2021 Feb 8;16(1). doi:10.1186/s13024-021-00427-6
- Leblhuber F, Geisler S, Steiner K, Fuchs D, Schütz B. Elevated fecal calprotectin in patients with alzheimer’s dementia indicates Leaky Gut. Journal of Neural Transmission. 2015 Sept 14;122(9):1319–22. doi:10.1007/s00702-015-1381-9
- Zerbato V, Di Bella S, Giuffrè M, Jaracz AW, Gobbo Y, Luppino D, et al. High fecal calprotectin levels are associated with SARS-COV-2 intestinal shedding in COVID-19 patients: A proof-of-concept study. World Journal of Gastroenterology. 2021 Jun 14;27(22):3130–7. doi:10.3748/wjg.v27.i22.3130
- BALAMTEKIN N, DEMIR H, BAYSOY G, USLU N, ORHAN D, AKCOREN Z, et al. Fecal calprotectin concentration is increased in children with celiac disease: Relation with histopathological findings. The Turkish Journal of Gastroenterology. 2012;23(5):503–8. doi:10.4318/tjg.2012.0366
- Scaioli E, Sartini A, Bellanova M, Campieri M, Festi D, Bazzoli F, et al. Eicosapentaenoic acid reduces fecal levels of calprotectin and prevents relapse in patients with ulcerative colitis [Internet]. W.B. Saunders; 2018 [cited 2023 Jun 28]. Available from: https://www.sciencedirect.com/science/article/pii/S154235651830106X
- Maioli TU, Trindade LM, Souza A, Torres L, Andrade ME, Cardoso VN, et al. Non-pharmacologic strategies for the management of intestinal inflammation. Biomedicine &amp; Pharmacotherapy. 2022 Jan;145:112414. doi:10.1016/j.biopha.2021.112414
- CASELLAS F, BORRUEL N, TORREJÓN A, VARELA E, ANTOLIN M, GUARNER F, et al. Oral oligofructose-enriched inulin supplementation in acute ulcerative colitis is well tolerated and associated with lowered faecal calprotectin. Alimentary Pharmacology &amp; Therapeutics. 2007 Feb 16;25(9):1061–7. doi:10.1111/j.1365-2036.2007.03288.x
- Ben-Horin S, Salomon N, Karampekos G, Viazis N, Lahat A, Ungar B, et al. Curcumin-QingDai combination for patients with active ulcerative colitis: A randomized double-blinded placebo-controlled trial. Clinical Gastroenterology and Hepatology. 2023 Jun 9; doi:10.1016/j.cgh.2023.05.023
- Morshedzadeh N, Shahrokh S, Aghdaei HA, Amin Pourhoseingholi M, Chaleshi V, Hekmatdoost A, et al. Effects of flaxseed and flaxseed oil supplement on serum levels of inflammatory markers, metabolic parameters and severity of disease in patients with ulcerative colitis. Complementary Therapies in Medicine. 2019 Oct;46:36–43. doi:10.1016/j.ctim.2019.07.012
- 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 Feb 17;6(2):101–8. doi:10.1159/000513473
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The above article was contributed by
Benjamin
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