Antioxidants for IBD: An emerging complementary treatment in gastro

By Naveed Saleh, MD, MS | Medically reviewed by Scott Cunningham, MD, PhD
Published March 7, 2024

Key Takeaways

  • Reactive oxygen species (ROS) can disrupt the mucosal barrier and exacerbate inflammation; some researchers say that antioxidants can help re-establish gut homeostasis.

  • Antioxidant treatments, particularly those targeting ROS in the GI tract, may be effective and safe for patients with IBD, helping to improve their quality of life.

  • Gastroenterologists may want to consider working with registered dietitians to offer natural antioxidant therapy options to their patients.

The goal of inflammatory bowel disease (IBD) treatment is to lengthen remission and prevent recurrence. Although 5-aminosalicylic acid, infliximab, and steroid hormones are effective for IBD treatment, these drugs have adverse effects and reduce quality of life.

Antioxidant treatments, however, may be an effective and safe option to include in an IBD treatment plan.

ROS and the GI tract

The GI tract is a principal producer of reactive oxygen species (ROS) in the body. Ingested food and enteric pathogens can lead to inflammation by triggering the production of pro-inflammatory cytokines, which contribute to oxidative stress. Such oxidative stress occurs despite the physical and microbial barrier via the gut epithelium. 

As explained by the authors of a review published in Frontiers in Endocrinology, oxidative stress contributes to the pathogenesis of several GI diseases, including ulcers, GI cancer, and IBD. Both acute and chronic GI diseases are characterized by heightened ROS production or hindered antioxidant mechanisms that disrupt redox homeostasis.[]

Oxidative stress–induced damage in chronic intestinal disorders is linked to mucosal infiltration by activated leukocytes.

These activated white blood cells produce excess ROS that overwhelms the antioxidant defense of tissues and further perpetuates mucosal inflammation. Superoxide ion, hydrogen peroxide, and hydroxyl radicals are all primary pro-oxidant molecules.

“The intestinal epithelium has been acknowledged as a crucial factor in the development of IBD due to its dual nature of exhibiting both immune and organ-specific functions,” write the review authors.

Excess ROS can damage cytoskeleton proteins, thus altering tight junctions and thereby boosting permeability. This disruption of the intestinal epithelial barrier can lead to excess mucosal inflammation. The initiation of IBD is due to inflammation of the GI tract secondary to oxidative stress. The microvascular network girding epithelial cells attracts inflammatory mediators, leading to increased tissue damage and an escalation of intestinal inflammation.

ROS and reactive nitrogen species (RNS) play a particularly prominent role in the initiation and progression of Crohn’s disease. Inflammation spurs the production of ROS by leukocytes and monocytes, along with prostaglandins and leukotrienes. Infiltrating neutrophils, macrophages, and intestinal epithelial cells produce ROS in the GI tract. Higher levels of 8-hydroxy-2′-deoxyguanosine (8-OHdG) could serve as a biomarker for oxidative stress in those with IBD.

By boosting the transcription of pro-inflammatory cytokines, including TNF-α, IL-6, IL-8, and IL-16, chronic NF-ĸB stimulation promotes cellular infiltration and mucosal inflammation. Chronic stimulation of this pathway also compromises the intestinal barrier via the increased apoptosis of intestinal epithelial cells, the up-regulation of metalloproteinases that break down mucosal cells, and the release of ROS metabolites that trigger NF-ĸB to further disrupt barrier stability.

Authors of a meta-analysis of antioxidant therapy for IBD underscored the role of oxidative stress in this disease.[]

“Oxidative stress,” they wrote in Pharmaceuticals, “characterized by an imbalance between pro-oxidants and antioxidants favoring the former, plays a critical role not only in the development of IBD but also in the exacerbation of its signs and symptoms. This imbalance can result in damage to macromolecules and is graded on an intensity scale ranging from eustress (physiological stress) to distress (excessive and toxic oxidative burden)."

Antioxidant capacity

Serum antioxidant capacity is the primary metric for assessing the extent and capacity of oxidative stress in various diseases, including IBD.

As discussed in Pharmaceuticals, it is gauged via total antioxidant status, total serum oxidizability, and total antioxidant potential/capacity. Serum antioxidant capacity plays an important role in the antioxidant defense system and reflects overall redox balance in patients with IBD. 

The body relies on many mechanisms to overcome redox imbalance, combat ROS/RNS, and repair damaged macromolecules. This system involves both enzymatic components (eg, superoxide dismutase, catalase, glutathione peroxidase, and peroxiredoxin) and non-enzymatic components, such as reduced glutathione. 

Gut microbiota

Prebiotics and probiotics have been used as adjuvant IBD treatments to help restore the diversity of gut microbiota.

Polyphenols, with their prebiotic-esque properties, have attracted interest, as they can increase the number of beneficial bacteria, thus reinforcing their antioxidant capabilities. Metabolites of polyphenols are catabolized by microbiota and potentiate anti-inflammatory activity.

Authors of a review on antioxidants and polyphenols in IBD reported the following:[]

“A great number of studies have shown that polyphenolic compounds positively regulate antioxidant signaling pathways, such as Nrf2, to intensify the intestinal mucosal barrier, which is also beneficial for the homeostasis of the gut microbiota. Intriguingly, some microbial phenolic metabolites, which are generated through the interaction of undigested phenolic compounds and the microbiota found in the colon, have greater relevance and bioavailability than their precursors.”

Antioxidant therapy

Based on human and animal studies, antioxidants have been proposed as a treatment in patients with IBD and other GI disorders.

Antioxidants may mitigate the adverse effects of conventional treatment such as anti-inflammatory or immunomodulatory drugs and improve patient quality of life.  

Natural antioxidant therapy may be safer than treatment with synthetic antioxidants, which have been linked to the development of GI disorders and cancer. Hormonal and phytochemical therapy may also help shift the balance from pro-inflammatory mediators toward homeostasis. Proposed hormone treatments include GLP-2 (enterohormones) and melatonin.

The following antioxidants may benefit patients with IBD:

  • Resveratrol (polyphenol)

  • Curcumin (polyphenol)

  • Quercetin (polyphenol)

  • Green tea flavonoids (polyphenol)

  • Luteolin (polyphenol)

  • Berberine (alkaloid)

  • Flaxseed oil

  • Sulforaphane (phytochemical)

  • Ginger

These antioxidants re-establish homeostasis via various mechanisms, including the inhibition of transcription factors and pro-inflammatory cytokines and the activation of anti-inflammatory cytokines. In addition, they are active in scavenging ROS/RNS, modulating antioxidant enzymes, and restoring tight junctions and intestinal barriers.

What this means for you

Conventional treatments for IBD leave something to be desired, resulting in adverse effects and decreased quality of life. The use of antioxidant therapy is emerging as an area of interest. Gastroenterologists may consider working with registered dietitians to offer natural antioxidant therapy options to their patients. 

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