Selenium and Inflammatory Bowel Disease: A Review

Herewith the conclusions from a review of the available research literature about selenium and inflammatory bowel disease [Ala & Kheyri 2021].

• Selenium deficiency is a common finding in Inflammatory Bowel Disease (IBD) patients, and there is a correlation between increasing selenium deficiency and disease severity.
• Selenium contributes to effective function of antioxidant systems
  and alleviates colitis.

  

• Selenium aids healing of the intestinal mucosa through modification of immune response.
• Selenium may improve the activity of gut protective microbiota, which are decreased in IBD.
• Selenium may reduce the risk of colorectal cancer by modulating several signaling pathways.  

How does Adequate Selenium Status Help Inflammatory Bowel Disease patients?

Adequate intakes of selenium are needed for the biosynthesis of selenoproteins, which contribute to antioxidative protection of cells and to the effective functioning of the immune system.

• Selenium through the action of selenoproteins is known to have anti-inflammatory properties.
• Adequate selenium status supports protective gut microbiota, which indirectly improves the management of IBD.
• Selenium may block some of the tumorigenesis pathways under investigation in colitis-associated colorectal cancer.

Intake of Selenium Varies from Region to Region

The dietary intake and individuals’ serum level of selenium varies from region to region. For example, the US population has higher serum level of selenium (ca. 124 – 193 mcg/L) compared to most of the European and Middle Eastern populations (ca. 50-120 mcg/L) simply because the soil in many regions of North America is rich in selenium.

• Normal blood selenium concentrations need to stay within a relatively narrow range of 100 – 170 mcg/L [Rayman 2012 figure 3].
• Daily combined dietary and supplemental intakes of 100-200 mcg/day should provide enough selenium for individuals with normal absorption. Daily intake of more than 350-700 mcg/day of selenium is thought to be toxic [Ala & Kheyri 2021].

Transportation and Distribution of Ingested Selenium in the Body

In the body, some of the elemental selenium replaces the sulfur in the amino acid cysteine, which in turn becomes selenocysteine. Selenocysteine is a component of 25 identified selenoproteins. These selenoproteins have many different functions, chief among them the antioxidative and anti-inflammatory functions.

The selenium containing selenocysteine needs a transporter to carry it to its target tissues. Selenoprotein P (SEPP) is the primary transporter in the blood. It is mainly produced in the liver cells [Ala & Kheyri 2021].

The distribution of selenium in the body follows a tissue hierarchy. Even in times of selenium deficiency, the brain and the testes maintain higher amounts of selenium than are needed for their function. Supply of selenium to the immune system, on the other hand, is not prioritized highly. Most of
the body selenium is stored in skeletal muscle [Ala & Kheyri 2020].

Antioxidant Action of Selenoproteins

Antioxidants convert harmful reactive oxygen species, commonly known as free radicals, to less harmful products. The free radicals are the by-products of cellular metabolism processes. In small amounts, these free radicals serve useful purposes such as cell propagation and cell signaling.

• In excessive amounts, the free radicals can do damage to lipids, nucleic acids, and proteins [Ala & Kheyri 2021]. This condition is called oxidative stress.
• The regulation and attenuation of uncontrolled oxidative stress aids in the management of IBD [Ala & Kheyri 2021].
• Selenium acts through selenoproteins as part of the body’s antioxidant defense. The most active antioxidant selenoproteins are member of the glutathione peroxidase (GPx) group and members of the thioredoxin reductase (Trx) group.

Selenium and the Immune System

There is a close relationship between adequate selenium status and immune system function. Selenium augments immune response and also modifies immune response.

• The functioning of the innate immunity depends considerably on the production of reactive oxygen species to disable harmful microorganisms. Phagocytes need selenium and selenoproteins to reduce their oxidized products.
• Selenium is also involved in the adaptive immunity. Selenium is an enhancer for IL2 receptor signaling. Moreover, selenium promotes human T cells activation through T cell receptors. It is the increased expression of glutathione peroxidase-1 and thioredoxin reductase-1 that is involved in this effect on the adaptive immune system.
• Furthermore, although selenium enhances T cell response when needed, it prevents the uncontrolled activation of immune system in autoimmune diseases [Ala & Kheyri 2021].

Clinical Trials of Selenium for the Treatment of Colitis

Preclinical studies show that selenium can alleviate colitis. Now, clinical trials are needed to verify the effect and to determine the best form and dosage of selenium.

Stedman study

Patients with mild to moderate ulcerative colitis received two tablets of selenium (300 mcg) combined with antioxidants such as beta-carotene, vitamin C, and vitamin E for eight weeks.

The selenium + antioxidants treatment increased selenium levels in the patients and decreased their iron level.

The treatment was associated with a significant reduction in the number of soft/liquid stool defecations [Stedman 1997].

Shapira study

Patients were given supplements containing 1000 mg curcumin, 200 mcg selenium, and 500 mg green tea extract daily for 8 weeks. The outcomes of the study were improved endoscopic inflammation and remission of mild to moderate ulcerative colitis [Shapira 2018].

ConclusionS

• Inflammatory Bowel Disease patients commonly have low selenium status.
• The lower the selenium status, the more severe the disease.
• Selenium supplementation to restore the deficiency provides the sub-stratum for the bio-synthesis of selenoproteins that have an antioxidative and anti-inflammatory effect.
• The researchers Ala and Kheyri conclude that selenium seems to be a good option to alleviate selenium deficient IBD in both short-term and long-term.

Sources

Ala M, Kheyri Z. The rationale for selenium supplementation in inflammatory bowel disease: A mechanism-based point of view.
Nutrition. 2021; 111153.

Ghishan FK, Kiela PR. Vitamins and Minerals in Inflammatory Bowel Disease. Gastroenterol Clin North Am. 2017 Dec;46(4):797-808.

Hariharan S, Dharmaraj S. Selenium and selenoproteins: its role in regulation of inflammation. Inflammopharmacology. 2020 Jun;28(3):667-695.

Kudva AK, Shay AE, Prabhu KS. Selenium and inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol. 2015;309(2):G71-G77.

Rayman MP. Selenium and human health. Lancet. 2012 Mar 31;379(9822):1256-68.

Shapira S, Leshno A, Katz D, Maharshak N, Hevroni G, Jean-David M, et al. Of mice and men: a novel dietary supplement for the treatment of ulcerative colitis. Therapeutic advances in gastroenterology. 2018;11:1756283X17741864.

Stedman JD, Spyrou NM, Millar AD, Altaf WJ, Akanle OA, Rampton DS. Selenium supplementation in the diets of patients suffering from ulcerative colitis. Journal of radioanalytical and nuclear chemistry. 1997;217:189-91.

The information presented in this review article is not intended as medical advice and should not be used as such.

30 March 2021