Improvement in Ulcerative Colitis Symptoms After Use of Fish Oil Enemas

Recent studies have demonstrated improved clinical response, sustained remission, and decreased dependence on corticosteroids in patients with ulcerative colitis (UC) after supplementing their therapy with oral omega-3 (n-3) fatty acids.¹ We report a case of a 75-year-old woman with active colitis who experienced improvement in her symptoms after adding to her treatment n-3 fatty acid supplements delivered via rectal enema.

Case Report

A 75-year-old Hispanic woman with a 7-year history of distal UC presented with bloody, loose stools that had recently worsened. At the time, her stool frequency remained 1–2 times daily, but the consistency of the stool was loose and mixed with blood in each movement. In addition, the patient complained of mild cramp-like lower abdominal pains and an occasional sensation of incomplete evacuation. The patient was on long-standing UC maintenance therapy of mesalamine 2.0 g daily, as well as mesalamine enemas 2–3 times weekly, and she reported that she was highly compliant with her medications. Her last colonoscopy had been 2 years earlier and demonstrated grade III colitis from the rectum to the proximal sigmoid colon. Pathologic findings had included chronic active inflammation and focal cryptitis in the rectum.

Although the conventional recommendations of changes to her medication were made, the patient opted to independently try a novel supplement to her treatment. Remaining on the current treatment regimen, the patient self-administered an additional enema daily of 3 g of fish oil. The over-the-counter preparation of fish oil she used was marketed as an oral gel-cap liquid supplement with eicosapentaenoic acid (EPA) 540 mg, docosahexaenoic acid (DHA) 360 mg, and vitamin E 3.3 IU, according to the package labeling. The liquid portion was separated from the gel cap and administered locally by the patient, without dilution in a solvent.

The patient's symptoms resolved within 3 weeks of starting this supplemental therapy. Subsequent colonoscopy demonstrated normal-appearing colonic mucosa in the rectum to 35 cm from the anus, as well as mild colitis in the descending colon. Histopathology revealed normal mucosa in the rectum and chronic active colitis in the proximal colon.

Discussion

N-3 fatty acids found in fish oil are long-chain fatty acids containing two or more double bonds.¹ Mammals cannot produce n-3 fatty acids, and so the acids are defined as “essential” and are only available by exogenous ingestion. A number of placebo-controlled studies have shown improved clinical response and decreased need for corticosteroids in symptomatic UC patients who were administered oral n-3 supplements.^2–5 Although no studies or case reports have examined clinical response of n-3 products administered rectally in humans, Yuceyar and associates investigated the protective role of n-3 fatty acid enemas in the trinitrobenzene-induced colitis model in rats.⁶ They found significant reductions in leukotriene levels in tissues exposed to n-3 enemas, but failed to demonstrate a decrease in pathologic tissue damage.

The mechanism by which n-3 fatty acids are believed to reduce inflammation results from the incorporation of the polyunsaturated fat components of EPA and DHA into the arachidonic acid precursors of inflammatory mediators. Incorporation of these products leads to increased production of 3-series prostoglandins and thromboxanes and 5-series leukotrienes, which have reduced inflammatory potential.^7,8 Interleukin-1B and tumor necrosis factor production may also be reduced by the presence of n-3 fatty acids.⁹ Thus, the propagation of inflammatory pathways are diminished.

Although structurally unrelated to n-3 fatty acids, short-chain fatty acid (SCFA) enemas have shown efficacy in treating diversion colitis,¹⁰ but not in UC.¹¹ The mechanism by which SCFA improves diversion colitis is entirely different from the anti-inflammatory mechanism of n-3 fatty acids. SCFA is believed to act as a direct metabolic energy source for epithelial cells. Deprivation of SCFA in a diverted bowel segment leads to inflammation.

Conclusion

This case report presents a case of UC in which the patient experienced significant improvement in symptoms after starting n-3 enemas and showed clear evidence of locally diminished rectal colitis on examination and histopathology. These events were either directly due to the use of n-3 enemas or represented an additional benefit of n-3 fatty acids in the induction of local remission, as her other therapies remained the same. Given prior research that oral supplementation of n-3 fatty acids is effective in UC, there is reason to believe that local rectal therapy may be of use in distal disease. Controlled studies are, therefore, warranted to investigate this possibility further. In vitro experiments may determine whether n-3 fatty acids work via systemic effect after intestinal absorption or via local contact with the gut mucosa.